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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

Diabetic nephropathy is the most important complication of diabetes, because it is a major cause of morbidity and mortality for diabetic subjects. Since not all subjects with diabetes are at risk of developing this complication, we conducted a study to determine if heredity might be a possible risk factor for diabetic nephropathy in non-insulin dependent diabetes. Twenty-one factors including inheritance of nephropathy and hypertension were investigated in 109 individuals with NIDDM: 50 patients without proteinuria (Group I), 20 patients with intermittent proteinuria (Group II), and 39 patients with continuous proteinuria (Group III) matched for age and duration of diabetes. Of those patients, 55 patients with inheritance of diabetes were also divided into three groups: 29 patients without proteinuria (Group I), 9 patients with intermittent proteinuria (Group II), and 17 patients with continuous proteinuria (Group III). Individuals in Groups II and III has significantly higher frequency of inheritance of diabetic nephropathy than those in Group I, and also individuals with inheritance of diabetic nephropathy had significantly higher frequency of diabetic nephropathy than those without it. Frequency of hypertension, retinopathy and body mass index in the past were significantly higher in subjects in Groups II or Group III than in those in Group I. There were no significant differences between subjects in Groups II and III. These findings suggest that susceptibility to diabetic nephropathy in NIDDM may be hereditary, although hypertension and obesity may also be important risk factors for diabetic nephropathy.
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PMID:[The possibility of hereditary factors in the susceptibility to diabetic nephropathy in NIDDM]. 163 29

Zinc is known to have important effects on insulin activity, to increase the body fat deposition, and thyroid hormones conversion (T4 to T3). It is also known to have intestinal absorption competition between zinc and copper. This study was to investigate the blood zinc and copper concentrations in NIDDM and obesity, the relationships among metals, insulin, and thyroid hormones were also determined. Blood samples of diabetic, obese, and healthy individuals were collected between 9-10 AM, and the blood levels of zinc, copper, insulin, T4 and T3 were assayed. The results showed that diabetics and obese individuals had higher insulin and T3 levels than healthy controls, but there was no difference in T4. The obese had lower serum zinc concentration. There were low levels of copper both in serum and erythrocyte, and a low erythrocyte zinc concentration in NIDDM. Blood zinc concentration was inversely related to T3 level in diabetics and obese individuals. It is suggested that zinc, insulin and T3 may have considerable correlations in the thermoregulation on NIDDM and obesity, and the true mechanisms still need more further studies in the future.
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PMID:[Investigation on the relationships among blood zinc, copper, insulin and thyroid hormones in non-insulin dependent diabetes mellitus and obesity]. 166 81

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

We have examined the relationships between obesity indices and various metabolic parameters in seven obese (body mass index (BMI) mean +/- s.e.m. 42 +/- 2.5 kg/m2), ten nonobese (BMI 25.3 +/- 1.2 kg/m2) nondiabetic female relatives of black patients with NIDDM and eight healthy controls (BMI 24.5 +/- 1.1 kg/m2). Despite the greater BMI in the obese relatives, percent body fat was not different from that of the nonobese relatives (38 +/- 2 vs 34 +/- 3 percent). Both values were, however, significantly (P less than 0.05) greater than that of the healthy controls (25 +/- 3 percent). Mean waist-to-hip circumference ratio (WHR) was greatest in obese relatives (0.89 +/- 0.01), intermediate in nonobese relatives (0.83 +/- 0.01) and least in the healthy controls (0.77 +/- 0.04). Mean sum of skinfold thickness from biceps, triceps and subscapular (SS) region was also greatest in obese relatives, intermediate in nonobese relatives and least in controls. Centrality index was not, however, different among the groups. Mean fasting serum glucose levels were slightly higher but not significantly different in the relatives compared to controls (obese 82 +/- 3; nonobese 81 +/- 4; controls 75 +/- 3 mg/dl). Following oral glucose ingestion, serum glucose rose to significantly (P less than 0.05) greater levels at 30, 60 and 90 min in the relative subgroups vs controls. Mean fasting and post-prandial peak serum insulin concentrations were significantly (P less than 0.05-0.01) greater in both relative subgroups vs controls. While mean serum glucose profiles and glucose disappearance decay (KG) following intravenous glucose load were identical in the relatives and controls, serum insulin responses were significantly greater in the relatives. The mean basal and post-stimulation serum C-peptide concentrations were similar in all the three groups, irrespective of the stimulus; thus suggesting a reduced hepatic insulin extraction in the relatives. Fasting serum cholesterol, triglyceride, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) as well as FFA levels were not different between the relatives and controls despite the hyperinsulinemia in the former group. WHR correlated with basal insulin in the relatives (r = 0.416, P less than 0.05) and controls (r = 0.68, P less than 0.01) but not with stimulated insulin, lipids and lipoproteins in any of the groups. In contrast, both percent BFM and SS thickness correlated significantly (P less than 0.001) with post-glucose insulin concentrations in the relatives only.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Relationships of obesity indices to serum insulin and lipoproteins in relatives of black patients with noninsulin-dependent diabetes mellitus (NIDDM). 189 21

