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

The metabolic syndrome (metS), a concurrence of abdominal fat, disturbed glucose and insulin metabolism, dyslipidemia, and hypertension has been strongly associated not only with subsequent development of type 2 diabetes but also with atherothrombosis. The physiopathology of this association is complex. The metS affects the thrombogenicity of circulating blood. Apart from its effect on platelets, a procoagulant and hypofibrinolytic state has been identified; mainly the result of the inflammatory state, dyslipidemia, and liver fat accumulation that accompany the MetS. Among haemostasis disturbances, the strong rise in the inhibitor of plasminogen activator type 1 plasma level is the most documented abnormality implicating the participation of the oxidative stress and inflammatory state developed during the metS. Endothelial dysfunction is also a central feature. Moreover, secretion products of fat tissues (adipokines) are now thought to have direct modulating effects on the vascular and the circulating cells. In support of these data, the metS, may predispose not only to atherosclerosis but also to venous thrombosis.
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PMID:Metabolic syndrome, haemostasis and thrombosis. 1852 99

Macro- and microvascular disorders currently represent the principal causes of morbidity and mortality in patients with diseases involving the cardiovascular system, such as atherosclerosis, hypertension, stroke, and diabetes. Abnormal vasomotor responses and impaired endothelium-dependent vasodilation have been demonstrated in a number of vessels in a variety of animal models and in humans with such diseases. Endothelial dysfunction plays a key role in the development of these diseases, yet the genesis of this endothelial dysfunction and its associated vasomotor abnormalities remain poorly understood. Peroxisome proliferator-activated receptor (PPAR)gamma is a nuclear receptor and transcription factor in the steroid superfamily, and PPARgamma agonists (the thiazolidinediones) are used clinically to treat type 2 diabetes. Recent studies have revealed that as well as being involved in adipogenesis and in increased sensitivity to insulin, PPARgamma plays critical roles in the vasculature. In the present review, we discuss the beneficial effects of PPARgamma agonists on vasomotor activities, focusing in particular on endothelium-dependent relaxation in vessels affected by cardiovascular diseases.
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PMID:Relationships among ET-1, PPARgamma, oxidative stress and endothelial dysfunction in diabetic animals. 1855 52

Endothelial dysfunction is a major characteristic of the atherosclerotic process and can be used to predict the outcome of cardiovascular disease in humans. Together with obesity and insulin resistance, such dysfunction is common among patients with type 2 diabetes and may explain their poor prognosis in connection with such a disease. Insulin resistance in skeletal muscle, adipose tissue, and the liver, a well-characterized feature of obesity and type 2 diabetes, contributes to the impairment of glucose homeostasis. Furthermore, the myocardial muscle can also be resistant to insulin, which might, at least in part, explain the frequent development of heart failure in individuals suffering from type 2 diabetes. The relationship between insulin resistance and endothelial dysfunction has prompted investigations, which reveal that regular exercise, dietary changes, and/or pharmacological agents can both increase insulin sensitivity and improve endothelial function. Glucagon-like peptide-1, an incretin, lowers blood levels of glucose and offers a promising new approach to the treatment of type 2 diabetes mellitus. Its extensive extra-pancreatic effects, including a favorable influence on cardiovascular parameters, are extremely interesting in this connection. The potential pharmacological effects of glucagon-like peptide-1 and its analogues on the endothelium and the heart are discussed in the present review.
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PMID:The potential beneficial role of glucagon-like peptide-1 in endothelial dysfunction and heart failure associated with insulin resistance. 1879 70

Endothelial dysfunction comprises a number of functional alterations in the vascular endothelium that are associated with diabetes and cardiovascular disease, including changes in vasoregulation, enhanced generation of reactive oxygen intermediates, inflammatory activation, and altered barrier function. Hyperglycemia is a characteristic feature of type 1 and type 2 diabetes and plays a pivotal role in diabetes-associated microvascular complications. Although hyperglycemia also contributes to the occurrence and progression of macrovascular disease (the major cause of death in type 2 diabetes), other factors such as dyslipidemia, hyperinsulinemia, and adipose-tissue-derived factors play a more dominant role. A mutual interaction between these factors and endothelial dysfunction occurs during the progression of the disease. We pay special attention to the possible involvement of endoplasmic reticulum stress (ER stress) and the role of obesity and adipose-derived adipokines as contributors to endothelial dysfunction in type 2 diabetes. The close interaction of adipocytes of perivascular adipose tissue with arteries and arterioles facilitates the exposure of their endothelial cells to adipokines, particularly if inflammation activates the adipose tissue and thus affects vasoregulation and capillary recruitment in skeletal muscle. Hence, an initial dysfunction of endothelial cells underlies metabolic and vascular alterations that contribute to the development of type 2 diabetes.
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PMID:Endothelial dysfunction and diabetes: roles of hyperglycemia, impaired insulin signaling and obesity. 1894 83

