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Pan CJ, Wang T, Yin RH, Tang XQ, Hu CH. Coronary imaging characteristics and risk factors in patients with type 2 diabetes mellitus with coronary heart disease complication. World J Diabetes 2025; 16:99151. [DOI: 10.4239/wjd.v16.i4.99151] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 12/10/2024] [Accepted: 01/18/2025] [Indexed: 02/28/2025] Open
Abstract
BACKGROUND Coronary heart disease (CHD) is a prevalent type 2 diabetes mellitus (T2DM) complication. Further, the risk stratification before angiography may help diagnose T2DM with CHD early. However, few studies have investigated the coronary imaging characteristics and risk factors of patients with T2DM complicated with CHD.
AIM To compare the differences in coronary imaging between patients with T2DM with and without CHD, determine the risk factors of T2DM complicated with CHD, and establish a predictive tool for diagnosing CHD in T2DM.
METHODS This study retrospectively analyzed 103 patients with T2DM from January 2022 to May 2024. They are categorized based on CHD occurrence into: (1) The control group, consisting of patients with T2DM without CHD; and (2) The observation group, which includes patients with T2MD with CHD. Age, sex, smoking and drinking history, CHD family history, metformin (MET) treatment pre-admission, body mass index, fasting blood glucose (FBG), triglyceride (TG), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), serum creatinine, blood urea nitrogen (BUN), alanine aminotransferase, aspartate aminotransferase, glycosylated hemoglobin (HbA1c), and coronary imaging data of both groups were collected from the medical record system. Logistic risk analysis was conducted to screen risk factors. The prediction model’s prediction efficiency was evaluated with receiver operating characteristic curves.
RESULTS The control and observation groups consisted of 48 and 55 cases, respectively. The two groups were statistically different in terms of age (t = 2.006, P = 0.048), FBG (t = 6.038, P = 0.000), TG (t = 2.015, P = 0.047), LDL-C (t = 2.017, P = 0.046), and BUN (t = 2.035, P = 0.044). The observation group demonstrated lower proportions of patients receiving MET (χ2 = 5.073, P = 0.024) and higher proportions of patients with HbA1c of > 7.0% (χ2 = 6.980, P = 0.008) than the control group. The observation group consisted of 15, 17, and 23 cases of moderate stenosis, severe stenosis, and occlusion, respectively, with a greater number of coronary artery occlusion cases than the control group (χ2 = 6.399, P = 0.041). The observation group consisted significantly higher number of diffuse lesion cases at 35 compared with the control group (χ2 = 15.420, P = 0.000). The observation group demonstrated a higher right coronary artery (RCA) stenosis index (t = 6.730, P = 0.000), circumflex coronary artery (LCX) stenosis index (t = 5.738, P = 0.000), and total stenosis index (t = 7.049, P = 0.000) than the control group. FBG [odds ratio (OR) = 1.472; 95% confidence interval (CI): 1.234-1.755; P = 0.000] and HbA1c (OR = 3.197; 95%CI: 1.149-8.896; P = 0.026) were independent risk factors for T2DM complicated with CHD, whereas MET (OR = 0.350; 95%CI: 0.129-0.952; P = 0.040) was considered a protective factor for CHD in T2DM.
CONCLUSION Coronary artery occlusion is a prevalent complication in patients with T2DM. Patients with T2MD with CHD demonstrated a higher degree of RCA and LCX stenosis than those with T2DM without CHD. FBG, HbA1c, and MET treatment history are risk factors for T2DM complicated with CHD.
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Affiliation(s)
- Chang-Jie Pan
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
- Department of Radiology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 215006, Jiangsu Province, China
| | - Tao Wang
- Department of Radiology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 215006, Jiangsu Province, China
| | - Ruo-Han Yin
- Department of Radiology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 215006, Jiangsu Province, China
| | - Xiao-Qiang Tang
- Department of Radiology, The Affiliated Changzhou No. 2 People’s Hospital of Nanjing Medical University, Changzhou 215006, Jiangsu Province, China
| | - Chun-Hong Hu
- Department of Radiology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
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Avogaro A, Buzzetti R, Candido R, Cosmo SD, Notarianni L, Consolo E, Luciano M. Exploring the benefits of alirocumab as lipid-lowering therapy in people with diabetes and very high cardiovascular risk. Diabetes Res Clin Pract 2025; 222:112055. [PMID: 40020784 DOI: 10.1016/j.diabres.2025.112055] [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: 12/23/2024] [Revised: 02/07/2025] [Accepted: 02/17/2025] [Indexed: 03/03/2025]
Abstract
People with diabetes mellitus (DM) are at a higher risk (2-4 times) for cardiovascular (CV) death and atherosclerotic CV disease (ASCVD) than the general population. A multifactorial approach is recommended to reduce CV risk. Since low-density lipoprotein cholesterol (LDL-C) is a major causal and cumulative risk factor for ASCVD, the management of lipids is a fundamental element in global risk reduction. Intensive lipid lowering therapy (LLT), such as the addition of a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i), to achieve LDL-C goals and reduce the risk of first or recurrent CV events in people with DM at very high CV risk (VHCVR) of ASCVD (i.e. acute coronary syndrome, coronary artery disease, peripheral artery disease) is often required. Alirocumab, a monoclonal antibody against PCSK9, as lipid-lowering therapy offers significant CV benefits and a favourable safety profile in people with DM and a VHCVR, with or without previous CV events. This review highlights the role of LDL-C in the complex pathogenesis of atherosclerosis, summarises the guidelines for CV risk reduction related to LDL-C in patients with DM and a VHCVR, and focuses on the role of alirocumab in managing LDL-C and consequent CV risk reduction in these patients.
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Affiliation(s)
- Angelo Avogaro
- Department of Medicine, Section of Diabetes and Metabolic Diseases, University of Padua Metabolic Diseases Division, University Hospital of Padova, Padua, Italy.
| | - Raffaella Buzzetti
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Riccardo Candido
- Diabetes Unit, Department of Medical Surgical and Health Sciences, University of Trieste, Trieste, Italy
| | - Salvatore De Cosmo
- Department of Medical Sciences, Unit of Internal Medicine, IRCCS "Casa Sollievo della Sofferenza" San Giovanni Rotondo (FG), Italy
| | | | | | - Myriam Luciano
- Medical and Scientific Department, Sanofi S.r.l., Milan, Italy
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Bi Y, Li M, Liu Y, Li T, Lu J, Duan P, Xu F, Dong Q, Wang A, Wang T, Zheng R, Chen Y, Xu M, Wang X, Zhang X, Niu Y, Kang Z, Lu C, Wang J, Qiu X, Wang A, Wu S, Niu J, Wang J, Zhao Z, Pan H, Yang X, Niu X, Pang S, Zhang X, Dai Y, Wan Q, Chen S, Zheng Q, Dai S, Deng J, Liu L, Wang G, Zhu H, Tang W, Liu H, Guo Z, Ning G, He J, Xu Y, Wang W. Intensive Blood-Pressure Control in Patients with Type 2 Diabetes. N Engl J Med 2025; 392:1155-1167. [PMID: 39555827 DOI: 10.1056/nejmoa2412006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/19/2024]
Abstract
BACKGROUND Effective targets for systolic blood-pressure control in patients with type 2 diabetes are unclear. METHODS We enrolled patients 50 years of age or older with type 2 diabetes, elevated systolic blood pressure, and an increased risk of cardiovascular disease at 145 clinical sites across China. Patients were randomly assigned to receive intensive treatment that targeted a systolic blood pressure of less than 120 mm Hg or standard treatment that targeted a systolic blood pressure of less than 140 mm Hg for up to 5 years. The primary outcome was a composite of nonfatal stroke, nonfatal myocardial infarction, treatment or hospitalization for heart failure, or death from cardiovascular causes. Multiple imputation was used for missing outcome data, with an assumption that the data were missing at random. RESULTS Of 12,821 patients (6414 patients in the intensive-treatment group and 6407 in the standard-treatment group) enrolled from February 2019 through December 2021, 5803 (45.3%) were women; the mean (±SD) age of the patients was 63.8±7.5 years. At 1 year of follow-up, the mean systolic blood pressure was 121.6 mm Hg (median, 118.3 mm Hg) in the intensive-treatment group and 133.2 mm Hg (median, 135.0 mm Hg) in the standard-treatment group. During a median follow-up of 4.2 years, primary-outcome events occurred in 393 patients (1.65 events per 100 person-years) in the intensive-treatment group and 492 patients (2.09 events per 100 person-years) in the standard-treatment group (hazard ratio, 0.79; 95% confidence interval, 0.69 to 0.90; P<0.001). The incidence of serious adverse events was similar in the treatment groups. However, symptomatic hypotension and hyperkalemia occurred more frequently in the intensive-treatment group than in the standard-treatment group. CONCLUSIONS Among patients with type 2 diabetes, the incidence of major cardiovascular events was significantly lower with intensive treatment targeting a systolic blood pressure of less than 120 mm Hg than with standard treatment targeting a systolic blood pressure of less than 140 mm Hg. (Funded by the National Key Research and Development Program of the Ministry of Science and Technology of China and others; BPROAD ClinicalTrials.gov number, NCT03808311.).
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Affiliation(s)
- Yufang Bi
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, National Research Center for Translational Medicine, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Mian Li
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, National Research Center for Translational Medicine, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yan Liu
- Department of Endocrine and Metabolic Diseases, Third People's Hospital of Datong, Datong, China
| | - Tingzhi Li
- Department of Endocrine and Metabolic Diseases, First People's Hospital of Loudi, Loudi, China
| | - Jieli Lu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, National Research Center for Translational Medicine, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Peng Duan
- Department of Endocrine and Metabolic Diseases, Third Hospital of Nanchang, Nanchang, China
| | - Fengmei Xu
- Department of Endocrine and Metabolic Diseases, General Hospital of Hebi Coal Industry Group, Hebi, China
| | - Qijuan Dong
- Department of Endocrine and Metabolic Diseases, People's Hospital of Zhengzhou, Zhengzhou, China
| | - Ailiang Wang
- Department of Endocrine and Metabolic Diseases, Yankuang New Journey General Hospital, Zoucheng, China
| | - Tiange Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, National Research Center for Translational Medicine, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ruizhi Zheng
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, National Research Center for Translational Medicine, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuhong Chen
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, National Research Center for Translational Medicine, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Min Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, National Research Center for Translational Medicine, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiaohu Wang
- Department of Endocrine and Metabolic Diseases, People's Hospital of Anyang City, Anyang, China
| | - Xinhuan Zhang
- Department of Endocrinology, Second Affiliated Hospital of Shandong First Medical University, Tai'an, China
| | - Yanbo Niu
- Department of Endocrine and Metabolic Diseases, Tieli People's Hospital, Tieli, China
| | - Zhiqiang Kang
- Department of Endocrine and Metabolic Diseases, Zhengzhou Central Hospital, Zhengzhou, China
| | - Chunru Lu
- Department of Endocrine and Metabolic Diseases, Yi'an County Hospital of Traditional Chinese Medicine, Qiqihar, China
| | - Jing Wang
- Department of Endocrine and Metabolic Diseases, Weifang Municipal Official Hospital, Weifang, China
| | - Xinwen Qiu
- Department of Endocrine and Metabolic Diseases, People's Hospital of Liuyang, Liuyang, China
| | - An Wang
- Department of Endocrine and Metabolic Diseases, Anqing Shihua Hospital of Nanjing Drum Tower Hospital Group, Anqing, China
| | - Shujing Wu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, National Research Center for Translational Medicine, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Cardiology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, China
| | - Jingya Niu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, National Research Center for Translational Medicine, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- School of Clinical Medicine, Shanghai University of Medicine and Health Sciences, Shanghai, China
| | - Jingya Wang
- Lifecycle Health Management Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhiyun Zhao
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, National Research Center for Translational Medicine, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Huanfeng Pan
- Department of Endocrine and Metabolic Diseases, Jilin Municipal People's Hospital, Jilin, China
| | - Xiaohua Yang
- Department of Endocrine and Metabolic Diseases, Hai'an People's Hospital, Hai'an, China
| | - Xiaohong Niu
- Department of Endocrine and Metabolic Diseases, Heji Hospital Affiliated to Changzhi Medical College, Changzhi, China
| | - Shuguang Pang
- Department of Endocrine and Metabolic Diseases, Jinan Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Xiaoliang Zhang
- Department of Endocrine and Metabolic Diseases, Weifang Hi-tech Zone People's Hospital, Weifang, China
| | - Yuancheng Dai
- Department of Endocrine and Metabolic Diseases, Sheyang County Diabetes Hospital, Yancheng, China
| | - Qin Wan
- Department of Endocrine and Metabolic Diseases, Affiliated Hospital of Southwest Medical University, Luzhou, China
| | - Shihong Chen
- Department of Endocrine and Metabolic Diseases, Second Hospital of Shandong University, Jinan, China
| | - Qidong Zheng
- Department of Endocrine and Metabolic Diseases, Yuhuan Second People's Hospital, Yuhuan, China
| | - Shaoping Dai
- Department of Endocrine and Metabolic Diseases, Lai'an Jianing Hospital, Chuzhou, China
| | - Juan Deng
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, National Research Center for Translational Medicine, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Leshan Liu
- Ruijin-Junshi Clinical Research Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Guixia Wang
- Department of Endocrine and Metabolic Diseases, First Hospital of Jilin University, Changchun, China
| | - Huiqi Zhu
- Department of Endocrine and Metabolic Diseases, Pingmei Shenma Medical Group General Hospital, Pingdingshan, China
| | - Weidong Tang
- Department of Endocrine and Metabolic Diseases, Wuchang People's Hospital, Wuchang, China
| | - Haixia Liu
- Department of Endocrine and Metabolic Diseases, Second Hospital of Dalian Medical University, Dalian, China
| | - Zhenfang Guo
- Department of Endocrine and Metabolic Diseases, Shanghe County People's Hospital, Jinan, China
| | - Guang Ning
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, National Research Center for Translational Medicine, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jiang He
- O'Donnell School of Public Health, University of Texas Southwestern Medical Center, Dallas
| | - Yu Xu
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, National Research Center for Translational Medicine, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Weiqing Wang
- Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
- National Clinical Research Center for Metabolic Diseases (Shanghai), Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the PR China, National Research Center for Translational Medicine, Shanghai Key Laboratory for Endocrine Tumor, State Key Laboratory of Medical Genomics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Warncke K, Hofer SE, von Sengbusch S, Ermer U, Niemeyer M, Lemmer A, Hilgard D, Welters A, Holl RW, Eckert AJ. Did smoking behavior change in adolescents and young adults with and without diabetes during the COVID-19 pandemic? A cohort study from the DPV registry. BMC Pediatr 2025; 25:236. [PMID: 40140736 PMCID: PMC11948826 DOI: 10.1186/s12887-025-05434-w] [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: 10/21/2024] [Accepted: 01/16/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND Smoking is a risk factor for cardiovascular complications and can promote a severe course of COVID-19 infection. The aim of this study was to compare smoking habits of young people with diabetes with the general population. METHODS We analyzed smoking behavior in the Diabetes Prospective Follow-up Registry (DPV) cohort (type 1 (T1D) and type 2 diabetes (T2D) from Germany and T1D from Austria aged 14-24 years) and compared it to data from the German survey on smoking behavior (DEBRA study) of the general population. Data were aggregated per year and patient for 2016-2023. Logistic regression models adjusted for gender and migration background were calculated stratified by age groups (14-17; 18-24 years), taking repeated measurements into account. Smoking behavior between T1D and T2D or between Germany and Austria was compared with similar regression models. RESULTS Thirty-four thousand two hundred seventy-five patients from the DPV cohort were included in data analysis. The overall proportion of people who smoked was lower in DPV than in the general population (13.4% vs. 24.0%), with the exception of young adults with T2D at the beginning of the pandemic (36.7% vs. 33.4%). For T1D, there was a significant upward trend in the number of patients who smoked in the group of 14-17 years (2.86%, CI 1.21-4.55 per year, p < 0.001) and also in the group of 18-24 years (4.94 per year, CI 1.37-8.63; p < 0.01) between 2016 and 2023. The proportion of smokers and the number of smoked cigarettes was higher in Austria than in Germany (10.7% vs. 8.0%; OR with 95%-CI 1.38 [1.22-1.56], p < 0.001; and 7.5 [6.8-8.1] vs. 5.9 [5.7-6.0] cigarettes/day, p < 0.001) and in T2D than T1D (11.0% vs. 7.9%; OR 1.44 [1.23-1.68], p < 0.001 and 8.0 [7.2-8.8] vs. 5.9 [5.7-6.1] cigarettes/day, p < 0.001). CONCLUSION The reported proportion of smokers among young people with diabetes was lower than in the general population. Only young adults with T2D temporarily smoked more than the general population at the beginning of the pandemic. This could be explained by stress, but also by a changed daily structure during the lockdown.
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Affiliation(s)
- Katharina Warncke
- Department of Pediatrics, Kinderklinik München Schwabing, Technical University of Munich School of Medicine, Kölner Platz 1, 80804, Munich, Germany.
