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Query: UMLS:C0011860 (type 2 diabetes)
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Acanthosis nigricans is a skin lesion characterized by thickening and apparent darkening of the keratin layer of the skin, usually on the neck and axillae. Recent studies reveal that this disorder is directly associated with hyperinsulinemia. A major implication of hyperinsulinemia is insulin resistance--a primary factor in the development of type II diabetes mellitus. Prolonged hypersecretion of insulin presumably leads to pancreatic exhaustion and subsequent glucose intolerance that can progress to type II diabetes. Prospective studies of individuals with acanthosis nigricans have shown very high prevalence rates of type II diabetes. Prevalence studies among adolescents have shown that the lesion appears early in life and is a common finding in some ethnic groups. These data suggest that acanthosis nigricans is an easily detected empirical marker for elevated risk of type II diabetes. The lesion can appear long before the onset of glucose intolerance. Thus, including acanthosis nigricans screening in a comprehensive disease-prevention program can help identify people at risk for type II diabetes prior to the actual onset of glucose intolerance, as well as individuals with undiagnosed diabetes. Interventions that reduce insulin resistance include weight loss and regular physical activity.
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PMID:Assessment of patients with acanthosis nigricans skin lesion for hyperinsulinemia, insulin resistance and diabetes risk. 154 62

We analyzed O-GTT obtained from 375 children (group A; 7-11 years old) and adolescents (group B; 12-16 years old), including 96 normal non-obese cases, 266 simple obese cases (172 with normal O-GTT, 79 with border line type O-GTT and 15 with diabetic type O-GTT), 8 obese NIDDM cases and 5 non-obese NIDDM cases. The results were as follows; 1) The levels of epsilon CPR (in terms of total sum of the values measured at 0, 30, 60, 120 and 180 minutes on O-GTT) in the obese children and adolescents were only 1.5 and 1.2 times as high as in the control group. The levels of epsilon CPR/epsilon IRI molar ratio in the control group were 2.0 and 2.3 times as high as in the obese children and adolescents. These data suggest that hyperinsulinemia in the obese children and adolescents is caused mainly by decreased hepatic insulin extraction rather than by increased insulin secretion. 2) In the non-obese NIDDM adolescents, the levels of epsilon CPR decreased to about 3/4 of those in the control group; in contrast, the epsilon CPR/epsilon IRI molar ratio increased. Therefore, it seems that there is increased hepatic insulin extraction as well as decreased insulin secretion in the non-obese NIDDM adolescents. 3) In the obese NIDDM adolescents, the levels of epsilon CPR were nearly the same as in the control group and the epsilon CPR/epsilon IRI molar ratios were slightly lower as the disease state of NIDDM counterbalanced obesity.
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PMID:[Studies on insulin secretion and clearance in obese and diabetic children (7-11 years old) and adolescents (12-16 years old) investigation by oral glucose tolerance tests (O-GTT)]. 154 73

It is well known that intensive insulin treatment of non-insulin-dependent diabetics (NIDDM) suppresses endogenous insulin secretion and thereafter improves it. To determine whether 'peripheral normo-insulinemia' or 'normoglycemia' established by the treatment is responsible for this suppression, the following five experiments were conducted on 15 well-controlled non-obese NIDDM patients. Experiment 1: a 100 g oral glucose load (OGL) was performed and blood glucose was monitored by an artificial endocrine pancreas (AP). Experiment 2: a 100 g OGL was done and blood glucose was normalized by AP-controlled insulin infusion. Experiments 3 and 4: a 100 g OGL was conducted while 'hyperglycemia' seen in experiment 1 was mimicked by AP-controlled glucose infusion with pre-programmed insulin infusion at the same rates as those in experiment 2 ('normoinsulinemia') or at rates 1.5 times higher than those in experiment 2 ('relative hyperinsulinemia'), respectively. Experiment 5: a 40 g OGL was conducted while AP-controlled insulin and glucose infusions were administered to make the plasma insulin level lower than in experiment 2 ('hypoinsulinemia') and to mimic the normoglycemic profile observed in experiment 2, respectively. In experiments 3 and 4, neither 'normoinsulinemia' nor 'relative hyperinsulinemia' suppressed the increase in plasma C-peptide after a 100 g OGL. In experiment 5, where the plasma insulin level showed a significantly (P less than 0.05) lower level than in experiment 2 and glycemia was normalized, C-peptide did not show a significant rise after OGL. These results indicate that 'normoglycemia' rather than 'normoinsulinemia' attained during exogenous insulin therapy, is responsible for suppressing endogenous insulin secretion against orally administered glucose.
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PMID:Normoglycemia per se but not normoinsulinemia is responsible for suppressing endogenous insulin secretion after oral glucose load in NIDDM. 156 27

