Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0311277 (abdominal obesity)
 2,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A relationship exists between obesity and non-insulin-dependent diabetes mellitus. Central, abdominal obesity carries a particularly high risk that is most likely associated with enlargement of visceral fat deposits. A multiple endocrine perturbation is associated with visceral obesity. This consists of a hypersensitive hypothalamic-pituitary-adrenal (HPA) axis, with resulting excess of cortisol secretion upon stimulation. Growth hormone levels in both sexes are diminished and testosterone concentrations in men are lower than normal. In women a moderate hyperandrogenism is often present. The elevated sensitivity of the HPA axis may be a primary event, followed by adrenal androgen production in women and by interaction at several levels, with inhibition of both the growth hormone and pituitary-gonadal axes. Together, these endocrine perturbations seem to be able to centralize body fat to visceral depots because of a high density of steroid hormone receptors. The endocrine perturbations are most likely followed by insulin resistance. Elevated cortisol levels, deficiencies in sex-specific steroid hormones and excess androgens result in insulin resistance. The endocrine abnormalities in visceral obesity are followed by insulin resistance, both directly and indirectly via contribution of excess free fatty acids from centralized body fat depots. The hyperactivity of the HPA axis may be due to frequent challenges and it is amplified by a deficient feedback inhibition. A depressive, helplessness reaction to stress may be involved. Such stress factors may be found in socioeconomic and psychosocial handicaps, as suggested by results of population studies. This hypothesis is strongly supported by the reproduction of an identical condition in non-human primates that react with a depressive reaction upon psychosocial types of stressors. The perturbations of the HPA axis may thus be in the centre of the syndrome. Studies of this axis in established non-insulin-dependent diabetes mellitus suggest similar perturbations, but the information is not conclusive.
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PMID:The origins and consequences of obesity. Diabetes. 901 75

Growth hormone (GH) deficiency in children results in increased body fat, reduced fat-free mass (FFM) including muscle (protein) and bone, and abdominal obesity. Thus, proper GH secretion likely has major developmental influences on later health risks including cardiovascular diseases and osteoporosis. However, the in vivo control of the development of the body composition and fat distribution by GH has not yet been accurately investigated using children with GH deficiency as a model. We determined the effect of GH therapy (GH replacement, n = 3; GH + physiologic cortisol and thyroxine replacement, n = 3) on body composition, the proportional composition of the FFM, and body fat distribution in GH-deficient prepubertal children compared with healthy control children (n = 6) not treated with GH. The GH-deficient and control children were initially matched for gender, bone age, and weight. As assessed by a 4-compartment model, GH therapy reduced percent body fat during the first 3 months of therapy but not thereafter. This change was primarily due to FFM, which increased 3-fold more in the GH-deficient group and accounted for 91.5% of the increase in body weight. Fat mass increased in the controls but was unchanged in the GH-deficient group. Therapy temporarily increased the proportional contribution of water to the FFM, decreased the proportion of mineral, and slightly increased the proportion of protein. Using magnetic resonance imaging (MRI), abdominal visceral fat was reduced in the GH-deficient group and unchanged in the controls. Abdominal subcutaneous fat measured in the same image was not changed. The abdominal and suprailiac skinfold thicknesses also were not decreased in the GH-deficient group. In conclusion, within 1 to 3 months, GH therapy accelerates lean tissue accrual, especially the water and protein components, but has a smaller effect on reducing fat mass. GH therapy has site-specific effects on reducing abdominal adiposity.
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PMID:Alterations in body composition and fat distribution in growth hormone-deficient prepubertal children during growth hormone therapy. 1131 14

Cardiovascular risk is increased in GH deficiency (GHD). GHD adults are frequently abdominally obese and display features of the metabolic syndrome. Otherwise healthy abdominally obese subjects have low GH levels and show features of the metabolic syndrome as well. We investigated in healthy nonobese males the effect of the GH receptor antagonist pegvisomant in different metabolic conditions. This is a model for acute GHD without the alterations in body composition associated with GHD. We compared the effect of pegvisomant with that of placebo before and after 3 d of fasting. In addition, we investigated the effect of pegvisomant under normal, i.e. fed, conditions. Three days of fasting as well as pegvisomant alone decreased serum free IGF-I levels (1.0 +/- 0.15 vs. 0.31 +/- 0.05 ng/ml and 0.86 +/- 0.23 vs. 0.46 +/- 0.23 ng/ml, respectively). Fasting in combination with pegvisomant also decreased serum free IGF-I levels (1.0 +/- 0.15 vs. 0.31 +/- 0.07 ng/ml). Treatment with pegvisomant had no additional influence on the decline of free IGF-I induced by fasting. Pegvisomant alone had no influence on insulin sensitivity. The increase in insulin sensitivity induced by fasting was comparable to the increase in insulin sensitivity induced by fasting combined with pegvisomant. Among serum lipid concentrations, only serum triglycerides increased significantly as a result of pegvisomant alone (1.0 +/- 0.2 vs. 1.6 +/- 0.4 mmol/liter). The changes in lipid concentrations induced by fasting alone or pegvisomant were not different from those induced by pegvisomant alone. von Willebrand factor antigen levels declined significantly under the influence of pegvisomant alone (1.1 +/- 0.07 vs. 0.8 +/- 0.06 U/ml). In conclusion, in different metabolic conditions the GH receptor antagonist pegvisomant induces no significant acute changes in the major risk markers for cardiovascular disease. These data suggest that the secondary metabolic changes, e.g. abdominal obesity or inflammatory factors, that develop as a result of long-standing GHD are of primary importance in the pathogenesis of atherosclerosis in patients with GHD.
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PMID:Acute effect of pegvisomant on cardiovascular risk markers in healthy men: implications for the pathogenesis of atherosclerosis in GH deficiency. 1170 72