- Institute of Diabetes Research, Helmholtz Munich, German Center for Environmental Health, Munich, Germany.
| | - Sabine E Hofer
- Department of Pediatrics 1, Medical University of Innsbruck, Innsbruck, Austria
| | - Simone von Sengbusch
- Department of Paediatrics and Adolescent Medicine, University Hospital Schleswig-Holstein, Campus Luebeck, Luebeck, Germany
| | - Uwe Ermer
- St Elisabeth Klinik, Neuburg an der Donau, Germany
| | - Mareike Niemeyer
- Diabetes Centre for Children and Adolescents, Kinder- und Jugendkrankenhaus Auf der Bult, Hannover, Germany
| | - Andreas Lemmer
- Department of Pediatrics and Adolescent Medicine, Helios Clinical Center, Erfurt, Germany
| | - Dörte Hilgard
- Pediatric Endocrinology and Diabetology, Primary Psychosomatic Care, Witten, Germany
| | - Alena Welters
- Department of General Pediatrics, Neonatology and Pediatric Cardiology, Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Reinhard W Holl
- Institute of Epidemiology and Medical Biometry, University of Ulm, CAQM, Ulm, Germany
- German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
| | - Alexander J Eckert
- Institute of Epidemiology and Medical Biometry, University of Ulm, CAQM, Ulm, Germany
- German Center for Diabetes Research (DZD), Munich-Neuherberg, Germany
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Guo R, Zhang S, Li A, Zhang P, Peng X, Lu X, Fan X. Ginsenoside Rb1 and berberine synergistically protect against type 2 diabetes mellitus via GDF15/HAMP pathway throughout the liver lobules: Insights from spatial transcriptomics analysis. Pharmacol Res 2025; 215:107711. [PMID: 40147680 DOI: 10.1016/j.phrs.2025.107711] [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: 11/01/2024] [Revised: 03/24/2025] [Accepted: 03/24/2025] [Indexed: 03/29/2025]
Abstract
Type 2 diabetes mellitus (T2DM) is a significant public health issue with high morbidity and mortality. Ginsenoside Rb1 (Rb1) and berberine (BBR), the main bioactive compounds of Panax ginseng and Coptis chinensis, respectively, are known for their hypoglycemic effects. Nevertheless, the synergistic effects and underlying mechanism of Rb1 and BBR on T2DM remain unclear. In this study, we utilized a leptin receptor-deficient (db/db) mouse model to investigate the protective effects of their combination treatment. Our findings demonstrated that the combined use of Rb1 and BBR at a 1:4 ratio had more pronounced effects than the first-line anti-diabetic drug metformin on reducing the weight ratio of white adipose tissue, ameliorating insulin resistance, and improving glucose and lipid metabolism. Using spatial transcriptomics, we revealed that metformin treatment improved gluconeogenesis and lipogenesis only in the periportal zone, while the combination treatment induced improvements throughout the liver lobule, with distinct key targets across different zones, thus underscoring a more comprehensive modulation of hepatic metabolism. This may be the key reason why this combination therapy demonstrated superior protective effects against T2DM. Additionally, the reversed expression of the key callback gene hepcidin (HAMP) and its regulator growth differentiation factor 15 (GDF15) following the combination therapy across all zones, along with validation experiments, further suggested that GDF15/HAMP pathway might be a key mechanism underlying the beneficial effects of Rb1 and BBR against T2DM. This study also indicates a path toward innovative drug cocktails for treating T2DM, offering a holistic approach to regulate the entire liver lobule metabolism.
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Affiliation(s)
- Rongfang Guo
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Shuying Zhang
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; School of Clinical Medicine, Shanghai University of Medicine & Health Sciences, Shanghai 201318, China
| | - Anyao Li
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Ping Zhang
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
| | - Xin Peng
- The Joint‑Laboratory of Clinical Multi‑Omics Research between Zhejiang University and Ningbo Municipal Hospital of TCM, Ningbo Municipal Hospital of TCM, Ningbo 315010, China
| | - Xiaoyan Lu
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; State Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing 314100, China; Jinhua Institute of Zhejiang University, Jinhua 321299, China.
| | - Xiaohui Fan
- Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; State Key Laboratory of Chinese Medicine Modernization, Innovation Center of Yangtze River Delta, Zhejiang University, Jiaxing 314100, China; The Joint‑Laboratory of Clinical Multi‑Omics Research between Zhejiang University and Ningbo Municipal Hospital of TCM, Ningbo Municipal Hospital of TCM, Ningbo 315010, China; Jinhua Institute of Zhejiang University, Jinhua 321299, China.
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Xiong X, Lee HC, Lu T. Impact of Sorbs2 dysfunction on cardiovascular diseases. Biochim Biophys Acta Mol Basis Dis 2025; 1871:167813. [PMID: 40139410 DOI: 10.1016/j.bbadis.2025.167813] [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: 09/05/2024] [Revised: 03/18/2025] [Accepted: 03/20/2025] [Indexed: 03/29/2025]
Abstract
Despite significant advancements in prevention and treatment over the past decades, cardiovascular diseases (CVDs) remain the leading cause of death worldwide. CVDs involve multifactorial inheritance, but our understanding of the genetic impact on these diseases is still incomplete. Sorbin and SH3 domain-containing protein 2 (Sorbs2) is ubiquitously expressed in various tissues, including the cardiovascular system. Increasing evidence suggests that Sorbs2 malfunction contributes to CVDs. This manuscript will review our current understanding of the potential mechanisms underlying Sorbs2 dysregulation in the development of CVDs.
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Affiliation(s)
- Xiaowei Xiong
- The Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States of America
| | - Hon-Chi Lee
- The Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States of America
| | - Tong Lu
- The Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN, United States of America.
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He J, Wan Y, Fan X, Yu H, Qin Y, Su J, Lu Y, Pan E, Hang D, Shen C, Zhou J, Wu M. Associations between kidney function with all-cause and cause-specific mortality in type 2 diabetes mellitus patients: a prospective cohort study in China. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2025; 44:77. [PMID: 40083037 PMCID: PMC11907967 DOI: 10.1186/s41043-025-00809-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 02/25/2025] [Indexed: 03/16/2025]
Abstract
BACKGROUND Abnormal kidney function is associated with adverse outcomes in patients with type 2 diabetes mellitus (T2DM). However, the evidence between kidney function and mortality among Chinese patients with T2DM were still limited. METHODS This cohort study included 19,919 participants with baseline T2DM from 2013 to 2014 in Jiangsu, China. Serum estimated glomerular filtration rate (eGFR), urea, and uric acid were measured at baseline, and Cox regression models were used to evaluate hazard ratios (HRs) and 95% confidential intervals (95%CIs) of all-cause and cause-specific mortality. Restricted cubic splines were used to analyze dose-response relationships, and we explored the best cut-off values by receiver operating characteristic (ROC) curves. RESULTS During a median follow-up of 9.77 years, 4,428 deaths occurred, including 1,542 (34.8%) due to cardiovascular disease (CVD), and 1,074 (24.3%) due to cancer. Compared to lowest quintile level (Q1), the highest quintile (Q5) of eGFR was negatively associated with all-cause (HR = 0.67, 95%CI: 0.58-0.77) and CVD mortality (HR = 0.57, 95%CI = 0.44-0.75). The higher levels of urea and uric acid were positively associated with all-cause mortality (Q5 vs. Q1: HR = 1.27, 95%CI: 1.16-1.39; HR = 1.21, 95%CI: 1.10-1.34), with an overall "U-shaped" dose-response relationships. Moreover, higher urea was negatively associated with cancer mortality (Q5 vs. Q1: HR = 0.79, 95%CI: 0.66-0.95). The best cut-off values with all-cause mortality were 88.50 ml/min/1.73m2, 6.95 mmol/L and 342.50 µmol/L for eGFR, urea, and uric acid, respectively. CONCLUSION We found abnormal kidney function was associated with mortality among people with T2DM. More clinical researches are needed to validate the effects and cut-off values of kidney function on mortality risk for T2DM prevention and management.
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Affiliation(s)
- Jialiu He
- Department of Epidemiology and Health Statistics, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China
| | - Ya'nan Wan
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China
| | - Xikang Fan
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China
| | - Hao Yu
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China
| | - Yu Qin
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China
| | - Jian Su
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China
- School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Yan Lu
- Department of Chronic Disease Prevention and Control, Suzhou City Center for Disease Control and Prevention, Suzhou, 215004, China
| | - Enchun Pan
- Department of Chronic Disease Prevention and Control, Huai'an City Center for Disease Control and Prevention, Huai'an, 223021, China
| | - Dong Hang
- School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Chong Shen
- School of Public Health, Nanjing Medical University, Nanjing, 211166, China
| | - Jinyi Zhou
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China.
- School of Public Health, Nanjing Medical University, Nanjing, 211166, China.
| | - Ming Wu
- Department of Epidemiology and Health Statistics, Southeast University, 87 Dingjiaqiao Road, Nanjing, 210009, China.
- Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 210009, China.
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Li H, Wang G, Tang Y, Wang L, Jiang Z, Liu J. Rhein alleviates diabetic cardiomyopathy by inhibiting mitochondrial dynamics disorder, apoptosis and hypertrophy in cardiomyocytes. Cell Signal 2025; 131:111734. [PMID: 40081546 DOI: 10.1016/j.cellsig.2025.111734] [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: 11/25/2024] [Revised: 02/18/2025] [Accepted: 03/09/2025] [Indexed: 03/16/2025]
Abstract
BACKGROUND Diabetic cardiomyopathy (DCM) is a significant cardiovascular complication in diabetic patients, and treatment regimens are limited. Rhein, a compound extracted from the herb rhubarb, was investigated in this study for its efficacy on DCM and the potential mechanism. METHODS Streptozotocin-induced DCM mice, high-glucose (HG)-treated neonatal rat cardiomyocytes (NRCMs), and H9c2 cells with ClpP knockdown were used for the study. We performed phenotypic and molecular mechanistic studies using immunoblotting, quantitative polymerase chain reaction, transmission electron microscopy, cardiac echocardiography, and histopathological analysis. RESULTS Rhein improved the cardiac function and myocardial fibrosis, and decreased the cross-sectional area of cardiomyocytes in the DCM mice. It also improved mitochondrial dynamic disorder as evidenced by a decreased ratio of mitochondrial fission-related proteins p-Drp1S616/ Drp1 and increased expression of mitochondrial fusion proteins (Opa1, Mfn1 and Mfn2). Rhein mitigated apoptosis as indicated by decreased apoptosis-related proteins (caspase 9, cleaved-caspase 3 and Bax) and increased anti-apoptosis protein Bcl2 in the heart tissue of DCM mice. Upregulations of cardiac hypertrophy associated genes (ANP, BNP and β-MHC) were significantly inhibited by Rhein treatment. In addition, the level of ClpP, a mitochondrial protease, was increased in DCM, but was normalized by Rhein treatment. However, ClpP knockdown exacerbated cardiomyocyte injury in the presence or absence of HG in H9c2 cells, indicating that a normal level of ClpP is essential for cardiomyocytes to survive. CONCLUSIONS Our results suggest that Rhein protects DCM by ameliorating mitochondrial dynamics disorder, inhibiting cardiomyocyte apoptosis, and myocardial hypertrophy. These protective effects of Rhein may be mediated by preventing ClpP upregulation.
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Affiliation(s)
- Hejuan Li
- New Drug Screening Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, China
| | - Genwang Wang
- Department of Health Service, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Yi Tang
- Department of Cardiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Lei Wang
- Department of Cardiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
| | - Zhenzhou Jiang
- New Drug Screening Center, Jiangsu Center for Pharmacodynamics Research and Evaluation, China Pharmaceutical University, Nanjing, China.
| | - Jing Liu
- Department of Cardiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
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Ollila MM, Hautakoski A, Arffman M, Morin-Papunen L, Koivikko M, Ebeling T, Sund R, Piltonen T. Diabetic complications in women with type 2 diabetes and polycystic ovary syndrome. Eur J Endocrinol 2025; 192:202-209. [PMID: 39980352 DOI: 10.1093/ejendo/lvaf026] [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: 08/21/2024] [Revised: 12/06/2024] [Accepted: 02/19/2025] [Indexed: 02/22/2025]
Abstract
OBJECTIVE To investigate whether increased prevalence of type 2 diabetes (T2DM) in women with polycystic ovary syndrome (PCOS) translates into increased risk of diabetic complications. DESIGN A cohort study based on the nationwide Diabetes in Finland database. The main analysis included 1288 women with PCOS and T2DM and 177 555 women with T2DM without PCOS (controls). Moreover, a sub-analysis that compared each woman with PCOS and T2DM to 5 controls with matching diagnosis date of T2DM and the age at onset of T2DM was conducted. METHODS The risk for diabetic complications (ie, a composite variable including retinopathy, neuropathy, nephropathy, cardiovascular, cerebrovascular or foot complications, and all-cause death) during the period 1996-2017 was analyzed using Cox regression with PCOS as the time-dependent variable and adjustment for education level, year of T2DM diagnosis, and age at T2DM diagnosis. The unadjusted cumulative incidence of diabetic complications was calculated among women with PCOS and matched controls. RESULTS The median age at T2DM diagnosis was significantly lower in women with PCOS compared with controls (33 [25th; 75th percentiles: 25; 41] versus 62 [53; 71] years). The 20-year cumulative incidence of diabetic complication after T2DM diagnosis was 35% in women with PCOS and 48% in matched controls. Women with PCOS had a smaller adjusted hazard ratio (0.70, 95% CI, 0.60-0.82) for diabetic complication. CONCLUSIONS The findings of the present register study suggest that PCOS does not seem to increase the risk of diabetic complications. However, studies with longer follow-up and clinical data, such as body mass index, are needed to verify this.
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Affiliation(s)
- Meri-Maija Ollila
- Department of Obstetrics and Gynaecology, Medical Research Center Oulu, Research Unit of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu 90220, Finland
| | - Ari Hautakoski
- Department of Obstetrics and Gynaecology, Medical Research Center Oulu, Research Unit of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu 90220, Finland
| | - Martti Arffman
- Department of Public Health and Welfare, Finnish Institute for Health and Welfare, P.O. Box 30, Helsinki 00271, Finland
| | - Laure Morin-Papunen
- Department of Obstetrics and Gynaecology, Medical Research Center Oulu, Research Unit of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu 90220, Finland
| | - Minna Koivikko
- Department of Somatics, Internal Medicine, Division of Endocrinology, Oulu University Hospital and University of Oulu, Box 23, Oulu 90029, Finland
| | - Tapani Ebeling
- Department of Somatics, Internal Medicine, Division of Endocrinology, Oulu University Hospital and University of Oulu, Box 23, Oulu 90029, Finland
| | - Reijo Sund
- Institute of Clinical Medicine, University of Eastern Finland, P.O. Box 1627, Kuopio 70211, Finland
- Knowledge Management Unit, Kuopio University Hospital, Kuopio 70211, Finland
| | - Terhi Piltonen
- Department of Obstetrics and Gynaecology, Medical Research Center Oulu, Research Unit of Clinical Medicine, University of Oulu and Oulu University Hospital, Oulu 90220, Finland
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Golden F, Tran J, Wong ND. Composite cardiovascular risk factor control in US adults with diabetes and relation to social determinants of health: The All of Us research program. Am J Prev Cardiol 2025; 21:100939. [PMID: 39990934 PMCID: PMC11846931 DOI: 10.1016/j.ajpc.2025.100939] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2024] [Revised: 01/25/2025] [Accepted: 01/29/2025] [Indexed: 02/25/2025] Open
Abstract
Background Data are limited on composite cardiovascular risk factor control in patients with type 2 diabetes mellitus (T2DM). This study aims to identify disparities in cardiovascular risk factor control based on most recent recommendations and relationships to social determinants of health in a large-scale real-world cohort of US adults. Methods We analyzed data from 88,416 participants with T2DM in the NIH Precision Medicine Initiative All of Us Research Program 2018-2022. We investigated the management of five key cardiovascular risk factors-glycated hemoglobin (HbA1c), LDL cholesterol (LDL-C), body mass index (BMI), blood pressure (BP), and smoking status. Statistical methods included Chi-square tests for categorical comparisons, t-tests for mean differences, and multiple logistic regression to assess the impact of demographic and socioeconomic factors on risk factor control. Results The study revealed low risk factor control with only 27.7 % of participants achieving recommended levels for three or more risk factors (RFs) and 4.9 % for four or more RFs. Overall, while 81.0% were at target for HbA1c, only 37.9% were at target for BP and 10.4% for LDL-C. Notably, only 1.9 % and 6.9 % were at target for HbA1c, LDL-C, and BP together, based on current and prior recommendations, respectively. Significant disparities were observed across race/ethnicity, sex, and socioeconomic lines with 43.1 % of Asian participants at control for ≥3 RFs compared to 21.1 % of non-Hispanic black participants. In logistic regression analysis, factors such as higher income, higher educational attainment, and health insurance were associated with better RF control, while higher polysocial risk scores linked to poorer control. Conclusions Despite some progress in managing individual CVD risk factors in T2DM, overall composite risk factor control remains poor, especially among underrepresented and socioeconomically disadvantaged groups. The findings highlight the necessity for integrated healthcare strategies that address both medical and social needs to improve control of CVD risk factors and outcomes in T2DM.
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Affiliation(s)
- Frances Golden
- Heart Disease Prevention Program, Division of Cardiology, University of California, C240 Medical Sciences, Irvine, CA 92697, United States
| | - Johnathan Tran
- Heart Disease Prevention Program, Division of Cardiology, University of California, C240 Medical Sciences, Irvine, CA 92697, United States
| | - Nathan D. Wong
- Heart Disease Prevention Program, Division of Cardiology, University of California, C240 Medical Sciences, Irvine, CA 92697, United States
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Li X, Wen H, Ke J, Zhao D. Association of constipation with all-cause mortality among individuals with type 2 diabetes: A retrospective cohort study. J Diabetes Investig 2025; 16:501-509. [PMID: 39718116 PMCID: PMC11871400 DOI: 10.1111/jdi.14375] [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: 10/06/2024] [Revised: 11/11/2024] [Accepted: 11/19/2024] [Indexed: 12/25/2024] Open
Abstract
BACKGROUND Constipation is a common complication in type 2 diabetes mellitus (T2DM), yet its impact on mortality remains unclear. This study aimed to investigate the association between constipation and all-cause mortality in patients with T2DM. METHODS We conducted a retrospective cohort study using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2010. Mortality outcomes were ascertained through linkage to National Death Index records until December 31, 2019. The association between constipation and all-cause mortality was assessed using weighted Cox proportional hazards regression models. Kaplan-Meier curves were then employed to visualize survival probabilities. Effect modification was explored through stratified analyses and interaction tests. RESULTS Of 1,339 participants with T2DM, 146 (10.90%) reported constipation. During a median follow-up of 10.75 years, 411 deaths occurred (57 in the constipation group, 354 in the non-constipation group). Fully adjusted weighted Cox regression analysis revealed that constipation was associated with increased all-cause mortality (HR 1.50, 95% CI 1.01-2.22, P = 0.04). Kaplan-Meier analysis demonstrated a significantly lower survival probability in patients with constipation (log-rank P < 0.05). Stratified analyses and interaction tests corroborated these findings across various subgroups. CONCLUSIONS Constipation is associated with elevated all-cause mortality risk in T2DM patients. These findings suggest that constipation management may be an important consideration in improving long-term outcomes for individuals with T2DM.