Diabetes mellitus and hypertension are common diseases that coexist at a greater frequency than chance alone would predict. Hypertension in the diabetic individual markedly increases the risk and accelerates the course of cardiac disease, peripheral vascular disease, stroke, retinopathy, and nephropathy. Our understanding of the factors that markedly increase the frequency of hypertension in the diabetic individual remains incomplete. Diabetic nephropathy is an important factor involved in the development of hypertension in diabetics, particularly type I patients. However, the etiology of hypertension in the majority of diabetic patients cannot be explained by underlying renal disease and remains "essential" in nature. The hallmark of hypertension in type I and type II diabetics appears to be increased peripheral vascular resistance. Increased exchangeable sodium may also play a role in the pathogenesis of blood pressure in diabetics. There is increasing evidence that insulin resistance/hyperinsulinemia may play a key role in the pathogenesis of hypertension in both subtle and overt abnormalities of carbohydrate metabolism. Population studies suggest that elevated insulin levels, which often occurs in type II diabetes mellitus, is an independent risk factor for cardiovascular disease. Other cardiovascular risk factors in diabetic individuals include abnormalities of lipid metabolism, platelet function, and clotting factors. The goal of antihypertensive therapy in the patient with coexistent diabetes is to reduce the inordinate cardiovascular risk as well as lowering blood pressure.
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PMID:Diabetes mellitus and hypertension. 156 57

Individual dietary regulation is still an important part of all forms of treatment of diabetes. In insulin dependent diabetes (IDDM) it is rational to advise the patient 1) to arrange his diet so that this results in a low glycaemic response, which implies a relatively high intake of dietary fibre and polysaccharides, 2) to distribute the food into 5-6 daily meals and 3) to consume a low-fat diet. This prevents too pronounced postprandial hyperglycaemia and hypoglycaemia between meals. Simultaneously, insulin sensitivity is increased and not only the insulin requirement but also peripheral hyperinsulinism tend to be reduced. Dietary regulation in IDDM is thus a compensation for the defective synchronization of variations in the plasma levels of glucose and insulin in the present day forms of insulin therapy. Nine out of ten diabetic patients are non-insulin dependent (NIDDM). The great majority are obese, 50% have essential hypertension and just as many have dyslipidaemia (raised serum triglyceride and reduced serum high density lipoprotein (HDL)-cholesterol). The condition is characterized pathophysiologically by insulin resistance in muscle, fat and liver tissue and delayed and frequently reduced glucose-stimulated secretion of insulin. The most important element in dietary regulation in NIDDM is, therefore, reduction of the energy content of the food with the object of achieving and maintaining reduction in weight. Even moderate reduction, in the majority of NIDDM patients, will have the effect that metabolism of carbohydrates and lipids becomes approximately normal on account of considerable increase in insulin sensitivity and to a lesser degree increased secretion of insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Dietary treatment of diabetes mellitus. Background and rationale for recommendations in the 1990's]. 141 88

