Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin resistance may occur in a wide variety of conditions. Some conditions such as obesity or the presence of insulin antibodies are common. We have reported three unusual cases in which the patients exhibited marked insulin resistance, absence of subcutaneous fat, absence of ketosis, and substantial hyperglycemia despite normal insulin levels.
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PMID:Diabetes mellitus and lipoatrophy. 234 36

Joint studies of the ALIMDA and Society of Actuaries, notably those of 1935, 1959 and 1979, established that there is a progressive rise in cardiovascular mortality with successive increments in blood pressure. This has provided the basis of underwriting. The converse is not true, or at least has not been true until very recently. Drugs that effectively reduce blood pressure have been available for several decades, but reduction and maintenance of blood pressure is still accomplished in only a minority of hypertensives. Long-term trials employing a combination of drugs, i.e., diuretics, vasodilators and reserpine and subsequently beta-blockers, almost without fail have not shown that treatment with these agents significantly reduces heart disease mortality and sudden death. This has been attributed, perhaps without basis, to an unfavorable countering effect of increased lipid levels, aggravating this risk factor, and other undesirable metabolic effect of diuretics, such as hypokalemia and depletion of body magnesium, increasing the propensity to ventricular arrhythmias, hyperglycemia, worsening diabetes, and hyperuricemia. A survey of 674 persons with hypertension seen personally during the period 1985-89, who were under the care of approximately that many physicians, reveals striking changes in drug prescription and use during this brief period that portend a major change in the outlook of hypertension. Two classes of drugs have increased rapidly in popularity: these are the angiotensin-converting enzyme inhibitors (ACE inhibitors) and the calcium blockers. Both classes of drugs effectively lower blood pressure and have minimal side effects with good compliance. They act not only to reduce peripheral vascular resistance, but also locally in the heart muscle to directly cause left ventricular hypertrophy to regress, an effect of great consequence. The drugs used in former trials such as the vasodilators and diuretics have no effect on left ventricular hypertrophy, unlike the ACE inhibitors and calcium antagonists. Left ventricular hypertrophy is the key lesion in hypertension and is only in part due to increased work load imposed by elevated pressure. It is associated with elevated blood pressure, but not closely and occurs independently; ventricular myocytes as well as myocytes of the vasculature being stimulated to growth by angiotensin and calcium, potentiating the effect of norepinephrine. Left ventricular hypertrophy greatly increases the propensity to ventricular arrhythmias and sudden death, and is a prime cause of cardiac mortality and sudden death not only in hypertension, but also in obesity, aging and diabetes, in which conditions left ventricular hypertrophy also is very common.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Major new developments affecting treatment and prognosis in hypertension. 235 5

Glucose has several disadvantages such as low pH, high osmolality and hyperglycemia. Rapid glucose absorption contributes to hyperlipidemia, obesity and ultrafiltration failure in peritoneal dialysis patients. Two commercially available plasma substitutes 10% hydroxyethylstarch (HES) and 6% dextran were studied for ultrafiltration and absorption patterns. 18 ml of each solution were instilled into the peritoneal cavity of 6 non-uremic rats. HES yielded a significantly (p less than 0.02) greater ultrafiltration after 6 h of dwell, whereas 2.3% glucose solution showed the typical ultrafiltration pattern of an easily absorbable osmotic agent. With 6% dextran ultrafiltration was markedly lower. At the end of cycle time the mean absorption rates for HES were 62.7% and 41.5% for dextran. It is concluded that HES is a potent osmotic agent due to sustained colloidal ultrafiltration. However, despite their high molecular weights both solutions were markedly absorbed probably by lymphatics. However, accumulation in tissues and undefined metabolic pathways might prove disadvantageous in patients with ESRD.
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PMID:Ultrafiltration and absorption characteristics of hydroxyethylstarch and dextran during long dwell peritoneal dialysis exchanges in rats. 248 83

