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Wei H, Zhao Q. CYP2D6 polymorphism rs1065852 significantly increases the risk of type 2 diabetes. Ann Med 2025; 57:2470956. [PMID: 40028882 PMCID: PMC11878161 DOI: 10.1080/07853890.2025.2470956] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2024] [Revised: 01/06/2025] [Accepted: 01/13/2025] [Indexed: 03/05/2025] Open
Abstract
BACKGROUND Genetic variations within the cytochrome P450 (CYP) gene family are significant determinants of type 2 diabetes mellitus (T2DM) susceptibility. This study aimed to investigate the association between CYP2C8 and CYP2D6 gene variants and the risk of T2DM. METHODS We conducted a case-control study involving 512 individuals with T2DM and 515 controls. Genotyping of CYP2C8 and CYP2D6 polymorphisms was performed using the Agena MassARRAY system. Logistic regression analysis was employed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs), thereby assessing the relationship between these genetic variants and T2DM risk. Additionally, multifactor dimensionality reduction (MDR) was utilized to assess the potential interaction effects of SNPs on T2DM risk. RESULTS The study found a strong correlation between rs1065852 and increased risk of T2DM in overall (A vs. G: OR = 1.22, 95% CI: 1.03-1.45, p = .024; AA vs. GG: OR = 1.46, 95% CI: 1.04-2.06, p = .031; AA-AG vs. GG: OR = 1.36, 95% CI: 1.04-1.79, p = .026; additive: OR = 1.21, 95% CI: 1.02-1.44, p = .027), males and age < 59 subgroups. However, there is no significant association between the CYP2C8 polymorphisms (rs1934953, rs1934951, rs2275620 and rs17110453) and T2DM risk. MDR analysis results showed that the best model was the one locus model (rs1065852, testing accuracy = 0.534; OR = 1.39; 95% CI: 1.05-1.85; p = .023; CVC = 10/10), indicating that rs1065852 is an independent risk factor for T2DM. CONCLUSIONS This study suggests that rs1065852 (CYP2D6) is an independent risk factor for T2DM. Further research is warranted to validate these results and explore their clinical implications.
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Affiliation(s)
- Huiyi Wei
- Medical College of Yan’an University, Yan’an, China
| | - Qingbin Zhao
- Department of Geratology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
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Jiang J, Huang W, Lan L, Zheng X, Luo S, Ding Y, Yan J, Ren W, Tang K, Yang D. Related factors for kidney disease and high chronic kidney disease progression risk in adult-onset type 1 diabetes mellitus patients from China: a multi-center cross-sectional study. Ren Fail 2025; 47:2483389. [PMID: 40159884 PMCID: PMC11951320 DOI: 10.1080/0886022x.2025.2483389] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Revised: 02/25/2025] [Accepted: 03/15/2025] [Indexed: 04/02/2025] Open
Abstract
BACKGROUND/AIM Concerning the related factors for kidney disease and high chronic kidney disease (CKD) progression risk, there is still a lack of study in the adult-onset type 1 diabetes mellitus (T1DM) patients from China. METHODS Four hundred and eighty-one adult-onset T1DM patients from the Guangdong T1DM translational medicine study were included. Logistic regression analysis (Forward: LR) was utilized to identify glycemic- and nonglycemic-related factors associated with moderate albuminuria, severe albuminuria, mildly reduced estimated glomerular filtration rate (eGFR), decreased eGFR, and high CKD progression risk, and to calculate the odds ratio (OR) and 95% confidence interval (CI). RESULTS High CKD progression risk was positively associated with males (OR = 3.13, 95% CI:1.20 - 8.14, p = 0.019), duration of T1DM (OR =1.13, 95% CI:1.05 - 1.21, p < 0.001), triglyceride (OR =1.52, 95% CI:1.11 - 2.08, p = 0.008), and systolic blood pressure (SBP) (OR =1.04, 95% CI:1.02 - 1.07, p = 0.001), and negatively correlated with BMI (OR = 0.80, 95% CI:0.68 - 0.95, p = 0.011). Meanwhile, moderate albuminuria, severe albuminuria, mildly reduced eGFR and decreased eGFR had different each of glycemic- and nonglycemic-related factors. CONCLUSIONS Hyperglycemia, hypertension, hyperuricemia, and BMI may be associated with different stages of kidney disease in adult-onset T1DM patients. Early-stage adult-onset T1DM patients with male, low BMI, prolonged diabetes duration, and comorbid hypertension and dyslipidemia should undergo a thorough evaluation of albuminuria and renal function to detect those at high CKD progression risk, who should be timely transferred to the nephrology specialty to receive professional treatment for kidney disease.
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Affiliation(s)
- Jun Jiang
- Department of Nephrology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
- Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Wenjuan Huang
- Department of Nephrology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Lei Lan
- Department of Nephrology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Xueying Zheng
- Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Sihui Luo
- Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Yu Ding
- Institute of Endocrine and Metabolic Diseases, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Jinhua Yan
- Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong, China
| | - Wei Ren
- Department of Nephrology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China
| | - Kuanxiao Tang
- Department of General Practice, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China
| | - Daizhi Yang
- Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Diabetology, Guangzhou, Guangdong, China
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Tangjittipokin W, Narkdontri T, Teerawattanapong N, Suthon S, Nakhonsri V, Wasitthankasem R, Sudtachat N, Preechasuk L, Lapinee V, Thongtang N, Tongsima S, Plengvidhya N. Investigation of the degree of family history of diabetes in different clusters of newly diagnosed type 2 diabetes in Thailand. Ann Med 2025; 57:2500697. [PMID: 40338056 PMCID: PMC12064116 DOI: 10.1080/07853890.2025.2500697] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/19/2024] [Revised: 04/17/2025] [Accepted: 04/23/2025] [Indexed: 05/09/2025] Open
Abstract
AIM Type 2 diabetes is a heterogeneous disease with strong genetic components. We showed earlier that newly diagnosed type 2 diabetes in Thai patients could be categorized into four clusters. This study aimed to determine the evidence of hereditary factors in these type 2 diabetes clusters. METHODS A total of 487 subjects who were diagnosed with type 2 diabetes in two years were enrolled in the Siriraj Diabetes Center, Siriraj Hospital Bangkok, Bangkok, Thailand. They were divided into four clusters as previously described. The associations between patients' characteristics, degree of family history of diabetes (FHD), and type 2 diabetes clusters were tested using multinomial logistic regression. RESULTS Among four clusters of newly diagnosed type 2 diabetes, there were significant differences in characteristics at baseline, including age at diagnosis, BMI, waist circumference, blood sugar levels, vital signs, triglyceride, HDL, calculated LDL, creatinine and eGFR (all p < .05). A relatively young age at the time of diabetes diagnosis was associated with having second-degree relatives with diabetes (p < .05) in all clusters when using mild age-related diabetes (MARD) cluster with no FHD as a control. Patients in the severe insulin-deficient diabetes (SIDD) cluster had more first-degree relatives with diabetes (odds ratio = 1.85; p = .0354), while patients in the metabolic syndrome diabetes (MSD) cluster (odds ratio = 10.73; p < .001) and the mild obesity-related diabetes (MOD) group (odds ratio = 6.66; p = .002), had more second-degree relatives with diabetes. CONCLUSIONS Genetic factors might have various roles in the pathogenesis of type 2 diabetes, at least in newly diagnosed Thai patients. Our findings supported that genetic heterogeneity contributed to clinical heterogeneity or four different clusters. Further studies are needed in a larger sample size of these patients is needed to identify genetic loci associated with each cluster.
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Affiliation(s)
- Watip Tangjittipokin
- Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Siriraj Center of Research Excellence for Diabetes and Obesity, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Tassanee Narkdontri
- Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Siriraj Center of Research Excellence for Diabetes and Obesity, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nipaporn Teerawattanapong
- Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Siriraj Center of Research Excellence for Diabetes and Obesity, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Sarocha Suthon
- Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Siriraj Center of Research Excellence for Diabetes and Obesity, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Vorthunju Nakhonsri
- National Biobank of Thailand, National Science and Technology Development Agency, Khlong Nueng, Thailand
| | - Rujipat Wasitthankasem
- National Biobank of Thailand, National Science and Technology Development Agency, Khlong Nueng, Thailand
| | - Nirinya Sudtachat
- National Biobank of Thailand, National Science and Technology Development Agency, Khlong Nueng, Thailand
| | - Lukana Preechasuk
- Siriraj Diabetes Center of Excellence, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Varisara Lapinee
- Siriraj Diabetes Center of Excellence, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Nuntakorn Thongtang
- Siriraj Diabetes Center of Excellence, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Sissades Tongsima
- National Biobank of Thailand, National Science and Technology Development Agency, Khlong Nueng, Thailand
| | - Nattachet Plengvidhya
- Siriraj Center of Research Excellence for Diabetes and Obesity, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
- Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Yang P, Chen X, Qin Y, Yu L, Ge G, Yin W, Zhang W, Li W, Li W, Xia W, Wu Z, Ding F, Bai J, Meng F, Geng D. Regulation of osteoimmune microenvironment via functional dynamic hydrogel for diabetic bone regeneration. Biomaterials 2025; 320:123273. [PMID: 40121832 DOI: 10.1016/j.biomaterials.2025.123273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2024] [Revised: 02/20/2025] [Accepted: 03/17/2025] [Indexed: 03/25/2025]
Abstract
Bone regeneration and repair face formidable challenges under diabetic conditions, primarily due to the disruption of macrophage polarization induced by diabetes and the inflammatory imbalance within the bone microenvironment. We have developed a novel dynamic hydrogel system (AG-CD@LINA), constructed through the coordination crosslinking of thiolated gelatin (SH-Gelatin) and gold ions (Au3+), followed by grafting with cyclodextrin to load the ligand linagliptin. This hydrogel effectively inhibits the formation of M1 macrophages and the expression of pro-inflammatory cytokines by gradually releasing linagliptin. Simultaneously, it promotes the formation of M2 macrophages and the expression of anti-inflammatory cytokines, thus improving the inflammatory microenvironment of diabetic bone defects. Consequently, it facilitates the migration of mesenchymal stem cells and angiogenic cells, augments osteogenic activity, and promotes vascularization, collectively accelerating the regeneration of diabetic bone tissue. Mechanistically, polarization occurs through the TLR3-NF-κB signaling pathway. In vivo experiments demonstrate that the in-situ injection of the hydrogel enhances the regeneration of bone tissue and the restoration of bone structure in diabetic bone defects, effectively modulating local inflammation and promoting vascular formation. This study suggests that functionalized dynamic hydrogels can improve the inflammatory microenvironment by regulating in situ macrophage polarization, thereby facilitating the reconstruction of bone microstructure. This approach represents a promising novel therapeutic strategy for diabetic bone defects.
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Affiliation(s)
- Peng Yang
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, 215006, Jiangsu, China; Department of Orthopedics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215006, Jiangsu, China; Suzhou Key Laboratory of Orthopedic Medical Engineering, Suzhou, 215006, Jiangsu, China
| | - Xu Chen
- Institute for Advanced Materials, School of Materials Science and Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China
| | - Yi Qin
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, 215006, Jiangsu, China
| | - Lei Yu
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, 215006, Jiangsu, China
| | - Gaoran Ge
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, 215006, Jiangsu, China.
| | - Weiling Yin
- Institute for Advanced Materials, School of Materials Science and Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China
| | - Wei Zhang
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, 215006, Jiangsu, China
| | - Wenming Li
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, 215006, Jiangsu, China
| | - Wenhao Li
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, 215006, Jiangsu, China
| | - Wenyu Xia
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, 215006, Jiangsu, China
| | - Zebin Wu
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, 215006, Jiangsu, China
| | - Fan Ding
- Institute for Advanced Materials, School of Materials Science and Engineering, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China
| | - Jiaxiang Bai
- Department of Orthopedics, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230022, China.
| | - Fanwen Meng
- Department of Implant Dentistry, Suzhou Stomatological Hospital, Suzhou, 215005, China.
| | - Dechun Geng
- Department of Orthopedics, The First Affiliated Hospital of Soochow University, Orthopedic Institute, Medical College, Soochow University, Suzhou, 215006, Jiangsu, China.
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Zheng B, Wang B, Sun W, Wang H, Yang C, Zeng M, Sheng R. MRI-based predictive model with obesity metabolic phenotype for postoperative survival in HBV-related hepatocellular carcinoma. Eur J Radiol 2025; 189:112201. [PMID: 40451092 DOI: 10.1016/j.ejrad.2025.112201] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2025] [Revised: 05/13/2025] [Accepted: 05/26/2025] [Indexed: 06/11/2025]
Abstract
PURPOSE Obesity metabolic phenotypes may influence survival outcomes in hepatocellular carcinoma (HCC) patients. This study aimed to develop an MRI-based model for postoperative survival prediction in HBV-related HCC patients, focusing on obesity metabolic phenotypes. METHODS A retrospective cohort of 381 HBV-related HCC patients (312 males; mean age 55.9 ± 10.7 years) who underwent preoperative MRI and curative surgery was studied. Patients were categorized into three phenotypes: normal weight (NW), metabolically healthy overweight/obesity (MHOO) and metabolically unhealthy overweight/obesity (MUOO). Univariate and multivariate Cox regression analyses identified independent predictors of overall survival (OS). A predictive model was established and validated with cross-validation. RESULTS MHOO patients showed significantly better overall survival (OS) than NW patients (adjusted HR = 0.42, P = 0.030), while MUOO had no significant effect on OS (adjusted HR = 0.92, P = 0.779). Independent predictors included MHOO (HR = 0.44, P = 0.036), AST/ALT ratio > 1 (HR = 2.61, P = 0.001), tumor burden score > 5.0 (HR = 3.02, P < 0.001) and arterial rim enhancement (HR = 3.61, P < 0.001). The combined model achieved good performance in both training (C-index = 0.737) and validation (C-index = 0.715) sets. The predicted high-risk patients had worse OS than low-risk patients in the whole cohort (P < 0.001) and in patients at BCLC stage A (P < 0.001). The model outperformed the BCLC and CNLC staging systems in predictive efficacy (all P < 0.001) and clinical net benefit. CONCLUSIONS MHOO is protective for OS in HBV-related HCC. The MRI-based model integrating obesity metabolic phenotype, AST/ALT ratio, tumor burden score and arterial rim enhancement is valuable in survival prediction, offering superior prognostic stratification compared to current staging systems.
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Affiliation(s)
- Beixuan Zheng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Shanghai Institute of Medical Imaging, Shanghai 200032, PR China
| | - Bin Wang
- Department of Radiology, Zhongshan Wusong Hospital, Shanghai, 200940, PR China
| | - Wei Sun
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Shanghai Institute of Medical Imaging, Shanghai 200032, PR China
| | - Heqing Wang
- Department of Radiology, Xiamen Branch, Zhongshan Hospital, Fudan University, Xiamen 361015, PR China
| | - Chun Yang
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Shanghai Institute of Medical Imaging, Shanghai 200032, PR China
| | - Mengsu Zeng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Shanghai Institute of Medical Imaging, Shanghai 200032, PR China.
| | - Ruofan Sheng
- Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Shanghai Institute of Medical Imaging, Shanghai 200032, PR China.
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Tsutsumi T, Kawaguchi T, Fujii H, Kamada Y, Suzuki Y, Sawada K, Tatsuta M, Maeshiro T, Tobita H, Akahane T, Hasebe C, Kawanaka M, Kessoku T, Eguchi Y, Syokita H, Nakajima A, Kamada T, Yoshiji H, Sakugawa H, Morishita A, Masaki T, Ohmura T, Watanabe T, Yoda Y, Enomoto N, Ono M, Fuyama K, Okada K, Nishimoto N, Ito YM, Takahashi H, Charlton MR, Rinella ME, Sumida Y. Low HDL cholesterol levels in women and hypertriglyceridemia in men: predictors of MASLD onset in individuals without steatosis. J Gastroenterol 2025; 60:891-904. [PMID: 40097845 DOI: 10.1007/s00535-025-02242-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Accepted: 03/08/2025] [Indexed: 03/19/2025]
Abstract
BACKGROUND Individuals with metabolic-associated steatotic liver disease (MASLD) have a worse prognosis compared to patients without steatosis, and its prevalence is increasing. However, detailed risk factors based on obesity and sex remain unclear. We aimed to investigate the impact of cardiometabolic risk factors (CMRFs) on the risk of MASLD in individuals without pre-existing SLD. METHODS SLD was diagnosed by ultrasonography. Non-SLD individuals were followed 65,657 person-years. Incidence rates of MASLD were assessed by Kaplan-Meier analysis. Furthermore, independent factors associated with the development of MASLD were identified using Cox regression analysis, stratified by four groups: obese men, non-obese men, obese women, and non-obese women. RESULTS The overall incidence rate of MASLD was 39.3/1,000 person-years. The cumulative incidence was highest in obese men, followed by obese women, non-obese men, and non-obese women. Two or more CMRFs increased the risk of MASLD in all groups. Low HDL cholesterol level was the strongest independent risk factor in both obese and non-obese women and hypertriglyceridemia for both obese and non-obese men. The impact of these CMRFs was stronger in non-obese individuals. (HR [95% CI]: women non-obese 1.9 [1.5-2.4], obese 1.4 [1.1-1.8]; men non-obese 2.3 [1.9-2.9], obese 1.5 [1.2-2.0]). CONCLUSIONS Multiple CMRFs are important to MASLD development, regardless of sex and obesity. In this Japanese cohort, low HDL cholesterol in women and hypertriglyceridemia in men were the most significant risk factors, especially among the non-obese group. These findings suggest that sex-specific CMRFs may play a role in the development of MASLD.
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Affiliation(s)
- Tsubasa Tsutsumi
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, 5841 South Maryland Ave., Chicago, IL, 60637, USA.
