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

Several epidemiological studies have reported that the regional distribution of body fat is a significant and independent risk factor for cardiovascular disease (CVD) and related mortality. Although these associations are well established, the causal mechanisms are not fully understood. Numerous studies have, however, shown that specific topographic features of adipose tissue are associated with metabolic complications that are considered as risk factors for CVD such as insulin resistance, hyperinsulinemia, glucose intolerance and type II diabetes mellitus, hypertension, and changes in the concentration of plasma lipids and lipoproteins. The present article summarizes the evidence on the metabolic correlates of body fat distribution. Potential mechanisms for the association between body fat distribution, metabolic complications, and CVD are reviewed, with an emphasis on plasma lipoprotein levels and plasma lipid transport. From the evidence available, it seems likely that subjects with visceral obesity represent the subgroup of obese individuals with the highest risk for CVD. Although body fat distribution is now considered as a more significant risk factor for CVD and related death rate than obesity per se, further research is clearly needed to identify the determinants of body fat distribution and the causal mechanisms involved in the metabolic alterations. It appears certain, however, that an altered plasma lipid transport is a significant component of the relation between body fat distribution and CVD.
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PMID:Regional distribution of body fat, plasma lipoproteins, and cardiovascular disease. 219 40

It is now well recognized that insulin resistance and/or hyperinsulinemia are characteristic of a number of common human disease states including obesity, non-insulin dependent diabetes mellitus (NIDDM), essential hypertension, and atherosclerotic cardiovascular disease. More recent evidence suggests that impaired insulin action and elevated levels of circulating insulin may also be present in a substantial proportion of apparently healthy nonobese individuals. Considerable attention is now being focused on the potential long term adverse consequences of elevated circulating insulin levels. In particular, the frequent concurrence of these clinical disorders of carbohydrate metabolism, lipid metabolism, and vascular disease has led to the hypothesis that insulin resistance and the ensuing hyperinsulinemia may be a common pathophysiologic factor in the etiology of these disease states. In this review, we will examine the evidence for this hypothesis with particular attention to the adverse effects of chronic hyperinsulinemia.
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PMID:Hyperinsulinemia and its sequelae. 220 24

Although the primary defect(s) responsible for the development of type 2 diabetes still is unknown, several recent cross-sectional and longitudinal studies have clarified the sequence of events leading to type 2 diabetes. Relatives of type 2 diabetic patients, who have normal glucose tolerance, are characterized by hyperinsulinemia and insulin resistance compared to relatives with no family history of diabetes. In individuals with impaired glucose tolerance, insulin resistance is more severe than in those with normal glucose tolerance. The acute insulin response is lower in subjects with impaired glucose tolerance than in those with normal glucose tolerance but the decrease in the acute insulin response is similarly related to increases in plasma glucose as in normal subjects. A high postprandial insulin concentration, as well as the degree of insulin resistance, predicts the transition of glucose tolerance from impaired to diabetic. These data suggest that hyperinsulinemia and insulin resistance rather than insulin deficiency predict the subsequent development of type 2 diabetes in individuals genetically susceptible to the disease. As insulin resistance can be ameliorated with therapeutic measures such as weight loss and exercise, apparently healthy individuals with high insulin concentrations and a family history of type 2 diabetes might be regarded as a high-risk group which will require intensive attention from health care professionals.
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PMID:Evidence for a primary role of insulin resistance in the pathogenesis of type 2 diabetes. 220 84

Type II diabetes mellitus may affect as many as 20% of the elderly US population. In the absence of data to support the need to maintain a specific level of glucose beyond that necessary to relieve symptoms, choice of therapy is problematic. Clearly, supervised dietary therapy for the obese type II diabetic patient represents a safe and cost-effective treatment. For those patients who fail dietary therapy because they fail to lose weight or regain lost weight, or because blood glucose levels remain high despite weight loss, further therapy must be individualized. The only rational criteria for drug treatment supportable by currently available data are (1) persistent symptoms associated with hyperglycemia, (2) ketonuria in the unstressed state, and (3) certain cases of hyperlipidemia, especially with triglyceride levels greater than 1000 mg/dl. In these clinical settings, drug therapy is necessary to eliminate symptoms, prevent development of ketoacidosis, and reduce the risk of pancreatitis, respectively. Consideration of drug therapy should also be made in the case of very elevated blood glucose levels, even in the absence of symptoms, when dehydration and risk of severe hyperosmolarity exist. The issues regarding insulin versus sulfonylureas have not been examined specifically in the elderly population. Extrapolating from published studies that generally include patients older than 65 years leads to the following conclusions: Caution regarding adverse side effects of insulin (hypoglycemia, theoretic risk of hyperinsulinemia) and sulfonylureas (hypoglycemia, drug interactions, increased risk of cardiovascular death) must be balanced against the theoretic benefit of treatment in the absence of symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin treatment in the elderly diabetic patient. 222 55

