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Feng Y, Yin L, Huang H, Hu Y, Lin S. Assessing the impact of insulin resistance trajectories on cardiovascular disease risk using longitudinal targeted maximum likelihood estimation. Cardiovasc Diabetol 2025; 24:112. [PMID: 40065358 PMCID: PMC11895167 DOI: 10.1186/s12933-025-02651-6] [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: 11/22/2024] [Accepted: 02/17/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Cardiovascular disease (CVD) is closely associated with Insulin Resistance (IR). However, there is limited research on the relationship between trajectories of IR and CVD incidence, considering both time-invariant and time-varying confounders. We employed advanced causal inference methods to evaluate the longitudinal impact of IR trajectories on CVD risk. METHODS The data for this study were extracted from a Chinese nationwide cohort, named China Health and Retirement Longitudinal Study (CHARLS). Triglyceride-glucose (TyG) index and TyG body mass index (BMI) were used as surrogate markers for IR, and their changes were recorded as exposures. Longitudinal targeted maximum likelihood estimation (LTMLE) was used to study how dynamic shifts in IR trajectories (i.e., increase, decrease, etc.) influence long-term CVD risk, adjusting for both time-invariant and time-varying confounders. RESULTS A total of 3,966 participants were included in the analysis, with 2,152 (54.3%) being female. The average age at baseline was 58.28 years. Over the course of a 7-year follow-up period, 499 (12.6%) participants developed CVD. Four distinct trajectories of TyG index and TyG-BMI were identified: low stable, increasing, decreasing, and high stable. LTMLE analyses revealed individuals in the 'high stable' and 'increasing' groups had a significantly higher risk of developing CVD compared to those in the 'low stable' group, while the 'decreasing' group showed no significant differences. Specifically, when the exposure was set as TyG-BMI, the odds of CVD in the 'high stable' group were 1.694 (95% CI: 1.361-2.108) times higher than in the 'low stable' group. Similar trends were observed across other models, with ORs of 1.708 (95% CI: 1.367-2.134) in Model 2, 1.389 (1.083-1.782) in Model 3, 1.675 (1.185-2.366) in Model 4, and 1.375 (95% CI:1.07 - 1.768) in Model 5. When the exposure was changed to the TyG index, the results remained consistent, with a slightly lower magnitude of the odds ratios. CONCLUSIONS High stable and increasing TyG-BMI and TyG index trajectories were associated with the risk of CVD. TyG-BMI consistently exhibited higher odds ratios (ORs) of CVD risk when comparing with TyG index. Early identification of IR trajectories could provide insights for preventing CVD later in life.
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Affiliation(s)
- Yaning Feng
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, China.
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China.
| | - Liangying Yin
- School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong, China
| | - Haoran Huang
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, China
| | - Yongheng Hu
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, China
| | - Sitong Lin
- School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, China
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Kim M, Zheng Z. Walking the VLDL tightrope in cardiometabolic diseases. Trends Endocrinol Metab 2025; 36:278-291. [PMID: 39191606 PMCID: PMC11861388 DOI: 10.1016/j.tem.2024.07.020] [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: 04/15/2024] [Revised: 07/22/2024] [Accepted: 07/26/2024] [Indexed: 08/29/2024]
Abstract
Very-low-density lipoprotein (VLDL), a triglyceride-rich lipoprotein secreted by hepatocytes, is pivotal for supplying peripheral tissues with fatty acids for energy production. As if walking on a tightrope, perturbations in the balance of VLDL metabolism contribute to cardiometabolic dysfunction, promoting pathologies such as cardiovascular disease (CVD) or metabolic dysfunction-associated steatotic liver disease (MASLD). Despite the advent of lipid-lowering therapies, including statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, risks for cardiovascular events persist. With limitations to currently available CVD therapeutics and no US Food and Drug Administration (FDA)-approved treatment for MASLD, this review summarizes the current understanding of VLDL metabolism that sheds light on novel therapeutic avenues to pursue for cardiometabolic disorders.
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Affiliation(s)
- Mindy Kim
- Medical Scientist Training Program, Medical College of Wisconsin, Milwaukee, 53226, USA; Department of Physiology, Medical College of Wisconsin, Milwaukee, 53226, USA.
| | - Ze Zheng
- Department of Physiology, Medical College of Wisconsin, Milwaukee, 53226, USA; Department of Medicine, Medical College of Wisconsin, Milwaukee, 53226, USA; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, 53226, USA; Thrombosis & Hemostasis Program, Versiti Blood Research Institute, Milwaukee, 53226, USA.
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Pickering RT, Yiannakou I, Lara-Castor L, Bradlee ML, Singer MR, Moore LL. Individual and Joint Associations Between Animal and Plant Protein Intakes with Impaired Fasting Glucose and Type 2 Diabetes in the Framingham Offspring Study. Nutrients 2024; 17:83. [PMID: 39796517 PMCID: PMC11723152 DOI: 10.3390/nu17010083] [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: 11/25/2024] [Revised: 12/25/2024] [Accepted: 12/26/2024] [Indexed: 01/13/2025] Open
Abstract
OBJECTIVES Given the considerable discrepancy in the literature regarding dietary protein and glucose homeostasis, we examined the prospective association between protein intake (total, animal, plant) and risk of type 2 diabetes mellitus or impaired fasting glucose (IFG). We also examined whether these associations differed by sex, body weight, or other risk factors. METHODS We included 1423 subjects, aged ≥ 30 years, in the Framingham Offspring Study cohort. Three-day dietary records at exams 3 and 5 were used to average protein intake and then adjusted for body weight residuals. Cox proportional hazard models were used to estimate hazard ratios (HR), adjusting for anthropometric, demographic, and lifestyle factors over ~16 years of follow-up. RESULTS Subjects with the highest total protein intakes (≥100 g men; ≥85 g women) had a 31% lower risk of type 2 diabetes/IFG (95% CI: 0.54, 0.87). The highest (vs. lowest) category of intake of animal protein was associated with a 32% lower risk of diabetes/IFG (95% CI: 0.55, 0.83), whereas plant protein was not. Beneficial trends of total protein, especially animal, were stronger for women (HR: 0.61; 95% CI: 0.42, 0.87) than for men (HR: 0.82; 95% CI 0.58, 1.15). Subjects with lower BMI who consumed more protein had the lowest risks of diabetes/IFG. CONCLUSIONS Overall, in this prospective study, higher intake of total dietary protein, including the consumption of animal protein, particularly among individuals with lower BMI and higher physical activity levels, was inversely associated with risk of incident type 2 diabetes and IFG.
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Affiliation(s)
- R. Taylor Pickering
- Preventive Medicine and Epidemiology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA; (I.Y.)
| | - Ioanna Yiannakou
- Preventive Medicine and Epidemiology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA; (I.Y.)
| | - Laura Lara-Castor
- Preventive Medicine and Epidemiology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA; (I.Y.)
- Gerald J. and Dorothy R. Friedman School of Nutrition Science and Policy, Tufts University, Boston, MA 02111, USA
| | - M. Loring Bradlee
- Preventive Medicine and Epidemiology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA; (I.Y.)
| | - Martha R. Singer
- Preventive Medicine and Epidemiology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA; (I.Y.)
| | - Lynn L. Moore
- Preventive Medicine and Epidemiology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, USA; (I.Y.)
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Oraby MI, Haddad MM, Nasser M, Hussein M. Insulin resistance, metabolic syndrome and micro-RNA-122 serum level in patients with cerebral venous sinus thrombosis: a case-control study. Thromb J 2024; 22:103. [PMID: 39563387 PMCID: PMC11575197 DOI: 10.1186/s12959-024-00654-z] [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: 04/13/2024] [Accepted: 09/12/2024] [Indexed: 11/21/2024] Open
Abstract
BACKGROUND The relationship between venous thromboembolism and both insulin resistance and metabolic syndrome is still a matter of debate. The objective of this work was to investigate the possible association between cerebral venous sinus thrombosis (CVST) and both insulin resistance and metabolic syndrome. We aimed also to assess micro-RNA-122 serum levels in patients with CVST in comparison to controls. METHODS This case-control study was conducted on patients having a clinical and neuroimaging diagnosis of acute CVST (within 1 week from the onset). Patients with inconclusive brain imaging, those with a history of malignancy, diabetic patients, and patients on drugs known to affect the insulin sensitivity or lipid profile were excluded from the study. Metabolic syndrome in the included cases and controls was evaluated by measuring waist circumference and blood pressure in addition to assessment of Triglycerides, HDL, and fasting blood sugar. The state of insulin resistance was established if the Homeostasis model assessment-insulin resistance (HOMA-IR) value > 2.5. Serum micro-RNA-122 serum level was measured for both patients and controls. RESULTS In the present study, 36 cases diagnosed as having CVST and 34 age & sex matched controls were included. There were statistically significant differences between patients with CVST and controls regarding BMI, waist circumference, TG, fasting glucose, fasting insulin & HOMA- IR (P-value = 0.002, 0.001, 0.004, 0.003, 0.021, 0.008 respectively). There was no statistically significant difference between patients with CVST and controls regarding micro-RNA-122 serum level (P-value = 0.376), whereas CVST patients with insulin resistance had a significantly higher micro-RNA-122 serum level in comparison to those without (P-value < 0.001). Patients with CVST had a significantly higher frequency of both metabolic syndrome and insulin resistance in comparison to controls (P-value = 0.008, 0.002 respectively). CONCLUSION There is a significant association between CVST and both insulin resistance and metabolic syndrome.
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Affiliation(s)
| | - Manar M Haddad
- Department of Neurology, Beni-Suef University, Beni-Suef, Egypt
| | - Mona Nasser
- Department of Clinical and Chemical pathology, Beni-Suef University, Beni-Suef, Egypt
| | - Mona Hussein
- Department of Neurology, Beni-Suef University, Beni-Suef, Egypt.
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Shaikh SB, Balaya RDA, Dagamajalu S, Bhandary YP, Unwalla H, Prasad TSK, Rahman I. A signaling pathway map of plasminogen activator inhibitor-1 (PAI-1/SERPINE-1): a review of an innovative frontier in molecular aging and cellular senescence. Cell Commun Signal 2024; 22:544. [PMID: 39543686 PMCID: PMC11566301 DOI: 10.1186/s12964-024-01910-5] [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: 05/15/2024] [Accepted: 10/26/2024] [Indexed: 11/17/2024] Open
Abstract
Plasminogen activator inhibitor-1 (PAI-1) is a vital regulator of the fibrinolytic mechanism and has been intricately involved in various physiological and clinical processes, including cancer, thrombosis, and wound healing. The PAI-1 signaling pathway is multifaceted, encompassing numerous signaling molecules and nodes. Recent studies have revealed a novel contribution of PAI-1 during cellular senescence. This review introduces a pathway resource detailing the signaling network events mediated by PAI-1. The literature curated on the PAI-1 system was manually compiled from various published studies, our analysis presents a signaling pathway network of PAI-1, which includes various events like enzyme catalysis, molecular association, gene regulation, protein expression, and protein translocation. This signaling network aims to provide a detailed analysis of the existing understanding of the PAI-1 signaling pathway in the context of cellular senescence across various research models. By developing this pathway, we aspire to deepen our understanding of aging and senescence research, ultimately contributing to the pursuit of effective therapeutic approaches for these complex chronic diseases.
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Affiliation(s)
- Sadiya Bi Shaikh
- Department of Environmental Medicine, University of Rochester Medical Centre, 601 Elmwood Avenue, Box 850, Rochester, NY, 14642, USA
| | | | - Shobha Dagamajalu
- Center for Systems Biology and Molecular Medicine, Yenepoya Research Centre, Yenepoya (Deemed to Be University), Mangalore, Karnataka, 575018, India
| | - Yashodhar Prabhakar Bhandary
- Division for Molecular Biology, Yenepoya Research Centre, Yenepoya (Deemed to Be University), Mangalore, Karnataka, 575018, India
| | - Hoshang Unwalla
- Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA
| | | | - Irfan Rahman
- Department of Environmental Medicine, University of Rochester Medical Centre, 601 Elmwood Avenue, Box 850, Rochester, NY, 14642, USA.
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Lee JH, Jeon S, Lee HS, Lee JW. Trajectories of triglyceride-glucose index changes and their association with all-cause and cardiovascular mortality: a competing risk analysis. Cardiovasc Diabetol 2024; 23:364. [PMID: 39407266 PMCID: PMC11481394 DOI: 10.1186/s12933-024-02457-y] [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: 08/08/2024] [Accepted: 09/24/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND The association between changes in insulin resistance, reflected by the triglyceride-glucose (TyG) index, and mortality remains unclear. This study investigated whether longitudinal trajectories of TyG index changes are associated with all-cause and cardiovascular disease (CVD) mortality. METHODS This retrospective cohort study analyzed data from 233,546 adults aged ≥ 19 years from the Korea National Health Insurance Service-National Sample Cohort. Participants were categorized as having increasing, stable, or decreasing TyG index changes during a 4-year exposure period (2009-2014). Mortality outcomes were assessed during an 8.13-year follow-up period (2015-2021). Cox proportional hazards regression and competing risk analysis were used to evaluate all-cause and CVD mortality. RESULTS A total of 7918 mortality events, including 651 CVD deaths, were recorded. Compared with the stable group, adjusted hazard ratios for all-cause mortality were 1.09 (95% CI 1.03-1.15) in the increasing group and 1.23 (95% CI 1.01-1.50) for CVD mortality. An increased TyG index was significantly associated with all-cause mortality in individuals aged < 50 years; men; and individuals with obesity, hypertension, diabetes, and/or dyslipidemia. For CVD mortality, significant associations were found in individuals aged 50-69 years, with obesity, with diabetes, or without dyslipidemia. CONCLUSION An increasing TyG index from baseline during follow-up was independently associated with higher risks of all-cause and CVD mortality. Serial monitoring of TyG index changes could enhance risk stratification and inform targeted interventions to reduce insulin resistance, and ultimately lower mortality risk.
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Affiliation(s)
- Jun-Hyuk Lee
- Department of Family Medicine, Nowon Eulji Medical Center, Eulji University School of Medicine, Seoul, 01830, Republic of Korea
| | - Soyoung Jeon
- Department of Research Affairs, Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, 03277, Republic of Korea
| | - Hye Sun Lee
- Department of Research Affairs, Biostatistics Collaboration Unit, Yonsei University College of Medicine, Seoul, 03277, Republic of Korea.
| | - Ji-Won Lee
- Department of Family Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
- Institute for Innovation in Digital Healthcare, Yonsei University, Seoul, 03722, Republic of Korea.