Computed-tomography scanning and magnetic-resonance imaging (MRI) have been used to quantify intraabdominal and subcutaneous fat depots. In this study MRI was used to define fat-distribution patterns in 24 obese females with non-insulin-dependent diabetes (NIDDM) and 12 females with simple obesity. Subjects had anthropometric measurements and single-slice abdominal scans performed at the umbilicus. In addition, in 10 of the nondiabetic females, measurements were repeated after 10 wk of a very-low-calorie diet. Nondiabetic females had significantly less intraabdominal fat (P less than 0.01) than did the diabetics but had equivalent subcutaneous fat. There was no significant relationship between waist-to-hip ratio and intraabdominal fat, subcutaneous fat, or their ratio. After a weight loss of 10.6 +/- 3.8 kg there were significant decreases in both intraabdominal and subcutaneous fat (P less than 0.01). Weight loss is associated with decreases in fat in both depots.
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PMID:Magnetic-resonance imaging used for determining fat distribution in obesity and diabetes. 189 68

Hyperinsulinaemia links non-insulin dependent diabetes (NIDDM), obesity, and hypertension, each an insulin-resistant state in its own right. Insulin resistance predicts the occurrence of NIDDM, and plays a major role in its pathogenesis. We tested the hypothesis that hyperinsulinaemia may also predict hypertension in a sample (n = 2905) of the mixed population of San Antonio, in which hyperinsulinaemia and NIDDM are more prevalent among Mexican-Americans than non-Hispanic whites. Whilst in the whole sample the hypertensives had significantly (P less than 0.001) higher plasma insulin concentrations than the normotensives, high blood pressure was significantly (P less than 0.01) more frequent among non-Hispanic whites than Mexican-Americans regardless of diabetes status. After adjusting for factors (age, sex, body mass, and body fat distribution) known to affect insulin levels, a direct relationship between post-glucose plasma insulin concentrations and prevalence of hypertension was still present in both ethnic groups. In Mexican-Americans, however, the standardized prevalence of hypertension was significantly (P less than 0.001) lower at any given insulin concentration. Post-glucose plasma glucose levels also were directly related to hypertension prevalence in both groups; again, the regression line was shifted downward and, furthermore, less steep (P less than 0.02) in Mexican-Americans, suggesting relative protection against the negative effect of hyperglycaemia on blood pressure. Dyslipidaemia (higher total cholesterol and triglyceride, and lower HDL-cholesterol concentrations) was strongly associated with hyperinsulinaemia and blood pressure in both ethnic groups. After adjusting for plasma insulin, only hypertriglyceridaemia was associated with high blood pressure, with no inter-ethnic difference.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:High blood pressure and insulin resistance: influence of ethnic background. 190 31

