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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 3 major components of the dyslipidemia of insulin resistance are increased triglyceride levels, decreased high-density lipoprotein (HDL) cholesterol, and changes in the composition of low-density lipoprotein (LDL) cholesterol. Hyperinsulinemia and the central obesity that typically accompanies insulin resistance are thought to lead to overproduction of very low-density lipoprotein (VLDL) cholesterol. The result is more triglyceride-rich particles, fewer HDL particles, and more small, dense LDL. Postprandial triglyceride levels and measures of postprandial remnants also may contribute to increased coronary artery disease (CAD) risk in individuals with insulin resistance. Deficiency of lipoprotein lipase, an insulin-sensitive enzyme, might explain the abnormal levels of remnant particles in insulin resistance. The potential benefits of successful treatment of dyslipidemia are illustrated by clinical trials in patients with the dyslipidemia characteristic of insulin resistance (i.e., normal or only moderately elevated LDL, elevated VLDL, and low HDL). Both weight loss and exercise can improve insulin resistance and associated dyslipidemia. In patients with type 2 diabetes mellitus, certain antidiabetic therapies can also improve the lipid profile by improving insulin resistance.
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PMID:Insulin resistance and lipid metabolism. 1041 56

Type 2 diabetes is a heterogeneous disorder. Clinical expression of the disorder requires both genetic and environmental factors. One theory concerning its etiology is that it is the result of the evolution of a thrifty genotype that had survival benefits in the past but is detrimental in the current environment. An opposing theory is that it represents an adult metabolic response to fetal malnutrition. Hyperglycemia in type 2 diabetes results from absolute or relative insulin deficiency. Most often relative insulin deficiency is attributable to an inability to adequately compensate for insulin resistance. Insulin resistance may be caused by a variety of genetic or metabolic factors. The most common etiological factor in insulin resistance is central obesity. Insulin resistance is associated with a cluster of metabolic abnormalities that include glucose intolerance, hypertension, a unique dyslipidemia, a procoagulant state, and an increase in macrovascular disease. Clinical intervention studies have demonstrated that reduction in the chronic microvascular and macrovascular complications of type 2 diabetes requires treatment of hyperglycemia to achieve hemoglobin A1c <7.0%, blood pressure </=130/80 mmHg, and plasma LDL-cholesterol </=2.6 mmol/L (</=100 mg/dL). Oral antihyperglycemic agents increase endogenous insulin secretion, decrease insulin resistance, or lower postprandial plasma glucose rise by delaying absorption of complex carbohydrates. Long-term glycemic control in type 2 diabetes requires progressive, stepwise, combination treatment with oral agents and eventually combination treatment with oral agents and insulin.
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PMID:Type 2 diabetes: an overview. 1043 Aug 16

Dietary restriction (DR) is the only intervention that has been shown to increase average and median life span in laboratory rodents. The effect of long-term, moderate DR on body composition and fat distribution was evaluated in male rhesus monkeys. Thirty animals (8-14 years of age)fed either 30% less than baseline intake (R, n = 15) or allowed to eat to satiety (C, n = 15), have been assessed semiannually using somatometrics and dual-energy alpha-ray absorptiometry (DXA)for 7.5 years. R subjects have reduced body weight (p <.0001), total body fat (p < .0001), and percentage body fat located in the abdominal region (p < .05). In addition, there has been a sustained reduction in plasma leptin concentrations (p <.001). These findings suggest reduced risk for common morbidities, such as insulin resistance, dyslipidemia, and type 2 diabetes mellitus, that are associated with advancing age and increased levels of bodyfat, especially in the visceral depot.
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PMID:Body fat distribution with long-term dietary restriction in adult male rhesus macaques. 1046 60