Non-insulin-dependent diabetes (NIDDM) has long been recognized as being associated with a cluster of disorders including obesity, hypertension, dyslipidemia, and atherosclerotic heart disease. It was only recently, however, that Reaven, DeFronzo, and Ferrannini with techniques to quantitate insulin resistance suggested that this represents a common factor in this group of disorders and that hyperinsulinemia resulting from insulin resistance could be the cause of the hypertension, dyslipidemia, and atherosclerosis. The names syndrome X or the insulin-resistance syndrome have been used to identify this pathological entity, and considerable investigations have been done and are in progress to establish whether or not these coexisting disorders represent an as yet unexplained association of cardiovascular risk factors or if, indeed, insulin resistance and hyperinsulinism represent the primary cause for most of the other disorders. To paraphrase a philosophical comment, if syndrome X did not exist, we probably would have had to invent it. In addition to the intellectual satisfaction of being able to "lump" these diverse ills under a single etiology, the main value of grouping these disorders as a syndrome is to continually remind physicians that the therapeutic goals are not only to correct hyperglycemia in NIDDM but also to manage the elevated blood pressure and dyslipidemia that cause cerebrovascular and cardiac morbidity as well as mortality in these patients. Having a syndrome X reduces the fragmentation of medical care among subspecialties and decreases the likelihood of prescribing drugs that correct hypertension but raise lipids or drugs that lower lipids but raise blood glucose. Finally, it encourages the selection of drugs that reduce hyperglycemia without increasing insulin secretion and to the development of new drugs for this purpose. Unfortunately, the concept of insulin resistance with hyperinsulinism being a cause of the other associated disorders is still unproved but continues to be open to experimental investigation. The remainder of this article reviewed the use of sulfonylureas in the management of NIDDM, discussed new molecular and cellular mechanisms by which they promote insulin secretion, and reviewed the controversy as to whether an extrapancreatic action contributes to their glucose-lowering effects in NIDDM. A closing section listed some other oral drugs that can lower blood glucose without stimulating the pancreatic beta cell. Their insulin-sparing hypoglycemic effect makes them potentially useful in NIDDM therapy, particularly if the fundamental premise of syndrome X is substantiated, which implicates hyperinsulinemia as contributing to the morbidity and mortality from atherosclerotic vascular disease.
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PMID:Type II diabetes and syndrome X. Pathogenesis and glycemic management. 161 69

Recent research has demonstrated that reduced insulin-stimulated glucose metabolism in skeletal muscle (insulin resistance) and hyperinsulinism are common features in widespread diseases such as essential hypertension, android obesity, non-insulin dependent diabetes mellitus, dyslipidemia (in the form of raised serum triglyceride and reduced serum high-density lipoprotein (HDL) cholesterol) and arteriosclerosis. Simultaneously, investigations in a comprehensive group of healthy middle-aged men have revealed insulin resistance in one fourth. On the basis of these observations, a working hypothesis is suggested which postulates that genetic abnormalities in one or more of the candidate genes in the modes of action of insulin occur in a great proportion of the population. These may result in insulin resistance (primary genetic insulin resistance). Primary insulin resistance may be potentiated by a series of circumstances such as ageing, high-fat diet, lack of physical activity, hormonal and metabolic abnormalities or drugs (secondary insulin resistance). As a consequence of the reduced effect of insulin on muscle tissue, compensatory hyperinsulinism develops. Depending on the remaining vulnerability of the individual the hyperinsulinism is presumed to result in development of one or more phenotypes. For example if the beta-cells of the pancreas are unable to secrete sufficient insulin to compensate the insulin resistance on account of genetic defects, glucose intolerance will develop. In a similar manner, hyperinsulinism in insulin-resistant individuals who are predisposed to essential hypertension is presumed to reveal genetic defects in the blood pressure regulating mechanisms and thus contribute to development of the disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Insulin resistance--a physiopathological condition with numerous sequelae: non-insulin-dependent diabetes mellitus (NIDDM), android obesity, essential hypertension, dyslipidemia and atherosclerosis]. 163 67