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Affiliation(s)
- Xianhua Li
- Center for Endocrine Metabolism and Immune Diseases, Beijing Lu He HospitalCapital Medical UniversityBeijingChina
| | - Haibin Wen
- Department of NephrologyJiang Bin Hospital of Guangxi Zhuang Autonomous RegionNanningChina
| | - Jing Ke
- Center for Endocrine Metabolism and Immune Diseases, Beijing Lu He HospitalCapital Medical UniversityBeijingChina
| | - Dong Zhao
- Center for Endocrine Metabolism and Immune Diseases, Beijing Lu He HospitalCapital Medical UniversityBeijingChina
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Rossi A, Masi D, Zilich R, Baccetti F, Baronti W, Falcetta P, Morviducci L, Musacchio N, Muselli M, Ozzello A, Salomone E, Verda D, Vezenkova M, Candido R, Ponzani P. Lipid-lowering therapy and LDL target attainment in type 2 diabetes: trends from the Italian Associations of Medical Diabetologists database. Cardiovasc Diabetol 2025; 24:94. [PMID: 40022078 PMCID: PMC11871825 DOI: 10.1186/s12933-025-02648-1] [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: 12/22/2024] [Accepted: 02/13/2025] [Indexed: 03/03/2025] Open
Abstract
BACKGROUND Hypercholesterolemia is a major cardiovascular risk factor, particularly in individuals with type 2 diabetes (T2DM), where cardiovascular events are more prevalent. Adherence to low-density lipoprotein cholesterol (LDL-c) targets remains suboptimal globally and in Italy. This study evaluates trends in LDL-c target achievement and lipid-lowering treatment with a stratification by cardiovascular risk among Italian patients with type 2 diabetes from 2019 to 2022. METHODS A cross-sectional analysis was conducted using the AMD Annals database, encompassing over 700,000 patients with T2DM. Patients were categorized by cardiovascular risk levels, LDL-c ranges and therapy types (statins, ezetimibe, PCSK9 inhibitors). Linear trends across the four years were evaluated. RESULTS The percentage of patients achieving LDL-c targets improved across all risk levels. In very high-risk patients, LDL-c < 55 mg/dL was achieved by 16.3% in 2019, increasing to 23.6% in 2022. High-risk patients achieving LDL-c < 70 mg/dL rose from 20.3 to 26.6% over the same period. Use of PCSK9 inhibitors, particularly in combination with statins, was associated with the highest target achievement rates, reaching 62% in very high-risk patients by 2022. We observed a reduction of moderate-intensity statins use in favor of combination therapies across the four years. Despite this, nearly one-third of patients still had LDL-c levels ≥ 100 mg/dL in 2022. CONCLUSIONS While LDL-c management in Italian patients with T2DM has improved, significant gaps remain, particularly for very high-risk individuals. Expanding the use of advanced therapies like PCSK9 inhibitors and adhering more closely to guideline-based recommendations are critical to improve cardiovascular risk in this population.
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Affiliation(s)
- Antonio Rossi
- IRCCS Ospedale Galeazzi-Sant'Ambrogio, 20149, Milan, Italy.
- Department of Biomedical and Clinical Sciences, Università di Milano, Milan, Italy.
| | - Davide Masi
- Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, 00161, Rome, Italy.
| | | | | | - Walter Baronti
- Diabetic and Metabolic Diseases Unit, Health Local Unit South-East Tuscany, Grosseto Hospital, Grosseto, Italy
| | - Pierpaolo Falcetta
- Department of Clinical and Experimental Medicine, Section of Metabolic Diseases and Diabetes, University of Pisa, Via Trivella, 56124, Pisa, Italy
| | - Lelio Morviducci
- Diabetology and Nutrition Unit, Department of Medical Specialities, ASL Roma 1, S. Spirito Hospital, 00193, Rome, Italy
| | | | - Marco Muselli
- Rulex Innovation Labs, Rulex Inc., 16122, Genoa, Italy
| | | | - Enrica Salomone
- Diabetology and Nutrition Unit, Department of Medical Specialities, ASL Roma 1, S. Spirito Hospital, 00193, Rome, Italy
| | - Damiano Verda
- Rulex Innovation Labs, Rulex Inc., 16122, Genoa, Italy
| | | | - Riccardo Candido
- Associazione Medici Diabetologi, Giuliano Isontina University Health Service, 34149, Trieste, Italy
| | - Paola Ponzani
- Diabetes and Metabolic Disease Unit, ASL 4 Liguria, 16043, Chiavari, Italy
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Evans AJ, Tu H, Li Y, Shabaltiy B, Whitney L, Carpenter K, Li YL. Altered leptin signaling and attenuated cardiac vagal activity in rats with type 2 diabetes. Front Physiol 2025; 16:1547901. [PMID: 40078371 PMCID: PMC11897569 DOI: 10.3389/fphys.2025.1547901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2024] [Accepted: 02/04/2025] [Indexed: 03/14/2025] Open
Abstract
Introduction The leading cause of death in type 2 diabetes mellitus (T2DM) patients is cardiovascular-related events, including myocardial infraction-induced ventricular arrhythmia. Previous studies have shown that T2DM-induced functional remodeling of cardiac vagal postganglionic (CVP) neurons contributes to ventricular arrhythmogenesis. As leptin resistance is common in T2DM patients, and CVP neurons are located in epicardial adipose pads, a tissue that secretes leptin, in this study we aimed to elucidate a correlation between leptin resistance and CVP neuronal dysfunction in T2DM. Methods A high fat-diet/low dose streptozotocin-induced T2DM rat model was used in this study to characterize T2DM-induced alterations in cardiac parasympathetic tone, determined by changes in baroreflex sensitivity and CVP neuronal excitability. The impact of leptin resistance on CVP neurons was also studied by examining the expression of leptin in epicardial adipose pads, and leptin receptors and uncoupling protein 2 (UCP2) in CVP neurons. Results T2DM rats exhibited diminished baroreflex sensitivity, and decreased CVP neuronal excitability, demonstrated by a reduced frequency of action potentials, diminished nAChR currents, and an attenuated response to nicotine stimulation. Additionally, compared to sham animals, the expression of leptin receptors and UCP2 in CVP neurons was reduced as early as 4 weeks post-T2DM although the leptin levels in epicardial adipose pads was increased during the progression of T2DM, which demonstrated the occurrence of leptin resistance in T2DM CVP neurons. Conclusion Cardiac parasympathetic dysfunction in T2DM rats is due, in part, to functional remodeling of CVP neurons. As leptin resistance develops as early as 4 weeks post-T2DM induction, diminished leptin receptors-UCP2 signaling may contribute to CVP neuronal dysregulation.
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Affiliation(s)
- Anthony J. Evans
- Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE, United States
| | - Huiyin Tu
- Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE, United States
| | - Yu Li
- Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE, United States
| | - Boris Shabaltiy
- Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE, United States
| | - Lauren Whitney
- Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE, United States
| | - Kassidy Carpenter
- Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE, United States
| | - Yu-long Li
- Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE, United States
- Department of Cellular & Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, United States
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Martin SS, Aday AW, Allen NB, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, Baker-Smith CM, Bansal N, Beaton AZ, Commodore-Mensah Y, Currie ME, Elkind MSV, Fan W, Generoso G, Gibbs BB, Heard DG, Hiremath S, Johansen MC, Kazi DS, Ko D, Leppert MH, Magnani JW, Michos ED, Mussolino ME, Parikh NI, Perman SM, Rezk-Hanna M, Roth GA, Shah NS, Springer MV, St-Onge MP, Thacker EL, Urbut SM, Van Spall HGC, Voeks JH, Whelton SP, Wong ND, Wong SS, Yaffe K, Palaniappan LP. 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association. Circulation 2025; 151:e41-e660. [PMID: 39866113 DOI: 10.1161/cir.0000000000001303] [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] [Indexed: 01/28/2025]
Abstract
BACKGROUND The American Heart Association (AHA), in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, nutrition, sleep, and obesity) and health factors (cholesterol, blood pressure, glucose control, and metabolic syndrome) that contribute to cardiovascular health. The AHA Heart Disease and Stroke Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, brain health, complications of pregnancy, kidney disease, congenital heart disease, rhythm disorders, sudden cardiac arrest, subclinical atherosclerosis, coronary heart disease, cardiomyopathy, heart failure, valvular disease, venous thromboembolism, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS The AHA, through its Epidemiology and Prevention Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States and globally to provide the most current information available in the annual Statistical Update with review of published literature through the year before writing. The 2025 AHA Statistical Update is the product of a full year's worth of effort in 2024 by dedicated volunteer clinicians and scientists, committed government professionals, and AHA staff members. This year's edition includes a continued focus on health equity across several key domains and enhanced global data that reflect improved methods and incorporation of ≈3000 new data sources since last year's Statistical Update. RESULTS Each of the chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS The Statistical Update represents a critical resource for the lay public, policymakers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.
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Zhang T, Zhang H, Gao X, Peng P, Chen T, Zhang X, Yang J, Zheng Y, Peng Y, Ma X, Shi D, Wang Z, Xu L, Zhou Y, Du Y. Association of pericoronary inflammation with atherosclerotic plaque progression in diabetic patients with improved modifiable cardiovascular risk factors: a longitudinal CCTA cohort study. Diabetol Metab Syndr 2025; 17:71. [PMID: 40001233 PMCID: PMC11853479 DOI: 10.1186/s13098-025-01645-4] [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: 12/23/2024] [Accepted: 02/18/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND Pericoronary adipose tissue (PCAT) attenuation, as assessed by coronary computed tomography angiography (CCTA), has been identified as a marker of pericoronary inflammation and a predictor of future adverse atherosclerotic events. However, the impact of changes in PCAT attenuation, as evaluated by consecutive CCTAs, on plaque progression in high-risk atherosclerotic patients with improved modifiable cardiovascular risk factors (mCRFs) remains unclear. METHODS Consecutive patients with type 2 diabetes mellitus (T2DM) who had improved mCRFs and underwent serial, clinically indicated CCTA examinations (time interval ≥ 12 months) at our center between July 2019 and July 2022 were screened. Eligible participants had at least one study plaque, defined as a plaque without significant anatomic stenosis, located in one of the major coronary arteries, which had not been intervened upon or caused adverse events between serial CCTA scans. Percent atheroma volume (PAV) and PCAT attenuation were measured for each study plaque at baseline and follow-up using CCTA plaque analysis software. Changes in PAV (δPAV = follow-up PAV - baseline PAV) were compared based on changes in PCAT attenuation [δPCAT attenuation] (> 0 or ≤ 0). Multivariate linear regression models were used to evaluate the relationship between δPCAT attenuation and δPAV. RESULTS A total of 98 T2DM patients (mean age: 59.9 years; 75.3% men; 152 plaques) had mCRFs that reached therapeutic targets at follow-up CCTA. However, overall PAV progressed from baseline in all patients [(41.68 ± 12.47)% vs. (43.71 ± 12.24)%, p = 0.035], accompanied by an increase in coronary inflammation (i.e., PCAT attenuation) during a median follow-up of 13.5 months (interquartile range [IQR]: 12.2, 17.5 months).Compared to patients with δPCAT attenuation ≤ 0, those with δPCAT attenuation > 0 had a significantly greater increase in overall PAV from baseline [(4.09 ± 12.09)% vs. (-0.82 ± 10.74)%, p = 0.011], calcified PAV [1.57% (IQR: 0.13%, 3.84%) vs. 0.38% (IQR: -0.26%, 2.58%), p = 0.008], and a numerical but non-significant increase in non-calcified PAV [(1.29 ± 11.75)% vs. (-1.87 ± 10.47)%, p = 0.089]. Multivariate linear regression models demonstrated that increased PCAT attenuation was significantly associated with the progression of overall PAV (β = 0.339, 95% CI: 0.129-0.549), non-calcified PAV (β = 0.237, 95% CI: 0.019-0.455), and calcified PAV (β = 0.109, 95% CI: 0.019-0.200), independent of age, sex, cardiovascular risk factors, medications, and baseline PCAT attenuation and PAV (all p < 0.05). The effect of elevated PCAT attenuation on overall plaque progression was consistent across subgroups (all p for interaction > 0.05). CONCLUSION In this longitudinal CCTA cohort of T2DM patients with improved mCRFs, increased pericoronary inflammation was associated with the progression of atherosclerotic plaque, particularly non-calcified plaque.
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Affiliation(s)
- Tianhao Zhang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Hongkai Zhang
- Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Xuelian Gao
- Department of Radiology, Beijing Anzhen Nanchong Hospital of Capital Medical University & Nanchong Central Hospital, Nanchong, 637000, China
| | - Pingan Peng
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Tianlong Chen
- Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, 100029, China
| | - Xiaoming Zhang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Jingyao Yang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Yang Zheng
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Yulu Peng
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Xiaonan Ma
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Dongmei Shi
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Zhijian Wang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Lei Xu
- Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Yujie Zhou
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
- Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing, 100029, China
| | - Yu Du
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
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Puddu A, Maggi DC. Molecular Research on Diabetes. Int J Mol Sci 2025; 26:1873. [PMID: 40076500 PMCID: PMC11899755 DOI: 10.3390/ijms26051873] [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: 02/06/2025] [Accepted: 02/17/2025] [Indexed: 03/14/2025] Open
Abstract
This Special Issue of the International Journal of Molecular Sciences collects the latest research on different biological processes and molecular mechanisms that cause diabetes [...].
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Affiliation(s)
- Alessandra Puddu
- Department of Internal Medicine and Medical Specialties, University of Genoa, 16132 Genoa, Italy;
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Chia AWY, Teo WLL, Acharyya S, Munro YL, Dalan R. Patient-physician communication of health and risk information in the management of cardiovascular diseases and diabetes: a systematic scoping review. BMC Med 2025; 23:96. [PMID: 39984943 PMCID: PMC11846366 DOI: 10.1186/s12916-025-03873-x] [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: 08/18/2024] [Accepted: 01/14/2025] [Indexed: 02/23/2025] Open
Abstract
BACKGROUND The communication of health and risk information is an integral part of patient-physician interaction. Effective communication of risk information for cardiovascular diseases and diabetes has been shown to improve medication adherence, increase physical activity levels, and improve dietary control. Patients who understand their risk profile are better able to work towards modifying their lifestyle behaviours as part of a shared decision-making process with physicians. This scoping review examines the evidence on patient-physician risk communication strategies, approaches and interventions for CVDs and diabetes management in primary care and secondary outpatient settings. METHODS A comprehensive database search for quantitative and qualitative studies was conducted in PubMed, Embase, Web of Science, Scopus, CINAHL, PsycINFO, and Cochrane Library from 1st January 2000 to 3rd October 2023. Two reviewers independently performed the screening of articles. Studies that report on patient-physician risk communication processes were included. Data were extracted and analysed using descriptive summaries and narrative synthesis. Results are reported in accordance with PRISMA-ScR guidelines. Included articles were appraised for quality following JBI critical appraisal and MMAT tools. RESULTS A total of 8378 articles published between 1st Jan 2000 to 3rd October 2023 were screened. After a full-text review of 88 articles, a total of 30 articles, consisting of 15 qualitative, 14 quantitative and 1 mixed method studies were included. Common areas of inquiry among articles include: (1) understanding and recalling risk information, (2) strategies and approaches used by physicians to communicate risk, and (3) interventions to improve the communication of risk. Studies reveal how physicians use a range of strategies, approaches and interventions to discuss risk with patients. We present and discuss each theme narratively in detail. CONCLUSIONS There is a critical need for further research into risk communication strategies for cardiovascular diseases (CVDs) and diabetes, with a focus on developing targeted approaches that enhance patients' understanding of their risk profiles. Evidence-based guidelines should assist healthcare professionals improve risk communication within clinical settings, with the goal of facilitating patient comprehension of health risks that can sustain lifestyle changes. Misalignment in communication may lead to dissatisfaction and confusion, which may impede the effective management of chronic conditions.
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Affiliation(s)
- Aloysius Wei-Yan Chia
- Department of Endocrinology, Tan Tock Seng Hospital, National Healthcare Group, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore.
| | - Winnie Li-Lian Teo
- Group Education, National Healthcare Group, Annex@National Skin Centre, Level 3, 1 Mandalay Road, Singapore, 308205, Singapore
| | - Sanchalika Acharyya
- Clinical Research and Innovation Office, Tan Tock Seng Hospital, Ng Teng Fong Centre for Healthcare Innovation (CHI), Level 2, 18 Jalan Tan Tock Seng, Singapore, 308443, Singapore
| | - Yasmin Lynda Munro
- Medical Library, Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore, 308232, Singapore
| | - Rinkoo Dalan
- Department of Endocrinology, Tan Tock Seng Hospital, National Healthcare Group, 11 Jalan Tan Tock Seng, Singapore, 308433, Singapore
- Lee Kong Chian School of Medicine, Nanyang Technological University, 11 Mandalay Road, Singapore, 308232, Singapore
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Chen Y, Huang R, Mai Z, Jin Z, Lai F, Chen X, Kong D, Ding Y. Association between physical activity and diabetes mellitus: mediation analysis involving Systemic Immune-Inflammatory Index in a cross-sectional NHANES study. BMJ Open 2025; 15:e082996. [PMID: 39971603 PMCID: PMC11840911 DOI: 10.1136/bmjopen-2023-082996] [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: 12/12/2023] [Accepted: 01/07/2025] [Indexed: 02/21/2025] Open
Abstract
OBJECTIVES In this study, we aimed to clarify the relationship between physical activity (PA) and diabetes mellitus (DM), as well as the mediating role of Systemic Immune-Inflammatory Index (SII) in the relationship. DESIGN A cross-sectional study. SETTING National Health and Nutrition Examination Survey (NHANES) data collection took place in the USA at participants' homes and mobile examination centres with specialised equipment. PARTICIPANTS The study population consisted of 9493 American adults aged 20 and above from the NHANES 2005 to 2018. PRIMARY AND SECONDARY OUTCOME MEASURES Information on the specific PA was reported through self-administered questionnaire by participants and we used this information to calculate a metabolic equivalent score for the particular PA. The calculation of SII follows a standard formula: SII=P (platelets)×N (neutrophils)/L (lymphocytes). RESULTS A total of 9493 participants were included, with 1672 diagnosed with DM. The participants with DM were more inclined to have lower levels of PA while having higher levels of SII. In all three models, high levels of PA were significantly negatively associated with the risk of DM compared with moderate levels of PA, and a non-linear association between natural logarithm-physical activity (Ln-PA) and DM was observed. Furthermore, there was a significant reduction in DM risk for Ln-PA >6.71 in all models. Mediation analysis showed that SII mediated the relationship between PA and DM, as well as between Ln-PA and DM, with respective mediation proportions of 4.32% and 12.141%, as well as 3.12% and 10.46% after adjusting for covariates. CONCLUSION This study investigated the relationship among PA, SII and DM. We provide robust evidence supporting the inverse association between PA and DM risk while highlighting the mediating role of inflammation, as reflected by SII. These findings contribute valuable insights to inform public health strategies and clinical interventions aimed at reducing the global burden of DM.