Obesity is associated with insulin resistance and type II diabetes mellitus. In the present study, we have characterized hepatic insulin receptor function in two animal models of obesity: the Zucker fatty rat (ZFR), a model of genetic obesity with severe hyperinsulinemia, and the Sprague-Dawley rat with dietary obesity, a model of acquired obesity. Zucker fatty rats were also treated with streptozotocin (STZ) in an effort to examine the effects of relative insulin deficiency and hyperglycemia in the setting of obesity. Using wheat germ agglutinin-purified insulin receptor extracted from liver, no significant difference in insulin binding was identified in either model of obesity. beta-Subunit autophosphorylation was significantly decreased in both obese models relative to that in controls (72% in the obese ZFR and 49% in the overfed Sprague-Dawley model). Kinase activity, as measured by phosphorylation of the 1142-1153 synthetic peptide, was also decreased in both models of obesity by 22% and 64%, respectively. In the Zucker rat, STZ treatment led to an 80% increase in receptor concentration and a further 70% increase in beta-subunit autophosphorylation per receptor, whereas tyrosine kinase activity toward substrate was not altered. Since kinase activity is closely linked to autophosphorylation, we determined the fraction of autophosphorylated (activated) receptors vs. non-phosphorylated (inactive) receptors by using antiphosphotyrosine antibody to precipitate receptors bound with [125I]insulin. There was no significant difference in the percentage of activated insulin receptors in the dietary obese, ZFR, or STZ-treated Zucker rat vs. that in the controls. In all models, the percentage of activated receptors ranged from 32-46% of the total receptor pool. These data suggest that in genetic and acquired obesity, autophosphorylation of the beta-subunit is reduced and is a limiting factor in insulin receptor activation. A similar fraction of all receptors appears to undergo some level of autophosphorylation; however, full autophosphorylation and, thus, activation of the receptor do not occur, and this results in a decrease in kinase activity. This block in autophosphorylation may account for significant reductions in insulin receptor kinase function in obesity.
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PMID:Alterations in the hepatic insulin receptor kinase in genetic and acquired obesity in rats. 255 53

Hyperglycemia and other metabolic derangements resulting from absolute or functional deficiency of insulin are accompanied by typical signs and symptoms of diabetes. The clinical signs and the findings of hyperglycemia over 200 mg/dl should establish a diagnosis of diabetes mellitus. An oral glucose tolerance test (O-GTT) is rarely necessary for diagnosis of diabetes in a child. A small proportion of children, however, present less severe symptoms, and may require an O-GTT. Approximately 14% of IDDM children were in coma at diagnosis in Tokyo, and 11 onset deaths (0.94%) were observed among the 1172 newly diagnosed IDDM cases in Japan. A significant decline in the onset mortality, however, has been observed in the past 20 years in Japan in association with the improvement of early management of childhood diabetes. The clinical distinction of IDDM from NIDDM is often difficult in diabetic children of Oriental origin without obesity. Japanese IDDM can be divided into two forms, abrupt and slow onset forms, but they may be essentially the same disease. There was no difference in the frequency of being tested positive for circulating ICA between the two groups of the patients. But a difference in the frequency of HLA DR4 and DRW9 was noticed between the two groups. Clinical features of 107 children with NIDDM were studied and about 75% of these cases were obese. All of them can be detected by routine urinalysis for glucose. Diet and exercise therapy in most of the newly diagnosed patients resulted in remission but some of them may require insulin or an oral hypoglycemic agent to get better glycemic control.
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PMID:Initial signs and diagnosis of diabetes--special considerations of Oriental patients. 263 91

Obese and lean male and female Wistar fatty rats were fed a high-sucrose (68% of calories) diet from 5 to 22 wk of age. Obese males, but not obese females, developed hyperglycemia in the fed state and were more glucose intolerant during an intragastric glucose tolerance test than obese females. Lean Wistar fatty rats did not become hyperglycemic on the sucrose diet. Obese males also showed a smaller insulin response during the glucose tolerance test than did obese females. The Wistar fatty rat is a sexually dimorphic model of non-insulin-dependent diabetes mellitus in which the male but not the female obese rats become diabetic. The diabetic condition and impaired glucose tolerance in the obese male Wistar fatty rat may be related to impaired pancreatic insulin release and peripheral insulin resistance.
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PMID:Sexual dimorphism of hyperglycemia and glucose tolerance in Wistar fatty rats. 264 38