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Takasawa K, Iemura R, Orimoto R, Yamano H, Kirino S, Adachi E, Saito Y, Yamamoto K, Matsuda N, Takishima S, Shuno K, Tajima H, Sugie M, Mizuno Y, Sutani A, Okamoto K, Masue M, Morio T, Kashimada K. Clinical management of diazoxide-unresponsive congenital hyperinsulinism: A single-center experience. Clin Pediatr Endocrinol 2024; 33:187-194. [PMID: 38993725 PMCID: PMC11234188 DOI: 10.1297/cpe.2024-0004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Accepted: 05/07/2024] [Indexed: 07/13/2024] Open
Abstract
The most common cause of persistent hypoglycemia in newborns and children is congenital hyperinsulinism (CHI). Remarkable advancements in diagnostic tools and treatments, including novel imaging and genetic techniques, and continuous subcutaneous octreotide administration, have improved the prognosis of diazoxide-unresponsive CHI; however, in clinical practice, some issues remain. Here, we report a case series consisting of four adenosine triphosphate-sensitive potassium-associated CHI cases, discuss the practical use of new international guidelines published in 2023, and suggest clinical issues associated with CHI management. Based on the clinical experience of two diffuse and two focal CHI cases, we employed an updated treatment strategy, including genetic diagnosis to determine treatment plans, careful catheter management, switching from octreotide to long-acting somatostatin, effective utilization of a continuous glucose monitoring (CGM) device, measures for feeding problems, and individualized and systematic developmental follow-up. Particularly, our cases suggest a safe method of switching from octreotide to lanreotide, elucidate the efficacy of home-based CGM monitoring, and indicate need for personalized support for feeding problems. Severe CHI is a rare and challenging disorder; thus, further accumulation of experience according to new treatment strategies is essential in generating high-quality evidence for the development and approval of new treatment options.
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Affiliation(s)
- Kei Takasawa
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ryosei Iemura
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Ryuta Orimoto
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Haruki Yamano
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shizuka Kirino
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Eriko Adachi
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yoko Saito
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan
- Division of Medical Genetics, Kanagawa Children's Medical Center, Yokohama, Japan
| | - Kurara Yamamoto
- Department of Human Pathology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Nozomi Matsuda
- Department of Pediatrics, Soka Municipal Hospital, Saitama, Japan
| | | | - Kumi Shuno
- Department of Pediatrics, Nippon Medical School, Tokyo, Japan
| | - Hanako Tajima
- Department of Pediatrics, Nippon Medical School, Tokyo, Japan
| | - Manabu Sugie
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yuki Mizuno
- Department of Pediatric Surgery, Tokyo Medical and Dental University Hospital, Tokyo, Japan
| | - Akito Sutani
- Department of Pediatrics, Kawaguchi Municipal Medical Center, Saitama, Japan
| | - Kentaro Okamoto
- Department of Pediatric Surgery, Tokyo Medical and Dental University Hospital, Tokyo, Japan
| | - Michiya Masue
- Department of Pediatrics, Central Japan International Medical Center, Gifu, Japan
| | - Tomohiro Morio
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kenichi Kashimada
- Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan
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Zhang X, Shan C, Hu K, Fang B, Zhang Z, Xie Q, Liu C, An X, Yang Y, Li X. Prognostic value of metabolic syndrome in patients with heart failure and malnutrition. BMC Cardiovasc Disord 2024; 24:136. [PMID: 38431559 PMCID: PMC10908134 DOI: 10.1186/s12872-024-03767-5] [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: 10/09/2023] [Accepted: 02/04/2024] [Indexed: 03/05/2024] Open
Abstract
BACKGROUND Malnutrition is severely associated with worst prognosis of patients with heart failure (HF). Malnourished patients with the metabolic syndrome (MS) can result in a double burden of malnutrition. We aimed to investigate the impact of the MS on clinical outcomes in malnourished HF patients. METHODS We examined 529 HF patients at risk of malnutrition with a mean age of (66 ± 10) years and 78% (415) were male. Nutritional status defined primarily by the prognostic nutritional index (PNI), with PNI < 40 being defined as malnutrition. The follow-up endpoint was cardiovascular death or all-cause death. RESULTS During the 36-month follow-up, survival rates for cardiovascular and all-cause death were significantly lower in the MS group than in the non-MS group (log-rank P < 0.01). Multivariate Cox proportional hazards regression models showed that MS was independently associated with cardiovascular death (HR:1.759, 95%CI:1.351-2.291, p < 0.001) and all-cause death (HR:1.326, 95%CI:1.041-1.689, p = 0.022) in malnourished patients with HF. MS significantly increased the predictive value of cardiovascular death (AUC:0.669, 95%CI:0.623-0.715, p < 0.001) and all-cause death (AUC:0.636, 95%CI:0.585-0.687, p < 0.001) on the basis of established risk factors. The predictive effect of MS on cardiovascular death was independent of sex, age, functional class and left ventricular ejection fraction. CONCLUSIONS In malnourished patients with HF, MS is an independent risk factor for cardiovascular and all-cause mortality. MS significantly enhance the predictive value for clinical events in patients.
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Affiliation(s)
- Xuehe Zhang
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, 830054, People's Republic of China
| | - Chunfang Shan
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, 830054, People's Republic of China
| | - Kaixuan Hu
- Department of Cardiology, Bayinguoleng Mongolian Autonomous Prefecture People's Hospital, Korla, China
| | - Binbin Fang
- State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi, China
| | - Zhiyang Zhang
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, 830054, People's Republic of China
| | - Qian Xie
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, 830054, People's Republic of China
| | - Chang Liu
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, 830054, People's Republic of China
| | - Xin An
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, 830054, People's Republic of China
| | - Yining Yang
- Department of Cardiology, People's Hospital of Xinjiang Uygur Autonomous Region, 91 Tianchi Road, Urumqi, 830054, People's Republic of China.
| | - Xiaomei Li
- Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, 137 Liyushan South Road, Urumqi, 830054, People's Republic of China.
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Yang B, Chen X, Li F, Zhang J, Dong D, Ou H, Lu L, He N, Xu X, Xin X, Lu J, Guan M, Qiao H, Xu A, Zhu H. Stress hyperglycemia increases short-term mortality in acute ischemic stroke patients after mechanical thrombectomy. Diabetol Metab Syndr 2024; 16:32. [PMID: 38297321 PMCID: PMC10829332 DOI: 10.1186/s13098-024-01272-5] [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: 09/26/2023] [Accepted: 01/19/2024] [Indexed: 02/02/2024] Open
Abstract
BACKGROUND AND PURPOSE Glucose-to-glycated hemoglobin ratio (GAR) is considered a more reliable marker of stress hyperglycemia by correcting for basal blood glucose levels. This study aimed to investigate the extent to which GAR is associated with 3 month and 1 year all-cause mortalities in patients with acute ischemic stroke (AIS) undergoing mechanical thrombectomy (MT). METHODS We retrospectively followed 553 AIS patients who underwent MT. The degree of stress hyperglycemia was quantified as the GAR, defined as fasting plasma glucose (mmol/L)/hemoglobin A1c (HbA1c) (%) on the second day after admission. According to the GAR quartiles, the patients were further categorized into four groups (group 1-group 4). We assessed the association between GAR and all-cause mortalities, clinical outcomes during hospitalization and function outcomes at 3 months. The associations between stress hyperglycemia and all-cause mortalities were analyzed using a Cox proportional-hazards model, while other outcomes were analyzed using multiple logistic regression analysis. RESULTS The follow-up lasted a median of 18 months (range 0-66 months). The 3 month mortality rate was 9.58% (n = 53) and the 1 year mortality rate was 18.62% (n = 103). The Kaplan-Meier analysis revealed a significant inverse relationship between GAR and mortality (P < 0.001). In the Cox proportional-hazards model at 3 months, compared with group1, group 4 of GAR was associated with a significant increase in the risk of 3 month mortality (hazard ratio [HR] = 4.11, 95% confidence interval [CI] 1.41-12.0, P = 0.01) after adjusting for potential covariates. On multivariate logistic regression analysis, GAR was strongly associated with an increased risk of 3 month poor function outcome. CONCLUSIONS Stress hyperglycemia, quantified by a higher GAR, is associated with all-cause mortality and poor functional outcomes in patients with AIS who undergo MT. Furthermore, GAR may contribute to improving the predictive efficiency of all-cause mortality in patients with AIS after MT, especially short-term all-cause mortality.
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Affiliation(s)
- Bing Yang
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue west, Guangzhou, China
- Clinical Neuroscience Institute, Jinan University, Guangzhou, China
| | - Xuefang Chen
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue west, Guangzhou, China
- Department of Neurology, The Dongguan Affiliated Hospital of Jinan University, Binhaiwan Central Hospital of Dongguan, Dongguan, China
| | - Fangze Li
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue west, Guangzhou, China
- Clinical Neuroscience Institute, Jinan University, Guangzhou, China
| | - Junrun Zhang
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue west, Guangzhou, China
- Clinical Neuroscience Institute, Jinan University, Guangzhou, China
| | - Dawei Dong
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue west, Guangzhou, China
- Department of Neurology, the Affiliated Shunde Hospital of Jinan University, Foshan, China
| | - Huiyue Ou
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue west, Guangzhou, China
- Clinical Neuroscience Institute, Jinan University, Guangzhou, China
| | - Longyan Lu
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue west, Guangzhou, China
- Clinical Neuroscience Institute, Jinan University, Guangzhou, China
| | - Niu He
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue west, Guangzhou, China
- Clinical Neuroscience Institute, Jinan University, Guangzhou, China
| | - Xiaohong Xu
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue west, Guangzhou, China
- Clinical Neuroscience Institute, Jinan University, Guangzhou, China
| | - Xiufeng Xin
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue west, Guangzhou, China
- Clinical Neuroscience Institute, Jinan University, Guangzhou, China
| | - Jingchong Lu
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue west, Guangzhou, China
- Clinical Neuroscience Institute, Jinan University, Guangzhou, China
| | - Min Guan
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue west, Guangzhou, China
- Clinical Neuroscience Institute, Jinan University, Guangzhou, China
| | - Hongyu Qiao
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue west, Guangzhou, China
- Clinical Neuroscience Institute, Jinan University, Guangzhou, China
| | - Anding Xu
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue west, Guangzhou, China.
- Clinical Neuroscience Institute, Jinan University, Guangzhou, China.
| | - Huili Zhu
- Department of Neurology and Stroke Center, The First Affiliated Hospital, Jinan University, 613 Huangpu Avenue west, Guangzhou, China.
- Clinical Neuroscience Institute, Jinan University, Guangzhou, China.
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10
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Caimi G, Urso C, Brucculeri S, Lo Presti R, Carlisi M. Calculated whole blood viscosity in non-diabetic subjects with asymptomatic carotid atherosclerosis: How insulin resistance may affect blood viscosity. Clin Hemorheol Microcirc 2024; 88:199-209. [PMID: 38905035 DOI: 10.3233/ch-221422] [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] [Indexed: 06/23/2024]
Abstract
BACKGROUND AND OBJECTIVE Asymptomatic atherosclerosis is an important early marker of vascular damage and, among its risk factors, hemorheological alterations play an important role. PATIENTS AND METHODS In a cohort of 85 non-diabetic subjects with asymptomatic carotid atherosclerosis (ACA), we have measured whole blood viscosity (cWBV) according to the haematocrit and plasma fibrinogen level. The cWBV distinguish the subgroup of ACA subjects with 3-5 cardiovascular risk factors (CRFs) from that with 1-2 CRFs and the same behavior is present for haematocrit and plasma fibrinogen level. Therefore, we divided the whole group of ACA subjects according to the medians of the four surrogate indexes with an insulin resistance degree of TG/HDL-C, TyG, VAI and LAP. RESULTS The analysis of the correlation between cWBV and each index of insulin resistance has shown that no correlation is present in the whole group and in the group of ACA subjects with 1-2 CRFs, while in the subgroup with 3-5 CRFs there is a positive correlation between cWBV with TG/HDL-C and TyG at a low degree of statistical significance. CONCLUSIONS The date underline that subjects with this clinical condition have an unaltered evaluation of the cWBV compared to the other indices.
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Affiliation(s)
- G Caimi
- Department of Health Promotion and Child Care, Internal Medicine and Medical Specialties, Università degli Studi di Palermo, Palermo, Italy
| | - C Urso
- Fondazione Istituto "G. Giglio" Cefalù, Palermo, Italy
| | - S Brucculeri
- Fondazione Istituto "G. Giglio" Cefalù, Palermo, Italy
| | - R Lo Presti
- Department of Psychology, Educational Science and Human Movement, Università degli Studi di Palermo, Palermo, Italy
| | - M Carlisi
- Department of Health Promotion and Child Care, Internal Medicine and Medical Specialties, Università degli Studi di Palermo, Palermo, Italy
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11
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Dai W, Zhang H, Lund H, Zhang Z, Castleberry M, Rodriguez M, Kuriakose G, Gupta S, Lewandowska M, Powers HR, Valmiki S, Zhu J, Shapiro AD, Hussain MM, López JA, Sorci-Thomas MG, Silverstein RL, Ginsberg HN, Sahoo D, Tabas I, Zheng Z. Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes. Science 2023; 381:eadh5207. [PMID: 37651538 PMCID: PMC10697821 DOI: 10.1126/science.adh5207] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 07/13/2023] [Indexed: 09/02/2023]
Abstract
Apolipoprotein B (apoB)-lipoproteins initiate and promote atherosclerotic cardiovascular disease. Plasma tissue plasminogen activator (tPA) activity is negatively associated with atherogenic apoB-lipoprotein cholesterol levels in humans, but the mechanisms are unknown. We found that tPA, partially through the lysine-binding site on its Kringle 2 domain, binds to the N terminus of apoB, blocking the interaction between apoB and microsomal triglyceride transfer protein (MTP) in hepatocytes, thereby reducing very-low-density lipoprotein (VLDL) assembly and plasma apoB-lipoprotein cholesterol levels. Plasminogen activator inhibitor 1 (PAI-1) sequesters tPA away from apoB and increases VLDL assembly. Humans with PAI-1 deficiency have smaller VLDL particles and lower plasma levels of apoB-lipoprotein cholesterol. These results suggest a mechanism that fine-tunes VLDL assembly by intracellular interactions among tPA, PAI-1, and apoB in hepatocytes.
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Affiliation(s)
- Wen Dai
- Versiti Blood Research Institute, Milwaukee, WI 53226, USA
| | - Heng Zhang
- Versiti Blood Research Institute, Milwaukee, WI 53226, USA
| | - Hayley Lund
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Ziyu Zhang
- Versiti Blood Research Institute, Milwaukee, WI 53226, USA
| | | | - Maya Rodriguez
- Versiti Blood Research Institute, Milwaukee, WI 53226, USA
- College of Arts and Sciences, Marquette University, Milwaukee, WI 53233, USA
| | - George Kuriakose
- Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA
| | - Sweta Gupta
- Indiana Hemophilia and Thrombosis Center, Indianapolis, IN 46260, USA
| | | | - Hayley R. Powers
- Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Swati Valmiki
- Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA
- Department of Foundations of Medicine, NYU Long Island School of Medicine, Mineola, NY 11501, USA
| | - Jieqing Zhu
- Versiti Blood Research Institute, Milwaukee, WI 53226, USA
- Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Amy D. Shapiro
- Indiana Hemophilia and Thrombosis Center, Indianapolis, IN 46260, USA
| | - M. Mahmood Hussain
- Department of Cell Biology, SUNY Downstate Medical Center, Brooklyn, NY 11203, USA
- Department of Foundations of Medicine, NYU Long Island School of Medicine, Mineola, NY 11501, USA
| | - José A. López
- Bloodworks Research Institute, Seattle, WA 98102, USA
- Department of Medicine, University of Washington, Seattle, WA 98195, USA
| | - Mary G. Sorci-Thomas
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Roy L. Silverstein
- Versiti Blood Research Institute, Milwaukee, WI 53226, USA
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Henry N. Ginsberg
- Department of Medicine, Columbia University Vagelos College of Physicians and Surgeons, New York, NY 10032, USA
| | - Daisy Sahoo
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Department of Biochemistry, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Ira Tabas
- Department of Medicine, Columbia University Irving Medical Center, New York, NY 10032, USA
- Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, NY 10032, USA
- Department of Physiology and Cellular Biophysics, Columbia University Irving Medical Center, New York, NY 10032, USA
| | - Ze Zheng
- Versiti Blood Research Institute, Milwaukee, WI 53226, USA
- Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI 53226, USA
- Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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12
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Morrow GB, Mutch NJ. Past, Present, and Future Perspectives of Plasminogen Activator Inhibitor 1 (PAI-1). Semin Thromb Hemost 2023; 49:305-313. [PMID: 36522166 DOI: 10.1055/s-0042-1758791] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Plasminogen activator inhibitor 1 (PAI-1), a SERPIN inhibitor, is primarily known for its regulation of fibrinolysis. However, it is now known that this inhibitor functions and contributes to many (patho)physiological processes including inflammation, wound healing, cell adhesion, and tumor progression.This review discusses the past, present, and future roles of PAI-1, with a particular focus on the discovery of this inhibitor in the 1970s and subsequent characterization in health and disease. Throughout the past few decades diverse functions of this serpin have unraveled and it is now considered an important player in many disease processes. PAI-1 is expressed by numerous cell types, including megakaryocytes and platelets, adipocytes, endothelial cells, hepatocytes, and smooth muscle cells. In the circulation PAI-1 exists in two pools, within plasma itself and in platelet α-granules. Platelet PAI-1 is secreted following activation with retention of the inhibitor on the activated platelet membrane. Furthermore, these anucleate cells contain PAI-1 messenger ribonucleic acid to allow de novo synthesis.Outside of the traditional role of PAI-1 in fibrinolysis, this serpin has also been identified to play important roles in metabolic syndrome, obesity, diabetes, and most recently, acute respiratory distress syndrome, including coronavirus disease 2019 disease. This review highlights the complexity of PAI-1 and the requirement to ascertain a better understanding on how this complex serpin functions in (patho)physiological processes.
