Endotheliopathy Precedes Type 2 Diabetes

Tooke, John E.; Goh, K.L.

doi:10.2337/diacare.21.12.2047

Cited by 57 publications

(44 citation statements)

References 14 publications

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“…Interestingly, we have also shown that higher oxidative stress was present in the prediabetic stage (IGT), in the absence of significant changes in endothelial function and insulin sensitivity. Our data support the contention that oxidative stress could precede endothelial dysfunction and the appearance of insulin resistance, as proposed recently [42,43].…”

Section: Discussionsupporting

confidence: 79%

Oxidative stress could precede endothelial dysfunction and insulin resistance in Indian Mauritians with impaired glucose metabolism

et al. 2001

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Type II (non-insulin-dependent) diabetes mellitus is characterised by insulin resistance, pancreatic betacell defect, hypertension, dyslipidaemia and central obesity, and is recognised as part of a cluster of cardiovascular risk factors generally known as the Metabolic Syndrome [1]. The Indian Ocean island of Mauritius recently provided the background for a longitudinal epidemiological study (1987±1998) which is now seen as an indicator of the potential global impact of Type II diabetes [2,3]. Mauritius has a multiethnic population of 1.2 million, including people of Asian Indian (66 %), mixed European-African-Indian (31 %) and Chinese (3 %) descent. In 1987, the agestandardised prevalence of Type II diabetes in adults aged 30 years or more was 14.3 %, increasing to Diabetologia (2001) Abstract Aims/hypothesis. To measure oxidative stress, endothelial dysfunction and insulin resistance in Indian Mauritians at different stages of development of Type II (non-insulin-dependent) diabetes mellitus. Methods. Plasma total 8-epi-PGF 2a , an indicator of oxidative stress, was determined in age-matched subjects with normal glucose metabolism (n = 39), impaired glucose tolerance (n = 14), newly diagnosed diabetes (n = 8) and established diabetes (n = 14). Plasma glucose and insulin were measured at baseline and 2 h following an oral glucose tolerance test. Endothelial function was assessed by non-invasive digital pulse wave photoplethysmography. Results. Plasma 8-epi-PGF 2a increased in subjects with impaired glucose tolerance (p < 0.05) compared with control subjects, and was even higher in newly diagnosed diabetic patients (p < 0.01) and established (p < 0.01) diabetic patients. A tendency towards reduced endothelial function in subjects with impaired glucose tolerance became significant in patients with newly diagnosed and established diabetes (p < 0.01), and was correlated with 8-epi-PGF 2a (r = 0.36, p < 0.01). Insulin resistance (homeostasis model assessment) did not change in subjects with impaired glucose tolerance compared with control subjects, but increased in newly diagnosed (p < 0.01) and established (p < 0.001) diabetic subjects. The 8-epi-PGF 2a was correlated with fasting glucose (r = 0.50, p < 0.001), triglycerides (r = 0.40, p < 0.001) and insulin resistance (r = 0.35, p < 0.001). Conclusion/interpretation. Oxidant stress is an early event in the evolution of Type II diabetes and could precede the development of endothelial dysfunction and insulin resistance. [Diabetologia (2001) 44: 706± 712

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Section: Discussionsupporting

confidence: 79%

Oxidative stress could precede endothelial dysfunction and insulin resistance in Indian Mauritians with impaired glucose metabolism

et al. 2001

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“…By contrast, in the prospective Atherosclerosis Risk in Communities (ARIC) study, levels of sTM were inversely associated with the risk of CHD [6]. It has been suggested that a prothrombotic state and endothelial dysfunction could enhance the risk of type 2 diabetes [7]. Thus, as a vasoprotective molecule, thrombomodulin may be involved in the pathophysiology of type 2 diabetes.…”

Section: Introductionmentioning

confidence: 75%

Soluble thrombomodulin as a predictor of type 2 diabetes: results from the MONICA/KORA Augsburg case–cohort study, 1984–1998

et al. 2006

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Aims/hypothesis Previous studies have shown an inverse association between soluble thrombomodulin (sTM) and incident CHD, but there is a lack of data on the association between sTM and type 2 diabetes. Since CHD and type 2 diabetes share many risk factors, the aim of this study was to assess whether elevated sTM levels are associated with a lower incidence of type 2 diabetes. Materials and methods A case-cohort study was performed in initially healthy middle-aged men and women based on data from the Monitoring of Trends and Determinants in Cardiovascular Disease/Cooperative Health Research in the Region of Augsburg (MONICA/KORA) studies conducted between 1984 and 1998. Levels of sTM were measured with an ELISA in serum samples from 138 men and 86 women who developed type 2 diabetes during follow-up (cases) and 534 men and 446 women who did not develop type 2 diabetes (non-cases).Results An inverse association was found between sTM and type 2 diabetes risk after multivariable adjustment for diabetes risk factors, including several other markers of inflammation and endothelial dysfunction. Markers of inflammation and endothelial dysfunction were particularly strong confounders of the observed association. In the fully adjusted model, a 1 SD increase in sTM was associated with a 27% decrease in the risk of type 2 diabetes (hazard ratio=0.73, 95% CI 0.58-0.91) in the total study population. We did not observe significant risk differences between men and women. Conclusions/interpretation These data suggest that, in initially healthy middle-aged men and women, levels of sTM are inversely associated with the risk of type 2 diabetes.