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, 830-0011, Japan.
| | - Takumi Kawaguchi
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-Machi, Kurume, 830-0011, Japan
| | - Hideki Fujii
- Department of Hepatology, Graduate School of Medicine, Osaka Metropolitan University, 1-4-3, Asahimachi, Abeno, Osaka, 545-8585, Japan
| | - Yoshihiro Kamada
- Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, 1-7, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yuichiro Suzuki
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo-Shi, Yamanashi, 409-3898, Japan
| | - Koji Sawada
- Division of Metabolism and Biosystemic Science, Gastroenterology, and Hematology/Oncology, Department of Medicine, Asahikawa Medical University, 2-1-1-1, Midorigaoka Higashi, Asahikawa-City, Hokkaido, 078-8510, Japan
| | - Miwa Tatsuta
- Department of Gastroenterology, KKR Takamatsu Hospital, 4-18 Tenjinmae, Takamatsu, Kagawa, 760-0018, Japan
| | - Tatsuji Maeshiro
- First Department of Internal Medicine, University of the Ryukyus Hospital, 207 Uehara, Nishihara, Nakagami, Okinawa, 903-0215, Japan
| | - Hiroshi Tobita
- Department of Hepatology, Shimane University Hospital, 89-1 Enya-Cho, Izumo, Shimane, 693-8501, Japan
| | - Takemi Akahane
- Department of Gastroenterology, Uda City Hospital, 815 Haibarahagihara, Uda, Nara, 633-0253, Japan
| | - Chitomi Hasebe
- Department of Gastroenterology, Japanese Red Cross Asahikawa Hospital, Akebono-1Jo 1Chome 1-1, Asahikawa-City, Hokkaido, 070-0061, Japan
| | - Miwa Kawanaka
- Department of General Internal Medicine 2, Kawasaki Medical School, Kawasaki Medical Center, 2-6-1, Nakayamashimo, Kita, Okayama, 700-8505, Japan
| | - Takaomi Kessoku
- Kanagawa Dental University Yokohama Clinic, Yokohama, Kanagawa, Japan
- Department of Palliative Medicine and Gastroenterology, International University Health and Welfare Narita Hospital, 4-3, Kimizunomori 4-Chome, Narita-Shi, Chiba, 286-8686, Japan
- Division of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9, Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan
| | - Yuichiro Eguchi
- Loco Medical General Institute, Mikatsukicho Kanada, Ogi-Shi, Saga, 845-0032, Japan
| | - Hayashi Syokita
- Department of Gastroenterology, Northern OKINAWA Medical Center, 1712-3 Umusa, Nago, Okinawa, 905-0006, Japan
| | - Atsushi Nakajima
- Division of Gastroenterology and Hepatology, Yokohama City University Graduate School of Medicine, 3-9, Fukuura, Kanazawa-Ku, Yokohama, 236-0004, Japan
| | - Tomoari Kamada
- Department of General Internal Medicine 2, Kawasaki Medical School, Kawasaki Medical Center, 2-6-1, Nakayamashimo, Kita, Okayama, 700-8505, Japan
| | - Hitoshi Yoshiji
- Department of Gastroenterology, Uda City Hospital, 815 Haibarahagihara, Uda, Nara, 633-0253, Japan
| | - Hiroshi Sakugawa
- Department of Gastroenterology, Heartlife Hospital, 208, Iju, Nakagusuku, Nakagami, Okinawa, 901-2492, Japan
| | - Asahiro Morishita
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Oaza Ikenobe Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan
| | - Tsutomu Masaki
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Oaza Ikenobe Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan
| | - Takumi Ohmura
- Department of Health Care, Asahikawa-Kosei General Hospital, 24-111, 1 Jo-Dori, Asahikawa-City, Hokkaido, 078-8211, Japan
| | - Toshio Watanabe
- Department of Advanced Metabolic Hepatology, Osaka University Graduate School of Medicine, 1-7, Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yoshioki Yoda
- JA Yamanashi Koseiren Health Care Center, 1-26, Iida 1, Kofu, Yamanashi, 400-0035, Japan
| | - Nobuyuki Enomoto
- First Department of Internal Medicine, Faculty of Medicine, University of Yamanashi, 1110, Shimokato, Chuo-Shi, Yamanashi, 409-3898, Japan
| | - Masafumi Ono
- Department of Gastroenterology and Neurology, Faculty of Medicine, Kagawa University, 1750-1 Oaza Ikenobe Miki-Cho, Kita-Gun, Kagawa, 761-0793, Japan
| | - Kanako Fuyama
- Data Science Center, Promotion Unit, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, 060-8648, Japan
| | - Kazufumi Okada
- Data Science Center, Promotion Unit, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, 060-8648, Japan
| | - Naoki Nishimoto
- Data Science Center, Promotion Unit, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, 060-8648, Japan
| | - Yoichi M Ito
- Data Science Center, Promotion Unit, Institute of Health Science Innovation for Medical Care, Hokkaido University Hospital, Sapporo, 060-8648, Japan
| | - Hirokazu Takahashi
- Liver Center, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Michael R Charlton
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, 5841 South Maryland Ave., Chicago, IL, 60637, USA
| | - Mary E Rinella
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Chicago, 5841 South Maryland Ave., Chicago, IL, 60637, USA
| | - Yoshio Sumida
- Graduate School of Healthcare Management, International University of Healthcare and Welfare, 4-1-26, Akasaka, Minato-Ku, Tokyo, Japan
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Vazquez-Agra N, Barrera-Lopez L, Marques-Afonso AT, Cruces-Sande A, Lopez-Paz JE, Pose-Reino A, Hermida-Ameijeiras A. Assessing the relationship between short-term blood pressure variability and glycation profile in young and middle-aged nondiabetic hypertensive individuals. J Hypertens 2025; 43:1148-1157. [PMID: 40265460 PMCID: PMC12144551 DOI: 10.1097/hjh.0000000000004029] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 03/14/2025] [Accepted: 03/16/2025] [Indexed: 04/24/2025]
Abstract
INTRODUCTION Elevated short-term blood pressure (BP) variability (BPV) has been associated with a poorer cardiovascular prognosis. The glycation profile is related to BPV in diabetic and prediabetic individuals. However, little is known about the relationship between glycation levels and BPV in hypertensive patients with optimal glycemic control. OBJECTIVES This observational study aimed to elucidate the relationship between glycated hemoglobin (HbA1c) levels and short-term BPV in young and middle-aged hypertensive patients over 18 years with HbA1c levels below 5.7%. METHODS We collected and analyzed data on 24-h ambulatory BP monitoring, demographic, epidemiological, clinical, and laboratory variables from 143 hypertensive patients. BPV was measured as the standard deviation (SD) and average real variability (ARV) in millimeters of mercury, as well as the dimensionless coefficient of variation (CV). RESULTS Depending on the index, each one unit increase in nighttime SD and CV indices was associated with a 17-24% higher likelihood of elevated HbA1c levels (higher than 5.2%). Regarding BPV dipping, each 1% decrease in nighttime SD and CV dipping was associated with a 10-20% higher risk of increased HbA1c levels. Additionally, each 1% decrease in nighttime ARV DBP dipping was also associated with a 10% higher risk of elevated HbA1c levels. A one-standardized-unit increase in the overall combined BPV index, as a pooled measure of BPV, was associated with a 45% higher likelihood of raised HbA1c levels. CONCLUSION Even within the optimal range, elevated HbA1c levels may reflect an underlying increase in BPV, which may be particularly relevant given the prognostic implications of short-term BPV.
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Affiliation(s)
- Nestor Vazquez-Agra
- Department of Internal Medicine, University Hospital of Santiago de Compostela
- Health Research Institute of Santiago de Compostela (IDIS)
- University of Santiago de Compostela (USC), Santiago de Compostela, A Coruña, Spain
| | - Lucia Barrera-Lopez
- Department of Internal Medicine, University Hospital of Santiago de Compostela
- Health Research Institute of Santiago de Compostela (IDIS)
| | - Ana-Teresa Marques-Afonso
- Department of Internal Medicine, University Hospital of Santiago de Compostela
- Health Research Institute of Santiago de Compostela (IDIS)
| | - Anton Cruces-Sande
- Health Research Institute of Santiago de Compostela (IDIS)
- University of Santiago de Compostela (USC), Santiago de Compostela, A Coruña, Spain
| | | | - Antonio Pose-Reino
- Department of Internal Medicine, University Hospital of Santiago de Compostela
- Health Research Institute of Santiago de Compostela (IDIS)
- University of Santiago de Compostela (USC), Santiago de Compostela, A Coruña, Spain
| | - Alvaro Hermida-Ameijeiras
- Department of Internal Medicine, University Hospital of Santiago de Compostela
- Health Research Institute of Santiago de Compostela (IDIS)
- University of Santiago de Compostela (USC), Santiago de Compostela, A Coruña, Spain
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Yuan Y, Isasi CR, Al-Rousan T, Ghosh AK, Mullachery PH, Palta P, Makarem N. Associations of Concurrent Hypertension and Type 2 Diabetes With Mortality Outcomes: A Prospective Study of U.S. Adults. Diabetes Care 2025; 48:1241-1250. [PMID: 40397766 PMCID: PMC12178617 DOI: 10.2337/dca24-0118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 04/12/2025] [Indexed: 05/23/2025]
Abstract
OBJECTIVE To investigate associations of concurrent hypertension and type 2 diabetes (T2D) with mortality in U.S. adults and elucidate differences by sex, race, and ethnicity. RESEARCH DESIGN AND METHODS The study population included 48,727 adults from the 1999-2018 National Health and Nutrition Examination Surveys. Participants were categorized into four mutually exclusive categories: 1) no hypertension and no T2D, 2) hypertension only, 3) T2D only, and 4) coexisting hypertension and T2D. Outcomes were all-cause and cardiovascular mortality defined using ICD-10 codes. Kaplan-Meier curves and multivariable Cox proportional hazards models were used to evaluate associations of hypertension and T2D status with mortality risk. RESULTS The burden of concurrent hypertension and T2D doubled between 1999 and 2018 from 6% to 12%. Overall, 50.5% of participants did not have T2D or hypertension, 38.4% had hypertension only, 2.4% had T2D only, and 8.7% had both. During a 9.2-year median follow-up, 7,734 deaths occurred. Concurrent hypertension and T2D versus no hypertension or T2D predicted higher all-cause (hazard ratio 2.46 [95% CI 2.45, 2.47]) and cardiovascular mortality risk (2.97 [2.94, 3.00]), with stronger associations in females versus males (P for interaction <0.01). Compared with having hypertension or T2D only, concurrent hypertension and T2D predicted up to 66% and more than twofold higher all-cause and cardiovascular mortality risk, respectively, and associations varied by sex and race and ethnicity (P for interaction <0.01), depending on the reference group (T2D only or hypertension only). Concurrent prediabetes and elevated blood pressure predicted up to 19% higher mortality risk compared with having neither or either condition. CONCLUSIONS Concurrent hypertension and T2D predict high mortality risk, underscoring the critical need for contextual interventions that extend healthspan in the U.S.
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Affiliation(s)
- Ye Yuan
- Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY
| | - Carmen R. Isasi
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY
| | - Tala Al-Rousan
- Herbert Wertheim School of Public Health and Human Longevity, University of California, San Diego, San Diego, CA
| | - Arnab K. Ghosh
- Department of Medicine, Weill Cornell Medical College, New York, NY
| | - Pricila H. Mullachery
- Department of Health Services Administration and Policy, College of Public Health, Temple University, Philadelphia, PA
| | - Priya Palta
- Department of Neurology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC
| | - Nour Makarem
- Department of Epidemiology, Mailman School of Public Health, Columbia University Irving Medical Center, New York, NY
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Si K, Shi C, Huang Y, Liu C, Chi J, Xu L, Chen Y, Wang Y. Joint association of the newly proposed dietary index for gut microbiota and sleep disorders with survival among US adult population with diabetes and pre-diabetes. Nutr J 2025; 24:95. [PMID: 40533747 PMCID: PMC12175418 DOI: 10.1186/s12937-025-01162-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2024] [Accepted: 06/06/2025] [Indexed: 06/22/2025] Open
Abstract
BACKGROUND Diet and sleep disorders are associated with risks of metabolic diseases such as diabetes. The dietary index for gut microbiota (DI-GM) is a newly proposed index designed to assess dietary quality associated with maintaining a healthy gut microbiota. The authors aim to investigate the separate and joint prognostic effect of DI-GM and sleep disorders on the survival of US population with diabetes and pre-diabetes. METHODS Data were from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 at baseline linked to the 2019 National Death Index records. Dietary recall data were collected to calculate the DI-GM and sleep disorders were assessed by self-reported questionnaires. The Cox proportional hazard model were used to evaluate the associations between separate and joint prognostic effects of DI-GM and sleep disorders with mortality outcomes among diabetic and pre-diabetic patients. RESULTS A total of 10718 Participants with diabetes and pre-diabetes were ultimately included in this study (weighted population: 67,232,394, weighted mean age [SE]: 57.0 [0.1] years; weighted female proportion: 51.8%). Among these participants, higher DI-GM was more prevalent in those without sleep disorders. During the median follow-up of 13.3 years, 1448 deaths occurred, including 346 participants died from cancer, and 367 died from cardiovascular disease (CVD)..Multivariable models indicated that the joint effects of DI-GM (≥ 6) and no sleep disorders were associated with lower risks for all-cause (HR 0.53, 95% CI: 0.38-0.79) and CVD mortality (HR 0.36, 95% CI: 0.19-0.65). CONCLUSIONS In a nationally representative sample of US population with diabetes and pre-diabetes, high DI-GM combined with no sleep disorders was associated with significantly reduced all-cause and CVD mortality risks.
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Affiliation(s)
- Ke Si
- Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Chuanqin Shi
- Marine Biomedical Research Institute of Qingdao, School of Medicine and Pharmacy, Key Laboratory of Marine Drugs, Chinese Ministry of Education, Ocean University of China, Qingdao, 266003, China
| | - Yajing Huang
- Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Chuanfeng Liu
- Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Jingwei Chi
- Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Lili Xu
- Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Ying Chen
- Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, 266003, China
| | - Yangang Wang
- Department of Endocrinology, Affiliated Hospital of Qingdao University, Qingdao, 266003, China.
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10
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Hsu JC, Yang YY, Chuang SL, Lin LY. Long-Term Glycemic Variability Predicts Adverse Outcomes in Diabetic Heart Failure With Preserved Ejection Fraction. J Clin Endocrinol Metab 2025; 110:1929-1937. [PMID: 39383298 DOI: 10.1210/clinem/dgae715] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 09/25/2024] [Accepted: 10/09/2024] [Indexed: 10/11/2024]
Abstract
CONTEXT Previous studies have shown associations between glycemic variability (GV) and cardiovascular outcomes in patients with type 2 diabetes. However, the effect of GV on outcomes in diabetic patients with heart failure with preserved ejection fraction (HFpEF) has not been investigated. OBJECTIVE To investigate the association between increased GV and cardiovascular outcomes in diabetic patients with HFpEF. METHODS Between 2014 and 2019, we conducted a retrospective cohort analysis using the electronic medical records of a tertiary medical center in Taiwan. Diabetic patients with HFpEF were enrolled. Each individual's coefficient of variability of fasting glucose (FGCV) was determined and the FGCVs were categorized into tertiles. Multivariable Cox regression models and the Kaplan-Meier with log-rank test were used to assess the association between the FGCV and the risk of hospitalization for heart failure (HHF), atrial fibrillation (AF), cardiovascular mortality, and overall mortality. RESULTS In a cohort comprising 74 835 individuals diagnosed with diabetes, a subset of 753 patients was identified with HFpEF and measurement of FGCV. The median follow-up duration was 38.1 months. In the model of full adjustment, the third FGCV tertile was statistically significantly associated with an increased risk of HHF compared to the first tertile (hazard ratio [HR] = 1.32; 95% CI, 1.04-1.69; P = .025). Likewise, the highest FGCV tertile was associated with an increased risk of death (HR 1.65; 95% CI, 1.16-2.35; P = .005), whereas it was not associated with increased of AF and cardiovascular mortality. Kaplan-Meier analyses revealed a statistically significant association between FGCV and both HHF and overall mortality (log-rank P = .022 and <.001, respectively). CONCLUSION Our study highlights a significant association between increased GV and a higher incidence of HHF as well as an elevated overall mortality rate in individuals with diabetes and HFpEF.
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Affiliation(s)
- Jung-Chi Hsu
- Department of Internal Medicine, National Taiwan University Hospital Jinshan Branch, New Taipei City 208204, Taiwan
- Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei 100225, Taiwan
| | - Yen-Yun Yang
- Department of Medical Research, National Taiwan University Hospital, Taipei 100225, Taiwan
| | - Shu-Lin Chuang
- Department of Medical Research, National Taiwan University Hospital, Taipei 100225, Taiwan
| | - Lian-Yu Lin
- Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei 100225, Taiwan
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin County 640203, Taiwan
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11
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Yang J, Ning P, Huang J, Ouyang H, Zhang J, Yang F, Cao H, Zhang F. Comparative efficacy of gas therapy for diabetic foot ulcers using network meta-analysis. PeerJ 2025; 13:e19571. [PMID: 40538733 PMCID: PMC12178245 DOI: 10.7717/peerj.19571] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 05/15/2025] [Indexed: 06/22/2025] Open
Abstract
Objective Diabetic foot ulcers (DFUs) pose significant clinical challenges, with gas therapy emerging as a promising intervention. However, the comparative efficacy of various gas therapy modalities remains unclear. This study evaluates the effectiveness of different gas therapies, particularly hyperbaric oxygen therapy (HBOT), in improving DFU outcomes. Methods We searched three major databases, PubMed, Embase, and the Cochrane Library, for randomized controlled trials (RCTs) published up to March 3, 2024, assessing the efficacy of different gas therapies in managing DFUs. Primary outcomes included ulcer healing and area reduction rates, while secondary outcomes encompassed healing time, amputation rate, and adverse events. A network meta-analysis was performed using R, with surface under the cumulative ranking curve (SUCRA) values calculated to rank therapies. Results A total of 34 RCTs involving 2,268 DFUs were included in this analysis. HBOT ranked highest for the healing rate (SUCRA = 0.8 14) and area reduction rate (SUCRA = 0.730) but also had a higher amputation rate (SUCRA = 0.621). Except for carbon dioxide therapy, HBOT demonstrated significantly greater healing rates than standard of care (SOC) (mean difference (MD) = -2.71, 95% confidence interval (CI) [-4.85 to -1.34]) and topical oxygen therapy (MD = -2.03, 95% CI [-4.50 to -0.32]), while pairwise comparisons among other gaseous therapies were non-significant (P > 0.05). For wound area reduction, HBOT was superior to SOC (MD = 0.39, 95% CI [0.11-0.67]), whereas differences among other gaseous therapies remained non-significant (P > 0.05). There was substantial heterogeneity in the area reduction rate in net work analysis (I 2 = 87%). Subgroup analyses revealed greater area reduction in DFUs treated with HBOT when the treatment duration exceeded six weeks. Conclusions HBOT improves ulcer healing and area reduction rates in DFU patients; however, its association with higher amputation rates warrants cautious use, considering resource availability. Given the limited number and quality of included studies, further high-quality research is needed to validate these findings.
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Affiliation(s)
- Jing Yang
- Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Geriatric Diseases Institute of Chengdu/Cancer Prevention and Treatment Institute of Chengdu, Chengdu, Sichuan, China
| | - Peng Ning
- Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Geriatric Diseases Institute of Chengdu/Cancer Prevention and Treatment Institute of Chengdu, Chengdu, Sichuan, China
| | - Jiali Huang
- Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Geriatric Diseases Institute of Chengdu/Cancer Prevention and Treatment Institute of Chengdu, Chengdu, Sichuan, China
| | - Hong Ouyang
- Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Geriatric Diseases Institute of Chengdu/Cancer Prevention and Treatment Institute of Chengdu, Chengdu, Sichuan, China
| | - Jiaxing Zhang
- Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Geriatric Diseases Institute of Chengdu/Cancer Prevention and Treatment Institute of Chengdu, Chengdu, Sichuan, China
| | - Fan Yang
- Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Geriatric Diseases Institute of Chengdu/Cancer Prevention and Treatment Institute of Chengdu, Chengdu, Sichuan, China
| | - Hongyi Cao
- Department of Endocrine and Metabolism, Chengdu Fifth People’s Hospital (The Second Clinical Medical College, Affiliated Fifth People’s Hospital of Chengdu University of Traditional Chinese Medicine), Geriatric Diseases Institute of Chengdu/Cancer Prevention and Treatment Institute of Chengdu, Chengdu, Sichuan, China
| | - Fan Zhang
- Department of Endocrine and Metabolism, Guang’an People’s Hospital (Sichuan University West China Hospital Guang’an Hospital), Guang’an, Sichuan, China
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12
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Wei S, Zhang J, Zheng H, Jiang W, Yang J, Wang Y, Chen W, Sun W. Association of the Appendicular Skeletal Muscle Mass-to-Visceral Fat Area Ratio with Cause-Specific Mortality in Diabetes. Calcif Tissue Int 2025; 116:85. [PMID: 40517189 PMCID: PMC12167329 DOI: 10.1007/s00223-025-01389-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2024] [Accepted: 05/05/2025] [Indexed: 06/16/2025]
Abstract
The relationship between muscle mass and visceral fat with mortality risk in diabetes has been extensively studied. This study investigates the association between the appendicular skeletal muscle mass-to-visceral fat area ratio (SVR) and cardiovascular and cancer-related mortality in diabetic patients in the United States. A nationwide cohort study was conducted using NHANES data (2011-2018), including 1439 diabetic patients with dual-energy X-ray absorptiometry (DXA) measurements. Weighted Cox proportional hazards models and restricted cubic splines (RCS) were employed to evaluate the association between SVR and cause-specific mortality rates. Weighted receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of SVR and other conventional indicators in predicting mortality. After adjusting for multiple confounding factors, SVR showed a linear negative association with cardiovascular and cancer-related mortality in diabetes. Each 0.01-unit increase in SVR was associated with a 3% reduction in the risk of cardiovascular death and a 2% reduction in cancer-related death. However, SVR demonstrated weak diagnostic performance for both cardiovascular and cancer mortality, with weighted AUCs of 0.520 and 0.527, respectively, compared to other metrics including BMI, WC, ASM, and VFA. Although SVR was significantly associated with cardiovascular and cancer mortality, its predictive performance was not superior to that of simpler or more established indicators, suggesting that it has limited clinical utility for predicting mortality in diabetic patients.
