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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence of obesity is increasing today in western industrialized countries: therefore, many authors are focusing their attention on its multiple endocrine and metabolic effects. Because of the pathogenetic linkage between obesity and dyslipidemia, we have studied serum lipid pattern in a group of obese women: HDL-Cholesterol (HDL-C) deficiency was the most striking lipoproteinemic disorder. This fact points out, in our opinion, that obesity must be considered as a risk factor for cardiovascular disease.
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PMID:[Dyslipidemia in obesity: pathogenetic considerations and our experience]. 849 62

The risks of cardiovascular disease associated with dyslipidemia differ in women and men, being more strongly associated with triglyceride/high-density lipoprotein in middle-aged women than in men. Although the incidence of heart disease is lower in women because they live longer, over a lifetime, cardiovascular disease in women is equal to that in men, with the greatest incidence after age 65 years. Major coronary events are rare among reproductive-age women who use oral contraceptives and are related to the concomitant effects of age, smoking, diabetes, hypertension, and obesity. Low estrogen-progestin dose oral contraceptives appear not to promote cardiovascular disease and can be used in women with controlled cholesterol elevations. Alternative contraceptive measures should be considered for patients with severe uncontrolled hypercholesterolemia or a lipid disorder that carries a high risk of coronary heart disease. In these conditions, thrombotic propensity associated with supraphysiologic doses of estrogen in oral contraceptives might accelerate coronary thrombosis should an arteriosclerotic plaque rupture. Treatment of hypercholesterolemia should follow the guidelines of the National Cholesterol Education Program and emphasize hygienic measures. Contraceptive selection in hyperlipidemic patients should reflect a balance between the risks--and their management--of developing cardiovascular disease versus the risks of pregnancy.
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PMID:Contraception and dyslipidemia. 851 44

Of the various types of diabetes mellitus, non-insulin-dependent diabetes (NIDDM) is by far the most common and is increasing rapidly in many populations around the world. It is a heterogeneous disorder, characterized by a genetic predisposition and interaction between insulin resistance and decreased pancreatic beta-cell function. There is a strong association between the presence of obesity and low levels of physical exercise and the development of NIDDM. However, NIDDM may also develop in lean individuals and the incidence increases significantly with increasing age. A diagnosis of impaired glucose tolerance or gestational diabetes is a strong predictor for future development of NIDDM and should signal appropriate interventions to prevent or delay the progression to NIDDM. NIDDM is frequently associated with other conditions such as hypertension, hypertriglyceridemia and decreased high-density lipoprotein which are additional risk factors for atherosclerosis and cardiovascular disease. The 'insulin resistance syndrome', which includes obesity, NIDDM, hypertension, hyperinsulinemia and dyslipidemia is a major and increasing cause of morbidity and mortality in many populations. In addition, people with NIDDM and poor glycemic control may develop severe microvascular complications of diabetes, including retinopathy, nephropathy and neuropathy. Appropriate diet, weight control and increased physical activity will increase insulin sensitivity in insulin resistant patients and are effective treatments for patients with NIDDM or may prevent the development of NIDDM in susceptible individuals. If these measures are unsuccessful, then oral hypoglycemic agents or insulin therapy may be required.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:NIDDM--the devastating disease. 852 17

Insulin resistance of skeletal muscle glucose disposal underlies the pathogenesis of NIDDM and is associated with hypertension, obesity, and dyslipidemia. Angiotensin-converting enzyme (ACE) inhibitors are used primarily in antihypertensive therapy but also are known to improve whole-body insulin-mediated glucose disposal. However, the exact site of action is not well characterized. We have used the isolated epitrochlearis muscle from a well-established animal model of skeletal muscle insulin resistance, the obese Zucker rat, to test the effect of oral administration of ACE inhibitors on insulin-sensitive muscle glucose transport activity. Both acute and chronic administration of a sulfhydryl-containing ACE inhibitor (captopril) or a non-sulfhydryl-containing ACE inhibitor (tran-dolapril) significantly enhanced in vitro insulin-mediated muscle glucose transport activity. In addition, the acute effect of oral captopril administration was completely abolished by pretreatment of the animal with a bradykinin B2 receptor antagonist (HOE 140). These findings indicate that ACE inhibitors may improve whole-body glucose metabolism by acting on the insulin-sensitive skeletal muscle glucose transport system. In addition, bradykinin or one of its metabolites may be involved in the action of the ACE inhibitor captopril on insulin-resistant muscle.
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PMID:Glucose transport activity in insulin-resistant rat muscle. Effects of angiotensin-converting enzyme inhibitors and bradykinin antagonism. 852 93