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Affiliation(s)
- Gael B Morrow
- Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom
- Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Nicola J Mutch
- Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom
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13
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Egg Intake Is Associated with Lower Risks of Impaired Fasting Glucose and High Blood Pressure in Framingham Offspring Study Adults. Nutrients 2023; 15:nu15030507. [PMID: 36771213 PMCID: PMC9920838 DOI: 10.3390/nu15030507] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2022] [Revised: 01/09/2023] [Accepted: 01/13/2023] [Indexed: 01/21/2023] Open
Abstract
The association between egg consumption and cardiometabolic risk factors such as high blood pressure (HBP) and impaired fasting glucose (IFG) or type 2 diabetes (T2D) is still under debate. This study examines the association between egg consumption and these outcomes among 2349 30-64 year-old adults in the prospective Framingham Offspring Study. Diet was assessed using three-day dietary records. Potential confounders retained in the final models included age, sex, body mass index, and other dietary factors. The analysis of covariance and Cox proportional hazard's models were used to assess the relevant continuous (i.e., FG, SBP, DBP) and categorical (i.e., T2D, HBP) outcomes. Consuming ≥5 eggs per week was associated with lower mean FG (p = 0.0004) and SBP (p = 0.0284) after four years of follow-up. Higher egg intakes led to lower risks of developing IFG or T2D (HR: 0.72; 95% CI: 0.51-1.03) and high blood pressure (HBP) (HR: 0.68; 0.50-0.93). The beneficial effects of egg consumption were stronger in combination with other healthy dietary patterns. This study found that regular egg consumption as part of a healthy diet had long-term beneficial effects on blood pressure and glucose metabolism and lowered the long-term risks of high blood pressure and diabetes.
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14
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Shao H, Chan WCL, Du H, Chen XF, Ma Q, Shao Z. A new machine learning algorithm with high interpretability for improving the safety and efficiency of thrombolysis for stroke patients: A hospital-based pilot study. Digit Health 2023; 9:20552076221149528. [PMID: 36636727 PMCID: PMC9829886 DOI: 10.1177/20552076221149528] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Background Thrombolysis is the first-line treatment for patients with acute ischemic stroke. Previous studies leveraged machine learning to assist neurologists in selecting patients who could benefit the most from thrombolysis. However, when designing the algorithm, most of the previous algorithms traded interpretability for predictive power, making the algorithms hard to be trusted by neurologists and be used in real clinical practice. Methods Our proposed algorithm is an advanced version of classical k-nearest neighbors classification algorithm (KNN). We achieved high interpretability by changing the isotropy in feature space of classical KNN. We leveraged a cohort of 189 patients to prove that our algorithm maintains the interpretability of previous models while in the meantime improving the predictive power when compared with the existing algorithms. The predictive powers of models were assessed by area under the receiver operating characteristic curve (AUC). Results In terms of interpretability, only onset time, diabetes, and baseline National Institutes of Health Stroke Scale (NIHSS) were statistically significant and their contributions to the final prediction were forced to be proportional to their feature importance values by the rescaling formula we defined. In terms of predictive power, our advanced KNN (AUC 0.88) outperformed the classical KNN (AUC 0.75, p = 0.0192 ). Conclusions Our preliminary results show that the advanced KNN achieved high AUC and identified consistent significant clinical features as previous clinical trials/observational studies did. This model shows the potential to assist in thrombolysis patient selection for improving the successful rate of thrombolysis.
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Affiliation(s)
- Huiling Shao
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong,Huiling Shao, Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Room Y934, 9/F, Lee Shau Kee Building, Hung Hom, Kowloon, 999077, Hong Kong.
| | - Wing Chi Lawrence Chan
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong
| | - Heng Du
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong
| | - Xiangyan Fiona Chen
- Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Kowloon, Hong Kong
| | - Qilin Ma
- Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China
| | - Zhiyu Shao
- Department of Neurology, The First Affiliated Hospital of Xiamen University, Xiamen, China
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15
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Temporal Changes in Extracellular Vesicle Hemostatic Protein Composition Predict Favourable Left Ventricular Remodeling after Acute Myocardial Infarction. Int J Mol Sci 2022; 24:ijms24010327. [PMID: 36613770 PMCID: PMC9820565 DOI: 10.3390/ijms24010327] [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: 11/07/2022] [Revised: 12/17/2022] [Accepted: 12/22/2022] [Indexed: 12/28/2022] Open
Abstract
The subset of plasma extracellular vesicles (EVs) that coprecipitate with low-density lipoprotein (LDL-EVs) carry coagulation and fibrinolysis pathway proteins as cargo. We investigated the association between LDL-EV hemostatic/fibrinolysis protein ratios and post-acute myocardial infarction (post-AMI) left ventricular (LV) remodeling which precedes heart failure. Protein concentrations of von Willebrand factor (VWF), SerpinC1 and plasminogen were determined in LDL-EVs extracted from plasma samples obtained at baseline (within 72 h post-AMI), 1 month and 6 months post-AMI from 198 patients. Patients were categorized as exhibiting adverse (n = 98) or reverse (n = 100) LV remodeling based on changes in LV end-systolic volume (increased or decreased ≥15) over a 6-month period. Multiple level longitudinal data analysis with structural equation (ML-SEM) model was used to assess predictive value for LV remodeling independent of baseline differences. At baseline, protein levels of VWF, SerpinC1 and plasminogen in LDL-EVs did not differ between patients with adverse versus reverse LV remodeling. At 1 month post-AMI, protein levels of VWF and SerpinC1 decreased whilst plasminogen increased in patients with adverse LV remodeling. In contrast, VWF and plasminogen decreased whilst SerpinC1 remained unchanged in patients with reverse LV remodeling. Overall, compared with patients with adverse LV remodeling, higher levels of SerpinC1 and VWF but lower levels of plasminogen resulted in higher ratios of VWF:Plasminogen and SerpinC1:Plasminogen at both 1 month and 6 months post-AMI in patients with reverse LV remodeling. More importantly, ratios VWF:Plasminogen (AUC = 0.674) and SerpinC1:Plasminogen (AUC = 0.712) displayed markedly better prognostic power than NT-proBNP (AUC = 0.384), troponin-I (AUC = 0.467) or troponin-T (AUC = 0.389) (p < 0.001) to predict reverse LV remodeling post-AMI. Temporal changes in the ratios of coagulation to fibrinolysis pathway proteins in LDL-EVs outperform current standard plasma biomarkers in predicting post-AMI reverse LV remodeling. Our findings may provide clinical cues to uncover the cellular mechanisms underpinning post-AMI reverse LV remodeling.
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16
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Li G, Wang C, Wang S, Hao Y, Xiong Y, Zhao X. Clinical Significance of Stress Hyperglycemic Ratio and Glycemic Gap in Ischemic Stroke Patients Treated with Intravenous Thrombolysis. Clin Interv Aging 2022; 17:1841-1849. [DOI: 10.2147/cia.s393952] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/18/2022] [Accepted: 12/06/2022] [Indexed: 12/15/2022] Open
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17
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Montilla M, Liberato A, Ruiz-Ocaña P, Sáez-Benito A, Aguilar-Diosdado M, Lechuga-Sancho AM, Ruiz FA. Proinflammatory Polyphosphate Increases in Plasma of Obese Children with Insulin Resistance and Adults with Severe Type 2 Diabetes. Nutrients 2022; 14:nu14214601. [PMID: 36364861 PMCID: PMC9654964 DOI: 10.3390/nu14214601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 10/25/2022] [Accepted: 10/28/2022] [Indexed: 11/06/2022] Open
Abstract
Obesity increases the risk of insulin resistance and type 2 diabetes through increased inflammation at cellular and tissue levels. Therefore, study of the molecular elements involved in obesity-related inflammation may contribute to preventing and controlling it. Inorganic polyphosphate is a natural phosphate polymer that has recently been attracting more attention for its role in inflammation and hemostasis processes. Polyphosphates are one of the main constituents of human platelets, which are secreted after platelet activation. Among other roles, they interact with multiple proteins of the coagulation cascade, trigger bradykinin release, and inhibit the complement system. Despite its importance, determinations of polyphosphate levels in blood plasma had been elusive until recently, when we developed a method to detect these levels precisely. Here, we perform cross sectional studies to evaluate plasma polyphosphate in: 25 children, most of them with obesity and overweight, and 20 adults, half of them with severe type 2 diabetes. Our results show that polyphosphate increases, in a significant manner, in children with insulin resistance and in type 2 diabetes patients. As we demonstrated before that polyphosphate decreases in healthy overweight individuals, these results suggest that this polymer could be an inflammation biomarker in the metabolic disease onset before diabetes.
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Affiliation(s)
- Marcela Montilla
- Research Unit, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cadiz, Spain
- Medical School, Universidad Cooperativa de Colombia, Villavicencio 500003, Colombia
| | - Andrea Liberato
- Research Unit, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cadiz, Spain
| | - Pablo Ruiz-Ocaña
- Pediatric Endocrinology and Diabetes, Department of Pediatrics, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain
| | - Ana Sáez-Benito
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cadiz, Spain
- Clinical Analysis Department, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain
| | - Manuel Aguilar-Diosdado
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cadiz, Spain
- Endocrinology and Metabolism Department, Hospital Universitario Puerta del Mar, and Universidad de Cádiz, 11009 Cadiz, Spain
| | - Alfonso Maria Lechuga-Sancho
- Research Unit, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cadiz, Spain
- Pediatric Endocrinology and Diabetes, Department of Pediatrics, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain
- Area of Pediatrics, Medical School, Universidad de Cádiz, 11003 Cadiz, Spain
| | - Felix A. Ruiz
- Research Unit, Hospital Universitario Puerta del Mar, 11009 Cadiz, Spain
- Instituto de Investigación e Innovación Biomédica de Cádiz (INiBICA), 11009 Cadiz, Spain
- Area of Nutrition and Bromatology, Medical School, Universidad de Cádiz, 11003 Cadiz, Spain
- Correspondence: ; Tel.: +34-690395217
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Prognostic Significance of Plasma Insulin Level for Deep Venous Thrombosis in Patients with Severe Traumatic Brain Injury in Critical Care. Neurocrit Care 2022; 38:263-278. [PMID: 36114315 DOI: 10.1007/s12028-022-01588-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 08/10/2022] [Indexed: 10/14/2022]
Abstract
BACKGROUND Whether insulin resistance underlies deep venous thrombosis (DVT) development in patients with severe traumatic brain injury (TBI) is unclear. In this study, the association between plasma insulin levels and DVT was analyzed in patients with severe TBI. METHODS A prospective observational study of 73 patients measured insulin, glucose, glucagon-like peptide 1 (GLP-1), inflammatory factors, and hematological profiles within four preset times during the first 14 days after TBI. Ultrasonic surveillance of DVT was tracked. Two-way analysis of variance was used to determine the factors that discriminated between patients with and without DVT or with and without insulin therapy. Partial correlations of insulin level with all the variables were conducted separately in patients with DVT or patients without DVT. Factors associated with DVT were analyzed by multivariable logistic regression. Neurological outcomes 6 months after TBI were assessed. RESULTS Among patients with a mean (± standard deviation) age of 53 (± 16 years), DVT developed in 20 patients (27%) on median 10.4 days (range 4-22), with higher Acute Physiology and Chronic Health Evaluation II scores but similar Sequential Organ Failure Assessment scores and TBI severity. Patients with DVT were more likely to receive insulin therapy than patients without DVT (60% vs. 28%; P = 0.012); hence, they had higher 14-day insulin levels. However, insulin levels were comparable between patients with DVT and patients without DVT in the subgroups of patients with insulin therapy (n = 27) and patients without insulin therapy (n = 46). The platelet profile significantly discriminated between patients with and without DVT. Surprisingly, none of the coagulation profiles, blood cell counts, or inflammatory mediators differed between the two groups. Patients with insulin therapy had significantly higher insulin (P = 0.006), glucose (P < 0.001), and GLP-1 (P = 0.01) levels and were more likely to develop DVT (60% vs. 15%; P < 0.001) along with concomitant platelet depletion. Insulin levels correlated with glucose, GLP-1 levels, and platelet count exclusively in patients without DVT. Conversely, in patients with DVT, insulin correlated negatively with GLP-1 levels (P = 0.016). Age (P = 0.01) and elevated insulin levels at days 4-7 (P = 0.04) were independently associated with DVT. Patients with insulin therapy also showed worse Glasgow Outcome Scale scores (P = 0.001). CONCLUSIONS Elevated insulin levels in the first 14 days after TBI may indicate insulin resistance, which is associated with platelet hyperactivity, and thus increasing the risk of DVT.