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Affiliation(s)
- Shuwu Wei
- Beijing University of Chinese Medicine, Beijing, China
| | - Jiale Zhang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Huijuan Zheng
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Weimin Jiang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Jie Yang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Yaoxian Wang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
- Beijing University of Chinese Medicine, Beijing, China
| | - Weihong Chen
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
| | - Weiwei Sun
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China.
- Beijing University of Chinese Medicine, Beijing, China.
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Tang LB, Peng YL, Chen J, Li JT, Zheng MM, Wu L, Lu C, Wei XW, Cai DX, Guo Z, Ren ZR, Lv SD, Deng Y, Chen ZH, Xu CR, Zhou Q. Rechallenge with immune-checkpoint inhibitors in patients with advanced-stage lung cancer. Nat Rev Clin Oncol 2025:10.1038/s41571-025-01029-7. [PMID: 40490476 DOI: 10.1038/s41571-025-01029-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/05/2025] [Indexed: 06/11/2025]
Abstract
Lung cancer remains the leading cause of cancer-related mortality globally, with many patients diagnosed with advanced-stage disease. Treatment in this setting relies on systemic therapies, including chemotherapy, targeted therapy and immunotherapy. Immune-checkpoint inhibitors (ICIs), which promote or restore antitumour immunity by inhibiting immunosuppressive signalling pathways, are currently the most widely used immunotherapies in these patients. However, immune-related adverse events (irAEs) or disease progression often necessitate discontinuation of these agents, leaving many patients with limited subsequent treatment options. In this scenario, ICI rechallenge has emerged as a potential strategy. Despite this potential, evidence for ICI rechallenge after either disease progression or irAEs in patients with non-small-cell lung cancer is limited and evidence for those with small cell lung cancer seems to be non-existent. In this Review, we provide a comprehensive overview of the available data on ICI rechallenge in the context of both disease progression and irAEs, including a summary of current guidance on clinical management and detailed discussions of safety and efficacy. We also highlight important unanswered questions in an attempt to guide future research in this area.
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Affiliation(s)
- Li-Bo Tang
- School of Medicine, South China University of Technology, Guangzhou, China
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Ying-Long Peng
- School of Medicine, South China University of Technology, Guangzhou, China
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Ji Chen
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Jia-Ting Li
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
- Shantou University Medical College, Shantou, China
| | - Mei-Mei Zheng
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Lv Wu
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Chang Lu
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Xue-Wu Wei
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Dong-Xuan Cai
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Zhi Guo
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Zi-Rui Ren
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Si-Di Lv
- School of Art, Soochow University, Suzhou, China
| | - Yu Deng
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Zhi-Hong Chen
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Chong-Rui Xu
- School of Medicine, South China University of Technology, Guangzhou, China
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China
| | - Qing Zhou
- School of Medicine, South China University of Technology, Guangzhou, China.
- Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
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Zhang B, Dai C, Jiang J, Wang J, Yang Y, Feng J. Serum metabolic profiling in diabetic kidney disease patients using ultra-high performance liquid chromatography-tandem mass spectrometry. Diabetol Metab Syndr 2025; 17:197. [PMID: 40481496 PMCID: PMC12144808 DOI: 10.1186/s13098-025-01780-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2025] [Accepted: 05/31/2025] [Indexed: 06/11/2025] Open
Abstract
Background Diabetic kidney disease (DKD) remains one of the leading causes of end-stage renal failure. The currently available diagnostic and classification markers, such as the urinary albumin-to-creatinine ratio and estimated glomerular filtration rate, demonstrate inadequate precision in forecasting the onset and progression of DKD. This study aims to investigate the serum metabolic profile of patients with DKD, with the objective of identifying reliable biomarkers that can enhance the prediction of the transition from diabetes mellitus (DM) to DKD and distinguishing DKD from nondiabetic kidney disease (NDKD). Methods Untargeted metabolomic analysis was performed on serum samples obtained from 53 DKD patients, 54 NDKD patients, 59 individuals diagnosed with simple diabetes mellitus (SDM), and 56 healthy controls utilizing ultra-high performance liquid chromatography-tandem mass spectrometry. Differential metabolites among the groups were identified, metabolic pathways were investigated, and the diagnostic efficacy of selected metabolites was evaluated. Results The metabolic enrichment pathways shared between DKD and NDKD encompassed glycerophospholipid metabolism, glycerolipid metabolism, and tryptophan metabolism. In contrast, pyrimidine metabolism and arginine biosynthesis were uniquely enriched in DKD. Compared to the NDKD group, significantly elevated levels of phosphatidylglycerol (PG, 14:0) and D-Maltose were observed in DKD patients. Additionally, in comparison to the SDM group, the DKD group exhibited significant increases in lysophosphatidic acid (LPA, 16:3), LPA (18:5), LPA (22:5), phosphatidic acid (PA, 18:3), PG (26:4), L-Glutamine, Uridine, Cytidine, Formyl-N-acetyl-5-methoxykynurenamine, 2-Oxoadipate, Thymidine, L-Citrulline, and 5-Hydroxy-L-tryptophan, while PG (28:4) levels were markedly reduced. Among these, Uridine, Cytidine, Thymidine, and L-Citrulline were associated with pyrimidine metabolism, whereas L-Glutamine and L-Citrulline participated in the arginine biosynthesis pathway. Furthermore, the differential metabolites exhibited varying degrees of correlation with renal function indicators in DKD patients. Conclusions PG (14:0) and D-Maltose may help distinguish DKD from NDKD, while L-Glutamine, Uridine, Cytidine, Thymidine, and L-Citrulline are linked to the progression from DM to DKD. Larger studies are needed to validate these findings and assess their diagnostic and causal significance.
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Affiliation(s)
- Bin Zhang
- Department of Medical Laboratory, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
- Department of Clinical Laboratory, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Chunmei Dai
- Department of Medical Laboratory, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
- Department of Clinical Laboratory, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Jiuyi Jiang
- Department of Medical Laboratory, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China
- Department of Clinical Laboratory, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Jun Wang
- Department of Laboratory Medicine, Sichuan Provincial Women's and Children's Hospital, The Affiliated Women's and Children's Hospital of Chengdu Medical College, Chengdu, 610045, China
| | - Yuwei Yang
- Department of Clinical Laboratory, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, China
| | - Jiafu Feng
- Department of Medical Laboratory, The Affiliated Hospital, Southwest Medical University, Luzhou, 646000, China.
- Department of Clinical Laboratory, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, China.
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Liu D, Lou M, Tang Y, Li C, He H. A J-shaped association between the atherogenic index of plasma and diabetes risk in a Japanese population: a large-scale retrospective cohort study. BMC Endocr Disord 2025; 25:141. [PMID: 40481490 PMCID: PMC12143047 DOI: 10.1186/s12902-025-01951-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2024] [Accepted: 05/05/2025] [Indexed: 06/11/2025] Open
Abstract
BACKGROUND Atherosclerotic dyslipidemia has been linked to an increased risk of type 2 diabetes (T2D). While previous studies have established an association between the atherogenic index of plasma (AIP) and insulin resistance, there is a notable lack of large-scale cohort studies examining the relationship between AIP and the risk of T2D in the general population. Therefore, the present longitudinal study aims to examine the association between AIP and the risk of T2D in a cohort of Japanese adults. METHODS This retrospective cohort study included a total of 15,453 adults. To evaluate the association between the AIP and the risk of developing T2D, hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox proportional hazards regression models. Furthermore, potential nonlinear relationships were explored through Cox proportional hazards regression combined with smooth curve fitting techniques. RESULTS During a mean follow-up period of 6.05 years, 373 adults developed T2D. Elevated AIP was independently associated with a significantly higher risk of T2D after adjusting for potential confounding factors (HR: 2.23, 95% CI: 1.55-3.20, P < 0.0001). Furthermore, a J-shaped relationship between AIP and the incidence of T2D was observed. When AIP levels were below - 0.45, no statistically significant association was found between AIP and T2D risk (HR: 0.35, 95% CI: 0.06-1.95, P = 0.2298). In contrast, AIP levels exceeding this threshold were positively associated with an increased risk of T2D (HR: 2.61, 95% CI: 1.77-3.85, P < 0.0001). CONCLUSION The AIP demonstrates a J-shaped relationship with the risk of developing T2D in Japanese adults. Consequently, maintaining AIP levels below the identified threshold (-0.45) may help reduce their chances of developing diabetes. CLINICAL TRIAL NUMBER Not applicable.
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Affiliation(s)
- Dong Liu
- Department of Critical Care Medicine, The Fourth Hospital of Changsha, No. 70, Lushan Road, Yuelu District, Changsha, 410000, Hunan Province, China
| | - Mingxing Lou
- Department of Rehabilitation, NHC Key Laboratory of Birth Defect for Research and Prevention (Hunan Provincial Maternal and Child Health Care Hospital), Changsha, 41000, Hunan Province, China
| | - Yue Tang
- Department of Neurosurgery, The Fourth Hospital of Changsha, Changsha, 410000, Hunan Province, China
| | - Cheng Li
- Department of Critical Care Medicine, The Fourth Hospital of Changsha, No. 70, Lushan Road, Yuelu District, Changsha, 410000, Hunan Province, China
| | - Hao He
- Department of Critical Care Medicine, The Fourth Hospital of Changsha, No. 70, Lushan Road, Yuelu District, Changsha, 410000, Hunan Province, China.
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Kassie MZ, Alemu C, Wudu H, Marine BT, Gebeyehu AA. Time to achieve optimal glycemic control and its determinants among diabetes mellitus patients receiving treatment: a retrospective study. Sci Rep 2025; 15:20031. [PMID: 40481244 PMCID: PMC12144107 DOI: 10.1038/s41598-025-96097-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 03/26/2025] [Indexed: 06/11/2025] Open
Abstract
Diabetes mellitus (DM) is a major public health problem responsible for morbidity and mortality. Maintaining blood sugar control helps patients achieve optimal glycemic levels. Therefore, this study aimed to identify the factors affecting the time to achieve optimal glycemic control among DM patients at Assosa General Hospital (AGH), Western Ethiopia. A retrospective study design was conducted from 427 randomly selected DM patients in the outpatient department (OPD) clinic at AGH under the follow-up period from September 2022 to September 2024. The median survival time, Kaplan-Meier survival estimate, and Log-Rank test were used to describe the data and compare the survival time between groups. The study used Cox PH model to analyze the time to achieve optimal glycemic control of DM patients, where hazard ratio, p-value, and 95% CI for hazard ratio were used for testing significance. Schoenfeld and Cox-Snell residuals were used to check the model assumptions. The median time to optimal glycemic control for DM patients was 12 months. At the end of the follow-up, 74.2% of the patients had developed an event and the rest 25.8% were censored. The significant predictors of time to optimal glycemic control include: older age (AHR = 0.871(95% CI 0.809, 0.937)), females (AHR = 1.295 (95% CI 1.024, 1.639)), having FHDM (AHR = 1.681(95% CI 1.313, 2.153)), rural residence(AHR = 0.463(95% CI 0.354, 0.607)), presence of comorbidity (AHR = 0.508(95% CI 0.302, 0.854)), DM related complications (AHR = 0.419(95% CI 0.326, 0.539)), high BLBGL AHR = 0.997(95% CI 0.995, 0.998)). This study found the factors that prolonged or shortened the time to reach optimal glycaemic control for T2DM patients. The study revealed that older age, male patients, patients having other related comorbidities and patients with no FHDM, patients having DM-related complications as poor prognostic factors of T2DM disease and also prolonged recovery time. Therefore, attention should be given to these patients to obtain good glycaemic levels and the patient being healthy.
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Affiliation(s)
- Maru Zewdu Kassie
- Department of Statistics, College of Natural and Computational Sciences, Assosa University, Assosa, Ethiopia.
| | - Chekol Alemu
- Department of Statistics, College of Natural and Computational Sciences, Gambella University, Gambella, Ethiopia
| | - Habitamu Wudu
- Department of Statistics, College of Natural and Computational Sciences, Gambella University, Gambella, Ethiopia
| | - Buzuneh Tasfa Marine
- Department of Epidemiology, Faculty of Public Health, Jimma University, Jimma, Ethiopia
| | - Asaye Alamneh Gebeyehu
- Department of Public Health, College of Health Sciences, Debre Tabor University, Debre Tabor, Ethiopia
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Wang P, Li Q, Yu X, Wu L, Liu J, Zheng Y, Liu Z, Yao J, Fan S, Li Y. Association between weekend catch-up sleep and glycemic control among individuals with diabetes: a population-based study. Front Endocrinol (Lausanne) 2025; 16:1461367. [PMID: 40538806 PMCID: PMC12176606 DOI: 10.3389/fendo.2025.1461367] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 03/14/2025] [Indexed: 06/22/2025] Open
Abstract
Objectives Weekend catch-up sleep (WCUS), a compensation for insufficient sleep during weekdays, was associated with desirable metabolic effects. However, its relationship with glycemic control among adults with diabetes was not fully established. Methods Participants from the 2017-2018 cycle of the National Health and Nutrition Examination Survey were included for analysis. WCUS was defined as a difference in sleep duration between weekends and weekdays of more than one hour. Glycemic control was assessed by hemoglobin A1C (HbA1c) and fasting plasma glucose levels. Poor glycemic control was defined as an HbA1c level exceeding 10.0%. Results The final analysis included 571 participants (weighted number: 38,714,135), and 24.90% of them practicing WCUS. No significant association was found between glycemic control and the presence of WCUS. However, significant negative associations were noted between WCUS with a duration of 1-2 hours and HbA1c level [β= -0.82, 95% CI: (-1.34, -0.30), P=0.004] and fasting glucose level [β= -1.67, 95% CI: (-2.51, -0.82), P<0.001] when compared with participants with no WCUS, which remained consistent across different subgroups. In addition, it was also associated with a reduced risk of developing poor glycemic control (OR=0.10, 95% CI: (0.01, 0.60), P=0.015). With WCUS duration of ≥ 2 hours, such associations became not significant. Conclusions WCUS for 1-2 hours was associated with lower levels of HbA1c and fasting glucose and reduced risk of developing poor glycemic control, while a duration of ≥ 2 hours was not. Further research is needed to determine the optimal duration of WCUS.
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Affiliation(s)
- Peiqing Wang
- Department of Endocrinology, Boai Hospital of Zhongshan (Zhongshan Women and Children’s Hospital), Zhongshan, China
| | - Qiuling Li
- Department of Nephrology, Blood Purification Center, Zhongshan People’s Hospital, Zhongshan, China
| | - Xiaojun Yu
- Department of Endocrinology, Boai Hospital of Zhongshan (Zhongshan Women and Children’s Hospital), Zhongshan, China
| | - Lifeng Wu
- Department of Endocrinology, Boai Hospital of Zhongshan (Zhongshan Women and Children’s Hospital), Zhongshan, China
| | - Jingyuan Liu
- Department of Endocrinology, Boai Hospital of Zhongshan (Zhongshan Women and Children’s Hospital), Zhongshan, China
| | - Yangxi Zheng
- Department of Endocrinology, Boai Hospital of Zhongshan (Zhongshan Women and Children’s Hospital), Zhongshan, China
| | - Zhenrui Liu
- Department of Endocrinology, Boai Hospital of Zhongshan (Zhongshan Women and Children’s Hospital), Zhongshan, China
| | - Jieying Yao
- Department of Endocrinology, Boai Hospital of Zhongshan (Zhongshan Women and Children’s Hospital), Zhongshan, China
| | - Sisi Fan
- Department of Endocrinology, Boai Hospital of Zhongshan (Zhongshan Women and Children’s Hospital), Zhongshan, China
| | - Yiqin Li
- Department of Endocrinology, Boai Hospital of Zhongshan (Zhongshan Women and Children’s Hospital), Zhongshan, China
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Shi C, He C, Qin L, Bai W. Association between atherogenic index of plasma and depression in individuals with different glucose metabolism status. Front Psychiatry 2025; 16:1530940. [PMID: 40530050 PMCID: PMC12170628 DOI: 10.3389/fpsyt.2025.1530940] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Accepted: 05/19/2025] [Indexed: 06/20/2025] Open
Abstract
Background The atherogenic index of plasma (AIP) has been implicated in various disease processes, yet its relationship with depression, particularly in the context of differing glucose metabolism status, remains underexplored. This study aimed to investigate the association between AIP and depression in middle-aged and older adults with varying glucose metabolism profiles. Methods Data were derived from the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2011 and 2018, encompassing 7,723 participants aged 45 years and above. Depression was defined using a cutoff score of ≥12 on the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10). The primary outcome of interest was incident depression. Logistic regression and restricted cubic spline (RCS) models were applied to assess the relationship between baseline AIP levels and depression risk across distinct glucose metabolism categories. Results Elevated AIP was strongly associated with increased odds of depression. In fully adjusted models, a graded relationship was observed, with higher quartiles of AIP corresponding to greater depression risk. Participants in the highest AIP quartile (Q4) had significantly increased odds of depression (odds ratio [OR]: 3.36, 95% confidence interval [CI]: 2.67-4.24, P < 0.001) compared to those in the lowest quartile (Q1). Furthermore, RCS analyses revealed a significant positive association between AIP and incident depression among individuals with prediabetes mellitus (Pre-DM) and diabetes mellitus (DM) (P < 0.001), whereas no such association was found in participants with normal glucose regulation (NGR) (P = 0.086). These findings suggest that glucose metabolism status modifies the relationship between AIP and depression risk. Conclusion Higher baseline AIP levels are significantly associated with an increased risk of depression in middle-aged and older adults, with distinct effects modulated by glucose metabolism status. These results highlight the potential utility of AIP as a biomarker for depression risk and suggest that metabolic health should be considered in the development of targeted strategies for depression prevention and intervention.
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Affiliation(s)
- Chunhui Shi
- Department of Endocrinology, The People’s Hospital of Danyang, Danyang Hospital of Nantong University, Danyang, Jiangsu, China
| | - Change He
- Department of Endocrinology, The People’s Hospital of Danyang, Danyang Hospital of Nantong University, Danyang, Jiangsu, China
| | - Lijie Qin
- Department of Emergency, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, China
| | - Weimin Bai
- Department of Emergency, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, China
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19
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Magodoro IM, Wilkinson KA, Claggett BL, Ntusi NAB, Siedner M MJ, Wilkinson RJ. Discordance between measures of Mycobacterium tuberculosis sensitization and type 2 diabetes mellitus in the United States (NHANES): A population-based cohort study. J Infect 2025; 90:106496. [PMID: 40315998 DOI: 10.1016/j.jinf.2025.106496] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 04/14/2025] [Accepted: 04/21/2025] [Indexed: 05/04/2025]
Abstract
OBJECTIVE We examined how latent TB infection (LTBI), evaluated by cell-mediated immune responses to Mycobacterium tuberculosis (Mtb) antigens, impacts glucose metabolism in US adults. METHODS Mtb sensitization was evaluated by interferon-γ (IFN-γ) release assay (IGRA+: assay reactivity) and tuberculin skin testing (TST+: skin induration ≥10 mm), and categorized as: IGRA-/TST- (TB uninfected controls); IGRA-/TST+; IGRA+/TST-; or IGRA+/TST+. Diabetes was ascertained by fasting plasma glucose (FPG) ≥7.0 mmol/L, HbA1c ≥6.5% and/or antidiabetic medication. Adjusted generalized additive models examined nonlinear effects of skin induration and IFN-γ reactivity on FPG and HbA1c; and LTBI on diabetes prevalence. RESULTS Among 1787 (IGRA-/TST-), 101 (IGRA-/TST+), 92 (IGRA+/TST-), and 99 (IGRA+/TST+) adults, skin induration linearly associated with FPG [effective degrees of freedom (EDF) =1.01; p<0.001] and non-linearly with HbA1c [EDF=1.76; p=0.003]. IFN-γ reactivity correlated with neither FPG [p=0.58] nor HbA1c [p=0.94]. Relatedly, adjusted diabetes prevalence was greater in IGRA-/TST+ [24.9%; p=0.048] and IGRA+/TST+ [27.3%; p=0.004] but not IGRA+/TST- [15.9%; p=0.69] individuals than among controls [15.3%]. CONCLUSIONS LTBI associated with glycemic measures and diabetes when assessed by skin induration, but not IFN-γ release. This suggests an association with innate immune activation rather than acquired T-cell response, as determined by ex vivo IFN-γ release assay.