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Affiliation(s)
- Yongze Chen
- Department of Epidemiology and Medical Statistics, School of Public Health, Guangdong Medical University, Dongguan, Guangdong, China
- Department of Gastroenterology, Affiliated Hospital of Guangdong Medical University, Guangdong Medical University, Zhanjiang, Guangdong, China
| | - Ruixian Huang
- Department of Epidemiology and Medical Statistics, School of Public Health, Guangdong Medical University, Dongguan, Guangdong, China
| | - Zhenhua Mai
- Department of Epidemiology and Medical Statistics, School of Public Health, Guangdong Medical University, Dongguan, Guangdong, China
| | - Zhimei Jin
- Department of Epidemiology and Medical Statistics, School of Public Health, Guangdong Medical University, Dongguan, Guangdong, China
| | - Fengxia Lai
- Department of Epidemiology and Medical Statistics, School of Public Health, Guangdong Medical University, Dongguan, Guangdong, China
| | - Xueqin Chen
- Department of Epidemiology and Medical Statistics, School of Public Health, Guangdong Medical University, Dongguan, Guangdong, China
| | - Danli Kong
- Department of Epidemiology and Medical Statistics, School of Public Health, Guangdong Medical University, Dongguan, Guangdong, China
| | - Yuanlin Ding
- Department of Epidemiology and Medical Statistics, School of Public Health, Guangdong Medical University, Dongguan, Guangdong, China
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Wen L, Lu Y, Li X, An Y, Tan X, Chen L. Association of frailty and pre-frailty with all-cause and cardiovascular mortality in diabetes: Three prospective cohorts and a meta-analysis. Ageing Res Rev 2025; 106:102696. [PMID: 39971101 DOI: 10.1016/j.arr.2025.102696] [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: 07/24/2024] [Revised: 11/29/2024] [Accepted: 02/14/2025] [Indexed: 02/21/2025]
Abstract
OBJECTIVE To investigate the association of frailty status with all-cause and cardiovascular disease (CVD) mortality in individuals with diabetes. METHODS Data was sourced from the Third National Health and Nutrition Examination Survey (NHANES III, 1988-1994), NHANES (1999-2006), and the UK Biobank. Frailty status was assessed using the Fried phenotype and classified as non-frailty, pre-frailty, and frailty. We further performed a meta-analysis involving 19 prospective cohort studies (753,480 patients) to summarize the existing evidence. RESULTS We included 31,225 diabetes patients from NHANES III (mean age 63.3 ± 0.8, 56.4 % female), NHANES 1999-2006 (mean age 61.6 ± 0.4, 49.7 % female), and the UK Biobank (mean age 59.6 ± 7.2, 39.5 % female). The prevalence of frailty was 9.9 %, 10.7 %, and 12.1 % across respective cohorts. During a follow-up period exceeding 13 years, we observed consistent results that frailty and pre-frailty were significantly associated with increased risks of all-cause and CVD mortality in diabetes. Notably, of the five domains used to assess frailty phenotypes, low gait speed showed the strongest association with all-cause and CVD mortality risks. Meta-analysis showed that, compared to non-frailty, frailty in patients with diabetes was associated with a 1.8-fold higher risk of all-cause mortality and a 2.0-fold higher risk of CVD mortality. Similarly, pre-frailty was associated with a 1.3-fold higher risk of all-cause mortality and a 1.4-fold higher risk of CVD mortality. CONCLUSIONS This study established a strong association between frailty, pre-frailty, and increased all-cause and CVD-related mortality in diabetes. Integrating frailty assessment into routine practice to identify frail and pre-frail status early on is recommended, followed by the implementation of targeted healthy lifestyle interventions to mitigate adverse outcomes.
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Affiliation(s)
- Lin Wen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yanhui Lu
- School of Nursing, Peking University, Beijing, China.
| | - Xin Li
- School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China
| | - Yu An
- Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Xiao Tan
- Department of Big Data in Health Science, Zhejiang University, Hangzhou, China; Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Liangkai Chen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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You S, Zheng D, Wang Y, Li Q, Nguyen TN, Peters R, Chen X, Wang X, Cao Y, Grobbee DE, Harrap S, Mancia G, Williams B, Poulter NR, Lisheng L, Marre M, Hamet P, Anderson CS, Woodward M, Chalmers J, Harris K. Healthy lifestyle factors and combined macrovascular and microvascular events in diabetes patients with high cardiovascular risk: results from ADVANCE. BMC Med 2025; 23:87. [PMID: 39939937 PMCID: PMC11823187 DOI: 10.1186/s12916-025-03932-3] [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: 09/25/2024] [Accepted: 02/07/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND To explore whether healthy lifestyle factors (HLFs) predict a lower risk of major macrovascular and microvascular events and death in people with type 2 diabetes (T2D) with a high risk of vascular complications. METHODS Post hoc analyses of 11,133 participants with T2D in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial who were assigned a score ranging from 0 to 4 based on the number of baseline HLFs: never smoked, moderate-to-vigorous physical activity, ideal waist/hip ratio, and low-to-moderate alcohol consumption. Multivariable Cox models were used to determine associations of 0, 1, 2, and ≥ 3 HLFs with vascular events and all-cause mortality. RESULTS Compared to participants with no HLFs, hazard ratios for participants with 3 or 4 HLFs were 0.68 (95% confidence interval [CI] 0.57-0.81) for the composite of major macrovascular or microvascular events, 0.58 (0.46-0.75) for major macrovascular events, 0.78 (0.61-0.99) for microvascular events, and 0.48 (0.37-0.63) for all-cause mortality during a median follow-up of 5 years. Each increment in HLF score was significantly associated with lower rates of these outcomes. There was no heterogeneity in the effect on any outcome by HLF across randomized intensive blood glucose control and blood pressure lowering treatments. CONCLUSIONS HLFs are associated with lower risks of major macrovascular and microvascular events and lower rates of death in high-risk adults with T2D.
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Affiliation(s)
- Shoujiang You
- Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of SooChow University, Suzhou, China
- The George Institute for Global Health, University of New South Wales, Level 18, International Towers 3, 300 Barangaroo Ave, Sydney, NSW, 2000, Australia
| | - Danni Zheng
- The George Institute for Global Health, University of New South Wales, Level 18, International Towers 3, 300 Barangaroo Ave, Sydney, NSW, 2000, Australia
| | - Yanan Wang
- Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Qiang Li
- The George Institute for Global Health, University of New South Wales, Level 18, International Towers 3, 300 Barangaroo Ave, Sydney, NSW, 2000, Australia
| | - Tu N Nguyen
- The George Institute for Global Health, University of New South Wales, Level 18, International Towers 3, 300 Barangaroo Ave, Sydney, NSW, 2000, Australia
| | - Ruth Peters
- The George Institute for Global Health, University of New South Wales, Level 18, International Towers 3, 300 Barangaroo Ave, Sydney, NSW, 2000, Australia
- School of Population Health, University of New South Wales, Sydney , NSW, Australia
| | - Xiaoying Chen
- The George Institute for Global Health, University of New South Wales, Level 18, International Towers 3, 300 Barangaroo Ave, Sydney, NSW, 2000, Australia
| | - Xia Wang
- The George Institute for Global Health, University of New South Wales, Level 18, International Towers 3, 300 Barangaroo Ave, Sydney, NSW, 2000, Australia
| | - Yongjun Cao
- Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of SooChow University, Suzhou, China
| | - Diederick E Grobbee
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Stephen Harrap
- Department of Anatomy and Physiology, University of Melbourne and Royal Melbourne Hospital, Parkville, Australia
| | | | - Bryan Williams
- Population Science & Experimental Medicine University College London, London, UK
| | - Neil R Poulter
- School of Public Health, Imperial College London, London, UK
| | - Liu Lisheng
- Beijing Hypertension League Institute, Beijing, China
| | - Michel Marre
- Clinique Ambroise Paré, Neuilly-sur-Seine, France & Institut Necker-Enfants Malades, INSERM, Université Paris Cité, Paris, France
| | - Pavel Hamet
- Montréal Diabetes Research Centre, Centre Hospitalier de L'Université de Montréal, Quebec, Montreal, Canada
| | - Craig S Anderson
- The George Institute for Global Health, University of New South Wales, Level 18, International Towers 3, 300 Barangaroo Ave, Sydney, NSW, 2000, Australia
- The Institute of Science and Technology for Brain-Inspired Research, Fudan University, Shanghai, China
- Neurology Department, Royal Prince Alfred Hospital, Sydney, Australia
| | - Mark Woodward
- The George Institute for Global Health, University of New South Wales, Level 18, International Towers 3, 300 Barangaroo Ave, Sydney, NSW, 2000, Australia
- The George Institute for Global Health, School of Public Health, Imperial College London, London, UK
| | - John Chalmers
- The George Institute for Global Health, University of New South Wales, Level 18, International Towers 3, 300 Barangaroo Ave, Sydney, NSW, 2000, Australia
| | - Katie Harris
- The George Institute for Global Health, University of New South Wales, Level 18, International Towers 3, 300 Barangaroo Ave, Sydney, NSW, 2000, Australia.
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Zhang YY, Yang XY, Wan Q. Association between atherogenic index of plasma and type 2 diabetic complications: a cross-sectional study. Front Endocrinol (Lausanne) 2025; 16:1537303. [PMID: 39968299 PMCID: PMC11832369 DOI: 10.3389/fendo.2025.1537303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2024] [Accepted: 01/14/2025] [Indexed: 02/20/2025] Open
Abstract
Background The Atherogenic Index of Plasma (AIP) was originally developed primarily as a marker for assessing atherosclerosis. Consequently, this study investigates the potential association between AIP and type 2 diabetic complications through a cross-sectional design. Methods The National Metabolic Management Center(MMC) serves as a comprehensive platform dedicated to the establishment of standardized protocols for the diagnosis, treatment, and long-term follow-up of metabolic diseases. Following the relevant inclusion and exclusion criteria, a total of 3,094 patients were enrolled for subsequent analysis. In this study, logistic regression, restricted cubic splines, and subgroup analyses were employed to evaluate the association between the AIP and four major complications of type 2 diabetes, namely, type 2 diabetes with carotid atherosclerosis (DA), diabetic kidney disease (DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN). Results The logistic regression results demonstrate that in the fully adjusted model, each SD increase in AIP correlates with an elevated risk of type 2 diabetic kidney disease (DKD), with the risk of kidney damage intensifying alongside higher AIP groupings. The RCS analysis and subgroup analyses similarly revealed a dose-response relationship between AIP levels and the risk of DKD. Furthermore, the AIP was not found to be statistically significantly associated with DA, DR,and DPN. Conclusions The AIP may serve as a valuable predictive indicator for evaluating kidney damage in patients with type 2 diabetes, and regular screening of AIP in this population could provide significant benefits in the prevention of DKD.
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Affiliation(s)
- Yue-Yang Zhang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Southwest Medical University, Luzhou, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, China
- Sichuan Clinical Research Center for Diabetes and Metabolism, Luzhou, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, China
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, China
| | - Xiao-Yu Yang
- Department of Endocrinology and Metabolism, Affiliated Hospital of Southwest Medical University, Luzhou, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, China
- Sichuan Clinical Research Center for Diabetes and Metabolism, Luzhou, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, China
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, China
| | - Qin Wan
- Department of Endocrinology and Metabolism, Affiliated Hospital of Southwest Medical University, Luzhou, China
- Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, China
- Sichuan Clinical Research Center for Diabetes and Metabolism, Luzhou, China
- Sichuan Clinical Research Center for Nephropathy, Luzhou, China
- Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, Luzhou, China
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Wang J, Zheng Y, Jiang Y, Suo C, Zhang T, Chen X, Xu K. Association between physical activity-related metabolic signature and cardiometabolic diseases and multimorbidity: A cohort study from UK biobank. Prev Med 2025; 191:108211. [PMID: 39708996 DOI: 10.1016/j.ypmed.2024.108211] [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: 09/01/2024] [Revised: 12/13/2024] [Accepted: 12/16/2024] [Indexed: 12/23/2024]
Abstract
OBJECTIVE Physical activity has protective effects on cardiometabolic diseases (CMDs), but the role of metabolism related to physical activity in this process is unclear. METHODS In the prospective cohort study from UK Biobank between 2006 and 2022, participants free of CMDs at baseline were included (n = 73,990). We identified physical activity-related metabolites and constructed metabolic signature using linear regression and elastic net regression. Association between physical activity, metabolic signature, and CMDs (type 2 diabetes [T2D], coronary heart disease [CHD], and stroke) were explored using Cox and mediation analyses. Interactions between the metabolic signature and genetic susceptibility (categorized into "low" and "high" based on the median of polygenic risk scores) were assessed by additive hazard models and relative excess risk due to interaction (RERI). Multi-state models evaluated the association between metabolic signature and disease progression. RESULTS We found 58 metabolites were related to physical activity, of which 17 were used to construct metabolic signature. The metabolic signature was associated with reduced risk of T2D (HR = 0.13[0.10-0.16]), CHD (HR = 0.40[0.34-0.47]), and stroke (HR = 0.67[0.53-0.86]), and mediated 40.56 % of the association between physical activity and T2D. The metabolic signature exhibited additive interactions with genetic risk for T2D (RERI = 1.57[1.09-2.05]) and CHD (RERI = 0.27[0.05-0.49]). Finally, the metabolic signature was associated with a reduced risk of transition from CMD to CMM (HR = 0.58[0.42-0.81]). CONCLUSION Physical activity-related metabolic signature is linked to reduced risks of CMDs and CMM. We once again emphasize the importance of physical activity for CMDs prevention from a metabolic perspective, especially for individuals at high genetic risk.
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Affiliation(s)
- Jiacheng Wang
- School of Public Health, and the Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China
| | - Yi Zheng
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China
| | - Yanfeng Jiang
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China
| | - Chen Suo
- School of Public Health, and the Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China
| | - Tiejun Zhang
- School of Public Health, and the Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China; Yiwu Research Institute of Fudan University, Yiwu, Zhejiang, China
| | - Xingdong Chen
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China; National Clinical Research Center for Aging and Medicine, Huashan Hospital Affiliated to Fudan University, Shanghai, China; Zhangjiang Fudan International Innovation Center, Fudan University, Shanghai, China; Yiwu Research Institute of Fudan University, Yiwu, Zhejiang, China.
| | - Kelin Xu
- School of Public Health, and the Key Laboratory of Public Health Safety of Ministry of Education, Fudan University, Shanghai, China; Fudan University Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
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Shen G, Liu Y, Zhou C, Luo W, Yang YX, Guo S, Yi J, Wang L, Li W, Zhi ZG, Chen XH, Li C, Jin Y, Gao H. Associations between neutrophil-percentage-to-albumin ratio level and all-cause mortality and cardiovascular disease-cause mortality in diabetes population. BMC Public Health 2025; 25:401. [PMID: 39891098 PMCID: PMC11786390 DOI: 10.1186/s12889-024-20924-9] [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] [Received: 07/20/2024] [Accepted: 12/02/2024] [Indexed: 02/03/2025] Open
Abstract
BACKGROUND The prevalence of type 2 diabetes mellitus (T2DM) remains high and biomarkers related to T2DM are needed to be investigated. This study aimed to investigate the association between neutrophil percentage-to-albumin ratio (NPAR) with all-cause mortality and the risk of cardiovascular disease (CVD) mortality in community-dwelling individuals with T2DM. METHODS This prospective cohort study included 3602 adults aged 20 or above who were diagnosed with diabetes by the American Diabetes Association criteria in the US National Health and Nutrition Examination Survey (NHANES) database from 1999 to 2016, and followed up until 2019. Multivariable Cox proportional hazards regression models were utilized to determine the relationship between NPAR with all-cause mortality and cardiovascular disease (CVD) mortality. Restricted cubic spline regression analyses were employed to explore the nonlinear relationship between NPAR and cardiovascular disease (CVD) mortality. The assessment of nonlinearity was conducted using the likelihood ratio test. RESULTS After adjustment, the risk ratio for all-cause mortality in the highest NPAR group (≥ 15.40) compared to the lowest serum NPAR reference group (< 13.30) was 1.62 (95% CI, 1.36, 1.94) with P values < 0.001. Nevertheless, the risk ratio for cardiovascular disease (CVD) mortality in the highest NPAR group (≥ 15.40) versus the lowest serum NPAR reference group (< 13.30) was 1.41 (95% CI, 0.99, 2.00) with a P value of 0.06. Among patients with T2DM, serum NPAR levels exhibited a nonlinear correlation with both CVD mortality risk and all-cause mortality risk, with P values < 0.001 for both. CONCLUSIONS This study identified a significant association between elevated levels of the neutrophil percentage-to-albumin ratio (NPAR) and an increased risk of all-cause mortality among individuals with type 2 diabetes mellitus (T2DM). Conversely, no correlation was found between NPAR levels and CVD mortality.