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Zhang Y, Jin A, Meng X, Wang M, Li H, Pan Y, Wang Y. Association between diabetes duration and 1-year prognosis of stroke: A national registry study. Brain Behav 2022; 12:e2725. [PMID: 35941828 PMCID: PMC9480956 DOI: 10.1002/brb3.2725] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Revised: 06/05/2022] [Accepted: 07/12/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND AND PURPOSE Diabetes mellitus is a strong independent risk factor for stroke recurrence. However, the association between diabetes duration and the prognosis of stroke remains uncertain. We aimed to characterize whether an association exists between diabetes duration and stroke outcomes in patients with ischemic stroke or transient ischemic attack (TIA). METHODS Between 2015 and 2018, 14,674 patients with ischemic stroke or TIA within 7 days and older than 18 years from the Third China National Stroke Registry (CNSR-III) were included in this analysis. Diabetes duration at baseline was collected by face-to-face interviews and further categorized into groups of without diabetes, diabetes < 4, 4 to <8 and ≥8 years. The association between diabetes duration and clinical outcomes, including stroke recurrence, poor function outcome (modified Rankin Scale score of 3-6), and all-cause mortality at the 1-year follow-up after stroke onset, was evaluated by a multivariable Cox proportional hazard regression model, competing risk model and logistic regression model with adjustment for demographic and clinical features. RESULTS Among the 14,674 patients included, the average age was 62.0 years, and 68.5% were male. There were 1419 (9.7%) patients who had stroke recurrence, 1912 (13.0%) who had poor function outcome, and 478 (3.3%) who had all-cause mortality at the 1-year follow-up. After adjusting for potential covariates, a diabetes duration ≥8 years was associated with an increased risk of 1-year stroke recurrence (adjusted hazards ratio [HR], 1.31; 95% CI, 1.05-1.64; p = .02) in comparison to those without Diabetes mellitus. Using a competing risk regression model, a diabetes duration ≥8 years was a significant risk factor for stroke recurrence (HR, 1.31; 95% CI, 1.12-1.53). In contrast, there was no significant association between diabetes duration < 4, 4 to <8 years and clinical outcomes. CONCLUSIONS Long-term diabetes duration (≥8 years), but not short-term diabetes duration, was associated with an increased risk of 1-year stroke recurrence in patients with ischemic stroke or TIA.
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Affiliation(s)
- Yanli Zhang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Aoming Jin
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Xia Meng
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Mengxing Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Hao Li
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Yuesong Pan
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Yongjun Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.,China National Clinical Research Center for Neurological Diseases, Beijing, China.,Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, China.,Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China
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20
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FAN HL, ZENG LH, CHEN PY, LIU YH, DUAN CY, HE WF, TAN N, CHEN JY, HE PC. Association of baseline hemoglobin A1c levels with bleeding in patients with non-ST-segment elevation acute coronary syndrome underwent percutaneous coronary intervention: insights of a multicenter cohort study from China. J Geriatr Cardiol 2022; 19:487-497. [PMID: 35975020 PMCID: PMC9361156 DOI: 10.11909/j.issn.1671-5411.2022.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
OBJECTIVE To investigate the association between baseline hemoglobin A1c (HbA1c) levels and bleeding in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) who underwent percutaneous coronary intervention (PCI). METHODS This observational cohort study enrolled 6283 consecutive NSTE-ACS patients undergoing PCI from January 1, 2010 to December 31, 2014. Based on baseline HbA1c levels, the patients were divided into the group with HbA1c < 7% ( n = 4740) and the group with HbA1c ≥ 7% (n = 1543). The primary outcomes are major bleeding (BARC grades 3-5) and all-cause death during follow-up. RESULTS Of patients enrolled, 4705 (74.9%) were male, and 2143 (34.1%) had a history of diabetes mellitus, with a mean (SD) age of 64.13 (10.32) years. The median follow-up duration was 3.21 years. Compared with the patients with HbA1c < 7%, the risk of major bleeding events during follow-up was higher in patients with HbA1c ≥ 7% (adjusted hazard ratio [HR] = 1.57; 95% confidence interval [CI]: 1.01-2.44; P = 0.044), while the risk of all-cause death during follow-up was not associated with the higher HbA1c levels (adjusted HR = 0.88; 95% CI: 0.66-1.18; P = 0.398). CONCLUSIONS Compared with the lower baseline HbA1c levels, the higher baseline HbA1c levels were associated with an increase in long-term bleeding risk in NSTE-ACS patients undergoing PCI, though higher baseline HbA1c levels were not associated with the higher risk in all-cause death.
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Affiliation(s)
- Hua-Lin FAN
- Department of Cardiology, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Li-Huan ZENG
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Peng-Yuan CHEN
- Department of Cardiology, the Second People’s Hospital of Nanhai District, Guangdong Provincial People’s Hospital’s Nanhai Hospital, Foshan, China
| | - Yuan-Hui LIU
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Chong-Yang DUAN
- Department of Biostatistics, School of Public Health, Southern Medical University, Guangzhou, China
| | - Wen-Fei HE
- Department of Cardiology, the Second People’s Hospital of Nanhai District, Guangdong Provincial People’s Hospital’s Nanhai Hospital, Foshan, China
| | - Ning TAN
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Ji-Yan CHEN
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Peng-Cheng HE
- Department of Cardiology, School of Medicine, South China University of Technology, Guangzhou, China
- Department of Cardiology, Guangdong Cardiovascular Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of Cardiology, Heyuan People’s Hospital, Heyuan, China
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21
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Bourdillon MT, Gaye B, Song RJ, Vasan RS, Xanthakis V. Notable paradoxical phenomena in associations between cardiovascular health score, subclinical and clinical cardiovascular disease in the community: The Framingham Heart Study. PLoS One 2022; 17:e0267267. [PMID: 35511823 PMCID: PMC9070900 DOI: 10.1371/journal.pone.0267267] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Accepted: 04/05/2022] [Indexed: 11/20/2022] Open
Abstract
Importance Cardiovascular Health (CVH) scores are inversely associated with prevalent subclinical (SubDz) and incident cardiovascular disease (CVD). However, the majority of people who develop CVD have intermediate or ideal CVH scores, while many with poor CVH profiles escape CVD development. Objective To describe the prevalence of paradoxical relations among CVH, SubDz, and CVD. Design Cohort study, Framingham Study data collected prospectively (1995–2016). Setting Population-based. Participants 7,627 participants (mean age 49 years, 53% women) attending Offspring examinations 6/7 and Third Generation examinations 1/2. Exposures CVH score (range 0–14) constructed from poor, intermediate, or ideal status for each metric (smoking, diet, physical activity, blood pressure, body mass index, fasting glucose, total cholesterol); and prevalent SubDz (≥1 of: increased carotid intimal media thickness, CIMT; left ventricular hypertrophy, LVH; microalbuminuria, MA; elevated ankle brachial index, ABI; coronary artery calcium score ≥100,CAC). Main outcome(s) and measure(s) Ideal CVH (scores 12–14), intermediate CVH (scores 8–11), and poor CVH (0–7). We described three distinct paradoxical phenomena, involving combinations of CVH, SubDz, and CVD, and generated CVD incidence rates and predicted CVD probabilities for all combinations. Results We observed 842 CVD events (median follow-up 13.7 years); 1,663 participants had SubDz. Most individuals with poor CVH (78%) or SubDz (57% for CIMT to 77% for LVH) did not develop CVD on follow-up. Among participants with incident CVD, the majority had intermediate or ideal CVH (68%) or absent SubDz (46% for CAC to 96% for ABI) at baseline. We observed similar paradoxical results in relations between CVH and prevalent SubDz. Poor CVH and prevalent SubDz were each associated with higher CVD incidence rates compared to intermediate or ideal CVH and absent SubDz, respectively. The predicted CVD probability was nearly three-times greater among participants with poor (22%) versus intermediate or ideal CVH (8%). Mean CVD predicted probabilities were nearly three (26% vs. 10% for MA) to six-times (29% vs. 5% for CAC) greater among participants with SubDz versus without SubDz. Findings were consistent within age and sex strata. Conclusions and relevance Although poor CVH and SubDz presence are associated with CVD incidence, paradoxical phenomena involving CVH, SubDz, and CVD are frequently prevalent in the community. Further studies to elucidate biological mechanisms underlying these phenomena are warranted.
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Affiliation(s)
| | - Bamba Gaye
- INSERM, U970, Paris Cardiovascular Research Center, University Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Rebecca J. Song
- Department of Epidemiology, Boston University School of Public Health, Boston, MA, United States of America
| | - Ramachandran S. Vasan
- Department of Epidemiology, Boston University School of Public Health, Boston, MA, United States of America
- Department of Medicine, Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, MA, United States of America
- Section of Cardiology, Boston University School of Medicine, Boston, MA, United States of America
- Center for Computing and Data Sciences, Boston University, Boston, MA, United States of America
- Boston University’s and National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, MA, United States of America
| | - Vanessa Xanthakis
- Department of Medicine, Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, MA, United States of America
- Boston University’s and National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, MA, United States of America
- Department of Biostatistics, Boston University School of Public Health, Boston, MA, United States of America
- * E-mail:
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22
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Eriksen PL, Thomsen KL, Sørensen M, Vilstrup H, Hvas AM. Impaired fibrinolysis without hypercoagulability characterises patients with non-alcoholic fatty liver disease. Thromb Res 2022; 213:9-15. [PMID: 35256195 DOI: 10.1016/j.thromres.2022.02.023] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2022] [Revised: 02/14/2022] [Accepted: 02/24/2022] [Indexed: 12/12/2022]
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23
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Khan S, Pati S, Singh S, Akhtar M, Khare P, Khan S, Shafi S, Najmi AK. Targeting hypercoagulation to alleviate Alzheimer's disease progression in metabolic syndrome. Int J Obes (Lond) 2022; 46:245-254. [PMID: 34686782 DOI: 10.1038/s41366-021-00977-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Revised: 09/17/2021] [Accepted: 09/27/2021] [Indexed: 11/09/2022]
Abstract
INTRODUCTION Metabolic Syndrome (MetS) constitutes an important risk factor for Alzheimer's disease (AD); however, the mechanism linking these two disorders has not been completely elucidated. Hence, hypercoagulation may account for the missing hallmark connecting MetS and AD. The present review proposes how hemostatic imbalance triggered in MetS advances in the context of AD. MetS causes interruption of insulin signaling and inflammation, inciting insulin resistance in the brain. Subsequently, neuroinflammation and brain endothelial dysfunction are prompted that further intensify the exorbitant infiltration of circulating lipids and platelet aggregation, thereby causing hypercoagulable state, impairing fibrinolysis and eventually inducing prothrombic state in the brain leading to neurodegeneration. OBJECTIVE This study aims to understand the role of hypercoagulation in triggering the progression of neurodegeneration in MetS. It also offers a few interventions to prevent the progression of AD in MetS targeting hypercoagulation. METHODS Literature studies based on MetS related neurodegeneration, the impact of coagulation on aggravating obesity and AD via the mechanisms of BBB disruption, neuroinflammation, and hypofibrinolysis. CONCLUSION The present paper proposes the hypothesis that hypercoagulation might amplify MetS associated insulin resistance, neuroinflammation, BBB disruption, and amyloid beta accumulation which eventually leads to AD.
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Affiliation(s)
- Sana Khan
- Department of Pharmacology, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India
| | - Soumya Pati
- Translational Neurobiology Laboratory. Host Pathogen Interactions & Disease Modeling Group, Dept. of Life Sciences, School of Natural Sciences, Shiv Nadar University, Greater Noida, Pin-201314, UP, India
| | - Shailja Singh
- Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi, 110067, India
| | - Mohd Akhtar
- Department of Pharmacology, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India
| | - Piush Khare
- Wave Pharma Regulatory Services Limited, New Delhi, India
| | - Saba Khan
- Department of Pharmacology, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India
| | - Sadat Shafi
- Department of Pharmacology, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India
| | - Abul Kalam Najmi
- Department of Pharmacology, School of Pharmaceutical Education & Research, Jamia Hamdard, New Delhi, 110062, India.
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24
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Zelko IN, Taylor BS, Das TP, Watson WH, Sithu ID, Wahlang B, Malovichko MV, Cave MC, Srivastava S. Effect of vinyl chloride exposure on cardiometabolic toxicity. ENVIRONMENTAL TOXICOLOGY 2022; 37:245-255. [PMID: 34717031 PMCID: PMC8724461 DOI: 10.1002/tox.23394] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 07/09/2021] [Accepted: 10/22/2021] [Indexed: 05/08/2023]
Abstract
Vinyl chloride (VC) is an organochlorine mainly used to manufacture its polymer polyvinyl chloride, which is extensively used in the manufacturing of consumer products. Recent studies suggest that chronic low dose VC exposure affects glucose homeostasis in high fat diet-fed mice. Our data suggest that even in the absence of high fat diet, exposure to VC (0.8 ppm, 6 h/day, 5 day/week, for 12 weeks) induces glucose intolerance (1.0 g/kg, i.p.) in male C57BL/6 mice. This was accompanied with the depletion of hepatic glutathione and a modest increase in lung interstitial macrophages. VC exposure did not affect the levels of circulating immune cells, endothelial progenitor cells, platelet-immune cell aggregates, and cytokines and chemokines. The acute challenge of VC-exposed mice with LPS did not affect lung immune cell composition or plasma IL-6. To examine the effect of VC exposure on vascular inflammation and atherosclerosis, LDL receptor-KO mice on C57BL/6 background maintained on western diet were exposed to VC for 12 weeks (0.8 ppm, 6 h/day, 5 day/week). Unlike the WT C57BL/6 mice, VC exposure did not affect glucose tolerance in the LDL receptor-KO mice. Plasma cytokines, lesion area in the aortic valve, and markers of lesional inflammation in VC-exposed LDL receptor-KO mice were comparable with the air-exposed controls. Collectively, despite impaired glucose tolerance and modest pulmonary inflammation, chronic low dose VC exposure does not affect surrogate markers of cardiovascular injury, LPS-induced acute inflammation in C57BL/6 mice, and chronic inflammation and atherosclerosis in the LDL receptor-KO mice.
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Affiliation(s)
- Igor N. Zelko
- Superfund Research Center, University of Louisville, KY 40202
- Envirome Institute, University of Louisville, KY 40202
- Department of Medicine, Division of Environmental Medicine, University of Louisville, KY 40202
| | - Breandon S. Taylor
- Superfund Research Center, University of Louisville, KY 40202
- Envirome Institute, University of Louisville, KY 40202
- Department of Medicine, Division of Environmental Medicine, University of Louisville, KY 40202
- Department of Pharmacology and Toxicology, University of Louisville, KY 40202
| | - Trinath P. Das
- Superfund Research Center, University of Louisville, KY 40202
- Envirome Institute, University of Louisville, KY 40202
- Department of Medicine, Division of Environmental Medicine, University of Louisville, KY 40202
| | - Walter H. Watson
- Department of Pharmacology and Toxicology, University of Louisville, KY 40202
- Hepatobiology and Toxicology Program, University of Louisville, KY 40202
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Louisville, KY 40202
| | - Israel D. Sithu
- Superfund Research Center, University of Louisville, KY 40202
- Envirome Institute, University of Louisville, KY 40202
- Department of Medicine, Division of Environmental Medicine, University of Louisville, KY 40202
- Department of Pharmacology and Toxicology, University of Louisville, KY 40202
| | - Banrida Wahlang
- Superfund Research Center, University of Louisville, KY 40202
- Department of Pharmacology and Toxicology, University of Louisville, KY 40202
- Hepatobiology and Toxicology Program, University of Louisville, KY 40202
| | - Marina V. Malovichko
- Superfund Research Center, University of Louisville, KY 40202
- Envirome Institute, University of Louisville, KY 40202
- Department of Medicine, Division of Environmental Medicine, University of Louisville, KY 40202
| | - Matthew C. Cave
- Superfund Research Center, University of Louisville, KY 40202
- Envirome Institute, University of Louisville, KY 40202
- Department of Pharmacology and Toxicology, University of Louisville, KY 40202
- Hepatobiology and Toxicology Program, University of Louisville, KY 40202
| | - Sanjay Srivastava
- Superfund Research Center, University of Louisville, KY 40202
- Envirome Institute, University of Louisville, KY 40202
- Department of Medicine, Division of Environmental Medicine, University of Louisville, KY 40202
- Department of Pharmacology and Toxicology, University of Louisville, KY 40202
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25
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Carneiro L, Pellerin L. Nutritional Impact on Metabolic Homeostasis and Brain Health. Front Neurosci 2022; 15:767405. [PMID: 35153657 PMCID: PMC8829049 DOI: 10.3389/fnins.2021.767405] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Accepted: 12/13/2021] [Indexed: 12/18/2022] Open
Abstract
Aging in modern societies is often associated with various diseases including metabolic and neurodegenerative disorders. In recent years, researchers have shown that both dysfunctions are related to each other. Although the relationship is not fully understood, recent evidence indicate that metabolic control plays a determinant role in neural defects onset. Indeed, energy balance dysregulation affects neuroenergetics by altering energy supply and thus neuronal activity. Consistently, different diets to help control body weight, blood glucose or insulin sensitivity are also effective in improving neurodegenerative disorders, dampening symptoms, or decreasing the risk of disease onset. Moreover, adapted nutritional recommendations improve learning, memory, and mood in healthy subjects as well. Interestingly, adjusted carbohydrate content of meals is the most efficient for both brain function and metabolic regulation improvement. Notably, documented neurological disorders impacted by specific diets suggest that the processes involved are inflammation, mitochondrial function and redox balance as well as ATP production. Interestingly, processes involving inflammation, mitochondrial function and redox balance as well as ATP production are also described in brain regulation of energy homeostasis. Therefore, it is likely that changes in brain function induced by diets can affect brain control of energy homeostasis and other brain functions such as memory, anxiety, social behavior, or motor skills. Moreover, a defect in energy supply could participate to the development of neurodegenerative disorders. Among the possible processes involved, the role of ketone bodies metabolism, neurogenesis and synaptic plasticity, oxidative stress and inflammation or epigenetic regulations as well as gut-brain axis and SCFA have been proposed in the literature. Therefore, the goal of this review is to provide hints about how nutritional studies could help to better understand the tight relationship between metabolic balance, brain activity and aging. Altogether, diets that help maintaining a metabolic balance could be key to both maintain energy homeostasis and prevent neurological disorders, thus contributing to promote healthy aging.