Published "normal" values of some hormones have an excessively wide range and unequal mean values because the material on which these values are based is from subjects suffering from different diseases which only apparently are not associated with the investigated hormone, or else the specimens are obtained under non-standard conditions (malnutrition, stress, alcohol etc.). This wide range of normal values may hide incipient pathological processes and is not suitable even as control group. The investigation is based on the assessment of insulin, growth hormone (GH), cortisol, thyroxine (T4) and triiodothyronine (T3) in a group of blood donors. The assembled results were compared with two other groups of blood donors and a group of obese subjects. The following findings were assembled: We recommend to lower the upper borderline of "normal" insulinaemia from the recommended value of 26 to 20 i.u./l, as the original range may comprise milder forms of hyperinsulinism which is recently assumed to participate in the genesis of type 2 diabetes, hypertension, coronary ischemia and polycystic ovaries. Elevated normal values of serum insulin may be obtained also from blood donors who usually have breakfast before the blood is collected. The wide range of cortisolaemia is due to the diurnal rhythm. The basal value is raised by a declining blood sugar level, alcohol, obesity and of course, varying forms of stress. The upper range of cortisolaemia at 8 a.m. should not be beyond the range of 140-690 nmol/l. GH secretion is governed by an individual 3.5-hour cycle as well as changes of the blood sugar level, e. g. during the OGTT: the declining blood sugar level raises the GH level.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Factors affecting normal levels of insulin, cortisol, STH, thyroxine and triiodothyronine]. 226 67

We studied the association of obesity with serum lipid and lipoprotein concentrations in 117 patients (62 males and 55 females) with NIDDY and in 40 nondiabetic control subjects (21 males and 19 females). Obesity at a young age was related to increased lipid and lipoprotein levels both in the patients with NIDDM and the control group. Moreover, low HDL-c levels were aggravated by diabetic status only in males. The BMI and fasting insulin level had a statistically significant correlation with the TG and HDL-c level and various atherogenic factors. Therefore, it is suggested that the lipid abnormalities seen in obesity may be associated with hyperinsulinemia. We conclude that obesity in adolescence leads to aberrations of the serum lipid and lipoprotein levels, particularly in obese males with NIDDY.
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PMID:Adverse effects of obesity on lipid and lipoprotein levels in the patients with non-insulin dependent diabetes in the young. 228 36

The serum levels of 34K insulin-like growth factor (IGF)-binding protein were measured by RIA in 88 type 1 diabetic patients, 9 patients with type 2 diabetes, 7 patients with insulinoma, 19 normal subjects (all after an overnight fast), and 82 normal subjects after a breakfast meal. In addition, the effect of 2- to 3-h euglycemic steady state hyperinsulinemia on serum IGF-binding protein and IGF-1 levels was studied in some subjects in each of the fasted groups. Compared with normal subjects, the mean serum IGF-binding protein levels were 4-fold (P less than 0.001) higher in type I diabetic patients treated with conventional insulin injections, 2.5-fold (P less than 0.001) higher in those treated with continuous sc insulin infusion, and 2-fold (P less than 0.05) higher in patients with type 2 diabetes. In the patients with insulinoma, the mean IGF-binding protein level was 63% below normal (P less than 0.001), and it normalized after removal of the tumor. There was a slight negative correlation between the IGF-binding protein level and insulin dose in the diabetic patients (r = -0.22; P less than 0.05). In normal subjects, serum insulin concentrations were 2-fold higher (P less than 0.001) and the IGF-binding protein level was 29% lower after a meal (P less than 0.05) than in the fasting state. Serum IGF-I concentrations were virtually identical in the type 1 and 2 diabetic patients, insulinoma patients, and normal subjects. During steady state euglycemic hyperinsulinemia, the IGF-binding protein level fell by 40-70% in each group (P less than 0.001), whereas the IGF-I level declined (P less than 0.05) in the type 2 diabetic patients only. The decline of binding protein was closely related to the baseline level (r = 0.94; P less than 0.001). No correlation was found between serum IGF-I and binding protein levels in any group. In conclusion, 1) serum 34K IGF-binding protein levels are elevated in type 1 and 2 diabetic patients and decreased in patients with insulinoma; 2) the serum binding protein, but not IGF-I concentration is decreased by acute hyperinsulinemia; and 3) these data suggest that the serum insulin concentration plays a role in regulation of the serum 34K IGF-binding protein concentration.
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PMID:Insulin regulates the serum levels of low molecular weight insulin-like growth factor-binding protein. 244 29

