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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the last two decades, it has become evident that the endothelium is more than an inert, single-cell lining covering the internal surface of blood vessels. Normally, the endothelium actively decreases vascular tone, maintains vascular permeability within narrow bounds, inhibits platelet adhesion and aggregation, limits activation of the coagulation system, and stimulates fibrinolysis. Endothelium dysfunction can be considered present when its functions, either in the basal state or after stimulation, are altered in a way that is inappropriate to the preservation of organ function. Endothelial dysfunction has been associated to many cardiovascular risk factors including diabetes, hypertension and hypercholesterolemia. In addition, endothelial dysfunction may play a crucial role in the development and progression of atherosclerosis. This review will give a brief overview of the different methods to assess endothelial function, and then will focus on the current knowledge on soluble cellular adhesion molecules in relation to the metabolic syndrome and type 2 diabetes.
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PMID:Endothelial dysfunction, cellular adhesion molecules and the metabolic syndrome. 1591 11

Endothelial dysfunction may precede development of type 2 diabetes. We tested the hypothesis that elevated levels of hemostatic markers of endothelial dysfunction, plasminogen activator inhibitor-1 (PAI-1) antigen, and von Willebrand factor (vWF) antigen predicted incident diabetes independent of other diabetes risk factors. We followed 2,924 Framingham Offspring subjects (54% women, mean age 54 years) without diabetes at baseline (defined by treatment, fasting plasma glucose > or =7 or 2-h postchallenge glucose > or =11.1 mmol/l) over 7 years for new cases of diabetes (treatment or fasting plasma glucose > or =7.0 mmol/l). We used a series of regression models to estimate relative risks for diabetes per interquartile range (IQR) increase in PAI-1 (IQR 16.8 ng/ml) and vWF (IQR 66.8% of control) conditioned on baseline characteristics. Over follow-up, there were 153 new cases of diabetes. Age- and sex-adjusted relative risks of diabetes were 1.55 per IQR for PAI-1 (95% CI 1.41-1.70) and 1.49 for vWF (1.21-1.85). These effects remained after further adjustment for diabetes risk factors (including physical activity; HDL cholesterol, triglyceride, and blood pressure levels; smoking; parental history of diabetes; use of alcohol, nonsteroidal anti-inflammatory drugs, exogenous estrogen, or hypertension therapy; and impaired glucose tolerance), waist circumference, homeostasis model assessment of insulin resistance, and inflammation (assessed by levels of C-reactive protein): the adjusted relative risks were 1.18 per IQR for PAI-1 (1.01-1.37) and 1.39 for vWF (1.09-1.77). We conclude that in this community-based sample, plasma markers of endothelial dysfunction increased risk of incident diabetes independent of other diabetes risk factors including obesity, insulin resistance, and inflammation.
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PMID:Hemostatic markers of endothelial dysfunction and risk of incident type 2 diabetes: the Framingham Offspring Study. 1644 91

The pathophysiology of insulin resistance and atherosclerosis may share a common inflammatory basis, maintaining endothelial dysfunction, suggesting why patients with T2DM (Type II diabetes mellitus) have an impaired prognosis after an MI (myocardial infarction), but it remains unclear how these parameters are inter-related. Forty patients with an MI (20 patients with and 20 patients without T2DM) took part in this cross-sectional study. Endothelium-dependent [FMD (flow-mediated dilation)] and -independent [NTG (nitroglycerine)] vasodilatation (determined by ultrasound), S(I) (insulin sensitivity index; determined by isoglycaemic-hyperinsulinaemic clamp) and serum levels of CRP (C-reactive protein), TNF-alpha (tumour necrosis factor-alpha), IL-6 (interleukin 6), resistin and adiponectin (determined by ELISA) were measured. Associations between FMD/NTG and S(I), and CRP, TNF-alpha, IL-6, adiponectin, resistin, lipids, blood pressure, BMI (body mass index) and brachial artery diameter were then assessed. FMD (2.1 compared with 4.7%; P<0.05), NTG (14.9 compared with 21.2%; P<0.05) and S(I) [4.3 compared with 6.6 10(-4) dl.kg(-1) of body weight.min(-1).(mu-units/ml)(-1); P<0.05], and adiponectin levels (3.1 compared with 6.4 microg/ml; P<0.01) were all lower in patients with T2DM. TNF-alpha (6.9 compared with 1.8 pg/ml; P<0.01) and IL-6 (2.3 compared with 1.2 pg/ml; P<0.01) levels were higher in patients with T2DM, whereas differences in CRP and resistin levels did not attain statistical significance between the two groups. TNF-alpha concentrations and brachial artery diameter were negatively, whereas S(I) was positively, correlated with FMD. Adjustment for age weakened the association for S(I), whereas TNF-alpha and brachial artery diameter remained significantly associated with FMD after adjustment for group, age and BMI. Endothelial dysfunction and low-grade inflammation co-exist in T2DM after MI. These results suggest that the endothelium is negatively impacted in multiple ways by the diabetic state after an MI.
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PMID:Increased levels of tumour necrosis factor-alpha (TNF-alpha) in patients with Type II diabetes mellitus after myocardial infarction are related to endothelial dysfunction. 1646 46

