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

Insulin resistance is an early and major feature in the development of non-insulin-dependent diabetes mellitus(NIDDM). It is also associated with hyperlipidemia, hypertension, obesity and cardiovascular disease. It is the clustor of the risk factors for atherosclerosis and recognized as 'insulin-resistance syndrome' (Syndrome X). Central (abdominal) obesity is much more strongly associated with insulin resistance than overall obesity. The increase of both the influx of free fatty acid to liver and the production of TNF-alpha in adipose tissue may play an important role in mechanism of insulin resistance associated with central obesity. Calorie restriction and weight loss improve insulin sensitivity in overweight humans. Exercise training also improves insulin sensitivity via increased oxidative enzymes, glucose transporters (GLUT4) and capillarity in muscle as well as by reducing abdominal fat. The new 'glitazones' (thiazolidinediones) is used clinically to improve insulin sensitivity.
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PMID:[Syndrome X]. 1019 44

Severe obesity, defined as a body mass index > or = 35 kg/m2, is frequently associated with various biological abnormalities, particularly in the presence of intra-abdominal adiposity. The most important disorders belong to the so-called insulin resistance syndrome, metabolic syndrome or syndrome X: hyperinsulinaemia, impaired glucose tolerance or type 2 diabetes, dyslipidaemias, hyperuricaemia, hyperfibrinogenaemia. All these metabolic abnormalities are considered as cardiovascular risk factors. They are also correlated with the severity of the liver steatosis which is commonly observed in individuals with severe obesity. We report our experience of the evolution of these metabolic abnormalities after a marked weight loss induced by gastroplasty. We will analyse the favourable effects of bariatric surgery on insulin sensitivity, biological components of the metabolic syndrome, type 2 diabetes and liver steatosis.
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PMID:[How I treat ... an individual with severe obesity and metabolic abnormalities with gastroplasty]. 1032 Nov 1

Hypertension and insulin resistance are often part of a complex set of abnormalities including obesity, hyperlipidemia, and glucose intolerance, described as syndrome X. Besides a common genetic basis, insulin resistance and hypertension might be linked by excessive activity of the sympathetic nervous system. We studied the effects of chronic inhibition of sympathetic activity with the antihypertensive agent moxonidine on glucose metabolism in the genetically obese SHR Koletsky rat (SHROB), a unique animal model which closely resembles human syndrome X, expressing genetic obesity, hypertension, and hyperlipidemia. Moxonidine, a selective I1-imidazoline receptor agonist, was administered to SHROB and SHR for 90 days in food at 8 mg/kg/day. Moxonidine not only lowered blood pressure, but also reduced fasting insulin levels by 49% in SHROB, and reduced plasma free fatty acids by 30%. In lean SHR, moxonidine treatment decreased circulating free fatty acids by 33% compared to controls. During oral glucose tolerance tests, blood glucose levels in moxonidine-treated SHROB were reduced from 60 min onwards, and there was a sharply higher insulin secretion post-challenge compared to control SHROB. Western blot analysis of insulin signaling proteins showed that IRS-1 was decreased 42% in control SHROB compared with SHR. Moxonidine treatment enhanced the expression of IRS-1 protein in skeletal muscle by 74% in SHROB and 40% in SHR. Moxonidine increased expression of IRS-1 protein in liver by 245% in SHROB and 268% in SHR. Long-term inhibition of sympathetic activity with moxonidine therapy lowered free fatty acids and significantly improved insulin secretion, glucose disposal, and expression of key insulin signaling intermediates. Thus, moxonidine should be considered for the treatment of multiple metabolic and cardiovascular abnormalities associated with syndrome X.
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PMID:Anti-hyperglycemic activity of moxonidine: metabolic and molecular effects in obese spontaneously hypertensive rats. 1032 53