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Affiliation(s)
- Lionel Carneiro
- Department of Biological Chemistry and Pharmacology, Ohio State University, Columbus, OH, United States
| | - Luc Pellerin
- Inserm U1082, Université de Poitiers and CHU de Poitiers, Poitiers, France
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26
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Razali NA, Mohd Daud TI, Woon LSC, Mohamed Saini S, Muhammad NA, Sharip S. Case report: Bipolar disorder in 48,XXYY syndrome. Front Psychiatry 2022; 13:1080698. [PMID: 36713919 PMCID: PMC9874087 DOI: 10.3389/fpsyt.2022.1080698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2022] [Accepted: 12/14/2022] [Indexed: 01/13/2023] Open
Abstract
48,XXYY syndrome is a rare condition. The presentations of impulsive and aggressive behavior have been reported in several case reports among patients with 48,XXYY syndrome. The management of the psychological impact and neuropsychiatric sequela of this condition is a significant issue faced by families, carers, and healthcare professionals. We report a patient, 21-year-old Malay male, with underlying 48,XXYY syndrome with attention deficit hyperactivity disorder (ADHD) and intellectual disability, diagnosed later in adulthood with a bipolar mood disorder and benefited after being started on lithium. We describe the key clinical features and diagnostic workouts that allowed the arrival of the correct psychiatric diagnosis. Challenges in psychopharmacotherapy, including the risks of metabolic syndrome and deep vein thrombosis associated with 48,XXYY syndrome, are also considered. We suggest that for patients with 48,XXYY syndrome, routine psychological screening for mood symptoms such as mania and depression should be done by healthcare professionals with early involvement of psychiatrist in the multidisciplinary team due to the challenges in the management of these patients.
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Affiliation(s)
- Nur Atikah Razali
- Department of Psychiatry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
| | - Tuti Iryani Mohd Daud
- Department of Psychiatry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
| | - Luke Sy-Cherng Woon
- Department of Psychiatry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
| | - Suriati Mohamed Saini
- Department of Psychiatry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
| | - Noor Azimah Muhammad
- Department of Family Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
| | - Shalisah Sharip
- Department of Psychiatry, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia
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27
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Yazdi F, Baghaei MH, Baniasad A, Naghibzadeh‐Tahami A, Najafipour H, Gozashti MH. Investigating the relationship between serum uric acid to high-density lipoprotein ratio and metabolic syndrome. ENDOCRINOLOGY DIABETES & METABOLISM 2021; 5:e00311. [PMID: 34705333 PMCID: PMC8754234 DOI: 10.1002/edm2.311] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/24/2021] [Revised: 10/02/2021] [Accepted: 10/09/2021] [Indexed: 11/07/2022]
Abstract
Aims This study aimed to determine a parameter to more easily diagnose metabolic syndrome and predict its probability of occurrence in high‐risk individuals. Methods In this cross‐sectional study, data related to the study population in the Kerman Coronary Artery Disease Risk Factor Study (KERCADRS) were examined. Subjects were divided into two groups with and without metabolic syndrome, and the relevant factors such as the ratios of uric acid to high‐density lipoprotein (HDL) (UHR) in these two groups were compared, and the best cut‐off point was determined. Results Data related to 817 people including 96 people with metabolic syndrome and 721 people without metabolic syndrome were analysed. The mean UHR was significantly higher in patients with metabolic syndrome (14.76 ± 6.33%) compared with those without metabolic syndrome (10.0 ± 3.10%) (p < .001). People with high UHR are 2.9 times more at risk of metabolic syndrome and the best cut‐off point was 9.50% with 86% sensitivity and 55% specificity. Conclusions According to our study, UHR is also helpful in diagnosing metabolic syndrome and can also be used to screen people at risk for metabolic syndrome.
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Affiliation(s)
- Farzaneh Yazdi
- Neuroscience Research CenterInstitute of NeuropharmacologyKerman University of Medical SciencesKermanIran
| | - Mohammad Hassan Baghaei
- Gastroenterology and Hepathology Research CenterInstitute of Basic and Clinical Physiology SciencesKerman University of Medical SciencesKermanIran
| | - Amir Baniasad
- Endocrinology and Metabolism Research CenterInstitute of Basic and Clinical Physiology ScienceKerman University of Medical SciencesKermanIran
| | - Ahmad Naghibzadeh‐Tahami
- Physiology Research CenterInstitute of Basic and Clinical Physiology SciencesKerman University of Medical SciencesKermanIran
| | - Hamid Najafipour
- Cardiovascular Research CenterInstitute of Basic and Clinical Physiology SciencesKerman University of Medical SciencesKermanIran
| | - Mohammad Hossein Gozashti
- Endocrinology and Metabolism Research CenterInstitute of Basic and Clinical Physiology SciencesKerman University of Medical SciencesKermanIran
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28
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Pekkala T, Hall A, Mangialasche F, Kemppainen N, Mecocci P, Ngandu T, Rinne JO, Soininen H, Tuomilehto J, Kivipelto M, Solomon A. Association of Peripheral Insulin Resistance and Other Markers of Type 2 Diabetes Mellitus with Brain Amyloid Deposition in Healthy Individuals at Risk of Dementia. J Alzheimers Dis 2021; 76:1243-1248. [PMID: 32623394 PMCID: PMC7504982 DOI: 10.3233/jad-200145] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
We explored the association of type 2 diabetes related blood markers with brain amyloid accumulation on PiB-PET scans in 41 participants from the FINGER PET sub-study. We built logistic regression models for brain amyloid status with12 plasma markers of glucose and lipid metabolism, controlled for diabetes and APOEɛ4 carrier status. Lower levels of insulin, insulin resistance index (HOMA-IR), C-peptide, and plasminogen activator (PAI-1) were associated with amyloid positive status, although the results were not significant after adjusting for multiple testing. None of the models found evidence for associations between amyloid status and fasting glucose or HbA1c.
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Affiliation(s)
- Timo Pekkala
- Institute of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, Finland
| | - Anette Hall
- Institute of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, Finland
| | - Francesca Mangialasche
- Division of Clinical Geriatrics, Center for Alzheimer Research, NVS, Karolinska Institutet, Stockholm, Sweden.,Aging Research Center, NVS, Karolinska Institutet and Stockholm University, Stockholm, Sweden
| | - Nina Kemppainen
- Turku PET Centre, University of Turku, Turku, Finland.,Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland
| | - Patrizia Mecocci
- Department of Medicine, Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy
| | - Tiia Ngandu
- Division of Clinical Geriatrics, Center for Alzheimer Research, NVS, Karolinska Institutet, Stockholm, Sweden.,Public Health Promotion Unit, Finnish Institute for Health and Welfare, Helsinki, Finland
| | - Juha O Rinne
- Turku PET Centre, University of Turku, Turku, Finland.,Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland
| | - Hilkka Soininen
- Institute of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, Finland.,Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland
| | - Jaakko Tuomilehto
- Public Health Promotion Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.,Department of Public Health, University of Helsinki, Helsinki, Finland.,National School of Public Health, Madrid, Spain
| | - Miia Kivipelto
- Institute of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, Finland.,Division of Clinical Geriatrics, Center for Alzheimer Research, NVS, Karolinska Institutet, Stockholm, Sweden.,Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.,Ageing Epidemiology Research Unit, School of Public Health, Imperial College London, London, United Kingdom
| | - Alina Solomon
- Institute of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, Finland.,Division of Clinical Geriatrics, Center for Alzheimer Research, NVS, Karolinska Institutet, Stockholm, Sweden
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29
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Morrow GB, Whyte CS, Mutch NJ. A Serpin With a Finger in Many PAIs: PAI-1's Central Function in Thromboinflammation and Cardiovascular Disease. Front Cardiovasc Med 2021; 8:653655. [PMID: 33937363 PMCID: PMC8085275 DOI: 10.3389/fcvm.2021.653655] [Citation(s) in RCA: 58] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 02/23/2021] [Indexed: 12/27/2022] Open
Abstract
Plasminogen activator inhibitor 1 (PAI-1) is a member of the serine protease inhibitor (serpin) superfamily. PAI-1 is the principal inhibitor of the plasminogen activators, tissue plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA). Turbulence in the levels of PAI-1 tilts the balance of the hemostatic system resulting in bleeding or thrombotic complications. Not surprisingly, there is strong evidence that documents the role of PAI-1 in cardiovascular disease. The more recent uncovering of the coalition between the hemostatic and inflammatory pathways has exposed a distinct role for PAI-1. The storm of proinflammatory cytokines liberated during inflammation, including IL-6 and TNF-α, directly influence PAI-1 synthesis and increase circulating levels of this serpin. Consequently, elevated levels of PAI-1 are commonplace during infection and are frequently associated with a hypofibrinolytic state and thrombotic complications. Elevated PAI-1 levels are also a feature of metabolic syndrome, which is defined by a cluster of abnormalities including obesity, type 2 diabetes, hypertension, and elevated triglyceride. Metabolic syndrome is in itself defined as a proinflammatory state associated with elevated levels of cytokines. In addition, insulin has a direct impact on PAI-1 synthesis bridging these pathways. This review describes the key physiological functions of PAI-1 and how these become perturbed during disease processes. We focus on the direct relationship between PAI-1 and inflammation and the repercussion in terms of an ensuing hypofibrinolytic state and thromboembolic complications. Collectively, these observations strengthen the utility of PAI-1 as a viable drug target for the treatment of various diseases.
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Affiliation(s)
- Gael B Morrow
- Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom.,Radcliffe Department of Medicine, University of Oxford, Oxford, United Kingdom
| | - Claire S Whyte
- Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom
| | - Nicola J Mutch
- Aberdeen Cardiovascular and Diabetes Centre, Institute of Medical Sciences, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom
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Regassa LD, Tola A, Ayele Y. Prevalence of Cardiovascular Disease and Associated Factors Among Type 2 Diabetes Patients in Selected Hospitals of Harari Region, Eastern Ethiopia. Front Public Health 2021; 8:532719. [PMID: 33614562 PMCID: PMC7892600 DOI: 10.3389/fpubh.2020.532719] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 12/21/2020] [Indexed: 12/28/2022] Open
Abstract
Background: Cardiovascular disease (CVD) is the most prevalent complication and the leading cause of death among patients with diabetes mellitus (DM). Type 2 diabetes mellitus (T2DM) patients have a 2- to 4-fold increased risk of CVD. There is a scarcity of data about the magnitude of CVD among patients with diabetes in Ethiopia. This study aimed to assess the prevalence and associated factors of CVD among T2DM patients at selected hospitals of Harari regional state of Ethiopia. Methods: This hospital-based retrospective data review was conducted among T2DM patients on follow-up in the diabetes clinics of selected hospitals of Harari regional state. The records of T2DM patients who have been diagnosed between January 1, 2013, and December 31, 2017, were reviewed from March to April 2018. Data were collected by using structured checklists from all necessary documents of T2DM patients. Statistical analysis was done using STATA 14.1. Bivariate and multivariate logistic regressions were used to identify factors associated with CVD. Result: The records of 454 T2DM patients were extracted from three government hospitals in Harari regional state. Their age was ranging from 15 to 86 years with a mean age (±SD) of 45.39 (14.76). The overall prevalence of CVD among T2DM patients was 42.51%, composed of hypertensive heart diseases (38.99%), heart failure (6.83%), and stroke (2.20%). The final multivariate logistic regression model revealed that age older than 60 years [adjusted odds ratio (AOR) = 3.22; 95% CI: 1.71-6.09], being physically inactive (AOR = 1.45; 95 CI: 1.06-2.38), drinking alcohol (AOR = 2.39; 95% CI: 1.17-6.06), hypertension (AOR = 2.41; 95% CI: 1.52-3.83), body mass index >24.9 kg/m2 (AOR = 1.81; 95% CI: 1.07-3.07), and experiencing microvascular diabetic complications (AOR = 3.62; 95% CI: 2.01-6.53) were significantly associated with the odds of having CVD. Conclusion: The prevalence of CVD was high and associated with advanced age, physical inactivity, drinking alcohol, higher body mass index, hypertension, and having microvascular complications. Health care workers should educate T2DM patients about healthy lifestyles like physical activity, weight reduction, blood pressure control, and alcohol secession, which can reduce the risk of CVD.