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Affiliation(s)
- Itai M Magodoro
- Department of Medicine, University of Cape Town, Observatory 7925, Republic of South Africa
| | - Katalin A Wilkinson
- Department of Medicine, University of Cape Town, Observatory 7925, Republic of South Africa; Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory 7925, Republic of South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, Republic of South Africa; Francis Crick Institute, Midland Road, London NW1 1AT, United Kingdom
| | - Brian L Claggett
- Harvard Medical School, Boston 02115, MA, USA; Cardiovascular Division, Brigham and Women's Hospital, Boston 02115, MA, USA
| | - Ntobeko A B Ntusi
- Department of Medicine, University of Cape Town, Observatory 7925, Republic of South Africa; South African Medical Research Council, Tygerberg 7505, Republic of South Africa; ARUA/GUILD Cluster of Research Excellence on Noncommunicable Diseases and Associated Multimorbidity
| | - Mark J Siedner M
- Harvard Medical School, Boston 02115, MA, USA; Medical Practice Evaluation Center and Division of Infectious Diseases, Massachusetts General Hospital, Boston 02114, MA, USA; Africa Health Research Institute, Mtubatuba 3935, Republic of South Africa; University of KwaZulu-Natal, Durban 4013, South Africa
| | - Robert J Wilkinson
- Department of Medicine, University of Cape Town, Observatory 7925, Republic of South Africa; Centre for Infectious Diseases Research in Africa, University of Cape Town, Observatory 7925, Republic of South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory 7925, Republic of South Africa; Francis Crick Institute, Midland Road, London NW1 1AT, United Kingdom; Department of Infectious Diseases, Imperial College, London W12 0NN, United Kingdom.
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20
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Kaku K, Shimoda M, Osonoi T, Iwamoto M, Kaneto H. Efficacy and safety of imeglimin add-on to DPP-4 inhibitor therapy in Japanese patients with type 2 diabetes mellitus: An interim analysis of the randomised, double-blind FAMILIAR trial. Diabetes Obes Metab 2025; 27:3212-3222. [PMID: 40116188 PMCID: PMC12046477 DOI: 10.1111/dom.16336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2025] [Revised: 02/27/2025] [Accepted: 03/05/2025] [Indexed: 03/23/2025]
Abstract
AIMS The ongoing FAMILIAR trial aims to provide evidence for clinical decision-making and offer a novel treatment paradigm in type 2 diabetes mellitus (T2DM) management. The interim findings of FAMILIAR through Week 24 are reported. MATERIALS AND METHODS FAMILIAR is a multicentre, randomised, double-blind study comparing the efficacy and safety of imeglimin versus placebo in adult Japanese patients with T2DM and inadequate glycaemic control despite dipeptidyl peptidase-4 (DPP-4) inhibitor monotherapy, plus diet/exercise modifications. Patients entered a 24-week double-blind treatment phase (oral imeglimin 1000 mg or placebo twice daily) followed by an 80-week open-label phase (oral imeglimin 1000 mg twice daily). The primary end-point was change in glycated haemoglobin (HbA1c) level from baseline at Week 24. Safety was also monitored. RESULTS Overall, 117 patients were randomised (imeglimin, n = 58; placebo, n = 54; excluded, n = 5). The least squares mean (standard error) changes in HbA1c level (baseline to Week 24) for the imeglimin and placebo groups, respectively, were -0.65% (0.11%) and 0.38% (0.11%) in the overall population (group-difference -1.02% [95% confidence interval -1.33%, -0.72%]; p < 0.001); -0.47% (0.17%) and 0.32% (0.18%) in patients aged <65 years (-0.79% [-1.29%, -0.29%]; p = 0.003); and -0.80% (0.14%) and 0.42% (0.14%) in patients aged ≥65 years (-1.22% [-1.61%, -0.82%]; p < 0.001). One patient in the imeglimin group had mild hypoglycaemia; the safety profile was favourable. CONCLUSIONS Imeglimin represents a potential new treatment option for patients with T2DM and inadequate glycaemic control with DPP-4 inhibitors, including those aged ≥65 years. CLINICAL TRIAL REGISTRATION jRCTs061210082.
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Affiliation(s)
- Kohei Kaku
- Department of Diabetes, Endocrinology and MetabolismKawasaki Medical SchoolOkayamaJapan
| | - Masashi Shimoda
- Department of Diabetes, Endocrinology and MetabolismKawasaki Medical SchoolOkayamaJapan
| | | | | | - Hideaki Kaneto
- Department of Diabetes, Endocrinology and MetabolismKawasaki Medical SchoolOkayamaJapan
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21
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Madhuri Y, Saifullah Q, Pandey M, Bhattamisra SK. An overview of recent developments in clinical trials of anti-diabetic drugs. Panminerva Med 2025; 67:87-100. [PMID: 40457780 DOI: 10.23736/s0031-0808.25.05314-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/11/2025]
Abstract
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder affecting over 90% of diabetes patients worldwide. The condition is driven by genetic predispositions, environmental factors, obesity, and physical inactivity. Pharmacological treatments range from metformin to newer agents, including GLP-1 analogues and SGLT-2 inhibitors, which target different aspects of glucose metabolism. The review highlights advancements in clinical trials for T2DM treatments, focusing on recent and ongoing research. Clinical trial data were sourced from ClinicalTrials.gov, and the search criteria focused on trials that were published with monotherapy of T2DM having results within the last six years, specifically from 2019 to 2024. The clinical trials of the patients under the age group of adults (18 to 64 years) and older adults (>64 years) were included. The data are mentioned in inverse chronological order with respect to study duration. The clinical trial data suggest promising results in managing hemoglobin A1c and body weight. However, adverse events such as cardiovascular, gastrointestinal, and bone-related issues and other issues such as diabetic ketoacidosis and pancreatitis were reported in some cases. Dulaglutide, tripeptide, and oral insulin showed promising therapeutic effects in clinical trials. Despite significant progress, the management of T2DM remains challenging, emphasizing the need for ongoing innovation in treatment approaches to improve patient quality of life and reduce the global burden of the disease.
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Affiliation(s)
- Yeduvaka Madhuri
- Gandhi Institute of Technology School of Pharmacy, Gandhi Institute of Technology in Visakhapatnam (deemed to be university), Visakhapatnam, India
| | - Qazi Saifullah
- Gandhi Institute of Technology School of Pharmacy, Gandhi Institute of Technology in Visakhapatnam (deemed to be university), Visakhapatnam, India
| | - Manisha Pandey
- Department of Pharmaceutical Sciences, Central University of Haryana, Mahendragarh, India
| | - Subrat K Bhattamisra
- Department of Pharmacy, School of Health Sciences, Central University of South Bihar, Gaya, India -
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Milic MS, Brkovic B, Vucetic M, Todorovic VS, Stojic D. EFFICACY AND SAFETY OF LIDOCAINE WITH CLONIDINE FOR MAXILLARY INFILTRATION ANESTHESIA IN PATIENTS WITH DIABETES MELLITUS TYPE 2: DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL. J Evid Based Dent Pract 2025; 25:102097. [PMID: 40335197 DOI: 10.1016/j.jebdp.2025.102097] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 08/28/2024] [Accepted: 01/23/2025] [Indexed: 05/09/2025]
Abstract
OBJECTIVES This clinical trial aimed to evaluate and compare parameters of intraoral soft tissue anesthesia and cardiovascular function, and prevalence of local side effects in patients with and without diabetes mellitus type 2 (DMT2), after maxillary infiltration anesthesia obtained with 2% lidocaine with either clonidine (15mcg/ml) or epinephrine (1:100.000). METHODS Sixty-three DMT2 and 52 nondiabetic (H) patients scheduled for tooth extraction were randomly assigned to receive one of the local anesthetic solutions for maxillary infiltration anesthesia: 2 mL of lidocaine with clonidine (LC) or 2 mL of lidocaine with epinephrine (LE). Parameters of soft tissue anesthesia (onset, duration and width of anesthetic field) were evaluated by pinprick test. Systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR) were monitored with patient monitor, before and until 30 minutes after anesthesia application. Presence of postoperative hyperalgesia and paresthesia during 7 postoperative days was tested with ethylene-chloride spray and monofilaments set for quantitative sensory testing, respectively. Requests for rescue analgesic were recorded for 24 hours after tooth extraction. RESULTS Onset of maxillary infiltration anesthesia was significantly shorter in DMT2 vs. H groups (P < .05), regardless of local anesthetic solution used. Duration of anesthesia was 59% longer in DMT2-LE vs. H-LE (P < .05), and 28% longer in DMT2-LC vs. H-LC groups (P < .05). Maxillary infiltration anesthesia lasted 37,9% longer in DMT2-LE vs. DMT2-LC (182.09 ± 57.86 min vs. 139.48 ± 21.86 min) (P < .05). Width of anesthetic field was significantly increased in diabetic vs. nondiabetic participants (P < .05), as well as in DMT2-LE vs. DMT2-LC (35.19 ± 1.67mm vs. 27.07 ± 1.06 mm) (P < .05). SBP was significantly decreased within DM-LC and H-LC groups from 15th to 30th minute, in comparison with baseline values. Significant increase in HR was observed from 5th to 30th minute in diabetic and nondiabetic patients who received LE, compared to baseline values. Postoperative paresthesia was significantly more present in DMT2-LE vs. DMT2-LC (P < .05), while it was not observed in nondiabetic patients. CONCLUSIONS Shorter onset and prolonged duration of maxillary infiltration anesthesia are present in DMT2 setting. Clonidine appears to be a safe alternative to epinephrine for intraoral anesthesia in DMT2, with respect to anesthetic efficacy, cardiovascular safety and prevalence of local side effects.
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Affiliation(s)
- Marija S Milic
- General and Oral Physiology Department, University of Belgrade School of Dental Medicine, Belgrade, Serbia.
| | - Bozidar Brkovic
- Oral Surgery Clinic, University of Belgrade School of Dental Medicine, Belgrade, Serbia
| | - Milan Vucetic
- Oral Surgery Clinic, University of Belgrade School of Dental Medicine, Belgrade, Serbia
| | - Vladimir S Todorovic
- Oral Surgery Clinic, University of Belgrade School of Dental Medicine, Belgrade, Serbia
| | - Dragica Stojic
- Pharmacology in Dentistry Department, University of Belgrade School of Dental Medicine, Belgrade, Serbia
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Raj S, Guest NS, Landry MJ, Mangels AR, Pawlak R, Rozga M. Vegetarian Dietary Patterns for Adults: A Position Paper of the Academy of Nutrition and Dietetics. J Acad Nutr Diet 2025; 125:831-846.e2. [PMID: 39923894 DOI: 10.1016/j.jand.2025.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2025] [Accepted: 02/03/2025] [Indexed: 02/11/2025]
Abstract
It is the position of the Academy of Nutrition and Dietetics that, in adults, appropriately planned vegetarian and vegan dietary patterns can be nutritionally adequate and can offer long-term health benefits such as improving several health outcomes associated with cardiometabolic diseases. Vegetarian dietary patterns exclude meat, poultry, and seafood, and vegan dietary patterns exclude all foods of animal origin. Registered dietitian nutritionists (RDNs) and nutrition and dietetics technicians, registered (NDTRs) play a pivotal role in providing meal-planning strategies and evidence-based nutrition information to clients currently following vegetarian or vegan dietary patterns or who may benefit from and express interest in following vegetarian or vegan dietary patterns. RDNs and NDTRs can work with their clients to create tailored, lifestyle-oriented, nutritionally balanced, and culturally suitable vegetarian and vegan dietary patterns that optimize health benefits while reducing concerns about nutrient inadequacies. Adults follow vegetarian and vegan dietary patterns for various reasons. The aim of this position paper is to inform health care practitioners, including RDNs and NDTRs, about the evidence-based benefits and potential concerns of following vegetarian and vegan dietary patterns for different populations of nonpregnant, nonlactating adults. This position paper is supported by current evidence, including several systematic reviews. As leaders in evidence-based nutrition care, RDNs and NDTRs should aim to support the development and facilitation of vegetarian and vegan dietary patterns and access to nutrient-dense plant-based meals. Promoting a nutrient-balanced vegetarian dietary pattern on both individual and community scales may be an effective tool for preventing and managing many diet-related conditions. This position was approved in January 2025 and will remain in effect until December 31, 2032.
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Affiliation(s)
- Sudha Raj
- Department of Nutrition and Food Studies, David B. Falk College of Sport and Human Dynamics, Syracuse University, Syracuse, New York
| | - Nanci S Guest
- Department of Nutritional Science, Temerty Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Matthew J Landry
- Joe C. Wen School of Population and Public Health, Department of Population Health & Disease Prevention, University of California Irvine, Irvine, California
| | | | - Roman Pawlak
- Department of Nutrition Science, East Carolina University, Greenville, North Carolina
| | - Mary Rozga
- Evidence Analysis Center, Academy of Nutrition and Dietetics, Chicago, Illinois.
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Sandforth L, Raverdy V, Sandforth A, Bauvin P, Chatelain E, Verkindt H, Mingrone G, Guidone C, Verrastro O, Zhou K, Archid R, Mihaljevic A, Caiazzo R, Baud G, Marciniak C, Chetboun M, Ganslmeier M, Minelli Faiao V, Heni M, Fritsche L, Moller A, Kantartzis K, Peter A, Lehmann R, Wagner R, Prystupa K, Fritsche A, Stefan N, Preissl H, Birkenfeld AL, Jumpertz von Schwartzenberg R, Pattou F. Subphenotype-Dependent Benefits of Bariatric Surgery for Individuals at Risk for Type 2 Diabetes. Diabetes Care 2025; 48:996-1006. [PMID: 40214701 DOI: 10.2337/dc25-0160] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Accepted: 03/23/2025] [Indexed: 05/22/2025]
Abstract
OBJECTIVE Bariatric surgery is an effective treatment option for individuals with obesity and type 2 diabetes (T2D). However, whether outcomes in subtypes of individuals at risk for T2D and/or comorbidities (Tübingen Clusters) differ, is unknown. Of these, cluster 5 (C5) and cluster 6 (C6) are high-risk clusters for developing T2D and/or comorbidities, while cluster 4 (C4) is a low-risk cluster. We investigated bariatric surgery outcomes, hypothesizing that high-risk clusters benefit most due to great potential for metabolic improvement. RESEARCH DESIGN AND METHODS We allocated participants without T2D but at risk for T2D, defined by elevated BMI, to the Tübingen Clusters. Participants had normal glucose regulation or prediabetes according to American Diabetes Association criteria. Two cohorts underwent bariatric surgery: a discovery (Lille, France) and a replication cohort (Rome, Italy). A control cohort (Tübingen, Germany) received behavioral modification counseling. Main outcomes included alteration of glucose regulation parameters and prediabetes remission. RESULTS In the discovery cohort, 15.0% of participants (n = 121) were allocated to C4, 22.3% (n = 180) to C5, and 62.4% (n = 503) to C6. Relative body weight loss was similar among all clusters; however, reduction of insulin resistance and improvement of β-cell function were strongest in C5. Prediabetes remission rate was lowest in low-risk C4 and highest in high-risk C5. Individuals from high-risk clusters changed to low-risk clusters in both bariatric surgery cohorts but not in the control cohort. CONCLUSIONS Participants in C5 had the highest benefit from bariatric surgery in terms of improvement in insulin resistance, β-cell function, and prediabetes remission. This novel classification might help identify individuals who will benefit specifically from bariatric surgery.
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Affiliation(s)
- Leontine Sandforth
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Violeta Raverdy
- INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, University Lille, Lille, France
- Integrated Center for Obesity, General and Endocrine Surgery, CHU Lille, Lille, France
| | - Arvid Sandforth
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Pierre Bauvin
- INSERM, CHU Lille, Institut Pasteur de Lille, U1190-EGID, University Lille, Lille, France
| | - Estelle Chatelain
- CNRS, INSERM, CHU Lille, Institut Pasteur de Lille, US 41-UAR 2014-PLBS, University Lille, Lille, France
| | - Helene Verkindt
- INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, University Lille, Lille, France
- Integrated Center for Obesity, General and Endocrine Surgery, CHU Lille, Lille, France
| | - Geltrude Mingrone
- Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
- Division of Diabetes and Nutritional Sciences, School of Cardiovascular and Metabolic Medicine & Sciences, King's College London, London, U.K
| | - Caterina Guidone
- Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | - Ornella Verrastro
- Department of Internal Medicine, Catholic University of the Sacred Heart, Rome, Italy
| | - Karin Zhou
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Rami Archid
- Department of General, Visceral, and Transplant Surgery, University Hospital of Tübingen, Tübingen, Germany
| | - André Mihaljevic
- Department of General, Visceral, and Transplant Surgery, University Hospital of Tübingen, Tübingen, Germany
| | - Robert Caiazzo
- INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, University Lille, Lille, France
- Integrated Center for Obesity, General and Endocrine Surgery, CHU Lille, Lille, France
| | - Gregory Baud
- INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, University Lille, Lille, France
- Integrated Center for Obesity, General and Endocrine Surgery, CHU Lille, Lille, France
| | - Camille Marciniak
- INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, University Lille, Lille, France
- Integrated Center for Obesity, General and Endocrine Surgery, CHU Lille, Lille, France
| | - Mikael Chetboun
- INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, University Lille, Lille, France
- Integrated Center for Obesity, General and Endocrine Surgery, CHU Lille, Lille, France
| | - Marlene Ganslmeier
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Vitória Minelli Faiao
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Martin Heni
- Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany
- Division of Endocrinology and Diabetology, Department of Internal Medicine I, University Hospital Ulm, Ulm, Germany
| | - Louise Fritsche
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Anja Moller
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Konstantinos Kantartzis
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Andreas Peter
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Rainer Lehmann
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany
| | - Robert Wagner
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf (DDZ), Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Hospital, Düsseldorf, Germany
| | - Katsiaryna Prystupa
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University Düsseldorf (DDZ), Düsseldorf, Germany
- Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Hospital, Düsseldorf, Germany
| | - Andreas Fritsche
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Norbert Stefan
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Hubert Preissl
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Department of Pharmacy and Biochemistry, Institute of Pharmaceutical Sciences, and Interfaculty Centre for Pharmacogenomics and Pharma Research, Eberhard Karls University Tübingen, Tübingen, Germany
| | - Andreas L Birkenfeld
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- School of Cardiovascular and Metabolic Medicine and Sciences, King's College London, London, U.K
| | - Reiner Jumpertz von Schwartzenberg
- Internal Medicine IV, Endocrinology, Diabetology and Nephrology, University Hospital of Tübingen, Tübingen, Germany
- Institute for Diabetes Research and Metabolic Diseases (IDM), Helmholtz Center Munich, University of Tübingen, Tübingen, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
- Cluster of Excellence EXC 2124 "Controlling Microbes to Fight Infections" (CMFI), University of Tübingen, Tübingen, Germany
- M3 Research Center, Tübingen, Germany
| | - François Pattou
- INSERM, CHU Lille, Institut Pasteur de Lille, UMR 1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, University Lille, Lille, France
- Integrated Center for Obesity, General and Endocrine Surgery, CHU Lille, Lille, France
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25
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Uchida A, Mihata T, Hasegawa A, Noguchi Y, Neo M. Superior Capsule Reconstruction for Irreparable Rotator Cuff Tears Yields Good Clinical Outcomes for Patients With and Without Diabetes Mellitus. Arthroscopy 2025; 41:1752-1762. [PMID: 39326570 DOI: 10.1016/j.arthro.2024.09.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 08/09/2024] [Accepted: 09/02/2024] [Indexed: 09/28/2024]
Abstract
PURPOSE To compare the clinical outcomes after superior capsule reconstruction (SCR) for irreparable rotator cuff tears (RCTs) in patients with and without diabetes mellitus (DM). METHODS Patients who underwent SCR using fascia lata autograft for irreparable RCTs between 2012 and 2020 with a minimum 2-year follow-up were divided into non-DM and DM groups. Propensity score matching was used to select controls matched for patients' characteristics. Only patients with glycosylated hemoglobin <8% were eligible. The visual analog scale for shoulder pain, American Shoulder and Elbow Surgeons and Japanese Orthopaedic Association scores, and acromiohumeral distance were evaluated preoperatively and at 2 years postoperatively. Shoulder active range of motion (ROM) was evaluated preoperatively and at 6 months, 1 year, and 2 years postoperatively. Graft integrity and postoperative complications that required additional surgery were evaluated. The Wilcoxon signed-rank test and Mann-Whitney U test were used to compare continuous variables. Pearson χ2 test and Fisher exact test were used for categorical variables. The interaction between the postoperative period and ROM was analyzed by the Friedman test and Wilcoxon rank-sum test with the Holm-Sidak post hoc test. RESULTS We studied 154 patients (non-DM, 130; DM, 24) who underwent SCR. After matching, 21 patients were selected in each group. All clinical outcomes significantly improved at 2 years (all P < .05) in both groups. We found no significant differences in clinical outcomes and rates of patients who achieved minimal clinically important differences in visual analog scale and American Shoulder and Elbow Surgeons scores between the groups (P = .10 to ≥.999). The rates of graft tear (both 9.5%) and complications (non-DM, 4.8%; DM, 0%) were not significantly different (both P ≥ .999). CONCLUSIONS SCR using fascia lata autograft for irreparable RCTs yields good clinical outcomes, including ROM, in patients with and without DM. No significant differences in postoperative outcomes were observed between the 2 groups. LEVEL OF EVIDENCE Level III, retrospective cohort study.