The main etiology for mortality and a great percentage of morbidity in patients with diabetes mellitus is atherosclerosis. The pathogenesis of cardiovascular disease (CVD) in diabetes is multifactorial and can be affected by metabolic and other factors. A hypothesis for the initial lesion of atherosclerosis is endothelial dysfunction, defined pragmatically as changes in the concentration of the chemical messengers produced by the endothelial cell and/or by blunting of the nitric oxide-dependent vasodilatory response to acetylcholine or hyperemia. Endothelial dysfunction has been documented in patients with diabetes and in individuals with insulin resistance or at high risk for developing type 2 diabetes. The way endothelial function altered in diabetic patients is not yet fully understood, but the loss of normal endothelial function could be involved in the pathogenesis of diabetic angiopathy, as endothelial dysfunction is associated with diabetic microangiopathy and macroangiopathy. Factors associated with endothelial dysfunction in diabetes include activation of protein kinase C, overexpression of growth factors and/or cytokines, and oxidative stress. Changes in endothelium function may lead to the coronary artery circulation being unable to cope with the increased metabolism of myocardial muscle independently of a reduced coronary artery diameter. Finally, recent reports indicate that an improved metabolic control in diabetic patients, whatever the treatment used, is associated with near normalization or restoration of normal endothelial function.
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PMID:Why does diabetes mellitus increase the risk of cardiovascular disease? 1647 30

Endothelial dysfunction, characterized by impaired nitric oxide activity, constitutes an early step in the pathogenesis of atherosclerotic disease. Prospective studies have shown that impaired endothelium-dependent vasorelaxation and the vasodilatory response of coronary arteries to acetylcholine predict cardiovascular events. Microalbuminuria and estimated glomerular filtration rate, which are both deeply influenced by renal nitric oxide activity, are predictors of cardiovascular outcome and total mortality but develop at a later stage of renal impairment. Endothelial dysfunction reflects early stage renal involvement in the atherosclerotic processes. The Telmisartan versus Ramipril in renal ENdothelium DYsfunction (TRENDY) trial examined endothelial function of the renal vasculature as a therapeutic target in patients with hypertension and type 2 diabetes, but without albuminuria. The rationale was that blockade of the renin-angiotensin system (RAS) is cardio- and renoprotective at later stages of the disease, but the impact of blockade of the RAS at earlier stages of disease is unknown. The results of TRENDY indicate that the endothelial function, as assessed by basal nitric oxide activity, can be improved after RAS blockade. These data complement the results of the Diabetics Exposed to Telmisartan And enalaprIL (DETAIL) trial, which demonstrated that telmisartan and enalapril similarly decelerate the progression of overt diabetic nephropathy. The results of TRENDY are in accordance with the observed changes in peripheral circulation. Endothelium-dependent vasorelaxation could be improved with angiotensin II receptor blockers, but not with diuretics or beta-blockers, in hypertensive patients. Intervention at the beginning of the renal and cardiovascular continuum offers the opportunity to prevent the fatal development towards renal and cardiac failure.
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PMID:Endothelial dysfunction: how can one intervene at the beginning of the cardiovascular continuum? 1660 59

Endothelial dysfunction contributes to cardiovascular diseases, including hypertension, atherosclerosis, and coronary artery disease, which are also characterized by insulin resistance. Insulin resistance is a hallmark of metabolic disorders, including type 2 diabetes mellitus and obesity, which are also characterized by endothelial dysfunction. Metabolic actions of insulin to promote glucose disposal are augmented by vascular actions of insulin in endothelium to stimulate production of the vasodilator nitric oxide (NO). Indeed, NO-dependent increases in blood flow to skeletal muscle account for 25% to 40% of the increase in glucose uptake in response to insulin stimulation. Phosphatidylinositol 3-kinase-dependent insulin-signaling pathways in endothelium related to production of NO share striking similarities with metabolic pathways in skeletal muscle that promote glucose uptake. Other distinct nonmetabolic branches of insulin-signaling pathways regulate secretion of the vasoconstrictor endothelin-1 in endothelium. Metabolic insulin resistance is characterized by pathway-specific impairment in phosphatidylinositol 3-kinase-dependent signaling, which in endothelium may cause imbalance between production of NO and secretion of endothelin-1, leading to decreased blood flow, which worsens insulin resistance. Therapeutic interventions in animal models and human studies have demonstrated that improving endothelial function ameliorates insulin resistance, whereas improving insulin sensitivity ameliorates endothelial dysfunction. Taken together, cellular, physiological, clinical, and epidemiological studies strongly support a reciprocal relationship between endothelial dysfunction and insulin resistance that helps to link cardiovascular and metabolic diseases. In the present review, we discuss pathophysiological mechanisms, including inflammatory processes, that couple endothelial dysfunction with insulin resistance and emphasize important therapeutic implications.
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PMID:Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. 1661 33