62 cases of polycystic ovary syndrome (PCO) were reviewed with regards to their clinical and endocrine features. The subgroup of patients with acanthosis nigricans (AN) was further studied in detail. The prevalence of the syndrome was significantly higher in the Indian (35.5% of cases). Obesity, AN, hirsutism, non-insulin dependent diabetes mellitus (NIDDM) and raised level of serum testosterone were present in 77.1%, 74%, 79%, 21% and 48% of the cases respectively. Patients with AN was associated with higher body mass index, serum testosterone level, and prevalence of hirsutism and NIDDM than patients without AN. These observations are in keeping with the hypothesis that hyperinsulinemia may be of importance in the pathogenesis of a sub-group of PCO associated with insulin resistant states.
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PMID:Clinical and endocrine profiles of 62 Malaysian women with polycystic ovary syndrome. 252 38

Obesity is associated with insulin resistance and type II diabetes mellitus. In the present study, we have characterized hepatic insulin receptor function in two animal models of obesity: the Zucker fatty rat (ZFR), a model of genetic obesity with severe hyperinsulinemia, and the Sprague-Dawley rat with dietary obesity, a model of acquired obesity. Zucker fatty rats were also treated with streptozotocin (STZ) in an effort to examine the effects of relative insulin deficiency and hyperglycemia in the setting of obesity. Using wheat germ agglutinin-purified insulin receptor extracted from liver, no significant difference in insulin binding was identified in either model of obesity. beta-Subunit autophosphorylation was significantly decreased in both obese models relative to that in controls (72% in the obese ZFR and 49% in the overfed Sprague-Dawley model). Kinase activity, as measured by phosphorylation of the 1142-1153 synthetic peptide, was also decreased in both models of obesity by 22% and 64%, respectively. In the Zucker rat, STZ treatment led to an 80% increase in receptor concentration and a further 70% increase in beta-subunit autophosphorylation per receptor, whereas tyrosine kinase activity toward substrate was not altered. Since kinase activity is closely linked to autophosphorylation, we determined the fraction of autophosphorylated (activated) receptors vs. non-phosphorylated (inactive) receptors by using antiphosphotyrosine antibody to precipitate receptors bound with [125I]insulin. There was no significant difference in the percentage of activated insulin receptors in the dietary obese, ZFR, or STZ-treated Zucker rat vs. that in the controls. In all models, the percentage of activated receptors ranged from 32-46% of the total receptor pool. These data suggest that in genetic and acquired obesity, autophosphorylation of the beta-subunit is reduced and is a limiting factor in insulin receptor activation. A similar fraction of all receptors appears to undergo some level of autophosphorylation; however, full autophosphorylation and, thus, activation of the receptor do not occur, and this results in a decrease in kinase activity. This block in autophosphorylation may account for significant reductions in insulin receptor kinase function in obesity.
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PMID:Alterations in the hepatic insulin receptor kinase in genetic and acquired obesity in rats. 255 53

Obesity and fat topography are risk factors for hyperinsulinemia, insulin resistance, and diabetes mellitus. The relative contribution of obesity and body fat distribution indices to fasting and oral glucose-stimulated C peptide, insulin, and glucose concentrations were determined in 33 healthy premenopausal women. Obesity level was assessed by hydrostatic weighing and fat topography by computerized tomography-derived intraabdominal fat area, waist to hip ratio, subscapular skinfold thickness and the ratio of subscapular to triceps skinfold thickness. Both fat mass and regional fat distribution indices were associated closely with changes in insulin secretion. Fat topography indices were more closely correlated (p less than 0.001) to insulin response than were fat mass indices (p less than 0.01). The subscapular skinfold thickness had the greatest integrity for reflecting fat mass and fat distribution as they relate to the metabolic profile. The subscapular skinfold thickness may help identify individuals at risk for noninsulin dependent diabetes mellitus.
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PMID:Relative contribution of obesity and body fat distribution to alterations in glucose insulin homeostasis: predictive values of selected indices in premenopausal women. 265 11


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