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Affiliation(s)
- Akihiro Uchida
- Department of Orthopedic Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Teruhisa Mihata
- Department of Orthopedic Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Japan; Department of Orthopedic Surgery, First Towakai Hospital, Takatsuki, Japan.
| | - Akihiko Hasegawa
- Department of Orthopedic Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Yusuke Noguchi
- Department of Orthopedic Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
| | - Masashi Neo
- Department of Orthopedic Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Japan
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26
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Lan J, Chen M, Zhang X, Yang J. Effect of dietary carbohydrate intake on glycaemic control and insulin resistance in type 2 diabetes: A systematic review and meta-analysis. Asia Pac J Clin Nutr 2025; 34:282-297. [PMID: 40419389 PMCID: PMC12126305 DOI: 10.6133/apjcn.202506_34(3).0003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 11/28/2024] [Accepted: 06/17/2024] [Indexed: 05/28/2025]
Abstract
BACKGROUND AND OBJECTIVES The aim of this study was to elucidate the dose-response relationship between dietary carbohydrate consumption and the improvement of glycemic control and insulin sensitivity in indi-viduals with type 2 diabetes mellitus (T2DM), following an intensive dietary intervention. METHODS AND STUDY DESIGN Randomized controlled trials published up to December 2023 were systematically reviewed from four databases: PubMed, Embase, Web of Science, and Cochrane Database of Systematic Reviews. Primary outcomes included: glycated hemoglobin (HbA1c), fasting glucose (FG); and secondary outcomes included: BMI, fasting insulin (FI), Homeostasis Model Assessment-Insulin Resistance (HOMA-IR). We performed a random-effects dose-response meta-analysis to estimate mean differences (MDs) for each 10% reduction in carbohydrate intake. RESULTS A total of 38 articles were analyzed, encompassing 2,831 total par-ticipants. Compared to the highest recorded carbohydrate intake (65%), reducing carbohydrate intake to 5% showed that for every 10% decrease, the following improvements were observed: HbA1c (MD: 0.39%; 95%CI: -0.5 to -0.28%), FG (MD: 0.55 mmol/L; 95%CI: -0.82 to -0.28 mmol/L), BMI (MD: -0.83 kg/m2; 95%CI: -1.27 to -0.38 kg/m2), FI (MD: -2.19 pmol/L; 95%CI: -3.64 to -0.73 pmol/L), HOMA-IR (MD: -1.53; 95%CI: -3.09 to 0.03). CONCLUSIONS Reducing dietary carbohydrate intake significantly improves glycemic control and insulin resistance in individuals with type 2 diabetes. A linear reduction in carbohydrate intake was observed, with significant effects occurring within the first 6 months of the intervention. However, these effects diminished beyond this period. Notably, the improvements in glycemic parameters were not significantly affected by whether calorie restriction was implemented.
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Affiliation(s)
- Junyu Lan
- School of Public Health, Ningxia Medical University, Yinchuan, China
- Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan, China
| | - Man Chen
- School of Public Health, Ningxia Medical University, Yinchuan, China
- Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan, China
| | - Xiaoke Zhang
- School of Public Health, Ningxia Medical University, Yinchuan, China
- Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan, China
| | - Jianjun Yang
- School of Public Health, Ningxia Medical University, Yinchuan, China.
- Ningxia Key Laboratory of Environmental Factors and Chronic Disease Control, Yinchuan, China
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27
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Javaid A, Hariri E, Ozkan B, Lang K, Khan SS, Rangaswami J, Stone NJ, Blumenthal RS, Ndumele CE. Cardiovascular-Kidney-Metabolic (CKM) Syndrome: A Case-Based Narrative Review. AMERICAN JOURNAL OF MEDICINE OPEN 2025; 13:100089. [PMID: 40104608 PMCID: PMC11919292 DOI: 10.1016/j.ajmo.2025.100089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Accepted: 01/17/2025] [Indexed: 03/20/2025]
Abstract
These 4 hypothetical cases highlight new features of the American Heart Association cardiovascular-kidney-metabolic (CKM) health construct. The cases incorporate the CKM staging system, estimates from the PREVENT risk calculator, and clinical approaches related to CKM stages and individual risk profiles. Topics include management considerations for (1) a patient with stage 1 obesity and impaired glucose tolerance, (2) a patient with metabolic risk factors and moderate-risk chronic kidney disease (CKD), (3) a patient with subclinical atherosclerotic cardiovascular disease and multiple comorbid conditions, and (4) a patient with metabolic risk factors, prior myocardial infarction, new-onset heart failure, atrial fibrillation, and CKD.
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Affiliation(s)
- Aamir Javaid
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md
| | - Essa Hariri
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md
| | - Bige Ozkan
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md
| | - Katherine Lang
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md
| | - Sadiya S Khan
- Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill
| | - Janani Rangaswami
- Division of Nephrology, Washington DC VA Medical Center
- George Washington University School of Medicine and Health Sciences, Washington, D.C
| | - Neil J Stone
- Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Ill
| | - Roger S Blumenthal
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md
| | - Chiadi E Ndumele
- Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Md
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28
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Zhang F, Chu A, Bai Y, Huang L, Zhong Y, Li Y. Association of sarcopenia index, a surrogate marker of muscle mass, and incident chronic kidney disease. Clin Nutr ESPEN 2025; 67:184-191. [PMID: 40112920 DOI: 10.1016/j.clnesp.2025.03.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Revised: 02/12/2025] [Accepted: 03/13/2025] [Indexed: 03/22/2025]
Abstract
BACKGROUND Sarcopenia, characterized by loss of muscle mass and strength, has been linked to various health outcomes, including chronic kidney disease (CKD). This study aims to investigate the association of sarcopenia index, based on serum creatinine and cystatin C levels, with incident CKD in middle-aged and older adults. METHODS This study extracted data from a nation cohort, including age ≥45 years adults without CKD at baseline. Sarcopenia index was calculated based on serum creatinine and cystatin C levels, and incident CKD was assessed through follow-up surveys. Cox proportional hazards regression models were used to analyze the association between sarcopenia index and incident CKD, adjusting for potential confounders, with hazard ratio (HR) with 95 % confidence interval (95 % CI) reported. RESULTS A total of 8618 participants were included in the analysis. The median age was 61.0 years, and 44.7 % were male. During a mean follow-up period of 5.0 years, 514 cases of incident CKD were identified. After adjusting for covariates, compared with participants in the lowest tertile, the corresponding CKD HRs (95 % CIs) for participants in the medium and highest tertile were 0.701 (95 % CI: 0.558-0.880, P = 0.002), 0.784 (95 % CI: 0.618-0.994; P = 0.045). Restricted cubic spline curves revealed that incident rate decreased with increase in sarcopenia index. CONCLUSION This study provides national longitudinal evidence on the association of higher sarcopenia index with lower incident CKD. Our findings suggest that sarcopenia index may be a useful biomarker for predicting the risk of CKD in this population.
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Affiliation(s)
- Fan Zhang
- Department of Nephrology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Aojiao Chu
- Department of Nephrology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yan Bai
- Department of Nephrology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Liuyan Huang
- Department of Nephrology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yifei Zhong
- Department of Nephrology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.
| | - Yi Li
- Department of Nephrology, Longhua Hospital Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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29
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Zhao B, Zhang M, Liao S, Jiang T, Li J, Yang Z. Implication of serum soluble IL-2 receptor α in type 2 diabetes mellitus. J Diabetes Metab Disord 2025; 24:22. [PMID: 39712341 PMCID: PMC11659525 DOI: 10.1007/s40200-024-01536-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Accepted: 10/01/2024] [Indexed: 12/24/2024]
Abstract
Objectives The aim of this study was to determine the association of serum soluble IL-2 receptor α (sIL-2RA) with T2DM-related characteristics and complications. Methods Serum sIL-2RA levels were determined in 156 T2DM patients, and the association with T2DM-related characteristics and complications was evaluated. Results Serum sIL-2RA levels were significantly increased in T2DM patients with diabetic kidney disease (DKD) (median, IQR, 1434.9, 958.1-1896.0, pg/ml), in comparison with those without DKD (median, IQR, 851.2, 660.2-1089.9, pg/ml)(P < 0.001). The ROC analysis revealed good performance of sIL-2RA for identifying DKD, with the areas under the curve of 0.789 (95%CI of 0.711-0.867, P < 0.001). The correlation analyses showed significantly positive correlations of serum sIL-2RA with urea (r = 0.458, P < 0.001), creatinine (r = 0.508, P < 0.001) and uACR (r = 0.469, P < 0.001), and negative correlation with eGFR (r=-0.561, P < 0.001). The multivariate analyses showed that serum sIL-2RA was independently associated with the increased risks of DKD (OR, 95%CI, 6.539, 1.401-30.529, P = 0.017) and DR (OR, 95%CI, 3.606, 1.073-12.114, P = 0.038). Additionally, serum sIL-2RA was significantly associated with inflammatory indicators in DKD patients, and with metablic indicators in non-DKD patients (all P < 0.05). Conclusion Serum sIL-2RA may be closely associated with inflammation, glucose and lipid metabolisms, DKD and DR risks in T2DM. Furthermore, it may be a potential biomarker for T2DM-related micro-vascular complications.
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Affiliation(s)
- Bing Zhao
- Department of Laboratory Medicine, Taizhou First People’s Hospital, Huangyan Hospital of Wenzhou Medical University, Taizhou, China
| | - Miaomiao Zhang
- Department of Laboratory Medicine, Taizhou First People’s Hospital, Huangyan Hospital of Wenzhou Medical University, Taizhou, China
| | - Shaoguang Liao
- Present Address: Department of Radiation Oncology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
- Department of Oncology, Taizhou First People’s Hospital, Huangyan Hospital of Wenzhou Medical University, Taizhou, China
| | - Tingwang Jiang
- Key Laboratory, Department of Science and Technology, The Second People’s Hospital of Changshu, The Affiliated Changshu Hospital of Xuzhou Medical University, Changshu, Jiangshu China
| | - Jie Li
- Department of Laboratory Medicine, Taizhou First People’s Hospital, Huangyan Hospital of Wenzhou Medical University, Taizhou, China
| | - Zaixing Yang
- Department of Laboratory Medicine, Taizhou First People’s Hospital, Huangyan Hospital of Wenzhou Medical University, Taizhou, China
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30
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Zhang B, Deng Y, Song Y, Yang F, He Y, Guo T. Inhibition effects of xanthohumol on α-amylase and α-glucosidase: Kinetics, multi-spectral and molecular docking. Int J Biol Macromol 2025; 311:143676. [PMID: 40316087 DOI: 10.1016/j.ijbiomac.2025.143676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2025] [Revised: 03/18/2025] [Accepted: 04/28/2025] [Indexed: 05/04/2025]
Abstract
α-Amylase and α-glucosidase, two therapeutic targets for diabetes management, play crucial roles in carbohydrate metabolism and glucose absorption. Xanthohumol, one chalcone derived from hops, has demonstrated potential as a natural healthy phytonutrient. But its inhibition effects against α-amylase and α-glucosidase were still unclear. This study employs a comprehensive analytical strategy, including kinetics, multi-spectral, and molecular docking methods, to dissect the inhibition effects of xanthohumol against α-amylase and α-glucosidase. Our findings indicated that xanthohumol exerted a reversible mixed-type inhibition on both enzymes, with IC50 values of 71.07 ± 5.82 μM for α-amylase and 32.58 ± 3.11 μM for α-glucosidase. Multi-spectral analyses (fluorescence quenching, synchronous fluorescence, 3D fluorescence, ANS-binding fluorescence, and CD) revealed that xanthohumol binding induced conformation changes and microenvironment alterations in the enzymes, thereby inhibiting their activities. Molecular docking and dynamics studies further substantiated the interaction forces between xanthohumol and the enzymes. This research provided insights into the effects of xanthohumol as an inhibitor of α-amylase and α-glucosidase, offering valuable data to support the development of xanthohumol as a natural therapeutic for diabetes management.
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Affiliation(s)
- Bin Zhang
- Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong 524045, China.
| | - Yuansheng Deng
- Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong 524045, China
| | - Yuanrui Song
- Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong 524045, China
| | - Fa Yang
- Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong 524045, China
| | - Yingying He
- Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong 524045, China
| | - Tao Guo
- Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong 524045, China
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Yu L, Sun G, Liu Y, Zhang D, Li X, Zhang Q, Xing X, Zhang X, Yang X. Optimal amount of vigorous-intensity physical activity for lowering incidence of microvascular diseases: A prospective cohort study from the UK Biobank. Diabetes Res Clin Pract 2025; 224:112203. [PMID: 40294653 DOI: 10.1016/j.diabres.2025.112203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2025] [Revised: 04/09/2025] [Accepted: 04/23/2025] [Indexed: 04/30/2025]
Abstract
AIMS To explore the amount-response associations between the duration of physical activity (PA) at different intensities and the risks of microvascular diseases (MVDs), with a particular focus on identifying the optimal amount of vigorous-intensity PA (VPA). METHODS In this prospective cohort study, PA of different intensities were measured using wrist-worn accelerometers. MVDs, including nephropathy, neuropathy, and retinopathy, were identified from hospital inpatient records. Cox models and restricted cubic splines were used to evaluate the associations. RESULTS This prospective study included 92,275 participants (40,256 males and 52,019 females) with a mean (SD) age of 61.7 (7.8) years. During a median follow-up of 7.9 years, a total of 5,201 individuals were diagnosed with MVDs, including 2,385 with nephropathy, 512 with neuropathy, and 2,666 with retinopathy. An L-shaped amount-response association for VPA and overall MVDs was observed (P value for non-linearity < 0.001), with the optimal amount of 38 (95 % CI: 34, 44) minutes/week, corresponding to an HR of 0.71 (95 % CI: 0.64, 0.77). CONCLUSION VPA of 34-44 min/week were associated with 23 %-36 % lower risks of overall MVDs, with a less pronounced decline in risk thereafter. These findings may have implications for the future revision of physical activity recommendations to better improve microvascular health.
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Affiliation(s)
- Lan Yu
- Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin Medical University, Tianjin, China
| | - Guangbin Sun
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Yinyue Liu
- Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin Medical University, Tianjin, China
| | - Dongfang Zhang
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Xiang Li
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Qiang Zhang
- Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin Medical University, Tianjin, China; Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China; Key Laboratory of Prevention and Control of Major Diseases in the Population, Ministry of Education, Tianjin Medical University, Tianjin, China
| | - Xiaolong Xing
- Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin, China
| | - Xumei Zhang
- Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin Medical University, Tianjin, China; Key Laboratory of Prevention and Control of Major Diseases in the Population, Ministry of Education, Tianjin Medical University, Tianjin, China
| | - Xueli Yang
- Tianjin Key Laboratory of Environment, Nutrition and Public Health, Tianjin Medical University, Tianjin, China; Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China; Key Laboratory of Prevention and Control of Major Diseases in the Population, Ministry of Education, Tianjin Medical University, Tianjin, China.
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Brady VJ, Willig AL, Christopoulos KA, Grelotti DJ, Yendewa GA, O'Cleirigh C, Moore RD, Napravnik S, Webel A, Crane HM, Saag MS, Ruderman SA. Impact of Depression and HIV Symptoms on Glycemic Outcomes among Patients with HIV and Type 2 Diabetes: A Clinical Cohort Study. AIDS Behav 2025; 29:1851-1858. [PMID: 39961951 DOI: 10.1007/s10461-025-04653-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/01/2025] [Indexed: 04/02/2025]
Abstract
Type 2 diabetes (T2DM) and depressive symptoms frequently co-occur among people with HIV (PWH). Depression may impact diabetes management in PWH. This study evaluated the prevalence of concurrent T2DM and depression among PWH and the impact of depression and HIV symptoms on glycemic outcomes (hemoglobin A1c [A1c], blood glucose [BG]) among people with both HIV and T2DM. We conducted a secondary analysis in the CFAR Network of Integrated Clinical Systems, a multisite clinical cohort including a diverse population of PWH in care from July 2005 through July 2023. Linear regression and linear mixed models were used to estimate the association between depression, HIV symptoms, and glycemic outcomes (A1C, BG) at baseline and over time. Of the 18,562 PWH, 2,945 (16%) also had T2DM. PWH with T2DM were older (56 vs. 49 years) and more often non-Hispanic Black and cis-gender men. The prevalence of depression was not significantly different between PWH with or without T2DM (20% vs. 21%) although more PWH with T2DM received antidepressant medications. Among people with both HIV and T2DM, HIV baseline symptoms and depression were not associated with a change in A1c. Increases in time-updated HIV symptom scores were associated with random (non-fasting) BG levels, with each additional HIV symptom resulting in 0.8 mg/dL increase in random BG level (95% CI: 0.04-1.60, p = 0.04). The prevalence of T2DM was higher among PWH than in the general population. Although depression appears to be well managed, other factors impacting glycemic outcomes among people with both HIV and T2DM require further study.
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Affiliation(s)
- Veronica Joyce Brady
- Department of Research, Cizik School of Nursing, The University of Texas Health Houston, Houston, TX, USA.