Plasma leptin levels are elevated in most obese individuals, and obesity is accompanied by a high incidence of cardiovascular disease. Therefore, leptin could be involved in the pathogenesis of cardiovascular disease. In the present study, the role of leptin was explored in the regulation of platelet function. The expression of the long form of the leptin receptor was detected in human platelets. At 50 ng/ml, human leptin induced phosphorylation of several proteins of platelets at the tyrosine residue. Neither leptin at concentrations < or = 100 ng/ml nor ADP at concentrations > or = 1 micromol/l affected platelet aggregation. However, after pretreatment with 100 ng/ml leptin for 5 min, 1 micromol/l ADP caused aggregation. Thus, leptin and ADP acted synergistically. At a concentration of 2 micromol/l, ADP induced platelet aggregation, which was markedly enhanced by 30-100 ng/ml leptin in a concentration-dependent manner. This concentration range corresponds to that of plasma leptin levels in obese individuals. At the lower concentrations (< 10 ng/ml) that are observed in normal individuals, leptin had no effect on platelet aggregation. In conclusion, leptin at high concentrations has the novel function of promoting platelet aggregation, which may be a key coupling factor between obesity and the cardiovascular disease associated with syndrome X and diabetes.
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PMID:Leptin promotes aggregation of human platelets via the long form of its receptor. 1033 26

This review examines whether the relations and metabolic parameters necessary for the development of syndrome X are present in children and whether the metabolic complications of obesity in children are explained by excess intraabdominal adipose tissue (IAAT), or visceral fat. Despite the limited use of imaging techniques in research studies, an increasing number of studies reported on IAAT and its relation to disease risk in children and adolescents. For this article we reviewed studies that documented the early accumulation of IAAT in children and adolescents and the factors that contribute to variation in the degree of IAAT accumulation. We also reviewed studies that showed the clinical relevance of IAAT in children and adolescents through significant relations with adverse health effects including dyslipidemia and glucose intolerance in obese and nonobese children and adolescents of different ethnic groups.
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PMID:Relation between visceral fat and disease risk in children and adolescents. 1039 63

Insulin resistance, a smaller than expected response to a given dose of insulin, is associated with many common diseases including, ageing, polycystic ovarian disease, syndrome X, cancer, infections, trauma and, most significantly, obesity and type 2 diabetes mellitus. The biochemical basis of insulin resistance in type 2 diabetes has been the subject of many studies. Earlier studies have indicated that quantitative regulation of the insulin sensitive glucose transporters (Glut-4) and insulin receptors themselves may contribute to this disorder, however, these two factors are probably inadequate to explain the extent of insulin resistance. This point also became apparent by the development of only mild hyperinsulinaemia in mice with a targeted mutation in the Glut-4 gene. Studies on postreceptor defects in type 2 diabetes has recently focused on the intrinsic catalytic activity of the insulin receptor and downstream signalling events. A reduction in tyrosine phosphorylation of both the insulin receptor (IR) and the insulin receptor substrate-1 (IRS-1) has been noted in both animal and human type 2 diabetes. Importantly, this appears to occur in all of the major insulin-sensitive tissues, namely the muscle, fat and liver. It is now clear that decreased signalling capacity of the insulin receptor is an important component of this disease. I will review some of the potential mechanisms underlying this deficiency.
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PMID:The role of TNFalpha and TNF receptors in obesity and insulin resistance. 1039 91

Overnutrition during critical developmental periods is suggested to be a risk factor for obesity and associated metabolic disorders in later life. Underlying mechanisms are unknown. Neuropeptides are essentially involved in the central nervous regulation of body weight. For instance, hypothalamic galanin (GAL) is a stimulator of food intake and body weight gain. To investigate long-term consequences of early postnatal overfeeding, the normal litter size of Wistar rats (n=10; controls) was reduced from day 3 to day 21 of life to only 3 pups per mother (small litters, SL; overnutrition). Throughout life, SL rats displayed hyperphagia (p<0.01), overweight (p<0.0001), hyperinsulinemia (p<0.01), impaired glucose tolerance (p<0.001), elevated triglycerides (p<0.001), and an increased systolic blood pressure (p<0.05). In adulthood, an increase of GAL-neurons in the arcuate hypothalamic nucleus (ARC) was found (p<0.001), positively correlated to body weight (p<0.001). A second experiment revealed hyperinsulinemia (p<0.001) and increased hypothalamic insulin levels (p<0.05) in SL rats during early postnatal life. Already on day 21 of life, i.e., at the end of the critical hypothalamic differentiation period, in SL rats the number of GAL-neurons was increased in the ARC (p<0.001), showing a positive correlation to body weight and insulin (p<0.05). In conclusion, neonatally acquired persisting malformation of hypothalamic galaninergic neurons, induced by early overfeeding and hyperinsulinism, might promote the development of overweight and syndrome X-like alterations during life.
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PMID:Perinatal elevation of hypothalamic insulin, acquired malformation of hypothalamic galaninergic neurons, and syndrome x-like alterations in adulthood of neonatally overfed rats. 1041 13