Due to global lifestyle changes, obesity (the main driver of type 2 diabetes and cardiovascular disease ) is reaching pandemic proportions. The metabolic syndrome, which is regarded as a prediabetic state, is characterized by a concurrence of interrelated cardiovascular risk factors, including abdominal obesity, insulin resistance, hypertension, dyslipidemia, and glucose intolerance. Endothelial dysfunction (ED) is common in the metabolic syndrome and is associated with increased risk for T2D and CVD. This review focuses on the mechanisms linking ED to the metabolic syndrome, T2D, and CVD, and the possible therapies that may improve ED and reduce T2D and CVD risk.
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PMID:The metabolic syndrome and endothelial dysfunction: common highway to type 2 diabetes and CVD. 1687 79

When normal endothelial function is shifted to a pathological degree, the foundation is laid for possibly following diseases. This endothelial dysfunction is characterized by a proinflammatory state, reduced vasodilation, and a prothrombotic state. In the continuation this dysfunction is strongly associated cardiovascular morbidity and mortality. Endothelial dysfunction is markedly enhanced in type 2 diabetes providing a major pathophysiological cause for the massively increased cardiovascular risk of diabetic patients. Subsequently future therapeutic approaches for the treatment of diabetic cardiovascular disease should target the dysfunctional endothelium first.
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PMID:Endothelial dysfunction and its role in diabetic vascular disease. 1695 85

Endothelial dysfunction is regarded as an early stage of atherosclerosis, and plays a role in the development of atherosclerotic diseases. Insulin resistance is related to the atherosclerotic process. In this study, we examined the association between endothelial function and insulin resistance in 48 subjects with type 2 diabetes. In addition, the effects of pioglitazone treatment on endothelial function and insulin resistance were investigated in a subgroup of subjects. Endothelial function of the brachial artery was non-invasively assessed using ultrasound technique. We measured flow-mediated endothelium-dependent vasodilation (FMD) and glyceryl trinitrate-induced endothelium-independent vasodilation (GTN). Insulin sensitivity was measured by the steady-state plasma glucose (SSPG) method. High SSPG levels indicate insulin resistance. There was a significant inverse correlation (r=-0.462, p<0.001) between SSPG and FMD. Systolic blood pressure was inversely correlated with FMD (r=-0.360, p<0.013). By multiple regression analysis, insulin resistance was the sole predictor of FMD. The effects of chronic treatment with pioglitazone were assessed in 10 subjects with type 2 diabetes. The increase in FMD significantly correlated with the decrease in SSPG. There is a significant association between vascular endothelial dysfunction and insulin resistance in type 2 diabetes. This result was supported by the effects of the insulin sensitizer, pioglitazone.
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PMID:Association between insulin resistance and endothelial dysfunction in type 2 diabetes and the effects of pioglitazone. 1700 57

Endothelial dysfunction (ED) is associated with the presence of atherosclerosis. However, ED is also considered a sign of the early vascular changes preceding atherosclerosis. By measuring flow-mediated vasodilation (FMD) and circulating markers of endothelial function we sought to explore whether impaired endothelial function is already present in healthy subjects at increased risk of developing type 2 diabetes mellitus. Furthermore, we aimed to assess the impact of short-term lifestyle intervention (10 weeks endurance exercise) on the potentially primary defects of endothelial function. Twenty-nine healthy but insulin-resistant first-degree relatives of patients diagnosed with type 2 diabetes mellitus (33 +/- 5 years; body mass index, 26.3 +/- 1.6 kg/m2) were compared with 19 control subjects without a family history of diabetes mellitus (31 +/- 5 years; body mass index, 25.8 +/- 3.0 kg/m2). At baseline the von Willebrand factor was significantly increased in the relatives (P < .05). Furthermore, mannose-binding lectin (P = .06), soluble intercellular adhesion molecule 1 (P = .08), and osteoprotegerin (P = .08) tended to be increased in relatives. The following markers of endothelial function were comparable at baseline: FMD, C-reactive protein, plasminogen activator inhibitor 1, and soluble vascular cell adhesion molecule 1. Exercise training resulted in a decrease in mannose-binding lectin (P = .02) and osteoprotegerin (P < .01) in relatives only, whereas other biochemical markers were unaffected in both groups. Moreover, the relatively high-intensity exercise training tended weakly to reduce FMD in the relatives (P = .15). In conclusion, healthy subjects predisposed for type 2 diabetes mellitus show only minor signs of endothelial dysfunction. Under these almost normal vascular conditions, exercise training has little effect on endothelial function.
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PMID:Endothelial function and biochemical vascular markers in first-degree relatives of type 2 diabetic patients: the effect of exercise training. 1704 54


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