- Cizik School of Nursing, The University of Texas Health Houston, 6901 Bertner Ave., Suite 567E, Houston, TX, 77030, USA.
| | - Amanda L Willig
- Division of Infectious Diseases, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
| | - Katerina A Christopoulos
- Division of HIV, ID and Global Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, USA
| | - David J Grelotti
- HIV Neurobehavioral Research Program, Department of Psychiatry, University of California San Diego School of Medicine, San Diego, CA, USA
| | - George A Yendewa
- Department of Medicine, Division of Infectious Diseases and HIV Medicine, Case Western Reserve University School of Medicine, Cleveland, USA
| | - Conall O'Cleirigh
- Fenway Institute, Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
| | - Richard D Moore
- Divisions of Infectious Diseases and General Internal Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Sonia Napravnik
- Division of Infectious Diseases, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Allison Webel
- School of Nursing, University of Washington, Seattle, WA, USA
| | - Heidi M Crane
- Division of Infectious Diseases, School of Medicine, University of Washington, Seattle, WA, USA
| | - Michael S Saag
- Division of Infectious Diseases, School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA
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Yu Y, Hu B, Yu XW, Cui YY, Cao XY, Ni MH, Li SN, Dai P, Sun Q, Bai XY, Tong Y, Jing XR, Yang AL, Liang SR, Du LJ, Guo S, Yan LF, Gao B, Cui GB. Neurovascular decoupling of frontoparietal cortex-putamen-cerebellum network in type 2 diabetes patient: Potential biomarker for abnormal eating patterns. Diabetes Res Clin Pract 2025; 224:112175. [PMID: 40233865 DOI: 10.1016/j.diabres.2025.112175] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2024] [Revised: 01/21/2025] [Accepted: 04/09/2025] [Indexed: 04/17/2025]
Abstract
AIM High rates of dropout and binge eating triggered by restrictive diet limit the effectiveness of dietary interventions in type 2 diabetes mellitus (T2DM). However, it remains unclear what the potential central underpinnings of T2DM-specific dietary behavior characteristics are. METHODS 41 T2DM patients and 43 matched healthy controls (HC) who underwent resting state functional MRI were enrolled to screen for the suspicious network by effective connectivity (EC) analysis and to explore its dynamic temporal and neurovascular coupling properties. Additionally, the timeline of neuropathological changes during T2DM progression was evaluated. RESULTS Increased uncontrolled eating, internal and external loci of hunger were found in T2DM. EC of the frontoparietal cortex-putamen-cerebellum network was significantly higher in T2DM patients (P = 0.023). The fractional windows (P = 0.009) and mean dwell time (P = 0.009) of the densest state were significantly higher in T2DM patients. Neurovascular decoupling of the frontoparietal cortex-putamen-cerebellum network was correlated with these T2DM-specific eating behavior characteristics. Neurovascular decoupling coefficient of right putamen (Putamen_R) changed at the very beginning of T2DM. CONCLUSION The frontoparietal cortex-putamen-cerebellum network was the suspicious T2DM-related abnormal eating pattern network. Neurovascular decoupling of the network, especially that of Putamen_R, occurred early and might serve as a biomarker for abnormal eating patterns in T2DM patients.
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Affiliation(s)
- Ying Yu
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an 710038 Shaanxi, China
| | - Bo Hu
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an 710038 Shaanxi, China
| | - Xin-Wen Yu
- Department of Endocrinology, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an, Shaanxi 710038, China
| | - Yan-Yan Cui
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an 710038 Shaanxi, China; Shaanxi University of Chinese Medicine, Middle Section of Century Avenue, Xian yang, Shaanxi, China
| | - Xin-Yu Cao
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an 710038 Shaanxi, China
| | - Min-Hua Ni
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an 710038 Shaanxi, China
| | - Si-Ning Li
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an 710038 Shaanxi, China
| | - Pan Dai
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an 710038 Shaanxi, China
| | - Qian Sun
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an 710038 Shaanxi, China
| | - Xiao-Yan Bai
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an 710038 Shaanxi, China; Shaanxi University of Chinese Medicine, Middle Section of Century Avenue, Xian yang, Shaanxi, China
| | - Yao Tong
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an 710038 Shaanxi, China
| | - Xiao-Rui Jing
- Department of Endocrinology, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an, Shaanxi 710038, China
| | - Ai-Li Yang
- Department of Endocrinology, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an, Shaanxi 710038, China
| | - Sheng-Ru Liang
- Department of Endocrinology, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an, Shaanxi 710038, China
| | - Li-Juan Du
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an 710038 Shaanxi, China
| | - Shuo Guo
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an 710038 Shaanxi, China
| | - Lin-Feng Yan
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an 710038 Shaanxi, China; Shaanxi University of Chinese Medicine, Middle Section of Century Avenue, Xian yang, Shaanxi, China.
| | - Bin Gao
- Department of Endocrinology, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an, Shaanxi 710038, China.
| | - Guang-Bin Cui
- Department of Radiology & Functional and Molecular Imaging Key Lab of Shaanxi Province, Tangdu Hospital, Fourth Military Medical University (Air Force Medical University), 569 Xinsi Road, Xi'an 710038 Shaanxi, China; Shaanxi University of Chinese Medicine, Middle Section of Century Avenue, Xian yang, Shaanxi, China.
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Balan P, Lim W, Bee YM, Chen Q, Leite FRM, Seneviratne CJ. Elevated Dipeptides and Agrochemicals in the Saliva of Type 2 Diabetes Mellitus Patients: A Dual Origin Metabolomic Insights. Int Dent J 2025; 75:100836. [PMID: 40449130 PMCID: PMC12166681 DOI: 10.1016/j.identj.2025.100836] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2024] [Revised: 04/08/2025] [Accepted: 05/02/2025] [Indexed: 06/02/2025] Open
Abstract
INTRODUCTION AND AIMS Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder influenced by internal metabolic disruptions and external exposures, known as exposomes, which increase disease risk. Identifying salivary metabolites is a promising method to detect biomarkers for both endogenous and environmental factors. This study utilised a dual approach to profile salivary endogenous metabolites and exposomes, aiming to provide a comprehensive understanding of T2DM by integrating biological and environmental factors, thereby improving biomarker discovery and risk prediction. METHODS Salivary metabolites were analysed via ultraperformance liquid chromatography coupled with Q-Exactive mass spectrometry in samples from women with T2DM (n = 39) and healthy controls (n = 40). The groups were matched for age, sex, periodontitis, dyslipidaemia, and hypertension. The identified metabolites were mapped to the Human Metabolome Database and the Blood Exposome List using U.S. Environmental Protection Agency resources. RESULTS Principal component analysis revealed distinct clusters for endogenous metabolites and exposomes, leading to separate analyses. In the endogenous metabolite category, 64.5% of the metabolites significantly differing between DM and non-DM groups were dipeptides (false discovery rate <0.05, variable importance for the projection >2). Among the dipeptides, Gln-Trp and Phe-Asn were identified as the top predictors of T2DM, with an area under the curve of 0.87, while His-Phe, His-Tyr, Met-Tyr, and Leu-Gln had area under the curve of 0.85. In the exposome category, univariate regression revealed significant associations between synthetic dipeptides and agrochemical exposomes and fasting plasma glucose levels, with daminozide exhibiting the greatest effect size. CONCLUSION Leveraging saliva's noninvasive collection, these findings underscore the diagnostic potential of salivary dipeptides and emphasise the importance of addressing exposomes in T2DM management. CLINICAL RELEVANCE By integrating endogenous and exposome profiling, this study offers a novel approach for identifying metabolic and environmental risk factors, advancing biomarker discovery and risk prediction to improve early diagnosis and personalised management of T2DM.
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Affiliation(s)
- Preethi Balan
- Singapore Oral Multiomics Initiative, National Dental Research Institute Singapore (NDRIS), National Dental Centre Singapore, Singapore, Singapore; Oral Health ACP, Duke NUS Medical School, Singapore, Singapore.
| | - Weiying Lim
- Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
| | - Yong Mong Bee
- Department of Endocrinology, Singapore General Hospital, Singapore, Singapore; Medicine ACP, Duke-NUS Medical School, Singapore
| | - Qifan Chen
- Department of Endocrinology, Singapore General Hospital, Singapore, Singapore
| | - Fabio R M Leite
- Singapore Oral Multiomics Initiative, National Dental Research Institute Singapore (NDRIS), National Dental Centre Singapore, Singapore, Singapore; Oral Health ACP, Duke NUS Medical School, Singapore, Singapore
| | - Chaminda Jaya Seneviratne
- Singapore Oral Multiomics Initiative, National Dental Research Institute Singapore (NDRIS), National Dental Centre Singapore, Singapore, Singapore; School of Dentistry, The University of Queensland, Brisbane, Queensland, Australia.
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Li C, Zhang D, Li X, Zhang Y, Sun G, Zhou H, Xi R, Yuan H, Zhang L, Zhang X, Li S, Zhang Q, Yang X. Effects of PM 2.5 constituents on gestational diabetes mellitus in Chinese pregnant women: The potential modifying role of vitamin B 12. ENVIRONMENTAL RESEARCH 2025; 282:122003. [PMID: 40449579 DOI: 10.1016/j.envres.2025.122003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/14/2024] [Revised: 05/26/2025] [Accepted: 05/28/2025] [Indexed: 06/03/2025]
Abstract
Associations of PM2.5 and its constituents with gestational diabetes mellitus (GDM) are still unclear, and little is known about the impact of vitamin B12. The Gene-Environment-Nutrient-Epigenetics interaction on Maternal and Children health study (GENEMaC) cohort was conducted during 2017-2018 in Tianjin, China, and 1396 eligible women were included in the final analysis. Spatiotemporal models were used to estimate PM2.5 exposure levels and its constituents, including sulfate (SO2- 4), ammonium (NH+ 4), nitrate (NO- 3), organic matter (OM), black carbon (BC). Logistic regression and distributed lag non-linear model (DLNM) were used to assess each pollutant-GDM association. Weighted quantile sum (WQS) regression was conducted to assess the extent of contributions of pollutants co-exposure to GDM. The logistic regression showed that exposures to PM2.5, NO- 3, and NH+ 4 during the 2nd trimester of pregnancy increased the risk of GDM. DLNM analyses observed a lag exposure-response relationship for each constituent, while black carbon(BC) exposed in the 2nd trimester was displayed as the top contributor in the WQS model. The joint effects of constituents exposure (high versus low) and serum B12 (tertiles) on GDM were further evaluated, and the highest risks of GDM were consistently observed in the low B12 level and high pollution groups for SO2- 4, NO- 3, and NH+ 4. These findings provide evidence of the impact of PM2.5 components on GDM and highlight the susceptibility of pregnant women with low B12 levels to air pollution.
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Affiliation(s)
- Chen Li
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Dongfang Zhang
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Xiang Li
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Yibin Zhang
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Guangbin Sun
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Hongyu Zhou
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Rui Xi
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Haoyang Yuan
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Liwen Zhang
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Xumei Zhang
- Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, China; Department of Nutrition and Food Science, School of Public Health, Tianjin Medical University, Tianjin, China
| | - Shuying Li
- Department of Endocrinology, Tianjin Xiqing Hospital, Tianjin, China; Tianjin Metabolic Disease Hospital, Tianjin Medical University, Tianjin, China
| | - Qiang Zhang
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, China.
| | - Xueli Yang
- Department of Occupational and Environmental Health, School of Public Health, Tianjin Medical University, Tianjin, China; Tianjin Key Laboratory of Environment, Nutrition and Public Health, School of Public Health, Tianjin Medical University, Tianjin, China.
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Uddin S, Sanchez Machado M, Alshahrouri B, Echeverri JI, Rico MC, Rao AD, Ruchalski C, Barrero CA. Empowering Pharmacists in Type 2 Diabetes Care: Opportunities for Prevention, Counseling, and Therapeutic Optimization. J Clin Med 2025; 14:3822. [PMID: 40507585 PMCID: PMC12155691 DOI: 10.3390/jcm14113822] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2025] [Revised: 05/27/2025] [Accepted: 05/27/2025] [Indexed: 06/16/2025] Open
Abstract
Diabetes is a growing chronic disease with complications that impose a significant burden on healthcare systems worldwide. Pharmacists are readily accessible for diabetes management beyond simply dispensing medications. Consequently, they are involved in disease prevention and detection, therapy management, and patient monitoring. However, with the current escalating impact of diabetes, pharmacists must upgrade their strategies by integrating guidelines from sources like the American Diabetes Association (ADA) 2024 with pharmacy expertise. This perspective serves as a guide for pharmacists, identifying key foundations involved in diabetes management, highlighting five crucial steps for optimal disease control, ranging from prevention strategies to pharmacist-led counseling interventions. We employed PubMed, CDC, WHO guidelines, and key reference texts. Searches were performed using combinations of terms such as "pharmacist", "type 2 diabetes", "diabetes prevention", "pharmacist intervention", and "diabetes management", covering publications from January 2010 to March 2025. Studies were included if they focused on pharmacist-led prevention, intervention, or management strategies related to type 2 diabetes (T2D) and were published in English. Studies focusing exclusively on type 1 diabetes were excluded. Generative artificial intelligence was employed to order and structure information as described in the acknowledgments. Conflicting evidence was resolved by giving relevance to recent systematic reviews, randomized trials, and major guidelines. Additional insights were gained through consultations with PharmD professionals experienced in diabetes care. Evidence from selected studies suggests that pharmacist-led care models may enhance and promote the early detection of T2D, improve therapy adherence, enhance glycemic control, and increase overall treatment efficiency. This work suggests that pharmacists must play a key role in diagnosing, preventing, managing, and mitigating the consequences associated with T2D. They must contribute to early treatments with appropriate training and involvement to improve therapeutic outcomes and reduce diabetes-related complications.
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Affiliation(s)
- Sarah Uddin
- Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA 19140, USA; (S.U.); (M.S.M.); (B.A.); (J.I.E.); (M.C.R.)
| | - Mathias Sanchez Machado
- Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA 19140, USA; (S.U.); (M.S.M.); (B.A.); (J.I.E.); (M.C.R.)
| | - Bayan Alshahrouri
- Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA 19140, USA; (S.U.); (M.S.M.); (B.A.); (J.I.E.); (M.C.R.)
| | - Jose I. Echeverri
- Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA 19140, USA; (S.U.); (M.S.M.); (B.A.); (J.I.E.); (M.C.R.)
| | - Mario C. Rico
- Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA 19140, USA; (S.U.); (M.S.M.); (B.A.); (J.I.E.); (M.C.R.)
| | - Ajay D. Rao
- Center for Metabolic Disease Research, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, USA;
| | - Charles Ruchalski
- Department of Pharmaceutical Practice, School of Pharmacy, Temple University, Philadelphia, PA 19140, USA
| | - Carlos A. Barrero
- Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, Philadelphia, PA 19140, USA; (S.U.); (M.S.M.); (B.A.); (J.I.E.); (M.C.R.)
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Yin M, Fan W, Yu Y, Liu Z, Zhang D, Deng C, Li X. Disparities in diabetes burden in China and globally, with projections to 2050: A systematic analysis for the Global Burden of Disease Study 2021. Diabetes Obes Metab 2025. [PMID: 40432376 DOI: 10.1111/dom.16482] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Revised: 04/27/2025] [Accepted: 05/10/2025] [Indexed: 05/29/2025]
Affiliation(s)
- Min Yin
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
- Department of Clinical Nutrition, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Wenqi Fan
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Yi Yu
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Zizhu Liu
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Danyi Zhang
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Chao Deng
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Xia Li
- National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China
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Zinabu E, Negash M, Goshu Y, Kebede T, Kelem A, Tsegaye A. Hematological parameters of newborns from diabetic mothers in Gandhi memorial hospital, Addis Ababa, Ethiopia. PLoS One 2025; 20:e0324163. [PMID: 40424230 PMCID: PMC12111266 DOI: 10.1371/journal.pone.0324163] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2025] [Accepted: 04/21/2025] [Indexed: 05/29/2025] Open
Abstract
BACKGROUND Diabetes mellitus during pregnancy can significantly affect a newborn's hematological profile. However, the hematological profiles among newborns of diabetic mothers and their clinical and prognostic implications are not well explored. Therefore, this study aimed to determine hematological parameters of newborns from diabetic mothers in Gandhi Memorial Hospital, Addis Ababa, Ethiopia, 2024. METHODS A comparative cross-sectional study was carried out at Gandhi Memorial Hospital from March to May 2024. A total of 196 newborns -98 from diabetic mothers and 98 from apparently healthy mothers-were conveniently enrolled in the study. A hematological profile test was assayed using a Sysmex XN-550 analyzer from the whole blood of mothers and cord blood of newborns collected in EDTA. Glucose was measured using a Cobas C311 analyzer from serum collected using SST test tube. Data was entered and analyzed using SPSS version 26, with descriptive statistics, proportions, and independent t-tests. A P-value of less than 0.05 was considered statistically significant. RESULTS The study found that the mean ± SD value of red blood cell count was 4.87 ± 0.68 vs 3.33 ± 0.98 x1012/L (P < 0.001), hemoglobin 17.48 ± 2.69 vs 12.08 ± 3.48 g/dL (P < 0.001), hematocrit 49.83 ± 7.47 vs 36.13 ± 8.97% (P < 0.001), red cell distribution width 18.35 ± 2.68 vs 17.27 ± 1.92% (P < 0.001), platelet distribution width 12.26 ± 1.80 vs 11.69 ± 1.76% (P = 0.028), and platelet large cell ratio was 26.05 ± 5.27 vs 24.07 ± 2.21% (P = 0.001) were significantly higher in newborns born to diabetic mothers compared to controls. Polycythemia was seen in large numbers in newborns born to diabetic mothers (56.1%, 55/98 vs 1%, 1/98). On the other hand, the platelet count and PCT values were significantly lower in newborns from diabetic mothers than controls, with a mean value of 239.69 ± 92.52 (103/µL) and 0.24 ± 0.09 (%), respectively, with a P value < 0.001. CONCLUSION The hematological profile shows a significant difference among newborns from mothers with diabetes and apparently healthy mothers. Therefore, it is better to consider hematological parameters as a screening tool for early detection of hematological complications in newborns from diabetic mothers, and this screening should be encouraged.
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Affiliation(s)
- Eden Zinabu
- Department of Medical Laboratory Sciences, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | - Mikias Negash
- Department of Medical Laboratory Sciences, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | | | | | - Amanuel Kelem
- Department of Medical Laboratory Sciences, Asrat Woldeyes Health Science Campus, Debre Berhan University, Debre Berhan, Ethiopia
| | - Aster Tsegaye
- Department of Medical Laboratory Sciences, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
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Tang Z, Qiu T, Ma R, Wang R, Wang B, Lu Y, Huang B, Luo S, Liu G. The influence of habitual tooth brushing frequency on individuals diagnosed with coronary artery disease. Sci Rep 2025; 15:18463. [PMID: 40425644 PMCID: PMC12116763 DOI: 10.1038/s41598-025-01910-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 05/09/2025] [Indexed: 05/29/2025] Open
Abstract
Coronary artery disease (CAD) is a prevalent and high-mortality condition globally. The awareness regarding adequate oral care in China was insufficient. This study investigates the outcomes of CAD patients in southwest China based on their tooth brushing frequency. A total of 841 CAD patients were selected from a cohort of 32,709 residents. Over a four-year follow-up period, the incidence of three-point major adverse cardiovascular events (3P-MACEs) was evaluated. The results indicated that the hazard ratios (HR) with 95% confidence intervals (CIs) for 3P-MACEs among the three groups of tooth brushing frequency (twice, once, and thrice daily) were: reference, 1.61 (1.09-2.37) (p = 0.017), and 0.49 (0.15-1.62) (p = 0.241). Patients who brushed their teeth only once a day had a 1.71 (1.18-2.46) times higher risk compared to those who brushed twice or more daily (p = 0.004). In conclusion, insufficient tooth brushing frequency appears to be associated with a higher risk of adverse outcomes among CAD patients.