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Affiliation(s)
- Geng Shen
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Yuting Liu
- Department of Cardiology, Peking University First Hospital, No. 8 Xishiku St, Xicheng District, Beijing, 100034, China
| | - Can Zhou
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Wei Luo
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Yun-Xiao Yang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Shuai Guo
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Jiayi Yi
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Lin Wang
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Wei Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Zhao-Gong Zhi
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Xiu-Huan Chen
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Chen Li
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China
| | - Yanyan Jin
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
| | - Hai Gao
- Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
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Mao T, Wang Y. PEDF Overexpression Ameliorates Cardiac Lipotoxicity in Diabetic Cardiomyopathy via Regulation of Energy Metabolism. Diabetes Metab Syndr Obes 2025; 18:217-231. [PMID: 39896707 PMCID: PMC11784309 DOI: 10.2147/dmso.s482346] [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: 06/12/2024] [Accepted: 01/22/2025] [Indexed: 02/04/2025] Open
Abstract
Background Early alterations in cardiac energy metabolism and lipotoxicity are crucial factors in the pathogenesis and progression of diabetic cardiomyopathy (DCM). The excessive accumulation of lipid metabolic intermediates within the myocardium can lead to increased production of reactive oxygen species (ROS) and promote apoptosis. Pigment epithelium-derived factor (PEDF) has been shown to regulate cardiac energy metabolism; however, its role in modulating energy metabolism, ROS generation, and apoptosis in the context of DCM requires further investigation. Methods PEDF was overexpressed in db/db mice via tail vein injection of adeno-associated virus 9(AAV9)-PEDF. At week 24, assessments were conducted on cardiac hypertrophy, fibrosis, cardiac function, and alterations in energy metabolism. Additionally, H9c2 cells were transfected with a PEDF plasmid and cultured under HG+PA conditions (33 mm glucose + 250 μM palmitic acid) for 24 hours. Subsequent analyses focused on changes in energy metabolism, ROS levels, and apoptosis. Results At 24 weeks, db/db mice exhibited hallmark features of DCM, including hyperglycemia, hyperlipidemia, cardiac hypertrophy, fibrosis, and diastolic dysfunction. Overexpression of PEDF reversed cardiac remodeling in these mice. In both db/db mice and HG+PA-treated H9c2 cells, PEDF overexpression modulated cardiac energy metabolism, mitigated lipotoxicity, and promoted the expression of adipose triglyceride lipase(ATGL) and glucose transporter type 4(Glut4) while inhibiting the expression of peroxisome proliferator-activated receptor alpha (PPARα), carnitine palmitoyltransferase 1 alpha (CPT1α), and scavenger receptor B2 (CD36). Additionally, PEDF overexpression reduced ROS generation and apoptosis in db/db mice myocardium and HG+PA-treated h9c2 cells. Conclusion PEDF can effectively prevent cardiac hypertrophy, fibrosis remodeling, and the deterioration of diastolic dysfunction in DCM by modulating cardiac energy metabolism and mitigating ROS production and apoptosis induced by lipotoxicity.
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Affiliation(s)
- Tuohua Mao
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China
| | - Ye Wang
- Department of Endocrinology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China
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Zhang S, Tang S, Liu Y, Xue B, Xie Q, Zhao L, Yuan H. Protein-bound uremic toxins as therapeutic targets for cardiovascular, kidney, and metabolic disorders. Front Endocrinol (Lausanne) 2025; 16:1500336. [PMID: 39931238 PMCID: PMC11808018 DOI: 10.3389/fendo.2025.1500336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2024] [Accepted: 01/02/2025] [Indexed: 02/13/2025] Open
Abstract
Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic clinical condition characterized by pathological and physiological interactions among metabolic abnormalities, chronic kidney disease, and cardiovascular diseases, leading to multi-organ dysfunction and a higher incidence of cardiovascular endpoints. Traditional approaches to managing CKM syndrome risk are inadequate in these patients, necessitating strategies targeting specific CKM syndrome risk factors. Increasing evidence suggests that addressing uremic toxins and/or pathways induced by uremic toxins may reduce CKM syndrome risk and treat the disease. This review explores the interactions among heart, kidney, and metabolic pathways in the context of uremic toxins and underscores the significant role of uremic toxins as potential therapeutic targets in the pathophysiology of these diseases. Strategies aimed at regulating these uremic toxins offer potential avenues for reversing and managing CKM syndrome, providing new insights for its clinical diagnosis and treatment.
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Affiliation(s)
| | | | | | | | | | | | - Huijuan Yuan
- Department of Endocrinology, Zhengzhou University People’s Hospital, Henan Provincial People’s Hospital, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Zhengzhou, China
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Chen X, Yu J, Liu Y, Wang X, Ping F, Li W, Zhang H, Xu L, Li Y. Positive Islet Cell Cytoplasmic Antibody and Long-Term Use of Lipid-Lowering Agents Are Positively Correlated With Peripheral Atherosclerosis in Patients With Autoimmune Diabetes: A Cross-Sectional Study. J Diabetes Res 2025; 2025:1933825. [PMID: 39949401 PMCID: PMC11824714 DOI: 10.1155/jdr/1933825] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Revised: 12/14/2024] [Accepted: 12/23/2024] [Indexed: 02/16/2025] Open
Abstract
Aims: This cross-sectional study is aimed at determining whether systemic inflammation, diabetic autoantibodies, and islet β cell dysfunction play a role in the progression of macrovascular complications in patients with autoimmune diabetes. Methods: 202 patients with autoimmune diabetes aged ≥ 35 years and hospitalized in Peking Union Medical College Hospital were enrolled in this study. The patients were divided into three groups based on the severity of peripheral atherosclerosis. Biomarkers of systemic inflammation, diabetes autoantibodies, islet β cell function, and other covariates validated to be associated with macrovascular complications were collected. Correlations between the severity of peripheral atherosclerosis and systemic inflammation, diabetic autoantibodies, and islet β cell function were examined using an ordinal logistic regression model. Results: Of the enrolled patients, 39.1% were male, with a median age of 53 (43, 60) years and a diabetes duration of 96 (36, 216) months. 58 patients had no lesions in the peripheral arteries, 72 had atherosclerosis in the carotid or lower extremity arteries, and the rest had lesions in both arteries. In the multifactor ordinal logistic regression test, positive islet cell cytoplasmic antibody (ICA) and long-term use of lipid-lowering agents were independently associated with peripheral atherosclerosis after adjusting for age and diabetes duration. Conclusions: The correlation between positive ICA and atherosclerosis suggests inflammation at an early stage plays a role in macrovascular complications in autoimmune diabetes. The association between long-term use of lipid-lowering agents and atherosclerosis suggests the need for early screening and intervention for dyslipidemia in patients with autoimmune diabetes.
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Affiliation(s)
- Xinyue Chen
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Jie Yu
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Yiwen Liu
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Xuechen Wang
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Fan Ping
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Wei Li
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Huabing Zhang
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Lingling Xu
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
| | - Yuxiu Li
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China
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Wang X, Kang Y, Yao J, Gao X, Feng Z, Song Y, Di X, Zhang Q, Zhang J. Effects of Exercises of Different Intensities on Bone Microstructure and Cardiovascular Risk Factors in Ovariectomized Mice. Int J Mol Sci 2025; 26:1005. [PMID: 39940771 PMCID: PMC11817207 DOI: 10.3390/ijms26031005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2024] [Revised: 01/19/2025] [Accepted: 01/22/2025] [Indexed: 02/16/2025] Open
Abstract
Postmenopausal women face increased risks of osteoporosis and cardiovascular diseases due to estrogen decline. This study investigated the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on bone microstructure and cardiovascular risk factors in ovariectomized (OVX) mice. Results showed that both exercise regimens improved blood lipid profiles and vascular structure, reducing systolic blood pressure (-11.81% and -10.89%) and undercarboxylated osteocalcin (ucOCN) levels (-52.14% and -52.05%). However, moderate-intensity exercise was more effective in enhancing bone mineral density (+82.38% and +45.02%) and microstructure recovery. No significant correlation was found between ucOCN and cardiovascular disease risk factors, such as lipid parameters, systolic blood pressure, and vascular wall thickness. This study suggests that both exercise intensities can mitigate cardiovascular risks in OVX mice, which is independent of OCN. MICT is superior for promoting osteoporosis recovery.
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Affiliation(s)
- Xiaoni Wang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; (X.W.); (Y.K.); (J.Y.); (X.G.); (Z.F.); (Y.S.); (X.D.); (Q.Z.)
| | - Yiting Kang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; (X.W.); (Y.K.); (J.Y.); (X.G.); (Z.F.); (Y.S.); (X.D.); (Q.Z.)
| | - Jie Yao
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; (X.W.); (Y.K.); (J.Y.); (X.G.); (Z.F.); (Y.S.); (X.D.); (Q.Z.)
- School of Nursing, Shaanxi University of Chinese Medicine, Xianyang 712046, China
| | - Xiaohang Gao
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; (X.W.); (Y.K.); (J.Y.); (X.G.); (Z.F.); (Y.S.); (X.D.); (Q.Z.)
| | - Zeguo Feng
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; (X.W.); (Y.K.); (J.Y.); (X.G.); (Z.F.); (Y.S.); (X.D.); (Q.Z.)
| | - Yifei Song
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; (X.W.); (Y.K.); (J.Y.); (X.G.); (Z.F.); (Y.S.); (X.D.); (Q.Z.)
| | - Xiaohui Di
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; (X.W.); (Y.K.); (J.Y.); (X.G.); (Z.F.); (Y.S.); (X.D.); (Q.Z.)
| | - Qianyu Zhang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; (X.W.); (Y.K.); (J.Y.); (X.G.); (Z.F.); (Y.S.); (X.D.); (Q.Z.)
| | - Jianbao Zhang
- Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China; (X.W.); (Y.K.); (J.Y.); (X.G.); (Z.F.); (Y.S.); (X.D.); (Q.Z.)
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Jiao M, Chen J, Wang X, Tao W, Feng Y, Yang H, Yang H, Zhao S, Yang Y, Li Y. Anthropometric and metabolic parameters associated with visceral fat in non-obese type 2 diabetes individuals. Diabetol Metab Syndr 2025; 17:28. [PMID: 39844248 PMCID: PMC11753141 DOI: 10.1186/s13098-025-01583-1] [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: 10/11/2024] [Accepted: 01/08/2025] [Indexed: 01/24/2025] Open
Abstract
BACKGROUND AND AIM Visceral fat (VF) was proved to be a more precise predictor of atherosclerotic cardiovascular disease (ASCVD) risk in individuals with type 2 diabetes mellitus (T2DM) than body mass index (BMI) itself. Even when the BMI was normal, visceral fat area (VFA) ≥ 90 cm² could raise the ten-year risk of developing ASCVD. Therefore, it was worth evaluating the association of influencing factors with high VF in non-obese T2DM individuals. METHODS This study enrolled 1,409 T2DM participants with T2DM, of whom 538 had a normal BMI. Based on VFA, these subjects were divided into two groups: VF (+) (VFA ≥ 90cm2) (n = 110) and VF (-) (VFA < 90cm2) (n = 428). The measurement of VFA was conducted using an Omron VF measuring device. Anthropometric and metabolic parameters were detected. Novel insulin resistance indices, such as lipid accumulation product (LAP) was calculated. Factors associated with VF were screened using univariate analysis, multifactorial binary logistic regression models and chi-squared automatic interaction detector decision tree model. RESULTS The VF (+) OB (-) (BMI ≤ 23.9 kg/m2) prevalence were 7.8% in T2DM subjects (n = 1,409) and 20.4% in T2DM subjects with normal BMI (n = 538), respectively. In T2DM subjects with normal BMI, the logistic regression model suggested that neck circumference (NC) had an odds ratio (OR) of 1.891 (95% CI: 1.165-3.069, P = 0.010). The OR for VF gradually increased from the 1st to the 4th in LAP quartile (P < 0.05). LAP emerged as the root node, followed by NC in the decision tree model. Receiver operating characteristic curve (ROC) analysis demonstrated that the area under the curve (AUC) for NC in predicting high VF levels was 0.640 for males and 0.682 for females. Optimal NC cut-off points were 37.75 cm for males and 34.75 cm for females, respectively. Additionally, the AUC values of LAP in predicting high VF levels were 0.745 for males and 0.772 for females, with optimal LAP cut-off points of 22.64 and 26.45 for males and females, respectively. CONCLUSION This study identified NC and LAP can be considered predictors of high VF in T2DM subjects with normal BMI.
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Affiliation(s)
- Ming Jiao
- Department of Endocrinology, The Second People's Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, Kunming, Yunnan, 650021, China
- Kunming Medical University, Kunming, Yunnan, 650021, China
| | - Jiaoli Chen
- Department of Endocrinology, The Second People's Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, Kunming, Yunnan, 650021, China
| | - Xiaoling Wang
- Department of Endocrinology, The Second People's Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, Kunming, Yunnan, 650021, China
| | - Wenyu Tao
- Department of Endocrinology, The Second People's Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, Kunming, Yunnan, 650021, China
| | - Yunhua Feng
- Department of Endocrinology, The Second People's Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, Kunming, Yunnan, 650021, China
| | - Huijun Yang
- Department of Endocrinology, The Second People's Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, Kunming, Yunnan, 650021, China
| | - Haiying Yang
- Department of Endocrinology, The Second People's Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, Kunming, Yunnan, 650021, China
| | - Shanshan Zhao
- Department of Endocrinology, The Second People's Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, Kunming, Yunnan, 650021, China
| | - Ying Yang
- Department of Endocrinology, The Second People's Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, Kunming, Yunnan, 650021, China.
| | - Yiping Li
- Department of Endocrinology, The Second People's Hospital of Yunnan Province, The Affiliated Hospital of Yunnan University, Kunming, Yunnan, 650021, China.
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Wang JK, Zhang D, Wang JF, Lu WL, Wang JY, Liang SF, Liu R, Jiang JX, Li HT, Yang X. Clinical study on the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes. World J Diabetes 2025; 16:99526. [PMID: 39817226 PMCID: PMC11718457 DOI: 10.4239/wjd.v16.i1.99526] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Revised: 09/04/2024] [Accepted: 11/08/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND At present, the existing internal medicine drug treatment can alleviate the high glucose toxicity of patients to a certain extent, to explore the efficacy of laparoscopic jejunoileal side to side anastomosis in the treatment of type 2 diabetes, the report is as follows. AIM To investigate the effect of jejunoileal side-to-side anastomosis on metabolic parameters in patients with type 2 diabetes mellitus (T2DM). METHODS We retrospectively analyzed the clinical data of 78 patients with T2DM who were treated via jejunoileal lateral anastomosis. Metabolic indicators were collected preoperatively, as well as at 3 and 6 months postoperative. The metabolic indicators analyzed included body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), 2-hour blood glucose (PBG), glycated hemoglobin (HbA1c), fasting C-peptide, 2-hour C-peptide (PCP), fasting insulin (Fins), 2-hour insulin (Pins), insulin resistance index (HOMA-IR), β Cellular function index (HOMA-β), alanine aminotransferase, aspartate aminotransferase, serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), high-density lipoprotein, and uric acid (UA) levels. RESULTS SBP, DBP, PBG, HbA1c, LDL-C, and TG were all significantly lower 3 months postoperative vs preoperative values; body weight, BMI, SBP, DBP, FBG, PBG, HbA1c, TC, TG, UA, and HOMA-IR values were all significantly lower 6 months postoperative vs at 3 months; and PCP, Fins, Pins, and HOMA-β were all significantly higher 6 months postoperative vs at 3 months (all P < 0.05). CONCLUSION Side-to-side anastomosis of the jejunum and ileum can effectively treat T2DM and improve the metabolic index levels associated with it.
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Affiliation(s)
- Ji-Kui Wang
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Di Zhang
- Department of Health Management Center, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Jin-Feng Wang
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Wan-Lin Lu
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Jing-Yuan Wang
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Shi-Feng Liang
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Ran Liu
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Jing-Xin Jiang
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Hong-Tao Li
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
| | - Xuan Yang
- Department of General Thoracic Surgery, Liaoning Electric Power Center Hospital, Shenyang 110000, Liaoning Province, China
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Khan AW, Jandeleit-Dahm KAM. Atherosclerosis in diabetes mellitus: novel mechanisms and mechanism-based therapeutic approaches. Nat Rev Cardiol 2025:10.1038/s41569-024-01115-w. [PMID: 39805949 DOI: 10.1038/s41569-024-01115-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/17/2024] [Indexed: 01/16/2025]
Abstract
Atherosclerosis is a disease of large and medium arteries that can lead to life-threatening cardiovascular and cerebrovascular consequences, such as myocardial infarction and stroke. Moreover, atherosclerosis is a major contributor to cardiovascular-related mortality in individuals with diabetes mellitus. Diabetes aggravates the pathobiological mechanisms that underlie the development of atherosclerosis. Currently available anti-atherosclerotic drugs or strategies solely focus on optimal control of systemic risk factors, including hyperglycaemia and dyslipidaemia, but do not adequately target the diabetes-exacerbated mechanisms of atherosclerotic cardiovascular disease, highlighting the need for targeted, mechanism-based therapies. This Review focuses on emerging pathological mechanisms and related novel therapeutic targets in atherosclerotic cardiovascular disease in patients with diabetes.
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Affiliation(s)
- Abdul Waheed Khan
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia.
| | - Karin A M Jandeleit-Dahm
- Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia
- German Diabetes Centre, Leibniz Centre for Diabetes Research at the Heinrich Heine University, Dusseldorf, Germany
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Wang F, Liu L, Wang J, Zhou Y, Feng X, Liu K. Therapeutic Potential of Curcumin in Diabetic Cardiomyopathy: Modulation of Pyroptosis Pathways. Cardiovasc Drugs Ther 2025:10.1007/s10557-024-07644-3. [PMID: 39786506 DOI: 10.1007/s10557-024-07644-3] [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] [Accepted: 10/31/2024] [Indexed: 01/12/2025]
Abstract
PURPOSE Cardiac inflammation is a basic pathological process of diabetic cardiomyopathy (DCM). Inflammatory response is closely related to pyroptosis, which is a recently identified programmed cell death type. Curcumin (CUR) is a polyphenol extracted from turmeric and has been reported to be crucial in alleviating pyroptosis in DCM. However, the exact mechanism by which CUR improves pyroptosis remains unclear. Therefore, we aimed to investigate the effect of CUR on pyroptosis in DCM and explore the potential mechanisms. METHODS The molecular docking (MOD) analysis was performed using AutoDock Tools to evaluate the binding patterns and affinities between CUR and tripartite motif containing 21 (TRIM21), as well as between TRIM21 and gasdermin D (GSDMD). Subsequently, DCM models were established in Sprague-Dawley (SD) rats (in vivo) by administering streptozotocin (STZ) and feeding them a high-fat diet. In addition, H9C2 cells were cultured in a high glucose and palmitate environment to construct in vitro models of DCM. Rats or cells were treated by CUR directly. Subsequently, body weight (BW), heart weight (HW)/BW ratio, fasting blood glucose level, and lipid metabolism were measured. Pathological changes were analyzed using hematoxylin and eosin (H&E) and Masson staining. Small interfering RNA (si-RNA) was used to knockdown TRIM21 expression, and the pyroptosis protein expression and cellular activity were evaluated in different groups. RESULTS MOD analysis revealed that CUR had a strong binding affinity with TRIM21, and TRIM21 showed a robust interaction with GSDMD. STZ-induced diabetic SD rats showed metabolic abnormalities, structural changes in the ventricle, and the expression of TRIM21 and pyroptosis markers, including nod-like receptor protein-3 (NLRP3), Caspase-1, and GSDMD, were upregulated. CUR reduced cardiac remodeling and improved cardiac function in vivo. CUR inhibited pyroptosis by regulating TRIM21 through in vivo and in vitro studies. CONCLUSION CUR improves DCM by regulating TRIM21 expression to inhibit pyroptosis. Furthermore, this study provides novel approaches and experimental evidence for the research and treatment of DCM and presents new insights into its potential mechanisms.