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Affiliation(s)
- Lemma Demissie Regassa
- Department of Epidemiology and Biostatistics, School of Public Health, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Assefa Tola
- Department of Epidemiology and Biostatistics, School of Public Health, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Yohanes Ayele
- Department of Clinical Pharmacy, School of Pharmacy, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
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Corlin L, Short MI, Vasan RS, Xanthakis V. Association of the Duration of Ideal Cardiovascular Health Through Adulthood With Cardiometabolic Outcomes and Mortality in the Framingham Offspring Study. JAMA Cardiol 2021; 5:549-556. [PMID: 32159731 DOI: 10.1001/jamacardio.2020.0109] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Importance The American Heart Association ideal cardiovascular health (CVH) score is associated with the risk of cardiovascular disease (CVD) and mortality. However, it is unclear whether the number of years spent in ideal CVH is associated with morbidity or with mortality. Objective To evaluate whether living longer with a higher CVH score in midlife is associated with lower risk of hypertension, diabetes, chronic kidney disease, CVD and its subtypes (coronary heart disease, stroke, congestive heart failure, and peripheral artery disease), or all-cause mortality in later life. Design, Setting, and Participants This prospective cohort study used data from 1445 participants from 1991 to 2015 who participated in the community-based Framingham Heart Study Offspring investigation conducted in Massachusetts. The CVH scores of participants were assessed at examination cycles 5, 6, and 7 (1991-1995; 1995-1998; and 1998-2001, respectively). Individuals were excluded from analyses of the association between duration of CVH score and outcomes if they had the outcome of interest at the seventh examination. The median follow-up was approximately 16 years. Data were analyzed from April 2018 to October 2019. The CVH score categories were poor for scores 0 to 7, intermediate for scores 8 to 11, and ideal for scores 12 to 14. A composite score was derived based on smoking status, diet, physical activity, resting blood pressure levels, body mass index, fasting blood glucose levels, and total serum cholesterol levels. Main Outcomes and Measures Number of events and number at risk for each main outcome, including incident hypertension, diabetes, chronic kidney disease, CVD, and all-cause mortality, after the seventh examination. Results Of 1445 eligible participants, the mean (SD) age was 60 (9) years, and 751 (52%) were women. Number of events/number at risk for each main outcome after the seventh examination were 348/795 for incident hypertension, 104/1304 for diabetes, 198/918 for chronic kidney disease, 210/1285 for CVD, and 300/1445 for all-cause mortality. At the seventh examination, participants mostly had poor (568 [39%]) or intermediate (782 [54%]) CVH scores. For each antecedent (before examination cycle 7) 5-year duration that participants had intermediate or ideal CVH, they were less likely to develop adverse outcomes (hazards ratios of 0.67 [95% CI, 0.56-0.80] for incident hypertension, 0.73 [95% CI, 0.57-0.93] for diabetes, 0.75 [95% CI, 0.63-0.89] for chronic kidney disease, 0.73 [95% CI, 0.63-0.85] for CVD, and 0.86 [95% CI, 0.76-0.97] for all-cause mortality) relative to living the same amount of time in poor CVH (referent group). No effect modification was observed by age or by sex. Conclusions and Relevance These results suggest that more time spent in better CVH in midlife may have salutary cardiometabolic benefits and may be associated with lower mortality later in life.
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Affiliation(s)
- Laura Corlin
- Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.,Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts
| | - Meghan I Short
- Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.,Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, University of Texas Health Science Center at San Antonio, San Antonio
| | - Ramachandran S Vasan
- Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.,Department of Epidemiology, Boston University School of Public Health, Boston, Massachusetts.,Framingham Heart Study, Framingham, Massachusetts
| | - Vanessa Xanthakis
- Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.,Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.,Framingham Heart Study, Framingham, Massachusetts
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Abstract
Plasminogen activator inhibitor 1 (PAI-1) is a functional biomarker of the metabolic syndrome. Previous studies have demonstrated that PAI-1 is a mechanistic contributor to several elements of the syndrome, including obesity, hypertension and insulin resistance. Here we show that PAI-1 is also a critical regulator of hepatic lipid metabolism. RNA sequencing revealed that PAI-1 directly regulates the transcriptional expression of numerous genes involved in mammalian lipid homeostasis, including PCSK9 and FGF21. Pharmacologic or genetic reductions in plasma PAI-1 activity ameliorates hyperlipidemia in vivo. These experimental findings are complemented with the observation that genetic deficiency of PAI-1 is associated with reduced plasma PCSK9 levels in humans. Taken together, our findings identify PAI-1 as a novel contributor to mammalian lipid metabolism and provides a fundamental mechanistic insight into the pathogenesis of one of the most pervasive medical problems worldwide.
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Ferns GA, Shahini Shams Abadi M, Arjmand MH. The potential association between metabolic syndrome and risk of post-surgical adhesion. Arch Physiol Biochem 2020; 129:649-654. [PMID: 33290664 DOI: 10.1080/13813455.2020.1856882] [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] [Indexed: 12/08/2022]
Abstract
Metabolic syndrome (MetS) is defined by the clustering of several associated with a group of disorders that include: obesity, dyslipidemia, hypertension, and insulin resistance. The incidence of MetS is increasing globally around the world. Indeed the rates of different types of surgery in older or younger patients with Mets are increasing and they are exposed to a wide range of operations including abdominal, pelvic, urologic, or any invasive procedures. Post-surgical adhesion is a common problem and is a challenge for the surgeon. Despite many studies on its pathogenesis, there remain many un-answered questions about it, for example why certain tissues and patients are more at higher risk of post-surgical adhesions. Many studies have suggested that MetS is associated with up-regulating molecular mechanisms leading to chronic inflammation and hypercoagulability. In this review, we discuss some of the molecular mechanisms by MetS may enhance post-surgical adhesion, and particularly regarding those involved in coagulation and inflammation.
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Affiliation(s)
- Gordon A Ferns
- Brighton & Sussex Medical School, Division of Medical Education, Brighton, UK
| | - Milad Shahini Shams Abadi
- Department of Microbiology and Immunology, Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
- Cancer Research Center, Shahrekord university of Medical Sciences, Shahrekord, Iran
| | - Mohammad-Hassan Arjmand
- Cancer Research Center, Shahrekord university of Medical Sciences, Shahrekord, Iran
- Medical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
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Idrovo JP, Shults JA, Curtis BJ, Chen MM, Kovacs EJ. Alcohol Intoxication and the Postburn Gastrointestinal Hormonal Response. J Burn Care Res 2020; 40:785-791. [PMID: 31102437 DOI: 10.1093/jbcr/irz083] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Gastrointestinal hormones are essential in postburn metabolism. Since near 50% of burn victims test positive for blood alcohol levels at hospital admission and have inferior outcomes compared to nonintoxicated burn patients; we hypothesized that the gastrointestinal hormone secretion is compromised in intoxicated burn victims. To test our theory, we quantified gastrointestinal hormones serum levels in a combine ethanol intoxication and burn injury mouse model. Thus, mice received a daily dose of ethanol for 3 days, rested 4 days, and were given ethanol 3 additional days. Mice underwent 15% TBSA scald burn 30 minutes after their last ethanol dose. Serum samples were collected 24 hours after burn injury. Nonintoxicated burned mice exhibited an increase in glucose, insulin, ghrelin, plasminogen activator inhibitor-1, leptin, and resistin by 1.4-, 3-, 13.5-, 6.2-, 9.4-, and 2.4-fold, respectively, compared to sham vehicle mice (P < .05). Burn injury also reduced serum gastric inhibitory polypeptide (GIP) by 32% compared to sham-injured, vehicle-treated mice. Leptin, resistin, glucagon-like peptide-1, as well as insulin, were not different from sham groups when intoxication preceded burn injury. Nevertheless, in burned mice treated with ethanol, gastric inhibitory polypeptide and glucagon serum levels exhibited a significant fold increase of 3.5 and 4.7, respectively. With these results, we conclude that 24 hours after burn injury, mice developed significant changes in gastrointestinal hormones, along with hyperglycemia. Moreover, the combined insult of burn and ethanol intoxication led to additional hormonal changes that may be attributed to a potential pancreatic dysfunction. Further multiday studies are required to investigate the etiology, behavior, and clinical significance of these hormonal changes.
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Affiliation(s)
- Juan-Pablo Idrovo
- Division of GI, Trauma and Endocrine Surgery, Department of Surgery, Burn Research and Alcohol Research Programs, University of Colorado, Denver, Aurora, Colorado
| | - Jill A Shults
- Department of Surgery, Alcohol Research Program, Loyola University Chicago, Maywood, Illinois
| | - Brenda J Curtis
- Division of GI, Trauma and Endocrine Surgery, Department of Surgery, Burn Research and Alcohol Research Programs, University of Colorado, Denver, Aurora, Colorado
| | - Michael M Chen
- Department of Surgery, Loyola University Chicago, Maywood, Illinois
| | - Elizabeth J Kovacs
- Division of GI, Trauma and Endocrine Surgery, Department of Surgery, Burn Research and Alcohol Research Programs, University of Colorado, Denver, Aurora, Colorado
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Mens Sana in Corpore Sano: Does the Glycemic Index Have a Role to Play? Nutrients 2020; 12:nu12102989. [PMID: 33003562 PMCID: PMC7599769 DOI: 10.3390/nu12102989] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2020] [Revised: 09/25/2020] [Accepted: 09/27/2020] [Indexed: 12/20/2022] Open
Abstract
Although diet interventions are mostly related to metabolic disorders, nowadays they are used in a wide variety of pathologies. From diabetes and obesity to cardiovascular diseases, to cancer or neurological disorders and stroke, nutritional recommendations are applied to almost all diseases. Among such disorders, metabolic disturbances and brain function and/or diseases have recently been shown to be linked. Indeed, numerous neurological functions are often associated with perturbations of whole-body energy homeostasis. In this regard, specific diets are used in various neurological conditions, such as epilepsy, stroke, or seizure recovery. In addition, Alzheimer’s disease and Autism Spectrum Disorders are also considered to be putatively improved by diet interventions. Glycemic index diets are a novel developed indicator expected to anticipate the changes in blood glucose induced by specific foods and how they can affect various physiological functions. Several results have provided indications of the efficiency of low-glycemic index diets in weight management and insulin sensitivity, but also cognitive function, epilepsy treatment, stroke, and neurodegenerative diseases. Overall, studies involving the glycemic index can provide new insights into the relationship between energy homeostasis regulation and brain function or related disorders. Therefore, in this review, we will summarize the main evidence on glycemic index involvement in brain mechanisms of energy homeostasis regulation.
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Lechner K, McKenzie AL, Kränkel N, Von Schacky C, Worm N, Nixdorff U, Lechner B, Scherr J, Weingärtner O, Krauss RM. High-Risk Atherosclerosis and Metabolic Phenotype: The Roles of Ectopic Adiposity, Atherogenic Dyslipidemia, and Inflammation. Metab Syndr Relat Disord 2020; 18:176-185. [PMID: 32119801 PMCID: PMC7196362 DOI: 10.1089/met.2019.0115] [Citation(s) in RCA: 65] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Current algorithms for assessing risk of atherosclerotic cardiovascular disease (ASCVD) and, in particular, the reliance on low-density lipoprotein (LDL) cholesterol in conditions where this measurement is discordant with apoB and LDL-particle concentrations fail to identify a sizeable part of the population at high risk for adverse cardiovascular events. This results in missed opportunities for ASCVD prevention, most notably in those with metabolic syndrome, prediabetes, and diabetes. There is substantial evidence that accumulation of ectopic fat and associated metabolic traits are markers for and pathogenic components of high-risk atherosclerosis. Conceptually, the subset of advanced lesions in high-risk atherosclerosis that triggers vascular complications is closely related to a set of coordinated high-risk traits clustering around a distinct metabolic phenotype. A key feature of this phenotype is accumulation of ectopic fat, which, coupled with age-related muscle loss, creates a milieu conducive for the development of ASCVD: atherogenic dyslipidemia, nonresolving inflammation, endothelial dysfunction, hyperinsulinemia, and impaired fibrinolysis. Sustained vascular inflammation, a hallmark of high-risk atherosclerosis, impairs plaque stabilization in this phenotype. This review describes how metabolic and inflammatory processes that are promoted in large measure by ectopic adiposity, as opposed to subcutaneous adipose tissue, relate to the pathogenesis of high-risk atherosclerosis. Clinical biomarkers indicative of these processes provide incremental information to standard risk factor algorithms and advanced lipid testing identifies atherogenic lipoprotein patterns that are below the discrimination level of standard lipid testing. This has the potential to enable improved identification of high-risk patients who are candidates for therapeutic interventions aimed at prevention of ASCVD.
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Affiliation(s)
- Katharina Lechner
- Department of Prevention, Rehabilitation and Sports Medicine, School of Medicine, Technical University of Munich, Munich, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany
| | | | - Nicolle Kränkel
- Klinik Für Kardiologie, Campus Benjamin Steglitz, Charité—Universitätsmedizin Berlin, Berlin, Germany
- DZHK (German Center for Cardiovascular Research), Partner Site Berlin, Berlin, Germany
| | - Clemens Von Schacky
- Preventive Cardiology, Ludwig-Maximilians University, Munich, Germany
- Omegametrix, Martinsried, Germany
| | - Nicolai Worm
- German University for Prevention and Health Care Management, Saarbrücken, Germany
| | | | - Benjamin Lechner
- Department of Internal Medicine IV, Ludwig-Maximilians University, Munich, Germany
| | - Johannes Scherr
- Department of Prevention, Rehabilitation and Sports Medicine, School of Medicine, Technical University of Munich, Munich, Germany
- University Center for Prevention and Sports Medicine, Balgrist University Hospital, University of Zurich, Zurich, Switzerland
| | | | - Ronald M. Krauss
- University of California, San Francisco, San Francisco, California, USA
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Cerbone M, Clement E, McClatchey M, Dobbin J, Gilbert C, Keane M, Boukhibar L, Williams H, Gagunashvili A, Dattani MT, Hurst J, Shah P. Sotos Syndrome Presenting with Neonatal Hyperinsulinaemic Hypoglycaemia, Extensive Thrombosis, and Multisystem Involvement. Horm Res Paediatr 2020; 92:64-70. [PMID: 30879005 DOI: 10.1159/000496545] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Accepted: 12/27/2018] [Indexed: 11/19/2022] Open
Abstract
Initially described as an uncommon presenting feature of Sotos syndrome (SoS), over the last decades, congenital hyperinsulinaemic hypoglycaemia (CHI) has been increasingly reported in association with this condition. The mechanism responsible for CHI in SoS is unclear. We report the case of a neonate presenting with CHI and extensive venous and arterial thrombosis associated with kidney, heart, liver, skeleton, and brain abnormalities and finally diagnosed with SoS on whole genome sequencing. Our case describes an extended phenotype associated with SoS presenting with CHI (including thrombosis and liver dysfunction) and reinforces the association of transient CHI with SoS. The case also shows that an early neonatal diagnosis of rare genetic conditions is challenging, especially in acutely unwell patients, and that in complex cases with incomplete, atypical, or overlapping phenotypes, broad genomic testing by whole exome or whole genome sequencing may be a useful diagnostic strategy.