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Grants
- 2023-01 the "Tomorrow Cup" Education and Teaching Reform Research of International Medical College, Chongqing Medical University
- 2023-01 the "Tomorrow Cup" Education and Teaching Reform Research of International Medical College, Chongqing Medical University
- 2023-01 the "Tomorrow Cup" Education and Teaching Reform Research of International Medical College, Chongqing Medical University
- 2023-01 the "Tomorrow Cup" Education and Teaching Reform Research of International Medical College, Chongqing Medical University
- 2023-01 the "Tomorrow Cup" Education and Teaching Reform Research of International Medical College, Chongqing Medical University
- 2023-01 the "Tomorrow Cup" Education and Teaching Reform Research of International Medical College, Chongqing Medical University
- 2023-01 the "Tomorrow Cup" Education and Teaching Reform Research of International Medical College, Chongqing Medical University
- 2023-01 the "Tomorrow Cup" Education and Teaching Reform Research of International Medical College, Chongqing Medical University
- 2023-01 the "Tomorrow Cup" Education and Teaching Reform Research of International Medical College, Chongqing Medical University
- W0010 the CQMU Program for Youth Innovation in Future Medicine
- W0010 the CQMU Program for Youth Innovation in Future Medicine
- W0010 the CQMU Program for Youth Innovation in Future Medicine
- W0010 the CQMU Program for Youth Innovation in Future Medicine
- W0010 the CQMU Program for Youth Innovation in Future Medicine
- W0010 the CQMU Program for Youth Innovation in Future Medicine
- W0010 the CQMU Program for Youth Innovation in Future Medicine
- W0010 the CQMU Program for Youth Innovation in Future Medicine
- W0010 the CQMU Program for Youth Innovation in Future Medicine
- the “Tomorrow Cup” Education and Teaching Reform Research of International Medical College, Chongqing Medical University
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Affiliation(s)
- Zihan Tang
- Chongqing Medical University, Chongqing, China
| | - Tian Qiu
- Chongqing Medical University, Chongqing, China
| | - Runfeng Ma
- Chongqing Medical University, Chongqing, China
| | - Ruoyu Wang
- Chongqing Medical University, Chongqing, China
| | | | - Yiduo Lu
- Naval Medical University, Shanghai, China
| | - Bi Huang
- Department of Cardiovascular Medicine, Cardiovascular Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Suxin Luo
- Department of Cardiovascular Medicine, Cardiovascular Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Gang Liu
- Department of Cardiovascular Medicine, Cardiovascular Research Center, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
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Xu DH, Zhang XY, Liu SY, Wei J, Zhan JH, Du JK, Liu YJ, Zhu XY. KLK8/HGF/Met signaling pathway mediates diabetes-associated hippocampal neuroinflammation in male mice. Theranostics 2025; 15:6290-6312. [PMID: 40521191 PMCID: PMC12159841 DOI: 10.7150/thno.109513] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2024] [Accepted: 04/30/2025] [Indexed: 06/18/2025] Open
Abstract
Rationale: Neuroinflammation plays a critical role in the pathogenesis of diabetes-associated depression. Tissue kallikrein-related peptidase 8 (KLK8), a secreted serine protease, has been implicated in the pathogenesis of depression- and anxiety-related behaviors across various etiologies, however the underlying mechanisms remain largely unexplored. This study elucidates a novel mechanism by which KLK8 upregulation contributes to diabetes-induced microglial activation and neuroinflammation in the hippocampus through modulating the hepatocyte growth factor (HGF)/Met signaling pathway. Methods and Results: Streptozotocin (STZ)-induced diabetic mice exhibited increased KLK8 expression in the hippocampus, an effect that was mitigated in KLK8-deficient or aerobic running-exercised mice. KLK8 deficiency significantly reduced depression-like behaviors, microglial activation, and neuroinflammation in diabetic mice. In BV2 mouse microglial cells, adenovirus-mediated overexpression of KLK8 (Ad-KLK8) was sufficient to induce microglial activation. Co-immunoprecipitation (Co-IP) coupled with mass spectrometry revealed that CD44 might interact with KLK8. KLK8 overexpression decreased CD44 levels in microglial cells. However, the CD44 activator Angstrom6 further exacerbated KLK8-induced microglial activation. Conversely, transcriptional profiling of KLK8-overexpressing microglial cells and subsequent validation demonstrated that the Met/Src/Btk/NF-κB signaling pathway played a central role in mediating the stimulatory effects of KLK8 on microglial activation in both Ad-KLK8-treated BV2 cells and human microglial cell line HMC3 cells stably transfected with KLK8 lentivirus (Lv-KLK8). The Met receptor is activated upon binding to its ligand HGF, which exists as an inactive precursor (pro-HGF). Our findings showed that KLK8 cleaved pro-HGF, promoting HGF release and subsequently activating the Met/Src/Btk/NF-κB signaling pathway in microglial cells. High glucose conditions increased KLK8 expression and enhanced HGF release, thereby stimulating the Met/Src/Btk/NF-κB signaling pathway and microglial activation in a KLK8-dependent manner. Systemic administration of a Met inhibitor inactivated the Met/Src/Btk/NF-κB pathway, reducing depression-like behaviors, microglial activation, and neuroinflammation in STZ-induced diabetic mice. Both Met inhibitor and KLK8 deficiency enhanced hippocampal neuroplasticity in STZ-induced diabetic mice. Finally, we demonstrated that running exercise reversed KLK8 upregulation and inactivated Met/Src/Btk/NF-κB signaling pathways, thereby attenuating neuroinflammation, improving neuroplasticity, and alleviating depression-like behaviors in STZ-induced diabetic mice. Conclusions: This study provides evidence that the KLK8/HGF/Met signaling pathway mediates diabetes-associated hippocampal neuroinflammation and depression-like behaviors, highlighting the therapeutic potential of targeting this pathway in diabetes-associated depression.
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Affiliation(s)
- Dan-Hong Xu
- Department of Physiology, Naval Medical University, Shanghai, 200433, China
| | - Xiao-Yong Zhang
- Department of Physiology, Naval Medical University, Shanghai, 200433, China
| | - Shi-Yu Liu
- School of Kinesiology, The Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, 200438, China
| | - Juan Wei
- School of Sports and Health, Nanjing Sport Institute, Nanjing, 210014, China
| | - Jun-Hui Zhan
- School of Kinesiology, The Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, 200438, China
| | - Jian-Kui Du
- Department of Physiology, Naval Medical University, Shanghai, 200433, China
| | - Yu-Jian Liu
- School of Kinesiology, The Key Laboratory of Exercise and Health Sciences of Ministry of Education, Shanghai University of Sport, Shanghai, 200438, China
| | - Xiao-Yan Zhu
- Department of Physiology, Naval Medical University, Shanghai, 200433, China
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Yan R, Zhang J, Ma H, Wu Y, Fan Y. Potential of seven insulin resistance indicators as biomarkers to predict infertility risk in U.S. women of reproductive age: a cross-sectional study. Reprod Biol Endocrinol 2025; 23:77. [PMID: 40413481 DOI: 10.1186/s12958-025-01416-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2025] [Accepted: 05/13/2025] [Indexed: 05/27/2025] Open
Abstract
BACKGROUND Insulin resistance(IR) is a key mechanism underlying both obesity and metabolic syndrome, with significant implications for the onset and progression of female infertility. This study systematically examines the associations between seven insulin resistance indicators and the risk of infertility in U.S. women of reproductive age, while also evaluating the diagnostic value of these indicators in predicting infertility. METHOD This cross-sectional study analyzed data from the 2013-2018 National Health and Nutrition Examination Survey (NHANES) to explore the relationship between seven insulin resistance indicators and infertility risk. The indicators included the Metabolic Score for Insulin Resistance (METS-IR), Triglyceride-Glucose Index (TyG), Triglyceride-Glucose-Waist Circumference (TyG-WC), Triglyceride-Glucose-Body Mass Index (TyG-BMI), Triglyceride-Glucose-Waist-to-Height Ratio (TyG-WHtR), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), and Triglyceride/High-Density Lipoprotein Ratio (TG/HDL). Receiver Operating Characteristic (ROC) curves were used to assess the diagnostic accuracy of each insulin resistance indicator in predicting infertility. Additionally, smooth curve fitting and threshold effect analysis were employed to further explore the relationship between insulin resistance indicators with high diagnostic efficacy and infertility. RESULTS This study included 1,100 women aged 20-45, of whom 140 (12.61%) were diagnosed with infertility. The results revealed significant positive correlations between METS-IR, TyG-BMI, TyG-WC, TyG-WHtR, and infertility risk. Specifically, as TyG-WC and TyG-WHtR levels increased, the risk of infertility rose linearly, while METS-IR and TyG-BMI exhibited a nonlinear positive association with infertility risk. No significant correlations were observed between TyG, HOMA-IR, TG/HDL, and infertility. Finally, ROC curve analysis indicated that METS-IR outperformed the other six insulin resistance indicators in predicting infertility risk. CONCLUSION METS-IR, TyG-BMI, TyG-WC, and TyG-WHtR are significantly associated with the risk of infertility in U.S. women of reproductive age, with METS-IR demonstrating the highest predictive power. These findings suggest that METS-IR may have substantial clinical utility in evaluating infertility risk.
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Affiliation(s)
- Ruihua Yan
- Department of Obstetrics and Gynecology, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China
| | - Jiao Zhang
- Department of Obstetrics and Gynecology, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China
| | - Hongyun Ma
- Department of Obstetrics and Gynecology, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China
| | - Yang Wu
- Department of Obstetrics and Gynecology, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China
| | - Yang Fan
- Department of Obstetrics and Gynecology, People's Hospital of Ningxia Hui Autonomous Region, Ningxia Medical University, Yinchuan, China.
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Biagetti B, Cordero Asanza E, Pérez-López C, Araujo-Castro M, Camara R, Guerrero-Pérez F, Vicente A, Lamas C, Serra G, Echarri AI, Ollero MD, González Molero I, Villar-Taibo R, Moure Rodríguez MD, García-Feijoo P, Berrocal VR, Sánchez Ramirez MN, Gutiéerrez Hurtado A, Capristan-Díaz V, Simó-Servat A, Gallach M, Safont Perez E, González Rosa V, Civantos S, Asensio-Wandosell D, Martinez-Saez E, Menéndez Torre E, Aulinas A, Iglesias P, Diez JJ, Bernabéu I, Álvarez-Escolá C, Puig-Domingo M. Pituitary Apoplexy: Comorbidities, Management, and Outcomes-A Spanish Observational Multicenter Study. J Clin Endocrinol Metab 2025; 110:e1811-e1820. [PMID: 39298667 DOI: 10.1210/clinem/dgae649] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Revised: 08/12/2024] [Accepted: 09/18/2024] [Indexed: 09/22/2024]
Abstract
BACKGROUND Pituitary apoplexy (PA) is the paradigm of endocrine and neurosurgical emergency. OBJECTIVE To evaluate the comorbidities, risk factors, clinical presentation, pituitary apoplexy score (PAS), and the outcomes of surgical vs conservative management of PA in Spain. METHODS Spanish multicenter, observational study of 301 patients with acute PA. Statistical analyses compared risk factors, clinical presentation, and outcomes between surgical and conservative treatment groups, adjusting for potential confounders. The prevalence of cardiovascular risk factors in patients with PA was compared with the Spanish population and with patients with nonfunctioning pituitary adenomas. RESULTS Median age was 59.3 years, 201 (66.8%) were men; nonfunctioning adenomas (77.9%) were the most common tumor type. The prevalence of diabetes (20.3% vs 13.9%, P < .01), hypertension (48.8% vs 33.4%, P < .01), and dyslipidemia (44.2% vs 23.3%, P < .01), exceeded the Spanish age-adjusted population prevalence. Overall, 209 (69.4%) underwent surgery and 92 (30.6%) received conservative treatment. Surgical patients had larger tumors (26.2 vs 21.0 mm, P < .01), more frequent chiasmal compression (77.2% vs 53.4%, P < .01), and higher values of PAS. In the follow-up, although there were no statistically significant differences in anterior pituitary hormonal deficits between treatments, permanent vasopressin deficiency was more frequent after surgery (14.8% vs 3.3%, P < .01). CONCLUSIONS There is a high burden of cardiovascular risk factors among patients with PA, suggesting that metabolic factors may play a potential role in the development of PA. This underscores the need for comprehensive management of these conditions in addition to treating the apoplexy itself in this population. Surgical management has a relevant place in PA approach mainly in patients with higher PAS. However, it leads a permanent vasopressin deficit more frequently than a conservative approach.
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Affiliation(s)
- Betina Biagetti
- Endocrinology & Nutrition Department, Hospital Universitario Vall de Hebrón, CIBERER U747 (ISCIII), ENDO-ERN, Universitat Autónoma de Bracelona, Barcelona, PC 08032, Spain
| | - Esteban Cordero Asanza
- Neurosurgery Department, Hospital Universitario Vall de Hebrón, Departament de Cirurgia i Ciències Morfològiques, Universitat Autónoma de Barcelona, PC 08032, Spain
| | - Carlos Pérez-López
- Department of Neurosurgery, Hospital Universitario La Paz, Madrid, PC 28046, Spain
| | - Marta Araujo-Castro
- Department of Endocrinology and Nutrition, Hospital Universitario Ramón y Cajal, Madrid, PC 28034, Spain
| | - Rosa Camara
- Endocrinology & Nutrition Service, La Fe University Hospital, Valencia, PC 46026, Spain
| | - Fernando Guerrero-Pérez
- Department of Endocrinology, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, PC 08907, Spain
| | - Almudena Vicente
- Endocrinology & Nutrition Department, Hospital Universitario de Toledo, PC 45007, Toledo, Spain
| | - Cristina Lamas
- Endocrinology & Nutrition Department, Hospital Universitario De Albacete, PC 02006, Albacete, Spain
| | - Guillermo Serra
- Department of Endocrinology, Son Espases University Hospital, Palma de Mallorca, PC 07120, Spain
| | - Ana Irigaray Echarri
- Department of Endocrinology, University Hospital of Navarre, Pamplona, PC 31008, Spain
| | - M Dolores Ollero
- Department of Endocrinology, University Hospital of Navarre, Pamplona, PC 31008, Spain
| | - Inmaculada González Molero
- Endocrinology & Nutrition Department, Hospital Regional Universitario de Málaga, IBIMA Plataforma BIONAND Málaga, PC 29010, Spain
| | - Rocío Villar-Taibo
- Endocrinology & Nutrition Department, Hospital Universitario de Santiago de Compostela, A Coruña, PC 15706, Spain
| | | | - Pablo García-Feijoo
- Department of Neurosurgery, Hospital Universitario La Paz, Madrid, PC 28046, Spain
| | | | | | - Alba Gutiéerrez Hurtado
- Endocrinology & Nutrition Department, Hospital Universitario Central de Asturias, Instituto de Investigación del Principado de Asturias (ISPA), Asturias, PC 33011, Spain
| | - Vanessa Capristan-Díaz
- Department of Endocrinology, Hospital Universitario Puerta de Hierro Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana, Majadahonda, PC 28220, Spain
| | - Andreu Simó-Servat
- Department of Endocrinology and Nutrition, Mutua de Terrassa University Hospital, Terrassa, PC 08221, Spain
| | - Marta Gallach
- Endocrinology & Nutrition Department, Hospital Universitario De Albacete, PC 02006, Albacete, Spain
| | - Eva Safont Perez
- Endocrinology & Nutrition Department, Hospital de la Santa Creu i Sant Pau, IR-SANTPAU, CIBERER-U747 (ISCIII), ENDO-ERN, Barcelona, PC 08025, Spain
| | - Victoria González Rosa
- Endocrinology & Nutrition Department, Hospital Universitario Insular de Gran Canaria, Las Palmas, PC 35016, Spain
| | - Soralla Civantos
- Endocrinology & Nutrition Department, Hospital Universitario Fuenlabrada, Madrid, PC 28942, Spain
| | - Diego Asensio-Wandosell
- Endocrinology & Nutrition Service, Germans Trias Hospital and Research Institute, Badalona, Centro de Investigación Biomédica en Red de Enfermedades Raras U747, Autonomous University of Barcelona, Barcelona, PC 8916, Spain
| | - Elena Martinez-Saez
- Pathology Department, Hospital Universitario Vall de Hebrón, Universitat Autónoma de Barcelona, Barcelona, PC 08032, Spain
| | - Edelmiro Menéndez Torre
- Endocrinology & Nutrition Department, Hospital Universitario Central de Asturias, Instituto de Investigación del Principado de Asturias (ISPA), Asturias, PC 33011, Spain
| | - Anna Aulinas
- Department of Endocrinology and Nutrition, Mutua de Terrassa University Hospital, Terrassa, PC 08221, Spain
| | - Pedro Iglesias
- Department of Endocrinology, Hospital Universitario Puerta de Hierro Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana, Majadahonda, PC 28220, Spain
- Department of Medicine, Universidad Autónoma de Madrid, Madrid, PC 28049, Spain
| | - Juan J Diez
- Department of Endocrinology, Hospital Universitario Puerta de Hierro Majadahonda, Instituto de Investigación Sanitaria Puerta de Hierro Segovia de Arana, Majadahonda, PC 28220, Spain
- Department of Medicine, Universidad Autónoma de Madrid, Madrid, PC 28049, Spain
| | - Ignacio Bernabéu
- Endocrinology & Nutrition Department, Hospital Universitario de Santiago de Compostela, A Coruña, PC 15706, Spain
| | | | - Manel Puig-Domingo
- Endocrinology & Nutrition Service, Germans Trias Hospital and Research Institute, Badalona, Centro de Investigación Biomédica en Red de Enfermedades Raras U747, Autonomous University of Barcelona, Barcelona, PC 8916, Spain
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Zhao J, Lu Q, Cong XX, Zhang XF. The skeletal muscle mass index is a predictor for all-cause mortality in US adults with type 2 diabetes or pre-diabetes. Diabetes Res Clin Pract 2025; 225:112254. [PMID: 40393540 DOI: 10.1016/j.diabres.2025.112254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Revised: 05/13/2025] [Accepted: 05/14/2025] [Indexed: 05/22/2025]
Abstract
AIMS To investigate the relationship between the skeletal muscle mass index (SMI) with all-cause mortality in patients with type 2 diabetes mellitus (T2DM) or pre-diabetes (pre-DM) among American adults. METHODS This study included 3684 patients with T2DM or pre-DM from the National Health and Nutrition Examination Survey 2011-2018. RESULTS Our study revealed an inverse J-shaped relationship between the SMI with all-cause mortality in US adults with T2DM or pre-DM. We determined the inflection points for all-cause mortality in patients with T2DM or pre-DM were 9.07 kg/m2 in males and 7.82 kg/m2 in females. In men, the all-cause mortality decreased by approximately 72 % (HR, 0.28; 95 % CI, 0.09-0.93) for each unit increased in the SMI below the inflection point. In women, all-cause mortality was reduced by 60 % (HR, 0.40; 95 % CI, 0.16-0.91) for each unit increased in SMI below the threshold. A reverse J-shaped SMI-mortality association emerged in patients with T2DM, contrasting with a U-shaped pattern in pre-DM individuals. CONCLUSIONS An inverse J-shaped association was observed between the SMI with all-cause mortality in in US adults with T2DM or pre-DM. SMI is a valuable tool for predicting all-cause mortality in patients with T2DM or pre-DM.
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Affiliation(s)
- Jiao Zhao
- Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Department of Endocrinology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China
| | - Qi Lu
- Shanghai Clinical Research Center of Bone Disease, Department of Osteoporosis and Bone Disease, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Xiao-Xia Cong
- Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, College of Medicine, Qingdao University, Qingdao, Shandong, China
| | - Xian-Feng Zhang
- Department of Endocrinology, Affiliated Hangzhou First People's Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang, China.
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Nunan E, Huff DR, Gore JL, Wright CL, Harris T, Butler L, Padgett CA, Rochowski MT, Lovern PC, Boolani A, Valdez C, Butcher JT. Targeting Myostatin as an Adjunct Treatment for the Preservation of Cardiometabolic and Skeletal Muscle Function in Type 1 Diabetes. Int J Mol Sci 2025; 26:4830. [PMID: 40429969 PMCID: PMC12112738 DOI: 10.3390/ijms26104830] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2025] [Revised: 05/05/2025] [Accepted: 05/09/2025] [Indexed: 05/29/2025] Open
Abstract
Type 1 Diabetes Mellitus (T1D) is a disease characterized by the destruction of pancreatic beta cells. The subsequent loss of insulin production results in hyperglycemia, muscle wasting, and vascular dysfunction. Due to an inability to appropriately maintain glucose homeostasis, patients afflicted with T1D suffer from increased morbidity and early mortality. Skeletal muscle is the body's largest metabolic reservoir, absorbing significant amounts of glucose from the bloodstream and physical exercise is known to improve and prevent the progression of pathological outcomes, but many T1D patients are unable to exercise at a level that conveys benefit. Thus, directly targeting muscle mass and function may prove beneficial for improving T1D patient outcomes, independent of exercise. A potent negative regulator of skeletal muscle has been identified as being upregulated in T1D patients, namely the myokine myostatin. Our hypothesis is that targeting myostatin (via genetic deletion) will prevent glucose dysfunction in a T1D model, preserve skeletal muscle function, and protect against vascular and renal dysfunction. Our methods utilized adult male mice with (WT) and without myostatin (Myo KO), in combination with the chemical induction of T1D (streptozotocin). Experimental outcomes included the assessment of glucose homeostasis (plasma glucose, HbA1c, IGTT), metabolism, muscle function (in vivo plantarflexion), and skeletal muscle vascular function (ex vivo pressure myography). Our results described systemic benefits from myostatin deletion in the T1D model, independent of insulin, including the following: inhibition of T1D-induced increases in plasma glucose, prevention of functional deficits in muscle performance, and preservation of fluid dynamics. Further, endothelial function was preserved with myostatin deletion. Taken together, these data inform upon the use of myostatin inhibition as a therapeutic target for effective treatment and management of the cardiometabolic and skeletal muscle dysfunction that occurs with T1D.