The prevalence of obesity has increased over the past three decades, in children as well as in adults. When obesity develops in the childhood years, excess adiposity generally continues into adult years, and adult obesity with childhood onset is frequently more severe. The health consequences of obesity in adults are well established, including greater rates of hypertension, non-insulin dependent diabetes mellitus, and heart disease. This paper will discuss the risk factors for these adult disorders that are detectable in obese children. Compared to normal weight children, obese children have higher blood pressure, higher plasma insulin levels, and a more atherogenic lipid pattern. Thus, the characteristic features of Syndrome X, or the insulin resistant syndrome, can be detected in obese children and adolescents. The vascular consequences of exposure to these metabolic risk factors beginning in childhood have yet to be completely determined. However, it is very likely that childhood obesity does contribute significantly to cardiovascular disease. For these reasons, greater efforts should be mounted to reduce the currently rising rates.
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PMID:Obesity and other risk factors in children. 1042 Oct 92

Obesity poses a serious health hazard and its treatment is often disappointing. Major advances have been made during recent years in the understanding of body weight regulation, with the discovery of leptin, a protein produced by adipocytes and acting on the central nervous system to reduce food intake, and that of beta-3 adrenergic receptors and uncoupling proteins which contribute to stimulate energy expenditure. Numerous metabolic complications are associated with abdominal obesity and most of them, such as diabetes mellitus, dyslipidaemias and arterial hypertension, appear to be linked to insulin resistance and may be part of the socalled metabolic syndrome or syndrome X. While very-low-calorie diets are usually effective in the short-term, they cannot, in the long-term and for most patients, solve the problem of severe obesity. Pharmacological antiobesity treatment may include drugs that reduce food intake, drugs that increase energy expenditure and drugs that affect nutrient partitioning or metabolism. All of these pharmacological approaches have potential efficacy, but unfortunately serious limitations. This is also the case of mechanical means, such as intragastric balloons. Consequently, bariatric surgery may be considered as a valuable alternative therapy in well-selected patients with morbid obesity refractory to classical treatments. In conclusion, obesity is a chronic disease and should be treated as such with reasonable expectations.
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PMID:Medical aspects of obesity. 1042 50

Cardiovascular risk factor clustering related to insulin resistance syndrome (Syndrome X) was examined in a community-based sample of 599 genetically unrelated school-aged children (5-17 years) and their parents. Risk factors used as components of Syndrome X included hyperinsulinemia, obesity, dyslipidemia and high blood pressure defined by values above the age-, sex- and race-specific 75th percentiles of fasting insulin, body mass index, triglycerides/high-density lipoprotein cholesterol ratio and mean arterial pressure, respectively. Based on observed to expected ratio there was an excess of parents (father and/or mother) and their offspring with clusters of three or four disorders (P < 0.05-0.001). In contrast, the number of parents and offspring with two disorders was significantly lower than expected by chance alone (P < 0.05-0.01). Based on paternal, maternal, and parental Syndrome X, the odds ratios (95% confidence interval) for offspring having the same cluster were 7.2 (1.9-27.2), 8.6 (3.1-23.6) and 7.9 (3.5-18.1), respectively. In terms of individual risk factors of parents used as predictors, adverse levels of their insulin and BMI significantly increased the risk of offspring having Syndrome X (P < 0.01-0.001), whereas the effect of parental insulin was considerably reduced after parental BMI was adjusted for. In contrast, parental dyslipidemia and high blood pressure were not associated with the occurrence of Syndrome X in their offspring. These results confirm the familial nature of Syndrome X and suggest that conditions of obesity and the attendant hyperinsulinemia in parents may underlie this familial association.
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PMID:The association of cardiovascular risk factor clustering related to insulin resistance syndrome (Syndrome X) between young parents and their offspring: the Bogalusa Heart Study. 1042 11


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