Cardiovascular disease is by far the most common complication of type 2 diabetes and also the most serious one. Suffering from type 2 diabetes mellitus not only dramatically increases the risk of cardiovascular disease but is also associated with poor survival, both acutely and in the long term after a myocardial infarction. In fact, total mortality from coronary artery disease in subjects with type 2 diabetes mellitus, without a previous myocardial infarction, is as high as that of non-diabetic individuals with a previous infarction. Intense research efforts have thus been directed towards exploring the reasons for why particularly type 2 diabetic patients have such a poor prognosis suffering from cardiovascular disease. Obesity-related type 2 diabetes ("diabesity"), including the metabolic syndrome, is rapidly rising in prevalence. About 80% of all type 2 diabetes co-exists with insulin resistance. Endothelial dysfunction is a ubiquitous abnormality in insulin-resistant states that might contribute to premature atherosclerosis in a multifactorial and complex way. Low grade inflammation may play a role in development insulin resistance and type 2 diabetes and it has been proposed that atherosclerosis is basically an inflammatory disease. Thus, the pathophysiology of insulin resistance, the metabolic syndrome, and atherosclerosis may share inflammatory basis as a common denominator. Also, insulin resistance is not confined to skeletal muscle, adipose tissue and the liver, but also to the endothelium. Insulin resistance and endothelial dysfunction co-exist, where chronic inflammation may be a crucial factor. Accordingly, the possibility that physical activity or pharmacological agents that increase insulin sensitivity also improve endothelial function, or vice versa, has been investigated. Many different alterations in life style and drugs that improve endothelial function are known to lower the risk of contracting diabetes. In this review, the pharmacological treatment available against type 2 diabetes mellitus is discussed with particular emphasis on its impact on the endothelium.
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PMID:Hypoglycemic pharmacological treatment of type 2 diabetes: targeting the endothelium. 1903 7

Endothelial dysfunction (ED) has been suggested as a possible causal link between postprandial hyperglycemia and cardiovascular events in patients with type 2 diabetes. Recent trials demonstrated a reduction of cardiovascular events by treatment with alpha-glucosidase inhibitor acarbose - a drug which mainly reduces postprandial glucose excursions. We were interested to know whether patients with newly diagnosed type 2 diabetes showed postprandial ED and if so whether acarbose was able to improve this condition. Forearm blood flow (FBF) measurements for assessment of ED were performed in the fasting and postprandial state in 20 newly diagnosed type 2 diabetic patients and 10 healthy control subjects. After baseline examination, patients were randomly assigned to a 20-week treatment of acarbose 100 mg t.i.d or matching placebo, thereafter FBF measurements were repeated. FBF of patients in the fasting state was significantly impaired compared to healthy control subjects (max. FBF 5.3+/-0.7 vs. 8.0+/-0.9 ml/100 ml, p<0.02) and did not change in the postprandial state (max. FBF 5.6+/-0.7 ml/100 ml). In contrast, healthy controls showed a significant improvement of FBF in the postprandial state (11.5+/-1.2 ml/100 ml), which is compatible with postprandial ED in the group of patients. Twenty weeks of acarbose treatment did not affect either fasting or postprandial FBF in patients. Early type 2 diabetes is a state of both fasting and postprandial ED, which is not sensitive to acarbose treatment. Protective cardiovascular effects of acarbose might involve other mechanisms.
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PMID:Effects of the alpha glucosidase inhibitor acarbose on endothelial function after a mixed meal in newly diagnosed type 2 diabetes. 1906 Nov 52

Obese patients with type 2 diabetes and impaired glucose tolerance are at increased risk of development of cardiovascular diseases. Endothelial dysfunction may be a reason for development of atherosclerosis and cardiovascular diseases. Lifestyle modification, increased physical activity, weight reduction, energy restricted diet and good glycaemia control can be useful for the endothelial function improvement and may decrease the risk of cardiovascular diseases. The aim of this study was to evaluate the effects of basal insulin analog and metformin on glycaemia control and weight as risk factors of endothelial dysfunction. Total of 15 patients (9 male and 6 female) with type 2 diabetes were studied. The patients were monitored over six months period. Glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and body mass index (BMI) were observed. Mean age of the subjects was 53,4 +/- 6,27 years. Mean diabetes duration was 3,71 +/- 1,89 years. At the end of the study mean body mass index decreased from 27,5 +/- 1,45 kg/m2 to 25,7 +/-1,22 kg/m2. In this study we included diabetic patients with fasting glycaemia over 7 mmol/dm3, postmeal glycaemia over 7,8 mmol/dm3 and glycated hemoglobin over 7%. Prior to the study, the patients were treated with premix insulin divided in two daily doses and metformin after the lunch, which did not result in sufficient regulation of glycaemia. We started treatment with one daily insulin basal analog and three daily doses of metformin and monitored the above mentioned parameters. We advised patients to change their lifestyle, to practice energy restricted diet and to increase their daily physical activity. Insulin doses were titrated separately for each patient (0,7-1 IU/kg). Weight reduction was recorded after the study. Mean fasting glycaemia decreased from 8,6+/-0,49 mmol/dm3 to 7,04+/-0,19 mmol/dm3 (p < 0,05). Mean postmeal glycaemia decreased from 9,74 +/- 0,79 mmol/dm3 to 7,6 +/- 0,43 mmol/dm3 (p<0,05). Mean HbA1c decreased from 8,80 +/- 0,59 % to 7,11 +/- 0,22 % (p<0,05). Treatment with one daily doses of basal insulin analog and three daily doses of metformin with lifestyle modification and weight reduction, in obese patients with type 2 diabetes can be useful for the endothelial function improvement and may decrease the risk of cardiovascular diseases.
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PMID:Effects of basal insulin analog and metformin on glycaemia control and weight as risk factors for endothelial dysfunction. 1912