There is experimental, clinical and epidemiological evidence that elevated insulin levels are associated with development of atherosclerosis. Early results came from studies in non-diabetics, but the situation with respect to diabetes is more complex and not so clear. The Diabetes Intervention Study is a population-based follow-up study in newly detected type II diabetics (30- to 55-yr-old). After 5 years 431 men and 320 women received a complex check up with oral glucose tolerance tests and measurements of plasma insulin and glucose levels, fasting and 2h post-load. Regarding the metabolic parameters, the fasting and postprandial insulin levels were higher among the patients having coronary heart disease (15% of men, 36% of women), as compared to patients without this disease. In multivariate analysis sex, age, antihypertensive treatment, blood pressure, body mass index, and fasting insulin levels were independently associated with the prevalence of coronary heart disease in patients with non-insulin dependent diabetes mellitus (NIDDM) treated with diet and/or oral antidiabetics. Body mass index and triglycerides were the only variables that independently correlated to insulin: fasting insulin = 0.4 (body mass index) + 0.1 (triglycerides) - 4,2. In future prospective studies of diabetics relating insulin concentrations to the development of vascular disease are of particular interest and necessity. Because hyperinsulinemia may contribute to accelerated atherosclerosis in NIDDM-patients, the aim of the treatment of type II-diabetes should be to correct hyperglycemia without aggravating insulin levels and other cardiovascular risk factors.
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PMID:[Coronary heart disease and insulin concentration in type II diabetic patients--results of a diabetes intervention study]. 164 23

The long-acting effect of a 10-min pulse infusion of the beta 2-adrenergic agonist fenoterol on oral glucose tolerance tests in controls and in normotensive patients with type 2 diabetes mellitus on diet was compared. During an oral glucose load starting 2 h after fenoterol control persons showed hyperglycemia (area: 25,950 +/- 467 vs. 22,650 +/- 410, P less than 0.01), hyperinsulinemia (area: 13,980 +/- 1050 vs. 8160 +/- 405, P less than 0.02) and a pronounced fall of serum potassium (area: 775 +/- 26 vs. 748 +/- 25, P less than 0.02). The patient group showed no late response to fenoterol: plasma glucose (area: 51,000 +/- 382 vs. 51,300 +/- 413, n.s.), serum insulin (area: 7215 +/- 233 vs. 8280 +/- 410, n.s.), serum potassium (area: 748 +/- 26 vs. 750 +/- 24, n.s.). The data show that there is a defect of the beta 2-adrenergic long-acting effect on glucose metabolism and on insulin release in type 2 diabetes mellitus.
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PMID:Lack of beta 2-adrenoceptor induced long-acting effect on glucose tolerance in type 2 diabetic patients. 166 46

Hyperinsulinemia, hypertension, hypertriglyceridemia and obesity are independent risk factors for coronary artery disease and are often found in the same person. This study investigated the effects of an intensive, 3-week, dietary and exercise program on these risk factors. The group was divided into diabetic patients (non-insulin-dependent diabetes mellitus [NIDDM], n = 13), insulin-resistant persons (n = 29) and those with normal insulin, less than or equal to 10 microU/ml (n = 30). The normal groups had very small but statistically significant decreases in all of the risk factors. The patients with NIDDM had the greatest decreases. Insulin was reduced from 40 +/- 15 to 27 +/- 11 microU/ml, blood pressure from 142 +/- 9/83 +/- 3 to 132 +/- 6/71 +/- 3 mm Hg, triglycerides from 353 +/- 76 to 196 +/- 31 mg/dl and body mass index from 31.1 +/- 4.0 to 29.7 +/- 3.7 kg/m2. Although there was a significant weight loss for the group with NIDDM, resulting in the decrease in body mass index, 8 of 9 patients who were initially overweight were still overweight at the end of the program, and 5 of the 8 were still obese (body mass index greater than 30 kg/m2), indicating that normalization of body weight is not a requisite for a reduction or normalization of other risk factors. Insulin was reduced from 18.2 +/- 1.8 to 11.6 +/- 1.2 microU/ml in the insulin-resistant group, with 17 of the 29 subjects achieving normal fasting insulin (less than 10 microU/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of diet and exercise in the management of hyperinsulinemia and associated atherosclerotic risk factors. 173 2


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