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Affiliation(s)
- Fei Wang
- Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226000, Jiangsu, China
| | - Lehan Liu
- Medical School of Nantong University, Nantong, 226000, Jiangsu, China
| | - Jiaxin Wang
- Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226000, Jiangsu, China
| | - Yizhu Zhou
- Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226000, Jiangsu, China
| | - Xiaochun Feng
- Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226000, Jiangsu, China.
| | - Kun Liu
- Department of Cardiothoracic Surgery, Affiliated Hospital of Nantong University, Nantong, 226000, Jiangsu, China.
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Caturano A, Rocco M, Tagliaferri G, Piacevole A, Nilo D, Di Lorenzo G, Iadicicco I, Donnarumma M, Galiero R, Acierno C, Sardu C, Russo V, Vetrano E, Conte C, Marfella R, Rinaldi L, Sasso FC. Oxidative Stress and Cardiovascular Complications in Type 2 Diabetes: From Pathophysiology to Lifestyle Modifications. Antioxidants (Basel) 2025; 14:72. [PMID: 39857406 PMCID: PMC11759781 DOI: 10.3390/antiox14010072] [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: 12/11/2024] [Revised: 12/30/2024] [Accepted: 01/08/2025] [Indexed: 01/27/2025] Open
Abstract
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that significantly increases the risk of cardiovascular disease, which is the leading cause of morbidity and mortality among diabetic patients. A central pathophysiological mechanism linking T2DM to cardiovascular complications is oxidative stress, defined as an imbalance between reactive oxygen species (ROS) production and the body's antioxidant defenses. Hyperglycemia in T2DM promotes oxidative stress through various pathways, including the formation of advanced glycation end products, the activation of protein kinase C, mitochondrial dysfunction, and the polyol pathway. These processes enhance ROS generation, leading to endothelial dysfunction, vascular inflammation, and the exacerbation of cardiovascular damage. Additionally, oxidative stress disrupts nitric oxide signaling, impairing vasodilation and promoting vasoconstriction, which contributes to vascular complications. This review explores the molecular mechanisms by which oxidative stress contributes to the pathogenesis of cardiovascular disease in T2DM. It also examines the potential of lifestyle modifications, such as dietary changes and physical activity, in reducing oxidative stress and mitigating cardiovascular risks in this high-risk population. Understanding these mechanisms is critical for developing targeted therapeutic strategies to improve cardiovascular outcomes in diabetic patients.
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Affiliation(s)
- Alfredo Caturano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (M.R.); (G.T.); (A.P.); (D.N.); (G.D.L.); (I.I.); (M.D.); (R.G.); (C.S.); (E.V.); (R.M.)
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy;
| | - Maria Rocco
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (M.R.); (G.T.); (A.P.); (D.N.); (G.D.L.); (I.I.); (M.D.); (R.G.); (C.S.); (E.V.); (R.M.)
| | - Giuseppina Tagliaferri
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (M.R.); (G.T.); (A.P.); (D.N.); (G.D.L.); (I.I.); (M.D.); (R.G.); (C.S.); (E.V.); (R.M.)
| | - Alessia Piacevole
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (M.R.); (G.T.); (A.P.); (D.N.); (G.D.L.); (I.I.); (M.D.); (R.G.); (C.S.); (E.V.); (R.M.)
| | - Davide Nilo
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (M.R.); (G.T.); (A.P.); (D.N.); (G.D.L.); (I.I.); (M.D.); (R.G.); (C.S.); (E.V.); (R.M.)
| | - Giovanni Di Lorenzo
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (M.R.); (G.T.); (A.P.); (D.N.); (G.D.L.); (I.I.); (M.D.); (R.G.); (C.S.); (E.V.); (R.M.)
| | - Ilaria Iadicicco
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (M.R.); (G.T.); (A.P.); (D.N.); (G.D.L.); (I.I.); (M.D.); (R.G.); (C.S.); (E.V.); (R.M.)
| | - Mariarosaria Donnarumma
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (M.R.); (G.T.); (A.P.); (D.N.); (G.D.L.); (I.I.); (M.D.); (R.G.); (C.S.); (E.V.); (R.M.)
| | - Raffaele Galiero
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (M.R.); (G.T.); (A.P.); (D.N.); (G.D.L.); (I.I.); (M.D.); (R.G.); (C.S.); (E.V.); (R.M.)
| | - Carlo Acierno
- Azienda Ospedaliera Regionale San Carlo, 85100 Potenza, Italy;
| | - Celestino Sardu
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (M.R.); (G.T.); (A.P.); (D.N.); (G.D.L.); (I.I.); (M.D.); (R.G.); (C.S.); (E.V.); (R.M.)
| | - Vincenzo Russo
- Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Department of Biology, College of Science and Technology, Temple University, Philadelphia, PA 19122, USA;
- Division of Cardiology, Department of Medical Translational Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy
| | - Erica Vetrano
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (M.R.); (G.T.); (A.P.); (D.N.); (G.D.L.); (I.I.); (M.D.); (R.G.); (C.S.); (E.V.); (R.M.)
| | - Caterina Conte
- Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy;
- Department of Endocrinology, Nutrition and Metabolic Diseases, IRCCS MultiMedica, 20099 Milan, Italy
| | - Raffaele Marfella
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (M.R.); (G.T.); (A.P.); (D.N.); (G.D.L.); (I.I.); (M.D.); (R.G.); (C.S.); (E.V.); (R.M.)
| | - Luca Rinaldi
- Department of Medicine and Health Sciences “Vincenzo Tiberio”, Università degli Studi del Molise, 86100 Campobasso, Italy
| | - Ferdinando Carlo Sasso
- Department of Advanced Medical and Surgical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy; (A.C.); (M.R.); (G.T.); (A.P.); (D.N.); (G.D.L.); (I.I.); (M.D.); (R.G.); (C.S.); (E.V.); (R.M.)
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Wang W, Li Y, Zhu M, Xu Q, Cui J, Liu Y, Liu Y. Danlian-Tongmai formula improves diabetic vascular calcification by regulating CCN3/NOTCH signal axis to inhibit inflammatory reaction. Front Pharmacol 2025; 15:1510030. [PMID: 39834821 PMCID: PMC11743396 DOI: 10.3389/fphar.2024.1510030] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2024] [Accepted: 12/04/2024] [Indexed: 01/22/2025] Open
Abstract
Background Vascular calcification (VC) commonly occurs in diabetes and is associated with cardiovascular disease incidence and mortality. Currently, there is no drug treatment for VC. The Danlian-Tongmai formula (DLTM) is a traditional Chinese medicine (TCM) prescription used for diabetic VC (DVC), but its mechanisms of action remain unclear. This study aims to elucidate the effects of DLTM on DVC and explore the underlying mechanisms of action. Methods Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to identify the metabolites of DLTM. A DVC rat model was established using streptozotocin (STZ) combined with vitamin D3 (VitD3). The effects of DLTM on DVC were evaluated through alizarin red staining, calcium deposition, and changes in osteogenic and contractile markers. The specific molecular mechanism of DLTM in treating diabetic VC was comprehensively analyzed by transcriptomics, molecular docking and in vivo experimental verification. Results We identified 108 major metabolites of DLTM. In vivo, high-dose DLTM significantly alleviated VC in diabetic rats. Transcriptomic analysis showed that DLTM treatment markedly altered the transcriptomic profile of rat aortas, which was associated with regulating the CCN3/NOTCH signaling pathway, promoting vascular smooth muscle contraction, and inhibiting the inflammatory responses. Molecular docking and molecular dynamics simulation demonstrated strong binding interactions between DLTM metabolites and key molecules within the CCN3/NOTCH pathway, including NOTCH1, DLL1, DLL4, hes1, and hey1. In vivo experiments confirmed that DLTM could upregulate CCN3, inhibit the activation of NOTCH signaling ligands DLL1 and downstream transcription factors hes1 and hey1, and reduce the release of inflammatory cytokines IL6, IL1β, and TNFα. Conclusion DLTM alleviates DVC by regulating the CCN3/NOTCH signaling axis to inhibit inflammatory responses. Our research provides experimental basis for clinical treatment and drug transformation of diabetic VC.
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Affiliation(s)
- Wenting Wang
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yiwen Li
- Beijing Key Laboratory of Traditional Chinese Medicine Basic Research on Prevention and Treatment for Major Diseases, Experimental Research Center, China Academy of Chinese Medical Sciences, Beijing, China
| | - Mengmeng Zhu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Qian Xu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Jing Cui
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yanfei Liu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
- The Second Department of Geriatrics, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yue Liu
- National Clinical Research Center for TCM Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
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Wu J, Yang D, Zhang Y, Xian H, Weng Z, Ji L, Yang F. Non-invasive imaging innovation: FFR-CT combined with plaque characterization, safeguarding your cardiac health. J Cardiovasc Comput Tomogr 2025; 19:152-158. [PMID: 39299900 DOI: 10.1016/j.jcct.2024.08.008] [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: 07/17/2024] [Revised: 08/27/2024] [Accepted: 08/29/2024] [Indexed: 09/22/2024]
Abstract
Studies have shown that high-risk plaque features (including thin fibrous caps, lipid-rich cores, large plaque volumes, and intraplaque microcalcifications) are closely associated with the occurrence of acute coronary events. CT-derived fractional flow reserve (CT-FFR) is a non-invasive imaging post-processing technique that utilizes artificial intelligence to analyze data obtained from conventional coronary CT angiography (CCTA). FFR-CT technology offers the hemodynamic assessment of coronary lesions, aiding in the prediction of potential cardiovascular risks. This review summarizes the latest research progress on the complex relationship between FFR-CT, plaque characteristics, and hemodynamics, closely linking plaque volume, composition, and distribution with the clinical significance of coronary artery stenosis. It is hoped that these research findings will provide valuable guidance for clinicians, promoting the application of CT in the non-invasive detection of vulnerable plaques, thereby more effectively preventing and managing coronary artery disease. In the future, further optimization of FFR-CT technology and expansion of its clinical application are expected to significantly reduce the incidence and mortality of coronary artery disease, offering new hope for the prevention and treatment of cardiovascular diseases.
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Affiliation(s)
- Jianjun Wu
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, 150001, China
| | - Dawei Yang
- Department of Orthopedics, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Youqi Zhang
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, 150001, China
| | - Huimin Xian
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Ziqian Weng
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Liu Ji
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, 150001, China
| | - Fan Yang
- Department of Cardiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, China; Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin Medical University, Harbin, 150001, China.
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Engal E, Kerem L, Gileles-Hillel A. Sleep-disordered breathing and diabetes mellitus: a deadly duo. J Clin Sleep Med 2025; 21:3-5. [PMID: 39484802 DOI: 10.5664/jcsm.11462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2024]
Affiliation(s)
- Eden Engal
- The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
| | - Liya Kerem
- The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
- Pediatric Endocrinology Unit, Department of Pediatrics, Hadassah Medical Center, Jerusalem, Israel
| | - Alex Gileles-Hillel
- The Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel
- Pediatric Pulmonary and Sleep Unit, Department of Pediatrics, Hadassah Medical Center, Jerusalem, Israel
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Zheng C, Wu J, Li N, Wei X, Huang Z, Chen L, Chen Z. Cost-effectiveness of finerenone added to standard of care for patients with type 2 diabetes-related chronic kidney disease in the United States. Diabetes Obes Metab 2025; 27:165-173. [PMID: 39377137 DOI: 10.1111/dom.15997] [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: 06/25/2024] [Revised: 09/11/2024] [Accepted: 09/21/2024] [Indexed: 10/09/2024]
Abstract
AIM To examine the cost-effectiveness of adding finerenone to standard of care (SoC) for treating type 2 diabetes mellitus (T2DM)-related chronic kidney disease (CKD) in the United States. MATERIALS AND METHODS Based on the clinical data analysed by FIDELITY, we referenced the validated FINE-CKD model (Markov model) to evaluate the cost-effectiveness of SoC versus SoC + finerenone from the perspective of US payers. The model was cycled for 35 years in 4-month cycles, with cost and utility values derived from the published literature. The primary outcomes were incremental cost-effectiveness ratio (ICER) and quality-adjusted life years (QALYs). Deterministic and probabilistic sensitivity analyses were conducted to assess the robustness of the base-case results. RESULTS The treatment strategy of finerenone plus SoC led to gains of 6.95 QALYs and had a lifetime cost of $491 745.31. Compared to SoC, that strategy yielded 0.48 more QALYs at an added cost of $65 305.72. The ICER for finerenone was $135 257.06 per QALY, which is below the willingness-to-pay threshold of United States ($150 000/QALY). The results were sensitive to the hazard ratios associated with the efficacy of finerenone and its cost. Probabilistic sensitivity analyses showed that the probability that finerenone plus SoC would be cost-effective was 57.6%. CONCLUSIONS For patients with T2DM-related CKD, adding finerenone to SoC may be a cost-effective option in the United States. Reasonable price reductions for finerenone could potentially benefit more patients.
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Affiliation(s)
- Cailin Zheng
- School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Jinneng Wu
- School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Na Li
- Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, China
| | - Xiaoxia Wei
- Department of Pharmacy, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou, China
| | - Zhixiong Huang
- School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Lingbin Chen
- School of Pharmacy, Fujian Medical University, Fuzhou, China
| | - Zhou Chen
- School of Pharmacy, Fujian Medical University, Fuzhou, China
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Li H, Li Y, Guo W, Liu X, Wang Y, Zeng T, Kong W. Monocyte-lymphocyte ratio predicts cardiovascular diseases death in individuals with type 2 diabetes. J Diabetes Investig 2025; 16:137-145. [PMID: 39503178 DOI: 10.1111/jdi.14329] [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: 03/22/2024] [Revised: 08/26/2024] [Accepted: 09/23/2024] [Indexed: 01/03/2025] Open
Abstract
PURPOSE Previous studies have shown higher cardiovascular mortality risk with higher monocyte-lymphocyte ratio levels in general population. However, the levels of oxidative stress in individuals with type 2 diabetes are higher than those in the general population, which may affect the link between monocyte-to-lymphocyte ratio and cardiovascular disease deaths. And the association between the monocyte-to-lymphocyte ratio and mortality risk in people with type 2 diabetes still be unknown. This study aimed to investigate the prognostic significance of monocyte-to-lymphocyte ratio in type 2 diabetes. METHODS This analysis involved 2,954 individuals with type 2 diabetes from the National Health and Nutrition Examination Survey 1999-2010. The National Death Index records through December 31, 2019, was used to determine all-cause and cardiovascular mortality. The prognostic roles were determined using Cox regression models, restricted cubic spline analysis, and time-dependent receiver operating characteristic curve analysis. RESULTS During an average follow-up period of 12.4 years, a total of 1,007 deaths occurred, while 252 were due to cardiovascular disease. An elevated monocyte-to-lymphocyte ratio level exhibited a significant dose-response relationship with an increased risk of all-cause mortality (1.34 [95% CI 1.12, 1.60] for all-cause mortality [P trend = 0.001]). The multivariable-adjusted HR was 1.81 (95% CI 1.25, 2.63) (P trend = 0.001) for cardiovascular mortality indicating a U-shaped relationship (P nonlinear = 0.013). CONCLUSIONS The results of this study indicate a U-shaped relationship between the monocyte-to-lymphocyte ratio and cardiovascular mortality in individuals with diabetes. Both very low and high monocyte-to-lymphocyte ratio monocyte-to-lymphocyte ratio values were found to be associated with increased cardiovascular mortality risk.
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Affiliation(s)
- Han Li
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, China
- Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, China
- Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, China
| | - Yixuan Li
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, China
- Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, China
- Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, China
| | - Wenwen Guo
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, China
- Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, China
- Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, China
| | - Xinwei Liu
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, China
- Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, China
- Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, China
| | - Yuhao Wang
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, China
- Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, China
- Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, China
| | - Tianshu Zeng
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, China
- Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, China
- Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, China
| | - Wen Kong
- Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Diabetes and Metabolic Disease Clinical Research Center of Hubei Province, Wuhan, China
- Hubei Key Laboratory of Metabolic Abnormalities and Vascular Aging, Wuhan, China
- Hubei Branch of National Center for Clinical Medical Research of Metabolic Diseases, Wuhan, China
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Ma J, Dong Y, Liu J, Gao S, Quan J. The role of GRB2 in diabetes, diabetes complications and related disorders. Diabetes Obes Metab 2025; 27:23-34. [PMID: 39478285 DOI: 10.1111/dom.16015] [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: 06/10/2024] [Revised: 09/28/2024] [Accepted: 09/30/2024] [Indexed: 12/06/2024]
Abstract
Growth factor receptor-bound protein 2 (GRB2) is a key adaptor protein involved in multiple signalling pathways, and its dysregulation is associated with various diseases. Type 2 diabetes is a systemic condition characterized by insulin resistance and impaired β-cell function. The complications of diabetes significantly reduce life expectancy and quality of life, imposing a substantial burden on society. However, the role of GRB2 in diabetes and associated complications is largely unknown. Emerging evidence suggests that GRB2 plays a crucial role in insulin resistance, inflammation, immune activation and the regulation of cellular processes such as cell proliferation, growth, metabolism, angiogenesis, apoptosis and differentiation. Dysregulation of GRB2-mediated pathways contributes to the progression of diabetic neuropathy, cognitive dysfunction, nephropathy, retinopathy and related disorders. This review provides a comprehensive overview of the current understanding of the role of GRB2 in diabetes, diabetes complications and related disorders, alongside recent advances in the development of GRB2-targeted therapies. Elucidating the complex role of GRB2 in these disorders provides valuable insights into potential therapeutic strategies targeting GRB2-mediated pathways.