Recent studies have suggested that hypercholesterolemia is associated with endothelial dysfunction. In patients with type 2 diabetes mellitus, dyslipidemia is mainly characterized by hypertriglyceridemia, low high density lipoprotein, and a preponderance of small dense low density lipoprotein (LDL) particles. We have examined the relationships among LDL subfractions, the susceptibility of LDL to oxidation in vitro, and endothelial function in type 2 diabetes mellitus. LDL subfractions were measured by density gradient ultracentrifugation. The susceptibility of LDL to oxidation was determined by measuring the kinetics of conjugated dienes formation during copper-mediated oxidation of LDL. Endothelium-dependent and independent vasodilation of the brachial artery were assessed by high resolution vascular ultrasound. Diabetic patients had a higher concentration of small dense LDL-III than matched controls (P < 0.01). The lag phase of conjugated dienes formation was shorter in the diabetic patients (P < 0.05), and the rate of LDL oxidation was faster (P < 0.05). Both endothelium-dependent (P < 0.01) and independent dilation of the brachial artery (P < 0.01) were impaired in the diabetic patients. On multivariate analysis, the rate of oxidation and LDL-III concentration accounted for 12% and 6%, respectively, of the variation in endothelium-dependent vasodilation (adjusted r2 = 0.18; P < 0.05), whereas LDL-III concentration and the maximum amount of conjugated dienes formed accounted for 27% and 5%, respectively, of the variation in endothelium-independent vasodilation (adjusted r2 = 0.32; P < 0.01) in the diabetic patients. In conclusion, endothelial and smooth muscle cell dysfunction in type 2 diabetes were related to abnormalities in LDL subfractions and in LDL oxidation.
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PMID:Influence of low density lipoprotein (LDL) subfraction profile and LDL oxidation on endothelium-dependent and independent vasodilation in patients with type 2 diabetes. 1048 89

Hypertensive subjects have increased cardiovascular risk factors including dyslipidemia and increased rates of diabetes and hypertension. Insulin resistance is increased in hypertensive subjects, especially lean subjects. Increased insulin resistance in hypertensive subjects may partially mediate the more atherogenic pattern of cardiovascular risk factors in diabetic subjects. Hypertensive subjects are also at increased risk of developing type 2 diabetes possibly by increasing insulin resistance. Hypertensive subjects at particularly high risk of developing type 2 diabetes (i.e. obese or with a family history of type 2 diabetes) should avoid beta-blockers and thiazides.
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PMID:Metabolic predictors of hypertension. 1048 95

Combined hyperlipidaemia, associating hypercholesterolaemia and hypertriglyceridaemia, is a common metabolic disorder with a prevalence of about 1/500. It has a genetic background, but its phenotype is triggered by various predisposing factors such as obesity, type 2 diabetes and alcohol consumption. Combined hyperlipidaemia is undoubtedly associated with an increased cardiovascular risk and thus deserves specific management. After diet failure, the first drug choice remains controversial. Indeed, fibrates are more active on hypertriglyceridaemia while statins are more active on hypercholesterolaemia (LDL subfraction). Both pharmacological classes have their advantages and disadvantages, and there is no prospective study comparing the cardiovascular protective efficacy of these two treatments in patients with such dyslipidemia. Furthermore, monotherapy is generally incapable of normalizing the lipid profile in the presence of severe combined hyperlipidaemia. Ideally, a statin-fibrate combination would be most appropriate in order to act on the two components of such hyperlipidaemia and to benefit of the complementary and additive action of the two pharmacological classes. Such association is still contra-indicated because of the description of some cases of rhabdomyolysis is high risk patients; however, it now deserves much interest and is currently being tested in large prospective studies, especially in the population with type 2 diabetes.
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PMID:[Treatment of combined hyperlipidemia: fibrate and/or statin?]. 1049 79

The relationship between insulin resistance, soluble adhesion molecules E-selectin (sE-selectin), intracellular adhesion molecule-1 (sICAM-1), and vascular adhesion molecule-1 (sVCAM-1), mononuclear cell binding to cultured endothelium, and lipoprotein concentrations were evaluated in 28 healthy, nondiabetic, and normotensive individuals. The mean (+/-SEM) lipid and lipoprotein concentrations were within the normal rage: cholesterol (199 +/- 18 mg/dL); triglyceride (128 +/- 12 mg/dL); low-density cholesterol (127 +/- 8 mg/dL; and high-density cholesterol (47 +/- 3 mg/dL). The results indicated that degree of insulin resistance was significantly correlated with concentrations of sE-selectin (r = 0.54, P < 0.005), sICAM-1 (r = 0.67, P < 0.001), and sVCAM-1 (r = 0.41, P < 0.05). Furthermore, the relationship between insulin resistance and both sE-selectin and sI-CAM-1 remained statistically significant when adjusted for differences in age, gender, body mass index, and all measures of lipoprotein concentrations. Finally, mononuclear cell binding correlated significantly with concentrations of sE-selectin (r = 0.54, P < 0.005) and sICAM-1 (r = 0.47, P < 0.01). These findings raise the possibility that previously described relationships between soluble adhesion molecules in patients with hypertension, type 2 diabetes, and dyslipidemia may be due to the presence of insulin resistance in these clinical syndromes and suggests that insulin resistance may predispose individuals to coronary heart disease by activation of cellular adhesion molecules.
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PMID:Relationship between insulin resistance, soluble adhesion molecules, and mononuclear cell binding in healthy volunteers. 1052 84