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“…There is increasing evidence that hyperglycemia is only a worsening factor for endothelial dysfunction and not the triggering one. It is hypothesized that endotheliopathy precedes type 2 diabetes (11). Therefore, comprehension of the mechanisms responsible for impaired insulin action are fundamental to understand possible favorable effects of insulin sensitizers.…”

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confidence: 99%

Metformin Improves Endothelial Vascular Reactivity in First-Degree Relatives of Type 2 Diabetic Patients With Metabolic Syndrome and Normal Glucose Tolerance

et al. 2006

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OBJECTIVE -Endothelial dysfunction is an early marker of atherosclerosis seen in type 2 diabetic subjects. Metformin is commonly used in the treatment of type 2 diabetes and has known vasculoprotective effects beyond its hypoglycemic ones. We aimed to investigate the vascular effects of metformin in first-degree relatives with metabolic syndrome of type 2 diabetic patients.RESEARCH DESIGN AND METHODS -The study included 31 subjects (age 38.3 Ϯ 7.6 years and BMI 36.3 Ϯ 5.2 kg/m 2 ), who were first-degree relatives of type 2 diabetic patients and who had metabolic syndrome and normal glucose tolerance. The subjects were randomly assigned 1:1 in a double-blind fashion to receive placebo (n ϭ 15) or metformin (n ϭ 16). Endothelial function was assessed by venous occlusion plethysmography, measuring forearm blood flow (FBF) and vascular resistance responses to three intra-arterial infusions of endothelium-dependent (acetylcholine 7.5, 15, and 30 g/min) and independent (sodium nitroprusside 2, 4, and 8 g/min) vasodilators. Weight, BMI, systolic and diastolic blood pressure, waist, and laboratory parameters (lipid profile and fasting plasma glucose [FPG]) were assessed at baseline and after treatment.RESULTS -The metformin and placebo groups did not differ in anthropometric, clinical, laboratory, and vascular measurements at baseline. The metformin group had decreased weight, BMI, systolic blood pressure, and FPG and improved lipid profile. Endothelium-dependent FBF responses were also improved, without any effect on endothelium-independent responses. There was no correlation between the improvement on FBF responses and the observed changes on anthropometric, clinical, and laboratory parameters.CONCLUSIONS -We concluded that metformin improved vascular endothelial reactivity in first-degree relatives with metabolic syndrome of type 2 diabetic patients, independently of its known antihyperglycemic effects. Diabetes Care 29:1083-1089, 2006T he precocious and accelerated atherosclerosis seen in type 2 diabetes raised the question about pathogenetic factors that initiate the development of vascular derangements in the prediabetic population. Metabolic syndrome, a pre-diabetic state, comprises an array of cardiovascular risk factors such as abdominal obesity, dyslipidemia, hypertension, impaired glucose tolerance, and insulin resistance. Insulin resistance, the central abnormality for the pathogenesis of metabolic syndrome, is considered an independent risk factor for cardiovascular mortality in general (1) and in the diabetic population (2) in particular.The endothelium is an important locus for the control of vascular function. It actively regulates vascular tone, permeability to leukocytes and macromolecules, the balance between coagulation and fibrinolysis, composition of the subendothelial matrix, and proliferation of vascular smooth muscle cells. The great variety of beneficial functions attributed to the endothelium is mainly associated with nitric oxide (NO) bioavailability. In experimental studies of atherogenesis,...

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Endotheliopathy Precedes Type 2 Diabetes

Cited by 57 publications

References 14 publications

Oxidative stress could precede endothelial dysfunction and insulin resistance in Indian Mauritians with impaired glucose metabolism

Oxidative stress could precede endothelial dysfunction and insulin resistance in Indian Mauritians with impaired glucose metabolism

Soluble thrombomodulin as a predictor of type 2 diabetes: results from the MONICA/KORA Augsburg case–cohort study, 1984–1998

Metformin Improves Endothelial Vascular Reactivity in First-Degree Relatives of Type 2 Diabetic Patients With Metabolic Syndrome and Normal Glucose Tolerance

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