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Affiliation(s)
- Jing Ma
- Department of Endocrinology and Metabolism, Gansu Provincial Hospital, The First Clinical Medical School, Lanzhou University, Lanzhou, China
- Department of Endocrinology and Metabolism, Gansu Provincial Hospital, Lanzhou, China
- Key Laboratory of Endocrine and Metabolic Diseases of Gansu Province, Lanzhou, China
| | - Yuyan Dong
- Clinical College of Ningxia Medical University, Yinchuan, China
| | - Juxiang Liu
- Department of Endocrinology and Metabolism, Gansu Provincial Hospital, Lanzhou, China
- Key Laboratory of Endocrine and Metabolic Diseases of Gansu Province, Lanzhou, China
| | - Shuo Gao
- Department of Endocrinology and Metabolism, Gansu Provincial Hospital, The First Clinical Medical School, Lanzhou University, Lanzhou, China
| | - Jinxing Quan
- Department of Endocrinology and Metabolism, Gansu Provincial Hospital, The First Clinical Medical School, Lanzhou University, Lanzhou, China
- Department of Endocrinology and Metabolism, Gansu Provincial Hospital, Lanzhou, China
- Key Laboratory of Endocrine and Metabolic Diseases of Gansu Province, Lanzhou, China
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Wada S, Iwanaga Y, Nakai M, Noguchi T, Miyamoto Y. Stepwise cardiovascular risk stratification in patients with type 2 diabetes based on coronary CT assessment. J Diabetes Complications 2025; 39:108908. [PMID: 39566374 DOI: 10.1016/j.jdiacomp.2024.108908] [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: 10/11/2024] [Accepted: 11/11/2024] [Indexed: 11/22/2024]
Abstract
BACKGROUND We aimed to examine the stepwise risk stratification for predicting major adverse cardiovascular events (MACE) in patients with DM and suspected coronary artery disease (CAD). METHOD 1187 patients with suspected CAD enrolled in a prospective cohort study were examined. The patients were evaluated step-by-step with coronary artery calcification (CAC), coronary artery stenosis (CAS), and FFRCT analysis. Hazard ratio (HR) and 95 % confidence interval (CI) for incidence MACE were calculated by Cox Proportional Hazards model for adjustment of Framingham risk score. RESULTS During a median follow-up of 4.0 years, MACE frequently occurred in DM patients than non-DM (15.9 % vs. 5.7 %). A lower CAC threshold with >0 or > 50 Agatston score was significantly associated with increased MACE in DM (HR [95 % CI], 3.62 [1.12-11.67] or 4.72 [2.11-10.55], respectively), but not in non-DM. DM patients with >50 CAC, CAS, and ≤ 0.71 FFRCT value showed the HR (95 % CI) for MACE was 9.84 (4.26-22.69) as compared with those with ≤50 CAC, whereas non-DM patients showed that it was 2.56 (1.02-6.43). CONCLUSION Step-by-step assessment using CAC, CAS, and FFRCT on top of clinical risk factors was useful for more accurate cardiovascular risk stratification in patients with DM.
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Affiliation(s)
- Shinichi Wada
- Department of Medical and Health Information Management, National Cerebral and Cardiovascular Center, Suita, Japan; Department of Neurology, Kansai Electric Power Hospital, Osaka, Japan
| | - Yoshitaka Iwanaga
- Department of Medical and Health Information Management, National Cerebral and Cardiovascular Center, Suita, Japan; Department of Cardiology, Sakurabashi Watanabe Advanced Healthcare Hospital, Osaka, Japan.
| | - Michikazu Nakai
- Department of Medical and Health Information Management, National Cerebral and Cardiovascular Center, Suita, Japan; Clinical Research Support Center, University of Miyazaki Hospital, Miyazaki, Japan
| | - Teruo Noguchi
- Department of Cardiology, National Cerebral and Cardiovascular Center, Suita, Japan
| | - Yoshihiro Miyamoto
- Department of Medical and Health Information Management, National Cerebral and Cardiovascular Center, Suita, Japan
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Chew EY, Burns SA, Abraham AG, Bakhoum MF, Beckman JA, Chui TYP, Finger RP, Frangi AF, Gottesman RF, Grant MB, Hanssen H, Lee CS, Meyer ML, Rizzoni D, Rudnicka AR, Schuman JS, Seidelmann SB, Tang WHW, Adhikari BB, Danthi N, Hong Y, Reid D, Shen GL, Oh YS. Standardization and clinical applications of retinal imaging biomarkers for cardiovascular disease: a Roadmap from an NHLBI workshop. Nat Rev Cardiol 2025; 22:47-63. [PMID: 39039178 DOI: 10.1038/s41569-024-01060-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/21/2024] [Indexed: 07/24/2024]
Abstract
The accessibility of the retina with the use of non-invasive and relatively low-cost ophthalmic imaging techniques and analytics provides a unique opportunity to improve the detection, diagnosis and monitoring of systemic diseases. The National Heart, Lung, and Blood Institute conducted a workshop in October 2022 to examine this concept. On the basis of the discussions at that workshop, this Roadmap describes current knowledge gaps and new research opportunities to evaluate the relationships between the eye (in particular, retinal biomarkers) and the risk of cardiovascular diseases, including coronary artery disease, heart failure, stroke, hypertension and vascular dementia. Identified gaps include the need to simplify and standardize the capture of high-quality images of the eye by non-ophthalmic health workers and to conduct longitudinal studies using multidisciplinary networks of diverse at-risk populations with improved implementation and methods to protect participant and dataset privacy. Other gaps include improving the measurement of structural and functional retinal biomarkers, determining the relationship between microvascular and macrovascular risk factors, improving multimodal imaging 'pipelines', and integrating advanced imaging with 'omics', lifestyle factors, primary care data and radiological reports, by using artificial intelligence technology to improve the identification of individual-level risk. Future research on retinal microvascular disease and retinal biomarkers might additionally provide insights into the temporal development of microvascular disease across other systemic vascular beds.
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Affiliation(s)
- Emily Y Chew
- Division of Epidemiology and Clinical Applications, National Eye Institute, NIH, Bethesda, MD, USA.
| | - Stephen A Burns
- School of Optometry, Indiana University, Bloomington, IN, USA
| | - Alison G Abraham
- Department of Epidemiology, Colorado School of Public Health, University of Colorado, Aurora, CO, USA
| | - Mathieu F Bakhoum
- Departments of Ophthalmology and Visual Science and Pathology, School of Medicine, Yale University, New Haven, CT, USA
| | - Joshua A Beckman
- Division of Vascular Medicine, University of Southwestern Medical Center, Dallas, TX, USA
| | - Toco Y P Chui
- Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York, NY, USA
| | - Robert P Finger
- Department of Ophthalmology, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany
| | - Alejandro F Frangi
- Division of Informatics, Imaging and Data Science (School of Health Sciences), Department of Computer Science (School of Engineering), University of Manchester, Manchester, UK
- Alan Turing Institute, London, UK
| | - Rebecca F Gottesman
- Stroke Branch, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, USA
| | - Maria B Grant
- Department of Ophthalmology and Visual Sciences, School of Medicine, University of Alabama Heersink School of Medicine, Birmingham, AL, USA
| | - Henner Hanssen
- Department of Sport, Exercise and Health, University of Basel, Basel, Switzerland
| | - Cecilia S Lee
- Department of Ophthalmology, University of Washington, Seattle, WA, USA
| | - Michelle L Meyer
- Department of Emergency Medicine, University of North Carolina, Chapel Hill, NC, USA
| | - Damiano Rizzoni
- Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
| | - Alicja R Rudnicka
- Population Health Research Institute, St. George's University of London, London, UK
| | - Joel S Schuman
- Wills Eye Hospital, Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, PA, USA
| | - Sara B Seidelmann
- Department of Clinical Medicine, Columbia College of Physicians and Surgeons, Greenwich, CT, USA
| | - W H Wilson Tang
- Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Bishow B Adhikari
- Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA
| | - Narasimhan Danthi
- Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA
| | - Yuling Hong
- Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA
| | - Diane Reid
- Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA
| | - Grace L Shen
- Retinal Diseases Program, Division of Extramural Science Programs, National Eye Institute, NIH, Bethesda, MD, USA
| | - Young S Oh
- Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD, USA
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Yu R, Zou L. Refining the understanding of cardiovascular risk following COPD exacerbations: Opportunities for stratified and multidisciplinary approaches. Eur J Intern Med 2024:S0953-6205(24)00530-2. [PMID: 39721927 DOI: 10.1016/j.ejim.2024.12.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Accepted: 12/19/2024] [Indexed: 12/28/2024]
Affiliation(s)
- Rujian Yu
- Department of Respiratory Medicine, Chengdu Pidu District Hospital of Traditional Chinese Medicine, Chengdu, China.
| | - Lamei Zou
- Department of Geriatrics, Chengdu Pidu District Hospital of Traditional Chinese Medicine, Chengdu, China
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Wu D, Yu Y, Zheng H, Xiang L, Wang X, Zhang Y, Sun Z, Miao D, Zhou J, Pan E, Hu W. Analysis of the risk of death and its associated risk factors in Chinese patients with young-onset type 2 diabetes. Front Endocrinol (Lausanne) 2024; 15:1451364. [PMID: 39749021 PMCID: PMC11693590 DOI: 10.3389/fendo.2024.1451364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Accepted: 12/03/2024] [Indexed: 01/04/2025] Open
Abstract
Objectives To examine the association between the age at onset of diabetes and the risk of all-cause mortality in a population of individuals diagnosed with type 2 diabetes mellitus (T2DM) and to identify risk factors associated with all-cause mortality in young-onset T2DM (YOD) patients in China. Methods This study utilized a cohort of 9759 patients who were diagnosed with T2DM and who were registered and enrolled in the National Basic Public Health Service Management Program in Qinghe District (now Qingjiangpu District) and Huai'an District, Huai'an City, Jiangsu Province, China. The patients were observed from November 2013 to July 2014, and all-cause mortality data were obtained by comprehensive matching with the Huai'an City Resident Mortality Database as of December 31, 2019. A Cox proportional hazards model was used to compute the hazard ratios (HRs) and their corresponding 95% confidence intervals (95% CIs) for all-cause mortality risk during the follow-up period among patients with varying disease onset ages. Additionally, subgroup analyses were conducted based on sex, age, lifestyle factors, and baseline clinical parameters. Results A total of 7572 patients with T2DM, including 2874 men and 4698 women aged 57.9 ± 8.0 years, were ultimately included in the study. 1) At baseline, a greater proportion of YOD patients were engaged in high-intensity activities, had a longer sleep duration, had a longer duration of T2DM, had a family history of T2DM, had microvascular complications (kidney disease, retinopathy, neuropathy, diabetic foot, etc.), and received glucose-lowering treatment. Moreover, patients in the YOD group also had significantly greater baseline HbA1c, FBG, and estimated glomerular filtration rate (eGFR) than did those in the onset at 41-60 years (MD) group and the onset at 61-75 years (SD) group. 2) During the six-year follow-up period, a total of 1057 deaths were documented. After adjusting for confounding factors and utilizing SD as the reference group, the HRs for deaths occurring in the YOD and MD groups were 1.383 (95% CI: 0.717-2.667) and 1.006 (95% CI: 0.763-1.326), respectively. Moreover, the risk of death in the YOD group remained highest in the sensitivity analysis that excluded patients with coronary heart disease at baseline, stroke patients, and patients who died within the first three years of follow-up. 3) Sleep duration was identified as an independent risk factor for mortality in the YOD group, with a notable increase in the risk of all-cause mortality when sleep duration exceeded 9 hours per day. Conclusion The risk of all-cause mortality in YOD patients was 1.38 times greater than that in MD and SD patients, and the longer the sleep duration was, the greater the risk of death, especially when sleep duration exceeded 9 hours per day.
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Affiliation(s)
- Dan Wu
- Department of Endocrinology, Huai’an Hospital Affiliated to Xuzhou Medical University and Huai’an Second People’s Hospital, Huai’an, Jiangsu, China
| | - Yang Yu
- Department of Endocrinology, Huai’an Hospital Affiliated to Xuzhou Medical University and Huai’an Second People’s Hospital, Huai’an, Jiangsu, China
| | - Haoran Zheng
- Department of Endocrinology, Huai’an Hospital Affiliated to Xuzhou Medical University and Huai’an Second People’s Hospital, Huai’an, Jiangsu, China
| | - Ling Xiang
- Department of Endocrinology, Huai’an Hospital Affiliated to Xuzhou Medical University and Huai’an Second People’s Hospital, Huai’an, Jiangsu, China
| | - Xiaoqing Wang
- Department of Endocrinology, Huai’an Hospital Affiliated to Xuzhou Medical University and Huai’an Second People’s Hospital, Huai’an, Jiangsu, China
| | - Yong Zhang
- Department of Endocrinology, Huai’an Hospital Affiliated to Xuzhou Medical University and Huai’an Second People’s Hospital, Huai’an, Jiangsu, China
| | - Zhongming Sun
- Department of Chronic Disease Prevention and Control, Huai’an City Center for Disease Control and Prevention, Huai’an, China
| | - Dandan Miao
- Department of Chronic Disease Prevention and Control, Huai’an City Center for Disease Control and Prevention, Huai’an, China
| | - Jinyi Zhou
- Department of Non-communicable Chronic Disease Control, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, China
| | - Enchun Pan
- Department of Chronic Disease Prevention and Control, Huai’an City Center for Disease Control and Prevention, Huai’an, China
| | - Wen Hu
- Department of Endocrinology, Huai’an Hospital Affiliated to Xuzhou Medical University and Huai’an Second People’s Hospital, Huai’an, Jiangsu, China
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Badran HM, Helmy JA, Ahmed NF, Yacoub M. Impact of Diabetes Mellitus on Left Ventricular Mechanics and Long-Term Outcome in Patients with Hypertrophic Cardiomyopathy. Echocardiography 2024; 41:e70048. [PMID: 39661017 DOI: 10.1111/echo.70048] [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: 10/30/2024] [Revised: 11/20/2024] [Accepted: 11/23/2024] [Indexed: 12/12/2024] Open
Abstract
BACKGROUND Type 2 diabetes mellitus (T2DM) intensifies the clinical symptoms of heart diseases and leads to a worse prognosis in heart failure patients. Although hypertrophic cardiomyopathy (HCM) and DM rarely co-occur, particularly in older individuals, the impact of DM on cardiac function and outcomes in individuals with HCM remains insufficiently understood. METHODS A total of 421 HCM patients were included and followed up in a prospective cohort study (mean 68.7 months). In the diabetic HCM group (n = 47), patients had a mean age of 47 ± 17 years, and 31 (66%) were male, while the non-diabetic HCM group (n = 374) had a mean age of 44 ± 14 years, and 246 (65%) were male. At study entry, all patients underwent echocardiographic evaluation, encompassing left ventricular (LV) regional and global longitudinal strain (GLS), as well as strain rate (SR) analysis. RESULTS In diabetic HCM, there was a greater prevalence of hypertension (p < 0.0001), while the ratio of septal to posterior wall thickness (PWT) (p < 0.003) and E' value were lower (p < 0.009) compared to non-diabetic HCM. No significant difference between groups in NYHA class or cardiac phenotype. Diabetic HCM exhibited notable reductions in GLS (p < 0.02), systolic SR (SRsys) (p < 0.04), and early diastolic SR (SRe) p < 0.006. Additionally, there was a significant inverse correlation between LVGLS and HbA1c levels (r = -0.58, p < 0.0001), and the duration of diabetes (r = -0.39, p < 0.006). Hospitalization rates were greater in the diabetic HCM than in the non-diabetic group (44.7% vs.19.5%, p < 0.001). Among all demographic characteristics, phenotypic data, conventional echocardiographic measurements, and LV mechanics, diabetes emerged as the sole determinant of hospitalization among HCM patients. The presence of diabetes nearly tripled the odds of hospitalization (odds ratio: 2.813 [1.448-5.465], p < 0.002). However, diabetes did not negatively affect long-term survival, and age remained the only independent predictor of all-cause mortality. CONCLUSIONS In HCM, T2DM is linked to more deterioration of cardiac mechanics and contributes to unfavorable consequences by frequent hospitalization on its own, independent of age, comorbidities, or phenotype.
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Affiliation(s)
- Hala Mahfouz Badran
- Cardiology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - John Anis Helmy
- Cardiology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Nagalaa Fahem Ahmed
- Cardiology Department, Faculty of Medicine, Menoufia University, Menoufia, Egypt
| | - Magdi Yacoub
- Cardiovascular surgery, Faculty of Medicine, Imperial College, London, UK
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Li M, Wang J, Ding S, Ding B, Oketunbi TJ, Song X, Li Y, Niu Q, Shi X, Gao D, Hu S, Jin G, Wang H. Cardiac magnetic resonance imaging-derived pathophysiology and prognosis of diabetes mellitus with acute myocardial infarction after revascularization: a prospective cohort study. Ann Med 2024; 56:2399751. [PMID: 39253848 PMCID: PMC11571787 DOI: 10.1080/07853890.2024.2399751] [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: 02/21/2024] [Revised: 04/11/2024] [Accepted: 04/24/2024] [Indexed: 09/11/2024] Open
Abstract
BACKGROUND Little is known about the underlying factors contributing to unfavourable clinical outcomes in patients with diabetes mellitus (DM) complicated by new-onset acute myocardial infarction (AMI). The aim of this study was to investigate the impact of DM on the pathophysiologic features and prognosis of patients with new-onset AMI following successful revascularization by utilizing cardiac magnetic resonance (CMR). METHODS Consecutive patients diagnosed with new-onset AMI between June 2022 and January 2024 were included. All patients underwent culprit vessel revascularization upon admission and CMR imaging 3-7 days later. The primary clinical endpoint of this study was the occurrence of major adverse cardiac and cerebrovascular events (MACCEs), for which the average follow-up was 10 months. RESULTS A total of 72 patients were divided into a DM group (n = 23) and a non-DM group (n = 49). Multivariate logistic regression analysis revealed that DM was an independent risk factor for the occurrence of microvascular obstruction. Multivariate linear regression analysis found that DM was the influencing factor of global radial strain (B = -4.107, t = -2.328, p = 0.023), while fasting blood glucose influenced infarct segment myocardial radial strain (B = -0.622, t = -2.032, p = 0.046). DM independently contributed to the risk of MACCEs following successful revascularization in patients with AMI (p < 0.05). CONCLUSION Comprehensive phenotypic characterization of myocardial injury and microcirculatory status could enable reliable identification of high-risk MACCEs in DM patients with new-onset AMI following successful revascularization.