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Affiliation(s)
- Manuela Cerbone
- Department of Endocrinology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom, .,Section of Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Program, UCL Great Ormond Street Institute of Child Health London, London, United Kingdom,
| | - Emma Clement
- Department of Clinical Genetics, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
| | - Martin McClatchey
- Department of Paediatrics, Barking Havering & Redbridge Trust, London, United Kingdom
| | - Joanna Dobbin
- Department of Paediatrics, Barking Havering & Redbridge Trust, London, United Kingdom
| | - Clare Gilbert
- Department of Endocrinology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
| | - Morgan Keane
- Department of Paediatrics, Barking Havering & Redbridge Trust, London, United Kingdom
| | - Lamia Boukhibar
- GOSgene, Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health London, London, United Kingdom
| | - Hywel Williams
- GOSgene, Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health London, London, United Kingdom
| | - Andrey Gagunashvili
- GOSgene, Genetics and Genomic Medicine, UCL Great Ormond Street Institute of Child Health London, London, United Kingdom
| | - Mehul T Dattani
- Department of Endocrinology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom.,Section of Genetics and Epigenetics in Health and Disease, Genetics and Genomic Medicine Program, UCL Great Ormond Street Institute of Child Health London, London, United Kingdom
| | - Jane Hurst
- Department of Clinical Genetics, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
| | - Pratik Shah
- Department of Endocrinology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom
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Neves JS, Correa S, Baeta Baptista R, Bigotte Vieira M, Waikar SS, Mc Causland FR. Association of Prediabetes With CKD Progression and Adverse Cardiovascular Outcomes: An Analysis of the CRIC Study. J Clin Endocrinol Metab 2020; 105:dgaa017. [PMID: 31943096 PMCID: PMC7069215 DOI: 10.1210/clinem/dgaa017] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2019] [Accepted: 01/14/2020] [Indexed: 12/19/2022]
Abstract
PURPOSE Despite our understanding of diabetes as an established risk factor for progressive kidney disease and cardiac complications, the prognostic significance of prediabetes in patients with chronic kidney disease (CKD) remains largely unknown. METHODS Participants of the Chronic Renal Insufficiency Cohort (CRIC) were categorized as having normoglycemia, prediabetes, or diabetes according to fasting plasma glucose, glycated hemoglobin A1c (HbA1c), and treatment with antidiabetic drugs at baseline. Unadjusted and adjusted proportional hazards models were fit to estimate the association of prediabetes and diabetes (versus normoglycemia) with: (1) composite renal outcome (end-stage renal disease, 50% decline in estimated glomerular filtration rate to ≤ 15 mL/min/1.73 m2, or doubling of urine protein-to-creatinine ratio to ≥ 0.22 g/g creatinine); (2) composite cardiovascular (CV) outcome (congestive heart failure, myocardial infarction or stroke); and (3) all-cause mortality. RESULTS Of the 3701 individuals analyzed, 945 were normoglycemic, 847 had prediabetes and 1909 had diabetes. The median follow-up was 7.5 years. Prediabetes was not associated with the composite renal outcome (adjusted hazard ratio [aHR] 1.13; 95% confidence interval [CI], 0.96-1.32; P = 0.14), but was associated with proteinuria progression (aHR 1.23; 95% CI, 1.03-1.47; P = 0.02). Prediabetes was associated with a higher risk of the composite CV outcome (aHR 1.38; 95% CI, 1.05-1.82; P = 0.02) and a trend towards all-cause mortality (aHR 1.28; 95% CI, 0.99-1.66; P = 0.07). Participants with diabetes had an increased risk of the composite renal outcome, the composite CV outcome, and all-cause mortality. CONCLUSIONS In individuals with CKD, prediabetes was not associated with composite renal outcome, but was associated with an increased risk of proteinuria progression and adverse CV outcomes.
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Affiliation(s)
- João Sérgio Neves
- Department of Endocrinology, Diabetes and Metabolism, Centro Hospitalar Universitário de São João, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
- Departamento de Cirurgia e Fisiologia, Unidade de Investigação Cardiovascular, Faculdade de Medicina, Universidade do Porto, Porto, Portugal
| | - Simon Correa
- Renal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA
| | - Rute Baeta Baptista
- Pediatrics Department, Hospital de Dona Estefânia, Centro Hospitalar Universitário de Lisboa Central, Portugal
- Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Miguel Bigotte Vieira
- Nephrology Department, Hospital Curry Cabral, Centro Hospitalar Universitário de Lisboa Central, Lisboa, Portugal
| | - Sushrut S Waikar
- Renal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA
- Harvard Medical School, Boston, MA
| | - Finnian R Mc Causland
- Renal Division, Department of Medicine, Brigham and Women’s Hospital, Boston, MA
- Harvard Medical School, Boston, MA
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Yusuff OT, Kolawole BA, Ikem RT, Soyoye DO, Amjo OO. Cardiovascular Risk Indices and Their Impact on Outcome in Patients with Hyperglycaemic Emergencies in a Nigerian Hospital. J Natl Med Assoc 2020; 112:28-35. [PMID: 31973880 DOI: 10.1016/j.jnma.2019.12.004] [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: 09/18/2019] [Revised: 12/14/2019] [Accepted: 12/24/2019] [Indexed: 10/25/2022]
Abstract
BACKGROUND High sensitivity C-reactive protein (hsCRP) and Plasminogen Activator Inhibitor-1 (PAI-1) are recognised independent novel risk factors for cardiovascular disease. Few studies have assessed cardiovascular risk factors in patients with hyperglycaemic emergencies (HE), despite it being a major cause of death in diabetics. OBJECTIVE The objective of this study was to determine cardiovascular risk indices in patients with hyperglycaemic emergencies and related these with outcome. METHODS This cross sectional study involved 45 patients that presented with HE and 45 age and sex matched diabetics without HE who served as controls. Historical features, physical findings and laboratory parameters including hsCRP and PAI-1 were compared between subjects and controls. RESULTS The mean values of serum hsCRP and PAI-1 were significantly higher in patients with HE compared to diabetic control. (49.52 ± 13.6 vs. 2.4 ± 1.35, 51.2 ± 28.7 vs. 33.2 ± 10.7 respectively). Traditional cardiovascular risk factors such as HbA1c, Atherogenic Index and microalbuminuria were also significantly higher in them. Mortality was associated with increasing age, higher values of waist circumference, pulse rate, respiratory rate, hsCRP, Atherogenic index and lower blood pressure and HDL values. CONCLUSION Cardiovascular risk indices are higher in patients with HE.
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Affiliation(s)
- Olaoluwatomi T Yusuff
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile Ife, Nigeria.
| | - Babatope A Kolawole
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile Ife, Nigeria
| | - Rosemary T Ikem
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile Ife, Nigeria
| | - David O Soyoye
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile Ife, Nigeria
| | - Oluwadamilola O Amjo
- Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile Ife, Nigeria
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Laboratory Parameters of Hemostasis, Adhesion Molecules, and Inflammation in Type 2 Diabetes Mellitus: Correlation with Glycemic Control. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2020; 17:ijerph17010300. [PMID: 31906326 PMCID: PMC6982208 DOI: 10.3390/ijerph17010300] [Citation(s) in RCA: 28] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Revised: 12/28/2019] [Accepted: 12/30/2019] [Indexed: 12/25/2022]
Abstract
Background: Type 2 diabetes mellitus (T2DM) is characterized by a prothrombotic state, predisposing to vascular complications. Some related markers, linking thrombophilia to hemostasis and inflammation, however, have been poorly explored in relation to patients’ glycemia. We therefore investigated the association of laboratory hemostatic parameters, circulating adhesion molecules (ADMs), white blood cell (WBC) count, and neutrophil/lymphocyte ratio (NLR) with T2DM and glycemic control. Research design: In this study, 82 subjects, grouped into T2DM patients (n = 41) and healthy individuals (n = 41) were enrolled. To evaluate glycemic control, the T2DM cohort was expanded to 133 patients and sub-classified according to glycated hemoglobin (HbA1c) <7% and ≥ 7% (n = 58 and n = 75, respectively). We assessed glycemia, HbA1c, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, plasminogen activator inhibitor-1 (PAI-1), platelet and leukocyte parameters, vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), and selectins (E-, P-, L-). Results: PT % activity, PAI-1, VCAM-1, WBC, and neutrophil counts were significantly higher in T2DM patients than in healthy subjects. Poor glycemic control (HbA1c ≥ 7%) was correlated with increased PT activity (p = 0.015), and higher levels of E-selectin (p = 0.009), P-selectin (p = 0.012), and NLR (p = 0.019). Conclusions: Both T2DM and poor glycemic control affect some parameters of hemostasis, inflammation, and adhesion molecules. Further studies are needed to establish their clinical utility as adjuvant markers for cardio-vascular risk in T2DM patients.
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Sobczak AIS, Stewart AJ. Coagulatory Defects in Type-1 and Type-2 Diabetes. Int J Mol Sci 2019; 20:E6345. [PMID: 31888259 PMCID: PMC6940903 DOI: 10.3390/ijms20246345] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2019] [Revised: 12/06/2019] [Accepted: 12/12/2019] [Indexed: 12/16/2022] Open
Abstract
Diabetes (both type-1 and type-2) affects millions of individuals worldwide. A major cause of death for individuals with diabetes is cardiovascular diseases, in part since both types of diabetes lead to physiological changes that affect haemostasis. Those changes include altered concentrations of coagulatory proteins, hyper-activation of platelets, changes in metal ion homeostasis, alterations in lipid metabolism (leading to lipotoxicity in the heart and atherosclerosis), the presence of pro-coagulatory microparticles and endothelial dysfunction. In this review, we explore the different mechanisms by which diabetes leads to an increased risk of developing coagulatory disorders and how this differs between type-1 and type-2 diabetes.
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Affiliation(s)
| | - Alan J. Stewart
- Medical and Biological Sciences Building, School of Medicine, University of St Andrews, St Andrews KY16 9TF, UK;
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Tahmasebpour N, Hosseinpour Feizi MA, Ziamajidi N, Pouladi N, Montazeri V, Farhadian M, Abbasalipourkabir R. Association of Omentin-1 with Oxidative Stress and Clinical Significances in Patients with Breast Cancer. Adv Pharm Bull 2019; 10:106-113. [PMID: 32002368 PMCID: PMC6983997 DOI: 10.15171/apb.2020.013] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2019] [Revised: 09/05/2019] [Accepted: 09/18/2019] [Indexed: 01/13/2023] Open
Abstract
Purpose: Breast cancer (BC) is globally the main reason of cancer-related deaths in women. Omentin-1, an anti-inflammatory and antioxidant adipokine, plays different roles in tumorigenesis and anti-oncogenic pathways. In present study, we investigated the association of omentin-1 with oxidative stress and clinical significances in healthy controls and BC patients to assess the prognostic and diagnostic value of omentin-1 in this cancer.
Methods: This case-control study included 88 BC patients and 86 healthy controls. The serum levels of omentin-1 were assessed by enzyme-linked immunosorbent assays methods. Also, total antioxidant capacity (TAC), total oxidant status (TOS) and malondialdehyde (MDA) serum levels were measured by spectrophotometer. quantitative real-time polymerase chain reaction (qRT-PCR) was applied to the measurement of gene expression of omentin-1.
Results: the serum levels of omentin-1 were significantly lower in the BC patients compared to the healthy controls (P<0.001). Moreover, gene expression of omentin-1was significantly downregulated in the BC tissues compared to the adjacent normal tissues (P<0.001). Gene expression of omentin-1and its serum levels were significantly higher in grade I compared with grade II and III (P=0.001, P<0.001, respectively). Additionally, the serum levels of omentin-1 in the p53-positive BC patients were significantly higher than the p53-negative BC patients (P=0.001). There was an inverse correlation between the serum levels of MDA and TOS with the serum levels of omentin-1 (r=-0.436, r=-461, respectively).
Conclusion: We conclude that omentin-1 may have a good prognostic and diagnostic roles in the BC patients and decreases oxidative stress in these patients.
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Affiliation(s)
- Nahideh Tahmasebpour
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | | | - Nasrin Ziamajidi
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Naser Pouladi
- Department of Biology, Faculty of Basic Sciences, Azarbaijan Shahid Madani University, Tabriz, Iran
| | - Vahid Montazeri
- Department of Thoracic Surgery, Faculty of Medicine, Surgery Ward, Nour-Nejat Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Maryam Farhadian
- Department of Biostatistics, School of Public Health and Research Center for Health Sciences, Hamadan University of Medical Sciences, Hamadan, Iran
| | - Roghayeh Abbasalipourkabir
- Department of Clinical Biochemistry, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
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Cederholm J, Zethelius B. SPISE and other fasting indexes of insulin resistance: risks of coronary heart disease or type 2 diabetes. Comparative cross-sectional and longitudinal aspects. Ups J Med Sci 2019; 124:265-272. [PMID: 31694444 PMCID: PMC6968630 DOI: 10.1080/03009734.2019.1680583] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Background: Fasting insulin resistance indexes are used extensively nowadays. We intended to analyze a new recently presented fasting index, SPISE (sensitivity formula: 600 × HDL-cholesterol0.185/triglycerides0.2/BMI1.338), in comparison with three previously known fasting indexes, regarding correlation with the insulin clamp index, and for the predictive effects of future long-term risks of coronary heart disease (CHD) or manifest type 2 diabetes.Methods: A total of 1049 71-year-old male subjects from the Swedish ULSAM study, median follow-up 8 years, were included. All subjects performed the euglycemic insulin clamp, and analyses of four fasting insulin resistance indexes: SPISE-IR (= 10/SPISE), QUICKI-IR, Log HOMA-IR, and Revised QUICKI-IR.Results: Spearman correlation coefficients with the insulin clamp were 0.60-0.62 for all indexes. Area under curve at ROC analysis was 0.80 for SPISE-IR, and 0.84 for QUICKI-IR, Log HOMA-IR, and Rev QUICKI-IR. Adjusted hazard ratios per 1 SD index increase for long-term risk CHD were similar in all patients: 1.20-1.24 (p = 0.02-0.03). However, comparing the highest quartile (recommended to define insulin resistance) with the lower quartiles, SPISE-IR was the strongest and the only statistically significant insulin resistance index: HR 1.53 (p = 0.02). Adjusted odds ratios per 1 SD index increase for long-term risk of type 2 diabetes were fairly similar (p < 0.001) in all patients: 1.62 for SPISE-IR, 1.97 for QUICKI-IR and Log HOMA-IR, and 2.04 for Rev QUICKI-IR, and also when comparing the highest versus the lower quartiles: 2.8-3.1 (p < 0.001).Conclusion: SPISE, easily applicable, performed equally well as other fasting insulin indexes previously recommended for clinical use, regarding correlation with the insulin clamp, and as predictor for future long-term risks of CHD or type 2 diabetes.
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Affiliation(s)
- Jan Cederholm
- Department of Public Health and Caring Sciences/Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden
- CONTACT Jan Cederholm Department of Public Health and Caring, Uppsala University, Box 564, Uppsala, S-75122, Sweden
| | - Björn Zethelius
- Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala, Sweden
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Harrison ML, Wolfe AS, Fordyce J, Rock J, García AA, Zuñiga JA. The additive effect of type 2 diabetes on fibrinogen, von Willebrand factor, tryptophan and threonine in people living with HIV. Amino Acids 2019; 51:783-793. [PMID: 30868261 DOI: 10.1007/s00726-019-02715-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2019] [Accepted: 02/22/2019] [Indexed: 01/07/2023]
Abstract
Chronic immune activation and ensuing inflammation that accompany HIV infection lead to adverse metabolic consequences and an increased risk of type 2 diabetes (T2D). We examined the additive effects of T2D on circulating biomarkers involved in inflammation, coagulation, and vascular function along with plasma amino acids in people living with HIV (PLWH). This cross-sectional study included PLWH with and without T2D (n = 32 total). Analyses involved a multiplex platform for circulating biomarkers and gas chromatography-vacuum ultraviolet spectroscopy for plasma amino acids. In PLWH and T2D, both fibrinogen (2.0 ± 0.6 vs 1.6 ± 0.4 µg/mL, p = 0.02) and von Willebrand factor (vWF) (40.8 ± 17.2 vs 26.7 ± 13.8 µg/mL, p = 0.02) were increased and tryptophan (47 ± 6 vs 53 ± 8 nmol/mL, p = 0.03) and threonine (102 ± 25 vs 125 ± 33 nmol/mL, p = 0.03) were decreased. Fibrinogen, as a biomarker of inflammation, and vWF, as a biomarker of endothelial dysfunction, are augmented by the combined effects of HIV and T2D and may contribute to the pathogenesis of T2D in PLWH. Chronic immune activation and inflammation compromise the integrity of the intestinal mucosa, which increases mucus production. Tryptophan metabolism is altered by a loss of intestinal membrane integrity and threonine is consumed in the production of mucus. Metabolic competition arising from increased protein synthesis in the setting of chronic inflammation along with the associated loss in intestinal membrane integrity may be a primary mechanism in the pathogenesis of T2D in PLWH and requires further investigation.