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Affiliation(s)
- Emily Nunan
- Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA
| | - Denton R. Huff
- Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA
| | - Jillian L. Gore
- Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA
| | - Carson L. Wright
- Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA
| | - Tag Harris
- Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA
| | - Landon Butler
- Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA
| | - Caleb A. Padgett
- Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA
| | - Matthew T. Rochowski
- Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA
| | - Pamela C. Lovern
- Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA
| | - Ali Boolani
- Human Performance and Nutrition Research Institute, Oklahoma State University, Stillwater, OK 74078, USA;
| | - Cammi Valdez
- Department of Physical Sciences, Northeastern State University, Tahlequah, OK 74464, USA;
| | - Joshua T. Butcher
- Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater, OK 74078, USA
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Skrzypek M, Słaboszewski M, Kolec R, Wojciechowska W, Olszanecka A, Wróbel P, Polak M, Stolarz-Skrzypek K, Rajzer MW. Blood Pressure and Blood Pressure Variability in Relation to Chronic Low Back Pain Among Patients with Hypertension. Healthcare (Basel) 2025; 13:1166. [PMID: 40428002 PMCID: PMC12111479 DOI: 10.3390/healthcare13101166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2025] [Revised: 05/13/2025] [Accepted: 05/14/2025] [Indexed: 05/29/2025] Open
Abstract
INTRODUCTION Chronic pain which tends to be localised particularly in the lower back and lower extremities is one of the risk factors for elevated blood pressure (BP). In this cross-sectional study, we evaluated whether chronic low back pain (cLBP) is associated with BP variability, which may be related to increased mortality and morbidity. METHODS We included 85 consecutive hypertensive patients with a median age of 62 years (IQR, 55-67) with cLBP, for which intensity was assessed using the Oswestry Disability Index (ODI). Ambulatory blood pressure monitoring (ABPM) was performed to evaluate the values and variability of systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) over 24 h, day- and nighttime BP variability assessed as BP standard deviation (SD). RESULTS In the whole study population, the median ODI questionnaire score was 16 (IQR, 11-20). Patients with an equal/higher than median ODI score had lower nighttime DBP compared with other patients (p = 0.028). Equal/higher than median ODI score correlated with 24 h SD values for SBP and MAP (r = 0.263; p = 0.016, and r = 0.229; p = 0.036, respectively), as well as with day-night differences in SBP (r = 0.229; p = 0.035), DBP (r = 0.253; p = 0.019), and MAP (r = 0.263; p = 0.015). We performed a multivariate regression analysis adjusted for potential confounders, and equal/higher than median ODI score was predicted by age (OR, 1.07; 95% CI, 1.006-1.14; p = 0.031) and day-night DBP difference (OR 1.07; 95% CI 1.002-1.15; p = 0.044). CONCLUSIONS To our knowledge, this is the first study to show that more intense cLBP is associated with BP variability among patients with hypertension.
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Affiliation(s)
- Maciej Skrzypek
- Department of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, 30-705 Kraków, Poland; (M.S.); (P.W.)
| | - Michał Słaboszewski
- Students Scientific Group, First Department of Cardiology, Interventional Electrocardiology and Hypertension, Faculty of Medicine, Jagiellonian University Medical College, 31-008 Kraków, Poland (R.K.)
| | - Rafał Kolec
- Students Scientific Group, First Department of Cardiology, Interventional Electrocardiology and Hypertension, Faculty of Medicine, Jagiellonian University Medical College, 31-008 Kraków, Poland (R.K.)
| | - Wiktoria Wojciechowska
- First Department of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College, 30-688 Kraków, Poland; (W.W.); (A.O.); (M.W.R.)
| | - Agnieszka Olszanecka
- First Department of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College, 30-688 Kraków, Poland; (W.W.); (A.O.); (M.W.R.)
| | - Piotr Wróbel
- Department of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, 30-705 Kraków, Poland; (M.S.); (P.W.)
| | - Maciej Polak
- Department of Epidemiology and Population Studies, Institute of Public Health, Jagiellonian University Medical College, 31-066 Kraków, Poland;
| | - Katarzyna Stolarz-Skrzypek
- First Department of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College, 30-688 Kraków, Poland; (W.W.); (A.O.); (M.W.R.)
| | - Marek W. Rajzer
- First Department of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College, 30-688 Kraków, Poland; (W.W.); (A.O.); (M.W.R.)
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Tapia Sanchiz MS, Navas Moreno V, Lopez Ruano M, Martínez Otero C, Carrillo López E, Sager La Ganga C, Raposo López JJ, Amar S, González Castañar S, Arranz Martín JA, Marazuela M, Sebastian-Valles F. Clinical and prognostic differences in diabetic ketoacidosis between type 2 and type 1 diabetes. Med Clin (Barc) 2025; 165:106973. [PMID: 40378631 DOI: 10.1016/j.medcli.2025.106973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2024] [Revised: 01/20/2025] [Accepted: 01/22/2025] [Indexed: 05/19/2025]
Abstract
INTRODUCTION The aim of this study was to analyze the differences in diabetic ketoacidosis (DKA) between type 2 diabetes (T2D) and type 1 diabetes (T1D) in a Spanish cohort. MATERIALS AND METHODS This retrospective cohort study included all cases of DKA between 2010 and 2024 in a Spanish tertiary hospital. Clinical and laboratory variables were collected to identify differences between DKA in T2D and T1D. Logistic regression models were used to evaluate 30-day mortality following a DKA event. RESULTS A total of 249 subjects (52.2% female) with a mean age of 50.2±19.9 years were included. Eighty-nine patients (35.7%) had T2D, and 160 (64.3%) had T1D. A higher proportion of cardiovascular precipitating events was observed in the T2D group (12.5% vs. 3.2%; P=.005), along with a more favorable blood gas profile, characterized by higher pH, bicarbonate levels, and lower ketone body concentrations (P<.05). However, 30-day mortality was 13.5% in T2D and 1.3% in T1D (P<.001). Logistic regression models identified cardiovascular events, lower Glasgow Coma Scale scores, and higher urea levels as predictors of mortality (P<.05), independent of age and diabetes type. CONCLUSION DKA in T2D is associated with a higher risk of mortality due to the severity of precipitating factors, despite a more favorable blood gas profile compared to T1D. Early identification of episodes is essential to prevent complications.
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Affiliation(s)
- Maria Sara Tapia Sanchiz
- Servicio de Endocrinología y Nutrición, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid; Instituto de Investigación Sanitaria de La Princesa, Madrid, España
| | - Victor Navas Moreno
- Servicio de Endocrinología y Nutrición, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid; Instituto de Investigación Sanitaria de La Princesa, Madrid, España
| | - Marta Lopez Ruano
- Servicio de Endocrinología y Nutrición, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid; Instituto de Investigación Sanitaria de La Princesa, Madrid, España
| | - Carmen Martínez Otero
- Servicio de Endocrinología y Nutrición, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid; Instituto de Investigación Sanitaria de La Princesa, Madrid, España
| | - Elena Carrillo López
- Servicio de Endocrinología y Nutrición, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid; Instituto de Investigación Sanitaria de La Princesa, Madrid, España
| | - Carolina Sager La Ganga
- Servicio de Endocrinología y Nutrición, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid; Instituto de Investigación Sanitaria de La Princesa, Madrid, España
| | - Juan José Raposo López
- Servicio de Endocrinología y Nutrición, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid; Instituto de Investigación Sanitaria de La Princesa, Madrid, España
| | - Selma Amar
- Servicio de Endocrinología y Nutrición, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid; Instituto de Investigación Sanitaria de La Princesa, Madrid, España
| | - Sara González Castañar
- Servicio de Endocrinología y Nutrición, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid; Instituto de Investigación Sanitaria de La Princesa, Madrid, España
| | - Jose Alfonso Arranz Martín
- Servicio de Endocrinología y Nutrición, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid; Instituto de Investigación Sanitaria de La Princesa, Madrid, España
| | - Mónica Marazuela
- Servicio de Endocrinología y Nutrición, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid; Instituto de Investigación Sanitaria de La Princesa, Madrid, España
| | - Fernando Sebastian-Valles
- Servicio de Endocrinología y Nutrición, Hospital Universitario de La Princesa, Universidad Autónoma de Madrid; Instituto de Investigación Sanitaria de La Princesa, Madrid, España.
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Zhang X, Qiu Y, Liu DA, Hu R, Chen S, Xu Y, Chen K, Yuan J, Li X. Recent advances in early diagnosis and treatment of T1D with miRNAs. Front Endocrinol (Lausanne) 2025; 16:1582963. [PMID: 40444240 PMCID: PMC12119303 DOI: 10.3389/fendo.2025.1582963] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2025] [Accepted: 04/22/2025] [Indexed: 06/02/2025] Open
Abstract
Type 1 diabetes (T1D) is an autoimmune disease characterized by T cell-mediated destruction of pancreatic β-cells and is one of the most common chronic diseases in adults and children. In recent years, the incidence of T1D has been increasing worldwide. Currently, the diagnosis of T1D relies on clinical manifestations and autoantibody detection, with a lack of early predictive biomarkers. MicroRNAs (miRNAs), as crucial post-transcriptional regulatory factors, which are involved in various biological processes, including cell division, proliferation, differentiation, development, and metabolism. Additionally, miRNAs participate in the regulation of inflammatory complications in T1D, and their aberrant expression is closely associated with the disease. The stability of miRNAs makes them potential candidates for early diagnostic biomarkers and therapeutic targets in T1D. This paper discusses the pathogenesis of T1D and the potential applications of miRNAs in early diagnosis and interventional therapy. It provides references for advancing precision diagnosis and personalized treatment strategies through more profound miRNA research in the future.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Xiaoping Li
- Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, China
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Wu C, Li M, Yang W, Shi Z, Qiu S, Zhou Q. Vitamin D deficiency in relation to different phenotypes of prediabetes: a population-based study. Endocrine 2025:10.1007/s12020-025-04256-1. [PMID: 40366544 DOI: 10.1007/s12020-025-04256-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 04/25/2025] [Indexed: 05/15/2025]
Abstract
PURPOSE Vitamin D deficiency is implicated in the development of prediabetes. However, it is unclear whether vitamin D deficiency showed any relationship with different phenotypes of prediabetes. This study was designed to address this issue. METHODS We included participants from the National Health and Nutrition Examination Survey 2011-2016. Prediabetes is classified into the following phenotypes: an isolated defect (that is, impaired fasting glucose [IFG], impaired glucose tolerance [IGT], or impaired hemoglobin A1c[IA1c]), two defects (that is, IFG+IGT, IFG+IA1c, or IGT+IA1c), or three defects (that is, IFG+IGT+IA1c). Multivariate logistic regression analysis was used to obtain the odds ratio (OR) and 95% confidence intervals (CIs). RESULTS A total of 4126 participants (2332 with prediabetes and 1794 with normal glycemia) were included in this study. Multivariate logistic regression analysis showed that prediabetes was associated with an increased odds of vitamin D deficiency than normal glycemia (OR 1.216, 95% CI 1.023-1.444). Further analysis showed that prediabetes phenotypes of IGT+IFG (OR 1.549, 95% CI 1.050-2.283) and IFG+IGT + IA1c (OR 1.507, 95% CI 1.062-2.138) had an increased odds of vitamin D deficiency. The odds of vitamin D deficiency was higher in individuals with glucose-defined prediabetes, but not in those with HbA1c-defined prediabetes when compared with individuals with normal glycemia. CONCLUSION Prediabetes was associated with an increased odds of vitamin D deficiency, and glucose-defined prediabetes might be a better predictor of vitamin D deficiency.
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Affiliation(s)
- Chunhua Wu
- Department of Clinical Nutrition, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, People's Republic of China
- Wuxi Medical Center, Nanjing Medical University, Wuxi, People's Republic of China
- Wuxi People's Hospital, Wuxi, People's Republic of China
| | - Mengmeng Li
- Department of Ophthalmology, Xuzhou First People's Hospital, Xuzhou, People's Republic of China
| | - Wenjuan Yang
- Department of Clinical Nutrition, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, People's Republic of China
- Wuxi Medical Center, Nanjing Medical University, Wuxi, People's Republic of China
- Wuxi People's Hospital, Wuxi, People's Republic of China
| | - Zihao Shi
- Department of Clinical Nutrition, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, People's Republic of China
- Wuxi Medical Center, Nanjing Medical University, Wuxi, People's Republic of China
- Wuxi People's Hospital, Wuxi, People's Republic of China
| | - Shanhu Qiu
- Department of General Practice, Zhongda Hospital, Institute of Diabetes, School of Medicine, Southeast University, Nanjing, People's Republic of China.
- Research and Education Centre of General Practice, Zhongda Hospital, Southeast University, Nanjing, People's Republic of China.
| | - Qunyan Zhou
- Department of Clinical Nutrition, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, People's Republic of China.
- Wuxi Medical Center, Nanjing Medical University, Wuxi, People's Republic of China.
- Wuxi People's Hospital, Wuxi, People's Republic of China.
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Lionetti N, Di Lago MG, Brescia T, Bevilacqua F, Gnoni A. Diabetes and brain: omics approaches to study diabetic encephalopathy. Front Endocrinol (Lausanne) 2025; 16:1570585. [PMID: 40421245 PMCID: PMC12104092 DOI: 10.3389/fendo.2025.1570585] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2025] [Accepted: 03/26/2025] [Indexed: 05/28/2025] Open
Abstract
Diabetes mellitus (DM) is a complex metabolic disorder associated with many complications, including diabetic encephalopathy (DE). DE is a severe neurological condition characterized by a progressive decline in cognitive and motor functions, significantly impacting patients' quality of life. Despite advancements in understanding DM, the intricate pathogenetic mechanisms underlying DE remain incompletely elucidated. This review comprehensively analyzes the application of omics technologies to decipher the molecular basis of DE and identify potential diagnostic biomarkers and therapeutic targets. Several studies on animal models of DE have revealed specific metabolic signatures and changes in gene expression in key memory brain regions, like the hippocampus, highlighting potential therapeutic targets. We explore how these "omics" approaches have provided novel insights into the complex interplay of factors contributing to DE. Recurrent alterations were identified upon evaluation of analysis from human tissues and in vitro models of DE. Findings indicate that this pathological condition is characterized by impaired energy metabolism, oxidative stress, neuroinflammation, neuroendocrine dysfunction and the influence of the gut microbiota. A multi-omics approach, integrating data from various models and limited human studies, enhances translational understanding of DE pathogenesis, with new implications for diagnosis and treatment.
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Affiliation(s)
- Nicoletta Lionetti
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, Section of
Clinical Biochemistry, University of Bari “Aldo Moro”, Bari, Italy
| | - Maria Grazia Di Lago
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, Section of
Clinical Biochemistry, University of Bari “Aldo Moro”, Bari, Italy
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Lang A, Schaefer E, Kupriyanova Y, Goletzke J, Weber KS, Buyken AE, Kahl S, Zaharia OP, Herder C, Schrauwen-Hinderling VB, Kuss O, Wagner R, Roden M, Schlesinger S. Cross-sectional association between the isocaloric replacement of carbohydrates with protein and fat in relation to fat compartments distribution and hepatic lipid content in recent-onset type 1 and type 2 diabetes. Nutr J 2025; 24:74. [PMID: 40349038 PMCID: PMC12066045 DOI: 10.1186/s12937-025-01145-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2024] [Accepted: 04/30/2025] [Indexed: 05/14/2025] Open
Abstract
BACKGROUND Diets restricted in carbohydrates may be beneficial for diabetes management. However, without reducing energy intake, carbohydrate restriction results in increased protein and fat intake. Understanding how this macronutrient substitution is associated with adipose tissue distribution is important to prevent diabetes progression. Therefore, the aim was to investigate the isocaloric substitution of carbohydrates with fat and protein in relation to subcutaneous (SAT) and visceral adipose tissue (VAT) and hepatic lipid (HL) content in individuals with recent-onset type 1 (T1D) and type 2 diabetes (T2D), accounting for macronutrient quality. METHODS This cross-sectional analysis includes participants with T1D (n = 137) and T2D (n = 170) from the German Diabetes Study (GDS). Dietary macronutrient intake was derived from dietary information assessed with a validated food frequency questionnaire. SAT and VAT were measured with magnetic resonance (MR) imaging, while HL content with 1H MR spectroscopy. Isocaloric substitution analyses based on multivariable linear regression models were conducted to examine the replacement of total and higher glycemic index (GI) carbohydrates in energy percent (En%) with total fat, monounsaturated (MUFA), polyunsaturated (PUFA), and saturated fatty acids (SFA), and protein in regard to SAT, VAT and HL content. RESULTS In individuals with T1D, substituting carbohydrates with total fat was not associated with SAT, while substituting carbohydrates with protein demonstrated higher SAT [β (95% CI) per 5 En%: 3100 cm3 (25, 6200)]. In individuals with T2D, replacing carbohydrates with total fat or protein showed no association with SAT and VAT. However, substituting carbohydrates with PUFA was associated with lower VAT [-970 cm3 (-1900, -40)] and HL content [-3.3% (-6.9, 0.4)], while replacing carbohydrates with SFA was associated with higher HL content [2.4% (-0.6, 5.4)]. Substituting carbohydrates with protein was associated with lower HL content in individuals with T2D [-2.4% (-4.9, 0.0)], mainly driven by plant-based protein. There were no substantial differences between the replacement of total and higher GI carbohydrates. CONCLUSIONS The quality of substituted nutrients may play an important role for adipose tissue and HL accumulation in individuals with T2D. Particularly, integrating PUFAs and plant-based proteins into the diet seems beneficial for VAT and HL content.
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Affiliation(s)
- Alexander Lang
- German Diabetes Center, Institute for Biometrics and Epidemiology, Research Group Systematic Reviews, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
| | - Edyta Schaefer
- German Diabetes Center, Institute for Biometrics and Epidemiology, Research Group Systematic Reviews, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Munich-Neuherberg, Germany
| | - Yuliya Kupriyanova
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Munich-Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Janina Goletzke
- Department of Sports and Health, Institute of Nutrition, Consumption and Health, Paderborn University, Paderborn, Germany
| | | | - Anette E Buyken
- Department of Sports and Health, Institute of Nutrition, Consumption and Health, Paderborn University, Paderborn, Germany
| | - Sabine Kahl
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Oana-Patricia Zaharia
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Munich-Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Division of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Christian Herder
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Munich-Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Division of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Vera B Schrauwen-Hinderling
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Munich-Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Oliver Kuss
- German Diabetes Center, Institute for Biometrics and Epidemiology, Research Group Systematic Reviews, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Munich-Neuherberg, Germany
- Centre for Health and Society, Faculty of Medicine, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Robert Wagner
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Munich-Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Division of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Michael Roden
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Munich-Neuherberg, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- Division of Endocrinology and Diabetology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Sabrina Schlesinger
- German Diabetes Center, Institute for Biometrics and Epidemiology, Research Group Systematic Reviews, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- German Center for Diabetes Research (DZD), Partner Düsseldorf, Munich-Neuherberg, Germany
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