The aim was to evaluate whether the metabolic syndrome associates with other endocrinopathies observed after allogeneic stem cell transplantation (SCT) in childhood. Thirty-one SCT long-term survivors, transplanted for leukemia (n=26) or nonmalignant hematologic diseases (n=5) were evaluated by oral glucose tolerance test and assessment of serum lipids at a median age of 15 (range 7 to 34) years. Hyperinsulinemia, hypertriglyceridemia, and abdominal obesity were required for the diagnosis of metabolic syndrome. Growth hormone (GH) secretion was evaluated either with GH releasing hormone and arginine (n=14), clonidine (n=15), or insulin-tolerance (n=2) test. A GH peak level of <20 mU/L was considered insufficient. The thyroid and gonadal functions were assessed. Twelve patients (39%) had metabolic syndrome. Nine out of 12 (75%) patients with metabolic syndrome had insufficient GH response in provocative testing as opposed to 6/19 (31%) of those without it (P=0.02). No difference was observed in thyroid or gonadal function between patients with versus without metabolic syndrome. In conclusion, metabolic syndrome is frequently associated with insufficient GH secretion in the SCT long-term survivors. This should implicate a close follow-up of the metabolic parameters in SCT patients with either frank GH insufficiency or signs of inadequate GH response in provocative testing.
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PMID:Insufficient growth hormone secretion is associated with metabolic syndrome after allogeneic stem cell transplantation in childhood. 1776 93

Growth hormone (GH) is the most important hormonal regulator of postnatal longitudinal growth in man. In adults GH is no longer needed for longitudinal growth. Adults with growth hormone deficiency (GHD) are characterised by perturbations in body composition, lipid metabolism, cardiovascular risk profile and bone mineral density. It is well established that adult GHD usually is accompanied by an increase in fat accumulation and GH replacement in adult patients with GHD results in reduction of fat mass and abdominal fat mass in particular. It is also recognized that obesity and abdominal obesity in particular results in a secondary reduction in GH secretion and subnormal insulin-like growth factor-I (IGF-I) levels. The recovery of the GH IGF-I axis after weight loss suggest an acquired defect, however, the pathophysiologic role of GH in obesity is yet to be fully understood. In clinical studies examining the efficacy of GH in obese subjects very little or no effect are observed with respect to weight loss, whereas GH seems to reduce total and abdominal fat mass in obese subjects. The observed reductions in abdominal fat mass are modest and similar to what can be achieved by diet or exercise interventions.
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PMID:Obesity, growth hormone and weight loss. 1972 58

Obesity has become one of the most common medical problems in developed countries, and this disorder is associated with high incidences of hypertension, dyslipidaemia, cardiovascular disease, type 2 diabetes mellitus and specific cancers. Growth hormone (GH) stimulates the production of insulin-like growth factor 1 in most tissues, and together GH and insulin-like growth factor 1 exert powerful collective actions on fat, protein and glucose metabolism. Clinical trials assessing the effects of GH treatment in patients with obesity have shown consistent reductions in total adipose tissue mass, in particular abdominal and visceral adipose tissue depots. Moreover, studies in patients with abdominal obesity demonstrate a marked effect of GH therapy on body composition and on lipid and glucose homeostasis. Therefore, administration of recombinant human GH or activation of endogenous GH production has great potential to influence the onset and metabolic consequences of obesity. However, the clinical use of GH is not without controversy, given conflicting results regarding its effects on glucose metabolism. This Review provides an introduction to the role of GH in obesity and summarizes clinical and preclinical data that describe how GH can influence the obese state.
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PMID:The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations. 2356 41