GENETIC PREDISPOSITION: Insulin resistance and reactive hyperinsulinemia occur not only with obesity, impaired glucose tolerance or non-insulin-dependent (type 2) diabetes mellitus, but also in many non-obese, non-diabetic patients with essential hypertension and their currently normotensive, lean, young offspring, as well as in some other conditions known to promote hypertension. Insulin resistance impairs glucose tolerance, while insulin resistance and/or hyperinsulinemia promote dyslipidemia, body fat deposition and probably atherogenesis. Therefore, the common coexistence of a genetic predisposition for hypertension with insulin resistance helps to explain the frequent, although temporally often dissociated, occurrence of hypertension together with dyslipidemia, obesity and type 2 diabetes in a given patient. INSULIN RESISTANCE AND HYPERINSULINEMIA AS SLOW PRESSOR MECHANISMS: In the pathogenesis of hypertension, inappropriate vasoconstriction (due to an imbalance of vasoactive substances and/or raised cytosolic calcium) and/or structural vasculopathy is particularly important. Among the mosaic of assumed pressor mechanisms, distinct Na+ retention is almost invariably involved in diabetes mellitus, while sympathetic activation tends to occur in essential hypertension, particularly in association with obesity. Insulin resistance may develop as a consequence of an intracellular excess of Ca2+ or a decrease in Mg2+, an impaired insulin-mediated rise in skeletal muscle blood flow, increased sympathetic activity or excess body weight. Acute hyperinsulinemia causes arterial vasodilation on one hand and increases sympathetic activity and renal Na+ reabsorption on the other. Chronically, hyperinsulinemia may promote cardiovascular muscle cell proliferation and atherogenesis, while insulin resistance may be associated with certain transmembraneous cation transporters, leading to an increase in cytosolic Ca2+. Hyperinsulinemia and/or insulin resistance may also be associated with an increased blood pressure sensitivity to high salt intake. In the mosaic of many different blood pressure-raising mechanisms, insulin resistance and/or hyperinsulinemia is likely to represent an amplifying slow or very slow pressor factor.
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PMID:Insulin resistance and hyperinsulinemia in hypertension. 857 90

The obese state has been recognized to accentuate the known risk factors for atherosclerotic disease as dyslipidemia, hypertension, glucose intolerance and insulin resistance. Among other risk factors, obesity is characterized by a series of lipid disturbances, such as hypercholesterolemia, high fasting (and postprandial) triglyceride levels, low HDL cholesterol, high apolipoprotein B, high small dense lipoprotein particles and alterations of serum and tissue LPL-activity. Although obesity is associated with such cluster of lipid abnormalities, these factors do not explain the complete process of atherogenesis in the obese subject. Other risk factors belonging to the polymetabolic syndrome-cluster, insulin resistance, hypertension, fibrinogen, add substantial but not full explanation to the atherothrombotic process. Over the last decade, a series of excellent studies have provided the background for a more indepth mechanism of atherosclerosis; the role of lipid peroxidation in particular has been one of the focuses of this current research. There exists a lot of evidence suggesting a major role for oxidized LDL and VLDL particles in the pathogenesis of atherosclerosis. Although obesity is characterized by dyslipidemia, less is known about the oxidation capacity of lipoproteins in obese subjects. We measured the oxidizability in vitro in 21 premenopausal women and compared them to 18 age-matched controls. The oxidizability of the non-HDL fraction is evaluated by measuring the fluorescence and thiobarbituric acid reactive substances (TBARS: MDA nM/mg non-HDL) at different time intervals of incubation. TBARS formation increased linearly with the increase of lipids both in non-obese and obese subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Human obesity: from lipid abnormalities to lipid oxidation. 858 Oct 73

There is good evidence that central (visceral) adiposity is important in the development of the insulin resistance or metabolic syndrome (obesity, hyperinsulinemia, dyslipidemia, glucose intolerance, hypertension, and coronary heart disease). It is proposed that some non-Caucasian populations are especially susceptible to development of this syndrome, and that lifestyle changes may play important etiologic roles. We postulate that this is due to the presence in these populations of a genetic predisposition to weight gain, perhaps related to a "thrifty" genotype, leading to the concentration of weight gain in visceral fat depots, when there is exposure to conditions associated with westernization.
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PMID:Susceptibility to development of central adiposity among populations. 858 74

Sex hormone-binding globulin (SHBG) is an important regulator of plasma sex steroids as well as a sensitive indicator of insulin resistance. SHBG may be an important diagnostic measure of risk for pathologies associated with insulin resistance syndrome (IRS) such as non-insulin-dependent diabetes mellitus (NIDDM), obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. In women, SHBG is also implicated in diverse pathologies such as cancers of steroid-sensitive tissues and hirsutism. Data from an ongoing ecological study linking diet and health in rural China were analyzed to determine the relation of selected plasma variables and diet to plasma concentrations of SHBG. All data represent county mean values, pooled by age and sex, to assess the relation between biochemical and lifestyle characteristics and disease-specific mortality rates at the county level. The study sample consisted of 3250 Chinese women between the ages of 35 and 64 y living in 65 widely dispersed rural counties. Consumption patterns for 21 different food groups were derived from a food-frequency questionnaire and a 3-d dietary survey and subsequently compared. Correlation analyses of county mean values demonstrated a significant association between SHBG and insulin, testosterone, triacylglycerols, body mass index, age at menarche, and several foods. In regression analyses, after adjustments, the strongest predictors of SHBG concentrations were the dietary intake of rice (beta = 0.42, P < 0.01), fish (beta = 0.34, P < 0.05), millet (beta = -0.27, P < 0.01), and wheat (beta = -0.34, P < 0.01). When insulin, testosterone, and triacylglycerols were added to the model only triacylglycerols (beta = -0.26, P < 0.05) remained a significant independent predictor of SHBG. Additional analyses suggested that the consumption of green vegetables was modestly positively correlated with SHBG and negatively with insulin values. Consumption of rice and fish in particular appeared to favorably influence the principle plasma variables associated with a reduction in the risk for IRS pathologies.
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PMID:Association of dietary factors and selected plasma variables with sex hormone-binding globulin in rural Chinese women. 860 65