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Affiliation(s)
- Miaonan Li
- Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Jun Wang
- Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Siyu Ding
- Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Bin Ding
- Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Temilola J. Oketunbi
- Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Xilong Song
- Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Yao Li
- Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Qilin Niu
- Department of Radiology, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Xiaojun Shi
- Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Dasheng Gao
- Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Sigan Hu
- Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Guoxi Jin
- Department of Endocrine, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
| | - Hongju Wang
- Department of Cardiovascular Disease, The First Affiliated Hospital of Bengbu Medical University, Bengbu, China
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Somsuan K, Aluksanasuwan S, Woottisin S, Chiangjong W, Wanta A, Munkong N, Jaidee W, Praman S, Fuangfoo K, Morchang A, Kamsrijai U, Woottisin N, Rujanapun N, Charoensup R. Mathurameha ameliorates cardiovascular complications in high-fat diet/low-dose streptozotocin-induced type 2 diabetic rats: insights from histological and proteomic analysis. J Mol Histol 2024; 55:1177-1197. [PMID: 39227510 DOI: 10.1007/s10735-024-10258-6] [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] [Received: 06/30/2024] [Accepted: 08/27/2024] [Indexed: 09/05/2024]
Abstract
Type 2 diabetes mellitus (T2DM) is a global health concern with increasing prevalence. Mathurameha, a Thai herbal formula, has shown promising glucose-lowering effects and positive impacts on biochemical profiles in diabetic rats. The present study investigated the protective effects of Mathurameha on cardiovascular complications in high-fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic rats using histological and proteomic analyses. Thirty-five male Sprague-Dawley rats were divided into seven groups: normal diet (ND), ND with aqueous extract (ND + AE450), ND with ethanolic extract (ND + EE200), diabetes (DM), DM with AE (DM + AE450), DM with EE (DM + EE200), and DM with metformin (DM + Met). Mathurameha, especially at 200 mg/kg EE, significantly reduced adipocyte size, cardiac and vascular abnormalities, collagen deposition, and arterial wall thickness in DM rats. Proteomic analysis of rat aortas revealed 30 significantly altered proteins among the ND, DM, and DM + EE200 groups. These altered proteins are involved in various biological processes related to diabetes. Biochemical assays showed that Mathurameha reduced lipid peroxidation (MDA), increased antioxidant levels (GSH), and decreased the expression of inflammatory markers (ICAM1, TNF-α). In conclusion, Mathurameha exhibited significant protective effects against cardiovascular complications in HFD/STZ-induced type 2 diabetic rats through its antioxidant and anti-inflammatory properties.
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Affiliation(s)
- Keerakarn Somsuan
- School of Medicine, Mae Fah Luang University, 365 Moo 12, Nang Lae, Mueang Chiang Rai District, Chiang Rai, 57100, Thailand.
- Cancer and Immunology Research Unit (CIRU), Mae Fah Luang University, Chiang Rai, 57100, Thailand.
| | - Siripat Aluksanasuwan
- School of Medicine, Mae Fah Luang University, 365 Moo 12, Nang Lae, Mueang Chiang Rai District, Chiang Rai, 57100, Thailand
- Cancer and Immunology Research Unit (CIRU), Mae Fah Luang University, Chiang Rai, 57100, Thailand
| | - Surachet Woottisin
- School of Medicine, Mae Fah Luang University, 365 Moo 12, Nang Lae, Mueang Chiang Rai District, Chiang Rai, 57100, Thailand
| | - Wararat Chiangjong
- Pediatric Translational Research Unit, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400, Thailand
| | - Arunothai Wanta
- School of Medicine, Mae Fah Luang University, 365 Moo 12, Nang Lae, Mueang Chiang Rai District, Chiang Rai, 57100, Thailand
- Cancer and Immunology Research Unit (CIRU), Mae Fah Luang University, Chiang Rai, 57100, Thailand
| | - Narongsuk Munkong
- Department of Pathology, School of Medicine, University of Phayao, Phayao, 56000, Thailand
| | - Wuttichai Jaidee
- Medicinal Plants Innovation Center of Mae Fah Luang University, Chiang Rai, 57100, Thailand
| | - Siwaporn Praman
- School of Medicine, Mae Fah Luang University, 365 Moo 12, Nang Lae, Mueang Chiang Rai District, Chiang Rai, 57100, Thailand
| | - Kawita Fuangfoo
- Medicinal Plants Innovation Center of Mae Fah Luang University, Chiang Rai, 57100, Thailand
| | - Atthapan Morchang
- School of Medicine, Mae Fah Luang University, 365 Moo 12, Nang Lae, Mueang Chiang Rai District, Chiang Rai, 57100, Thailand
- Cancer and Immunology Research Unit (CIRU), Mae Fah Luang University, Chiang Rai, 57100, Thailand
| | - Utcharaporn Kamsrijai
- School of Medicine, Mae Fah Luang University, 365 Moo 12, Nang Lae, Mueang Chiang Rai District, Chiang Rai, 57100, Thailand
| | - Nanthakarn Woottisin
- School of Integrative Medicine, Mae Fah Luang University, Chiang Rai, 57100, Thailand
| | - Narawadee Rujanapun
- Medicinal Plants Innovation Center of Mae Fah Luang University, Chiang Rai, 57100, Thailand
- School of Integrative Medicine, Mae Fah Luang University, Chiang Rai, 57100, Thailand
| | - Rawiwan Charoensup
- Medicinal Plants Innovation Center of Mae Fah Luang University, Chiang Rai, 57100, Thailand
- School of Integrative Medicine, Mae Fah Luang University, Chiang Rai, 57100, Thailand
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Fan X, Liu Y, Chen X, Xu Y, Wu W, Li F, Liu G, Chen X, Zhang C, Zhou Y. Synergies between diabetes and hyperhomocysteinaemia: New insights to predict and prevent adverse cardiovascular effects. Diabetes Obes Metab 2024; 26:5776-5785. [PMID: 39434446 DOI: 10.1111/dom.15947] [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: 06/03/2024] [Revised: 08/21/2024] [Accepted: 08/28/2024] [Indexed: 10/23/2024]
Abstract
AIM To explore the association of hyperhomocysteinaemia (HHcy) and diabetes synergies with cardiovascular events in the adult population of northern China. METHODS Data were collected from the Asymptomatic Polyvascular Abnomalities Community study for 2010 to 2019. Serum homocysteine (Hcy) levels were determined by enzyme-linked immunosorbent assay. The participants were categorized into four groups based on their Hcy levels and diabetes status: non-diabetes/non-HHcy, non-diabetes/HHcy, diabetes/non-HHcy and diabetes/HHcy. The composite endpoint consisted of the occurrence of first-ever stroke, myocardial infraction (MI) or all-cause mortality. Cox regression analyses were performed to evaluate the associations of diabetes and HHcy with cardiovascular disease (CVD) events. RESULTS In total, 5278 participants were eligible (average age 55.1 years, 60% male). Over a follow-up of 9.1 years, 618 events were identified, 202 stroke, 52 MI and 406 all-cause deaths. Compared with the non-diabetes/non-HHcy group, hazard ratios with 95% confidence intervals in the diabetes/HHcy group for stroke, MI, major adverse cardiovascular event (MACE), all-cause death and composite endpoint were 1.85 (1.12-3.04), 1.33 (0.42-4.23), 1.78 (1.13-2.80), 2.24 (1.56-3.23) and 1.97 (1.47-2.65), respectively. Significant interactions between HHcy and diabetes status were found for stroke, MI and MACE (P for interaction = .002, .027 and .044, respectively). In addition, the association of diabetes/HHcy with stroke was modified by age (< 60 and ≥ 60 years; P for interaction = .016). CONCLUSIONS The findings highlight the synergistic impact of diabetes and HHcy on CVD. Joint assessments of diabetes and Hcy levels should be emphasized for risk stratification and primary prevention of CVD.
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Affiliation(s)
- Xue Fan
- Department of Research Center for Cardiovascular and Cerebrovascular Disease, Clinical Research Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yuhe Liu
- Department of Biochemistry and Molecular Biology, Hengyang Medical School, University of South China, Hengyang, China
| | - Xueyu Chen
- Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Yuehao Xu
- Department of Research Center for Cardiovascular and Cerebrovascular Disease, Clinical Research Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Wenqian Wu
- Department of Research Center for Cardiovascular and Cerebrovascular Disease, Clinical Research Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fengchang Li
- Department of Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute for Nutrition and Health, Chinese Academy of sciences, Shanghai, China
| | - Gang Liu
- Department of Internal Medicine, Tangshan, China
| | - Xiaoli Chen
- Department of Internal Medicine, Tangshan, China
| | - Caiping Zhang
- Department of Biochemistry and Molecular Biology, Hengyang Medical School, University of South China, Hengyang, China
| | - Yong Zhou
- Department of Research Center for Cardiovascular and Cerebrovascular Disease, Clinical Research Institute, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Elías-López D, Wadström BN, Vedel-Krogh S, Kobylecki CJ, Nordestgaard BG. Impact of Remnant Cholesterol on Cardiovascular Risk in Diabetes. Curr Diab Rep 2024; 24:290-300. [PMID: 39356419 DOI: 10.1007/s11892-024-01555-1] [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] [Accepted: 09/13/2024] [Indexed: 10/03/2024]
Abstract
PURPOSE OF REVIEW Individuals with diabetes face increased risk of atherosclerotic cardiovascular disease (ASCVD), in part due to hyperlipidemia. Even after LDL cholesterol-lowering, residual ASCVD risk persists, part of which may be attributed to elevated remnant cholesterol. We describe the impact of elevated remnant cholesterol on ASCVD risk in diabetes. RECENT FINDINGS Preclinical, observational, and Mendelian randomization studies robustly suggest that elevated remnant cholesterol causally increases risk of ASCVD, suggesting remnant cholesterol could be a treatment target. However, the results of recent clinical trials of omega-3 fatty acids and fibrates, which lower levels of remnant cholesterol in individuals with diabetes, are conflicting in terms of ASCVD prevention. This is likely partly due to neutral effects of these drugs on the total level of apolipoprotein B(apoB)-containing lipoproteins. Elevated remnant cholesterol remains a likely cause of ASCVD in diabetes. Remnant cholesterol-lowering therapies should also lower apoB levels to reduce risk of ASCVD.
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Affiliation(s)
- Daniel Elías-López
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark
- The Copenhagen General Population Study, Copenhagen University Hospital - Herlev Gentofte, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark
- Department of Endocrinology and Metabolism and Research Center of Metabolic Diseases, National Institute of Medical Sciences and Nutrition Salvador Zubirán, Vasco de Quiroga 15, Belisario Domínguez Secc. 16, Tlalpan, 14080, México City, México
| | - Benjamin Nilsson Wadström
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark
- The Copenhagen General Population Study, Copenhagen University Hospital - Herlev Gentofte, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark
| | - Signe Vedel-Krogh
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark
- The Copenhagen General Population Study, Copenhagen University Hospital - Herlev Gentofte, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark
| | - Camilla Jannie Kobylecki
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark
- The Copenhagen General Population Study, Copenhagen University Hospital - Herlev Gentofte, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark
| | - Børge Grønne Nordestgaard
- Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.
- The Copenhagen General Population Study, Copenhagen University Hospital - Herlev Gentofte, Borgmester Ib Juuls Vej 1, 2730, Herlev, Denmark.
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.
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Evans AJ, Li YL. Remodeling of the Intracardiac Ganglia During the Development of Cardiovascular Autonomic Dysfunction in Type 2 Diabetes: Molecular Mechanisms and Therapeutics. Int J Mol Sci 2024; 25:12464. [PMID: 39596529 PMCID: PMC11594459 DOI: 10.3390/ijms252212464] [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] [Received: 09/24/2024] [Revised: 11/15/2024] [Accepted: 11/16/2024] [Indexed: 11/28/2024] Open
Abstract
Type 2 diabetes mellitus (T2DM) is one of the most significant health issues worldwide, with associated healthcare costs estimated to surpass USD 1054 billion by 2045. The leading cause of death in T2DM patients is the development of cardiovascular disease (CVD). In the early stages of T2DM, patients develop cardiovascular autonomic dysfunction due to the withdrawal of cardiac parasympathetic activity. Diminished cardiac parasympathetic tone can lead to cardiac arrhythmia-related sudden cardiac death, which accounts for 50% of CVD-related deaths in T2DM patients. Regulation of cardiovascular parasympathetic activity is integrated by neural circuitry at multiple levels including afferent, central, and efferent components. Efferent control of cardiac parasympathetic autonomic tone is mediated through the activity of preganglionic parasympathetic neurons located in the cardiac extensions of the vagus nerve that signals to postganglionic parasympathetic neurons located in the intracardiac ganglia (ICG) on the heart. Postganglionic parasympathetic neurons exert local control on the heart, independent of higher brain centers, through the release of neurotransmitters, such as acetylcholine. Structural and functional alterations in cardiac parasympathetic postganglionic neurons contribute to the withdrawal of cardiac parasympathetic tone, resulting in arrhythmogenesis and sudden cardiac death. This review provides an overview of the remodeling of parasympathetic postganglionic neurons in the ICG, and potential mechanisms contributing to the withdrawal of cardiac parasympathetic tone, ventricular arrhythmogenesis, and sudden cardiac death in T2DM. Improving cardiac parasympathetic tone could be a therapeutic avenue to reduce malignant ventricular arrhythmia and sudden cardiac death, increasing both the lifespan and improving quality of life of T2DM patients.
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Affiliation(s)
- Anthony J. Evans
- Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA;
| | - Yu-Long Li
- Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE 68198, USA;
- Department of Cellular & Integrative Physiology, University of Nebraska Medical Center, Omaha, NE 68198, USA
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49
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Sawami K, Tanaka A, Node K. Updated evidence on cardiovascular and renal effects of GLP-1 receptor agonists and combination therapy with SGLT2 inhibitors and finerenone: a narrative review and perspectives. Cardiovasc Diabetol 2024; 23:410. [PMID: 39548500 PMCID: PMC11568621 DOI: 10.1186/s12933-024-02500-y] [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: 07/16/2024] [Accepted: 11/02/2024] [Indexed: 11/18/2024] Open
Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have a reliable hypoglycaemic and weight-loss effect that can intervene in obesity, which is the basis of type 2 diabetes pathology. GLP-1RA therapy has shown potential benefits in reducing the risk of major adverse cardiovascular events and improving kidney outcomes in patients with diabetes at high risk for cardiovascular disease. More recent evidence is expanding their benefits to heart failure with preserved ejection fraction and clinically important renal outcomes in patients with and without diabetes. Some sub-analyses of large clinical trials suggest that GLP-1RA and sodium-glucose cotransporter 2 inhibitor combination therapy may provide more significant reductions in heart failure hospitalization and renal composite events than each alone. Moreover, the addition of finerenone to this combination therapy could potentially provide stronger cardiorenal protective benefits. Further studies are needed to assess the potential cardiovascular and renal benefits of combination therapy and to determine suitable patient population for the therapy.
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Affiliation(s)
- Kosuke Sawami
- Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
| | - Atsushi Tanaka
- Department of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan.
| | - Koichi Node
- Department of Cardiovascular Medicine, Saga University, 5-1-1 Nabeshima, Saga, 849-8501, Japan
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50
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Chen F, Wang J, He S, He Y, An Y, Gong Q, Chen X, Shuai Y, Wang X, Chen Y, Zhang B, Li G. Influence of impaired glucose tolerance and type 2 diabetes on the multimorbidity cluster of cardiovascular disease and cancer: a post hoc analysis of the Da Qing Diabetes Prevention Outcome Study. BMC Med 2024; 22:534. [PMID: 39548507 PMCID: PMC11566220 DOI: 10.1186/s12916-024-03749-6] [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: 03/26/2024] [Accepted: 10/31/2024] [Indexed: 11/18/2024] Open
Abstract
BACKGROUND This study explored the influence of type 2 diabetes and impaired glucose tolerance (IGT) on the risk of the multimorbidity cluster of cardiovascular disease (CVD) and cancer. METHODS A total of 1629 participants in the Da Qing Diabetes Prevention Outcome Study were recruited in the present analysis, including normal glucose tolerance (NGT, N = 492), IGT (N = 540), and newly diagnosed type 2 diabetes (N = 597) groups. Cox proportional hazards analyses were performed to assess the relationship between NGT, IGT, and newly diagnosed type 2 diabetes and the risk of the multimorbidity cluster of CVD and cancer. RESULTS The incidence rates for multimorbidity cluster CVD and cancer were 1.25, 3.17, and 3.23 per 1000 person-years in people with NGT, IGT, and the newly diagnosed type 2 diabetes groups, respectively, over 34-year follow-up. Cox analysis revealed that diabetes status (as time-dependent variable) was significantly associated with the subsequent increased risk of multimorbidity cluster of CVD and cancer compared with non-diabetes (hazard ratios [HR] = 2.55, 95% confidence interval [CI] 1.51-4.31) after adjustment of potential confounders. Similar analysis showed that this risk was significantly higher in the IGT and newly diagnosed type 2 diabetes groups compared with NGT, with HR of 3.28 (95% CI 1.83-5.87) and HR of 3.90 (95% CI 2.14-7.09), respectively. Whereas compared diabetes with IGT group, this risk was not significantly different. CONCLUSIONS Similar to newly diagnosed type 2 diabetes, IGT is significantly associated with an increased risk of the multimorbidity cluster of CVD and cancer compared with NGT. This finding highlights the urgent need for an active detection of IGT and effective prevention and management of diabetes.
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Affiliation(s)
- Fei Chen
- Department of Endocrinology, China-Japan Friendship Hospital, Beijing, China
| | - Jinping Wang
- Department of Cardiology, Da Qing First Hospital, Da Qing, China
| | - Siyao He
- Center of Endocrinology, National Center of Cardiology & Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yifan He
- Department of Endocrinology, China-Japan Friendship Hospital, Beijing, China
| | - Yali An
- Center of Endocrinology, National Center of Cardiology & Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Qiuhong Gong
- Center of Endocrinology, National Center of Cardiology & Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaoping Chen
- Department of Endocrinology, China-Japan Friendship Hospital, Beijing, China
| | - Ying Shuai
- Department of Endocrinology, China-Japan Friendship Hospital, Beijing, China
| | - Xuan Wang
- Center of Endocrinology, National Center of Cardiology & Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yanyan Chen
- Center of Endocrinology, National Center of Cardiology & Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bo Zhang
- Department of Endocrinology, China-Japan Friendship Hospital, Beijing, China.
| | - Guangwei Li
- Department of Endocrinology, China-Japan Friendship Hospital, Beijing, China.
- Center of Endocrinology, National Center of Cardiology & Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
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