Plasma insulin-like growth factor-I (IGF-I) concentrations and the effects of exogenous IGF-I administration were determined in 26 rhesus monkeys; each animal was well characterized regarding its degree of obesity, plasma glucose and insulin levels, and glucose tolerance (KG). Five separate groups were identified: lean normal, obese normoinsulinemic and normoglycemic, obese hyperinsulinemic with normal glucose tolerance, impaired glucose tolerant, and spontaneously diabetic (type II, non-insulin-dependent diabetes mellitus [NIDDM]). Basal plasma IGF-I levels in all monkeys ranged from 249 to 1,093 ng/mL and were strongly associated with age (r = -.66; P less than .001) and KG (r = .59; P less than .001), but not with body weight, body fat, or fasting plasma glucose or insulin levels. In addition, the acute insulin-like effects of exogenously administered IGF-I on glucose disappearance were studied in vivo in a dose-response comparison to insulin (subcutaneous administration of IGF-I at doses of 50, 100, or 200 micrograms/kg v insulin at 0.3 U/kg). Five hyperinsulinemic normoglycemic monkeys (fasting plasma glucose, 67 +/- 2 mg/dL; insulin, 163 +/- 42 microU/mL) and overt type II diabetic monkeys (fasting plasma glucose, 201 +/- 13 mg/dL; insulin, 38 +/- 6 microU/mL) each underwent a series of three to five experiments to determine the time course and degree of hypoglycemia induced by IGF-I as compared with insulin or with control (saline) injection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin-like growth factor-I in non-insulin-dependent diabetic monkeys: basal plasma concentrations and metabolic effects of exogenously administered biosynthetic hormone. 194 41

Women with GDM have a greater risk of developing diabetes in the future compared with those women who have normal glucose tolerance during pregnancy. Using life table techniques, 17 years after the initial diagnosis of GDM, 40% of women were diabetic compared with 10% in a matched control group of women who had normal glucose tolerance in pregnancy. The incidence of diabetes was higher among women who were older, more obese, of greater parity and with more severe degrees of glucose intolerance during pregnancy. Diabetes also occurred more commonly among women who had a first-degree relative who was diabetic, in women born in Mediterranean and East Asian countries, and in those who had GDM in two or more pregnancies. Despite differing testing techniques and varying criteria for the diagnosis of GDM, follow-up studies from across the world consistently show a higher rate of subsequent diabetes among GDM mothers. NIDDM is associated with increased morbidity and a higher mortality rate, especially in women. Cardiovascular and cerebrovascular diseases are the leading causes of death. High lipid levels, hypertension and obesity are often already present when diabetes is diagnosed and may antedate the development of overt diabetes; treatment of diabetes at this stage may therefore be too late to prevent complications occurring. A follow-up programme for women with GDM facilitates screening of a group known to be at increased risk of developing diabetes so that the diagnosis can be made before associated risk factors for complications develop. Intervention in the form of counselling regarding cigarette smoking, exercise and a healthy, high-residue, unrefined carbohydrate, low cholesterol diet, given together with weight monitoring, may prevent the onset of both diabetes and its associated cerebrovascular and cardiovascular problems.
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PMID:Long-term implications of gestational diabetes for the mother. 195 23

Abnormalities of plasma lipid and lipoprotein concentrations are common in both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. In general, individuals with IDDM who are untreated or inadequately treated have elevations in both postprandial and fasting triglyceride levels in association with reduced activity of lipoprotein lipase. Low-density lipoprotein (LDL) cholesterol levels can rise when insulin deficiency impacts on LDL-receptor function. When patients with IDDM are treated and plasma glucose levels well controlled, plasma very-low-density lipoprotein (VLDL) triglyceride and LDL cholesterol levels are usually normal. In addition, plasma high-density lipoprotein (HDL) cholesterol levels are normal or elevated in well-controlled IDDM subjects. In NIDDM, increased VLDL triglyceride and reduced HDL cholesterol concentrations are common and are only partially related to glycemic control. Overproduction of VLDL leads to hypertriglyceridemia, which can be exacerbated if lipoprotein lipase activity is also reduced. The regulation of LDL levels is complex; catabolism can be reduced if significant insulin deficiency exists or increased if significant hypertriglyceridemia is present. The reduced levels of HDL cholesterol in NIDDM appear to be related to increased exchange of HDL cholesteryl esters for VLDL triglycerides, although other mechanisms may exist. The roles of insulin resistance, obesity, and independently inherited abnormalities of lipoprotein metabolism in the etiology of dyslipidemia of NIDDM are complex and require further investigation. Finally, the effects of diabetes on glycosylation of apoproteins; on other lipid enzymes, particularly hepatic triglyceride lipase; on lipoprotein surface lipids; and on hepatic uptake of remnants have only just begun to be defined. In view of the marked increase in atherosclerotic cardiovascular disease in individuals with diabetes mellitus, prompt attention to and aggressive therapy for dyslipidemia should be a central component of care for these patients.
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PMID:Lipoprotein physiology in nondiabetic and diabetic states. Relationship to atherogenesis. 195 76


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