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Affiliation(s)
- Michelle L Harrison
- Department of Kinesiology and Health Education, University of Texas at Austin, 2109 San Jacinto Blvd, Austin, TX, 78712, USA.
| | - Anthony S Wolfe
- Department of Kinesiology and Health Education, University of Texas at Austin, 2109 San Jacinto Blvd, Austin, TX, 78712, USA
| | | | - Jamie Rock
- School of Nursing, University of Texas, Austin, USA
| | - Alexandra A García
- School of Nursing, University of Texas, Austin, USA.,Department of Population Health, Dell Medical School, University of Texas, Austin, USA
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Cremona A, O'Gorman C, Cotter A, Saunders J, Donnelly A. Effect of exercise modality on markers of insulin sensitivity and blood glucose control in pregnancies complicated with gestational diabetes mellitus: a systematic review. Obes Sci Pract 2018; 4:455-467. [PMID: 30338116 PMCID: PMC6180709 DOI: 10.1002/osp4.283] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2017] [Revised: 05/24/2018] [Accepted: 05/27/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND/AIM Exercise can be used as a strategy to attenuate hyperglycaemia experienced during gestational diabetes mellitus (GDM). To maximize its use for clinical management, the most effective modality should be identified. The purpose of this review is to elucidate the most effective modality of exercise on insulin sensitivity and blood glucose control in pregnant women with or at risk of GDM. METHODS A search was undertaken in MEDLINE, PubMed, Scopus, CINAHL, the Cochrane Library, Embase and the Maternity & Infant Healthcare Database. Studies that met inclusion criteria were randomized controlled trials and case-controlled studies, which compared exercise interventions with standard care during pregnancy in women with or at risk of GDM. RESULTS Two interventions using resistance training, eight using aerobic exercise and two using a combination of both modalities were included. The interventions showed consistently that requirements of insulin therapy, dosage, and latency to administration were improved in the exercise groups. Less consistent results were observed for capillary blood glucose measurements; however, both modalities and combination of modalities were effective at improving blood glucose control in already diagnosed patients and pregnant women with obesity. Discrepancies in the timing of intervention, GDM diagnostic criteria, and the different measures used to assess glucose metabolism make it difficult to draw clear recommendations. CONCLUSION Exercising three times per week for 40-60 min at 65-75% age-predicted heart rate maximum using cycling, walking or circuit training as a modality improved glycaemic control in GDM patients and reduced incidence of GDM in pregnant women with obesity. Further studies looking specifically at the effects of different modalities of exercise on glucose metabolism with combined strategies to enhance insulin sensitivity should be explored to maximize benefits for GDM pregnancies. Consistency in design and delivery of exercise-only interventions is required to make recommendations on a suitable exercise prescription in this population. In practice, adherence to consensus in diagnostic cut-offs for GDM diagnosis is fundamental for standardizing future research.
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Affiliation(s)
- A. Cremona
- Graduate Entry Medical SchoolUniversity of LimerickLimerickIreland
- Irish Nutrition and Dietetic InstituteDublinIreland
| | - C. O'Gorman
- Graduate Entry Medical SchoolUniversity of LimerickLimerickIreland
| | - A. Cotter
- Graduate Entry Medical SchoolUniversity of LimerickLimerickIreland
| | - J. Saunders
- SCU/CSTAR @ ULUniversity of LimerickLimerickIreland
| | - A. Donnelly
- Physical Education and Sports ScienceUniversity of LimerickLimerickIreland
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Kim JT, Lee SY, Yoo DS, Lee JS, Kim SH, Choi KH, Park MS, Cho KH. Clinical Implications of Serial Glucose Measurements in Acute Ischemic Stroke Patients Treated with Intravenous Thrombolysis. Sci Rep 2018; 8:11761. [PMID: 30082824 PMCID: PMC6078974 DOI: 10.1038/s41598-018-30028-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2018] [Accepted: 07/20/2018] [Indexed: 12/28/2022] Open
Abstract
Serial glucose might more accurately reflect glycemic status in acute ischemic stroke (AIS) than presenting glucose. We sought to investigate the clinical implications of various parameters of serial glucose on the outcomes of patients with AIS treated with intravenous thrombolysis (IVT). This was a single-center, prospective, observational study of stroke patients treated with IVT. Blood glucose (BG) was serially measured at 6-time points during the first 24 h of IVT. The primary endpoint analyzed was a good outcome at 3 m. Among the 492 patients in the cohort (age, 70 ± 12 y; men, 57%), the overall BG level was 131 ± 33 mg/dl. At 3 m, 40.4% of the patients had a good outcome. Patients with good outcomes had significantly lower mean BG (121 vs 128 mg/dl) and higher coefficient of variance (CoV, 17% vs 14%) but no differences in the others. For patients with higher mBG (every 30 mg/dl), the likelihood of achieving a good outcome decreased (OR 0.82, 95% CI 0.67–1.02). For patients with higher CoV (every 10%), the likelihood of a good outcome increased (OR 1.38, 95% CI 1.12–1.71). The results showed that higher mBG and lower CoV were consistently associated with worse outcomes in IV-thrombolyzed stroke patients, suggesting that lowering BG might be potential therapeutic target.
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Affiliation(s)
- Joon-Tae Kim
- Department of Neurology, Chonnam National University Hospital, Gwangju, Republic of Korea.
| | - Se-Young Lee
- Department of Neurology, KS Hospital, Gwangju, Republic of Korea
| | - Deok-Sang Yoo
- Department of Neurology, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - Ji Sung Lee
- Clinical Trial Center, Asan Medical Center, Seoul, Republic of Korea
| | - Sang-Hoon Kim
- Department of Neurology, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - Kang-Ho Choi
- Department of Neurology, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - Man-Seok Park
- Department of Neurology, Chonnam National University Hospital, Gwangju, Republic of Korea
| | - Ki-Hyun Cho
- Department of Neurology, Chonnam National University Hospital, Gwangju, Republic of Korea
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Petrikova J, Janicko M, Fedacko J, Drazilova S, Madarasova Geckova A, Marekova M, Pella D, Jarcuska P. Serum Uric Acid in Roma and Non-Roma-Its Correlation with Metabolic Syndrome and Other Variables. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2018; 15:ijerph15071412. [PMID: 29973567 PMCID: PMC6069053 DOI: 10.3390/ijerph15071412] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/24/2018] [Revised: 06/22/2018] [Accepted: 06/28/2018] [Indexed: 12/13/2022]
Abstract
Background: The Roma population is one of the major marginalized groups in Europe, having higher incidence of all spectrums of disease and a shorter life expectancy. Yet, the reasons for higher morbidity and its exact prevalence were not properly studied. Objectives: The objective of our study was to compare the frequency of metabolic syndrome (MetS) in Roma people to the non-Roma population in Slovakia, and to compare levels of uric acid and its correlation with components of metabolic syndrome. Methods: A group of 452 Roma people aged 18–55 years, was compared to a control group of 403 non-Roma people. The data were obtained by questionnaire, anthropometric measures, and analyzed blood and urine samples Results: The prevalence of MetS was significantly higher among Roma participants (131; 29.6%) compared with non-Roma participants (80; 20.1%), p = 0.001. Roma people significantly more often fulfilled obesity and low high-density lipoprotein (HDL) criteria of MetS (257, 58.9% vs. 180, 45.8%, p < 0.0001, and 312, 70.0% vs. 140, 34.9%, p < 0.0001). There was no difference in the triacylglycerols (TG), glycemia or blood pressure (BP) criteria of MetS. The Roma also presented with greater levels of high sensitivity C-reactive protein (hs-CRP). Baseline levels of uric acid (UA) among the Roma population were significantly lower compared with the majority population (226.54 ± 79.8 vs. 259.11 ± 84.53) (p < 0.001). The levels of UA significantly correlated with fulfilled criteria of MetS. Univariate regression showed that UA is a significant predictor of MetS in the whole cohort (unadjusted odds ratio (OR) 1.005; 95% CI 1.004–1.007; p < 0.0001) also after the adjustment for age, sex, and ethnicity (adjusted OR 1.008; 95% CI 1.005–1.010; p < 0.0001). Conclusions: We were able to show that prevalence of MetS among the Roma is higher than in the majority population. Moreover, the uric acid levels are significantly lower in the Roma group as well as when it comes to a cohort with MetS. Levels of UA, besides others, depend on ethnicity, age, and sex.
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Affiliation(s)
- Jana Petrikova
- 1st Department of Internal Medicine, Faculty of Medicine, PJ Safarik University, 040 11 Kosice, Slovakia.
- Louis Pasteur University Hospital, 040 01 Kosice, Slovakia.
| | - Martin Janicko
- 1st Department of Internal Medicine, Faculty of Medicine, PJ Safarik University, 040 11 Kosice, Slovakia.
- Louis Pasteur University Hospital, 040 01 Kosice, Slovakia.
| | - Jan Fedacko
- Department of Gerontology and Geriatrics, Faculty of Medicine, PJ Safarik University, 040 01 Kosice, Slovakia.
- Air Force Military Hospital, 040 86 Kosice, Slovakia.
| | - Sylvia Drazilova
- Department of Internal Medicine, Poprad Hospital, 058 01 Poprad, Slovakia.
| | - Andrea Madarasova Geckova
- Department of Health Psychology, Faculty of Medicine, PJ Safarik University, 040 11 Kosice, Slovakia.
| | - Maria Marekova
- Department of Medical and Clinical Biochemistry, Faculty of Medicine, PJ Safarik University, 040 11 Kosice, Slovakia.
| | - Daniel Pella
- 1st Department of Internal Medicine, Faculty of Medicine, PJ Safarik University, 040 11 Kosice, Slovakia.
- Louis Pasteur University Hospital, 040 01 Kosice, Slovakia.
| | - Peter Jarcuska
- 1st Department of Internal Medicine, Faculty of Medicine, PJ Safarik University, 040 11 Kosice, Slovakia.
- Louis Pasteur University Hospital, 040 01 Kosice, Slovakia.
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Midlife weight gain is a risk factor for obesity-related cancer. Br J Cancer 2018; 118:1665-1671. [PMID: 29895939 PMCID: PMC6008441 DOI: 10.1038/s41416-018-0106-x] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2017] [Revised: 04/11/2018] [Accepted: 04/13/2018] [Indexed: 12/22/2022] Open
Abstract
Background Overweight and diabetes are known cancer risk factors. This study examines independent and combined effects of weight gain and metabolic dysfunction during middle-adult years on obesity-related cancer risk. Methods Subjects (n = 3850) aged 45–69 years at exams 3–5 in the Framingham Offspring Study were classified according to current and prior (~14 years earlier) weight status, interim weight change and prevalent metabolic dysfunction. Cancer risk among subjects who were overweight at baseline and remained overweight, as well as those who became overweight during follow-up, was compared with risk among normal-weight individuals. Results Gaining ≥0.45 kg (≥1.0 pound)/year (vs. maintaining stable weight) over ~14 years increased cancer risk by 38% (95% confidence interval (CI), 1.09, 1.76); combined with metabolic dysfunction, weight gain increased cancer risk by 77% (95% CI, 1.21, 2.59). Compared with non-overweight adults, men and women who became overweight during midlife had 2.18-fold and 1.60-fold increased cancer risks; those who were overweight from baseline had non-statistically significant 28 and 33% increased cancer risks, respectively, despite having a midlife body mass index that was 3.4 kg/m2 higher than those who gained weight later. Conclusion Midlife weight gain was a strong cancer risk factor. This excess risk was somewhat stronger among those with concurrent metabolic dysfunction.
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Elevated leptin and decreased adiponectin independently predict the post-thrombotic syndrome in obese and non-obese patients. Sci Rep 2018; 8:6938. [PMID: 29720688 PMCID: PMC5932041 DOI: 10.1038/s41598-018-25135-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Accepted: 04/10/2018] [Indexed: 01/25/2023] Open
Abstract
Post-thrombotic syndrome (PTS) is a common complication of deep vein thrombosis (DVT). Little is known about the involvement of adipokines in the pathogenesis of DVT. We evaluated whether adipokines can predict PTS. In a prospective cohort study, 320 DVT patients aged 70 years or less were enrolled. Serum adiponectin, leptin and resistin levels were measured three months since the index first-ever DVT. After 2 years’ follow-up PTS was diagnosed in 83 of 309 available patients (26.9%) who had 13.9% lower adiponectin and 16% higher leptin levels compared with the remainder (both p < 0.0001). No PTS-associated differences in C-reactive protein, fibrinogen, D-dimer, plasminogen activator inhibitor-1 and resistin were observed. The multivariable logistic regression adjusted for age, sex, obesity and tissue plasminogen activator (tPa) showed that lower adiponectin (odds ratio [OR], 0.42; 95% confidence interval [CI], 0.31–0.56) and higher leptin levels (OR, 1.49; 95% CI, 1.31–1.69) are independent predictors for PTS. Obesity-stratified logistic regression analysis confirmed that lower adiponectin (OR, 0.49; 95% CI, 0.38–0.64) and higher leptin (OR, 1.41; 95% Cl, 1.25–1.58) levels predicted PTS. Our findings showed that lower adiponectin and higher leptin measured 3 months after DVT, regardless of obesity, can independently predict PTS, which suggests novel links between adipokines and thrombosis.
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50
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Effects of gastric bypass surgery followed by supervised physical training on inflammation and endothelial function: A randomized controlled trial. Atherosclerosis 2018; 273:37-44. [PMID: 29677629 DOI: 10.1016/j.atherosclerosis.2018.04.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2018] [Revised: 03/13/2018] [Accepted: 04/05/2018] [Indexed: 12/28/2022]
Abstract
BACKGROUND AND AIMS Obesity and physical inactivity are both associated with low-grade inflammation and endothelial dysfunction. Bariatric surgery improves markers of inflammation and endothelial function, but it is unknown if physical training after bariatric surgery can improve these markers even further. Therefore, we aimed to investigate the effects of Roux-en-Y gastric bypass (RYGB) followed by physical training on markers of low-grade inflammation and endothelial function. METHODS Sixty patients approved for RYGB underwent examinations pre-surgery, 6, 12, and 24 months post-surgery. Six months post-surgery, they were randomized 1:1 to an intervention group or a control group. The interventions consisted of two weekly sessions of supervised moderate intensity physical training for a period of 26 weeks. Fasting blood samples were analyzed for concentrations of interleukin 6 (IL-6), C-reactive protein (CRP), intercellular adhesion molecule 1 (ICAM-1), tissue-type plasminogen activator antigen (t-PA:Ag) and von Willebrand factor (vWF). RESULTS RYGB markedly improved markers of inflammation (IL-6, CRP) (p < 0.001) and endothelial function (ICAM-1, t-PA:Ag, vWF) (p < 0.05), and the improvements were sustained 24 months post-surgery (p < 0.01), except for the effects on vWF. We found no correlations between the changes in weight or BMI and the changes in markers of inflammation and endothelial function, except that the change in vWF was found to be inversely correlated with the changes in weight and BMI. We observed no effects of supervised physical training on markers on inflammation or endothelial function (p>0.1 for all). CONCLUSIONS RYGB causes substantial and sustained favorable effects on markers of inflammation and endothelial function. Supervised physical training after RYGB did not cause additional improvements.
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