Most of the late diabetic complications such as retinopathy, nephropathy, and neuropathy, have their basis in disturbed microvascular function. Structural and functional changes in the micro-circulation are present in diabetes mellitus irrespective of the organ studied, and the pathogenesis is complex. Endothelial dysfunction, characterized by an imbalance between endothelium-derived vasodilator and vasoconstrictor substances, plays an important role in the pathogenesis of diabetic microangiopathy. Increased circulating levels of endothelin-1 (ET-1), a potent vasoconstrictor peptide, has been found in patients with diabetes, and a positive correlation between plasma ET-1 levels and microangiopathy in patients with type 2 diabetes has been demonstrated. In addition to its direct vasoconstrictor effects, enhanced levels of ET-1 may contribute to endothelial dysfunction through inhibitory effects on nitric oxide (NO) production. Vascular endothelial dysfunction may precede insulin resistance, although the feature of insulin resistance syndrome includes factors that have negative effects on endothelial function. Furthermore, ET-1 induces a reduction in insulin sensitivity and may take part in the development of the metabolic syndrome. In the following, the mechanisms by which ET-1 contributes to the development of diabetic microangiopathy and the potentially beneficial effect of selective ET(A) receptor antagonists are discussed.
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PMID:The importance of endothelin-1 for microvascular dysfunction in diabetes. 1918 53

Endothelial dysfunction is considered to be an early event in the development of atherosclerosis. The present study was undertaken to evaluate endothelial function and biochemical markers in type 2 diabetes mellitus (T2DM) patients before and after treatment with or without pioglitazone (PIO). Forty-one T2DM patients without macroangiopathy were randomized to treatment with (n=20) or without (control, n=21) PIO for 12 weeks. Endothelial function was assessed by flow-mediated vasodilation (FMD) using a high-resolution ultrasound method before and after treatment. After treatment, HbA1c levels equally decreased in both groups, but PIO-treated group had significantly increased high-density lipoprotein cholesterol (HDL-C) levels, and decreased triglyceride, fasting insulin levels and HOMA-R. After treatment, increases in %FMD, plasma HDL-C and adiponectin (APN) levels were significantly greater in PIO-treated group than those in control group. Changes of %FMD showed significant positive correlations with those of plasma APN and HDL-C levels. In conclusion, the present study showed that treatment of T2DM improved endothelial function with greater increases in %FMD, APN and HDL-C levels in PIO-treated group than those in control group, suggesting the beneficial effect of PIO on endothelial function in T2DM.
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PMID:Pioglitazone improves endothelial function with increased adiponectin and high-density lipoprotein cholesterol levels in type 2 diabetes. 1950 30

Insulin resistance, a key feature of obesity, the metabolic syndrome and Type 2 diabetes mellitus, results in an array of metabolic and vascular phenomena which ultimately promote the development of atherosclerosis. Endothelial dysfunction is intricately related to insulin resistance through the parallel stimulatory effects of insulin on glucose disposal in metabolic tissues and NO production in the endothelium. Perturbations characteristic of insulin resistance, including dyslipidaemia, inflammation and oxidative stress, may jeopardize the structural or functional integrity of the endothelium. Recent evidence suggests that endothelial damage is mitigated by endogenous reparative processes which mediate endothelial regeneration. EPCs (endothelial progenitor cells) are circulating cells which have been identified as mediators of endothelial repair. Several of the abnormalities associated with insulin resistance, including reduced NO bioavailability, increased production of ROS (reactive oxygen species) and down-regulation of intracellular signalling pathways, have the potential to disrupt EPC function. Improvement in the number and function of EPCs may contribute to the protective actions of evidence-based therapies to reduce cardiometabolic risk. In the present article, we review the putative effects of insulin resistance on EPCs, discuss the underlying mechanisms and highlight potential therapeutic manoeuvres which could improve vascular repair in individuals with insulin resistance.
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PMID:Effects of insulin resistance on endothelial progenitor cells and vascular repair. 1963 Jul 51


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