Genetic studies of the type 2 diabetes-like GK rat have revealed several susceptibility loci for the compound diabetes phenotype. Congenic strains were established for Niddm1, the major quantitative trait locus (QTL) for postprandial glucose levels, by transfer of GK alleles onto the genome of the normoglycemic F344 rat. Despite the polygenic nature of diabetes in GK, the locus-specific diabetes phenotype was retained in the congenic strain Niddmla, containing a GK-derived genomic fragment of 52 cM from the Niddm1 locus. Furthermore, Niddm1 was divided into two non-overlapping loci, physically separated in the two congenic strains Niddmlb and Niddm1i with distinct metabolic phenotypes. Both strains displayed postprandial hyperglycemia and reduced insulin action in isolated adipose cells. Furthermore, Niddm1i already exhibits a pronounced in vivo insulin secretion defect at 65 days, while Niddm1b develops a relative insulin secretory defect at 95 days. This suggests that Niddm1i impairs mechanisms common to insulin secretion in pancreatic B-cells and insulin action in adipocytes. Niddm1b rats show signs of increasing insulin resistance with age associated with obesity, hyperinsulinemia, and dyslipidemia. Moreover, the data indicated nonallelic interaction (epistasis) between Niddm1b and Niddm1i on the postprandial glucose levels. These data emphasize the pathophysiological complexity of diabetes, even within an apparently single QTL, and demonstrate the potential of the GK model in transforming the multifactorial diabetes phenotype into single traits, suitable for positional cloning.
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PMID:Pathophysiological and genetic characterization of the major diabetes locus in GK rats. 1058 Apr 37

The prevalence of overweight and obesity has increased dramatically in the recent decades, and obesity is now a major public health problem. Obesity negatively influences an individual's health by increasing mortality and raising the risk for multiple medical conditions such as type 2 diabetes mellitus, hypertension, dyslipidemia, and coronary heart disease. In addition, the obese individual is often the brunt of social discrimination. Weight loss has been shown to reduce the risk for many of these comorbid conditions. A multifaceted approach to the obese patient should include identifying potential causes for weight gain, outlining medical conditions that would benefit by weight loss, and tailoring a weight loss program that is safe and effective for the individual. Components of a successful weight loss program include dietary intervention, recommendations for physical activity, behavior modification, and, in a select group of patients, pharmacologic or surgical intervention.
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PMID:Safe and effective management of the obese patient. 1059 55

The purpose of this study was to examine characteristics associated with the insulin metabolic syndrome, including insulin resistance, abnormal glucose tolerance, dyslipidemia, obesity, and elevated blood pressure, among women who have experienced gestational diabetes. 39 nondiabetic, young (20-42 years), postpartum (3-18 months) white women were recruited from obstetrical clinics. Twenty-one women had a history of gestational diabetes; 18 had uncomplicated pregnancies. Multivariate analyses revealed a significant difference between groups in insulin resistance (M, measured by euglycemic clamp) and insulin levels (from an oral glucose tolerance test), with insulin resistance showing a statistically stronger difference than insulin levels. Groups also differed significantly when compared on a set of variables associated with insulin metabolic syndrome: glucose tolerance, triglycerides, blood pressure, and body-mass index. Using insulin resistance as a covariate eliminated these group differences, suggesting that insulin resistance is the key factor underlying insulin metabolic syndrome. The higher risk of later developing type 2 diabetes and hypertension in women who have a history of gestational diabetes is explicable by their poorer profile on variables associated with insulin metabolic syndrome, and appears to be attributable to insulin resistance. Thus, insulin resistance appears to distinguish young women at risk for cardiovascular disease.
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PMID:History of gestational diabetes, insulin resistance and coronary risk. 1061 62


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