Insulin resistance is part of a metabolic syndrome that also includes non-insulin-dependent diabetes mellitus, dyslipidemia, obesity, and hypertension. It has been hypothesized that insulin resistance represents the primary physiological defect underlying this syndrome. Since insulin resistance is at least partially genetically determined, we hypothesized that genes influencing insulin resistance would have pleiotropic effects on a number of other traits, including triglyceride (TG) and HDL cholesterol levels, body mass index (BMI) and body fat distribution, and blood pressure levels. To investigate this hypothesis, we analyzed data obtained from individuals in 41 families enrolled in the San Antonio Family Heart Study. Statistical methods that take advantage of the relatedness among individuals were used to differentiate between genetic and nongenetic (ie, environmental) contributions to phenotypic variation between traits. Serum levels of fasting and 2-hour insulin (measured in 767 and 743 nondiabetic family members, respectively) were used as a measure of insulin resistance. The genetic correlations were high between insulin levels (both fasting and 2-hour) and each of the following: BMI, HDL level, waist-to-hip ratio, and subscapular-to-triceps ratio, indicating that the same gene, or set of genes, influences each pair of traits. In contrast, the genetic correlations of insulin levels with systolic and diastolic blood pressures were low. We have previously shown that a single diallelic locus accounts for 31% of the phenotypic variation in 2-hour insulin levels in this population. We conducted a bivariate segregation analysis to see if the common genetic effects on insulin and these other traits could be attributable to this single locus. These results indicated a significant effect of the 2-hour insulin locus on fasting insulin levels (P = .02) and BMI (P = .05), with the "high" insulin allele associated with higher levels of fasting insulin but lower levels of BMI. There was no detectable effect of this locus on HDL level, TG level, subscapular-to-triceps ratio, or blood pressure. Overall, these results suggest that a common set of genes influencing insulin levels also influences other insulin resistance syndrome-related traits, although for the most part this pleiotropy is not attributable to the 2-hour insulin level major locus.
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PMID:Genetic analysis of the IRS. Pleiotropic effects of genes influencing insulin levels on lipoprotein and obesity measures. 862 Mar 44

Impaired skeletal muscle insulin receptor function is a feature of common forms of insulin resistance, including obesity and noninsulin-dependent diabetes mellitus. However, the extent to which this defect accounts for impaired muscle glucose disposal or altered in vivo glucose homeostasis remains to be established. We recently showed that transgenic mice that overexpress dominant-negative insulin receptors specifically in striated muscle have a severe defect in muscle insulin receptor-mediated signaling and modest hyperinsulinemia. Here we performed hindlimb perfusion studies to determine the impact of this defect on muscle glucose uptake and metabolism. Maximal rates of insulin-stimulated muscle 3-O-methylglucose transport were reduced by 32-40% in transgenic mice with proportional defects involving total hindlimb [14C]glucose uptake, lactate production, and muscle glycogen synthesis. To address the hypothesis that muscle insulin resistance could promote an increase in the accretion of body fat, carcass analysis was performed using two independent lines of transgenic mice. Although body weights were normal, transgenic mice had a 22-38% increase in body fat, with a reciprocal decrease (10-15%) in body protein. Mean gonadal fat pad weight was also increased in transgenic mice. Skeletal muscle histology and fiber type distribution were not affected. To determine whether muscle-specific insulin resistance was sufficient to cause impaired glucose tolerance, oral glucose tolerance tests were performed with 6-month-old transgenic and control mice. Fasting glucose levels were increased by 25%, and peak values were 22-40% higher in transgenic mice. Transgenic mice also had a 37% decrease in plasma lactate levels and modest increases in levels of plasma triglycerides and FFA (29% and 15%, respectively). We conclude that 1) severe defects in muscle insulin receptor function result in impaired insulin-stimulated glucose uptake and metabolism in this tissue; 2) muscle-specific insulin resistance can contribute to the development of obesity; and 3) a "pure" defect in insulin-mediated muscle glucose disposal is sufficient to result in impaired glucose tolerance and other features of the insulin resistance syndrome, including hyperinsulinemia and dyslipidemia.
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PMID:Transgenic mice with muscle-specific insulin resistance develop increased adiposity, impaired glucose tolerance, and dyslipidemia. 864 Nov 92


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