Obese diabetic SHR/N-(cp/cp) rats are a genetic model for non-insulin-dependent diabetes mellitus. When SHR/N-cp rats are overtly diabetic, they are hyperinsulinemic and hyperglycemic in the fed state when consuming commercial chow or semipurified high-carbohydrate diets. Obese SHR/N-cp rats were hyperinsulinemic by 4 wk of age, although hyperglycemia did not appear until 3-4 wk later and was exacerbated by a high-sucrose diet (mean +/- SE 1488 +/- 238 microU/ml insulin and 425 +/- 51 mg/dl glucose). The control SHR/N-cp rats (+/?) on the sucrose diet remained lean and normoglycemic. The obese diabetic SHR/N-cp rats showed three alterations in pancreas perfusion data (not present in control rats): 1) paradoxically high insulin secretion at low glucose levels (2.5 mM), 2) secretion of insulin in response to arginine (10 mM) in the absence of glucose, and 3) impaired response of insulin secretion to high glucose (16.7 mM). To determine whether hyperglycemia was responsible for the abnormalities of insulin secretion, perfusion studies were conducted in obese nondiabetic LA/N-cp rats and compared with the SHR/N-cp rats. The obese LA/N-cp rats resembled the corpulent SHR/N-cp rats in every way, except that they were normoglycemic on the sucrose diet. The obese LA/N-cp rats had two of the three alterations in insulin secretion shown by obese SHR/N-cp rats, lacking only the impaired response to high glucose, suggesting that hyperglycemia was required for that defect to occur.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparison of insulin secretory patterns in obese nondiabetic LA/N-cp and obese diabetic SHR/N-cp rats. Role of hyperglycemia. 265 38

Children with Prader-Willi syndrome (PWS) are characterized by obesity, hyperphagia, hypogonadism, and mental retardation with underlying hypothalamic dysfunction and are known to have blunted or absent pancreatic polypeptide (PP) secretion in response to protein meals. In this communication, adults (26 +/- 3 years of age) with PWS were compared with age-matched normal obese and normal weight controls in regards to plasma glucose, insulin, PP, cholecystokinin (CCK), cholesterol, and triglyceride after a high protein meal. Compared with normal weight controls, adults with PWS showed a smaller and delayed rise in plasma insulin, and relatively smaller and delayed PP elevation whereas obese controls revealed hyperglycemia, markedly higher insulin, and moderately higher PP, cholesterol, and triglyceride levels than those with PWS. There was a small increment of CCK levels after a protein meal in all groups of adults. After a protein meal, the molar ratio of PP to CCK doubled in normal weight and PWS groups, and this ratio tripled in the normal obese group, suggesting no reduced PP secretion in PWS in response to CCK stimulation. PP hyposecretion in PWS thus appears to be a part of multiple endocrinopathy associated with hypothalamic dysfunction.
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PMID:Protein meal-stimulated pancreatic polypeptide secretion in Prader-Willi syndrome of adults. 266 31

Hyperinsulinemia secondary to a poorly characterized disorder of insulin action is a feature of the polycystic ovary syndrome (PCO). However, controversy exists as to whether insulin resistance results from PCO or the obesity that is frequently associated with it. Thus, we determined in vivo insulin action on peripheral glucose utilization (M) and hepatic glucose production (HGP) with the euglycemic glucose-clamp technique in obese (n = 19) and nonobese (n = 10) PCO women and age- and body-composition-matched normal ovulatory women (n = 11 obese and n = 8 nonobese women). None had fasting hyperglycemia. Two obese PCO women had diabetes mellitus, established with an oral glucose tolerance test; no other women had impairment of glucose tolerance. However, the obese PCO women had significantly increased fasting and 2-h glucose levels after an oral glucose load and increased basal HGP compared with their body-composition-matched control group. There were statistically significant interactions between obesity and PCO in fasting glucose levels and basal HGP (P less than .05). Steady-state insulin levels of approximately 100 microU/ml were achieved during the clamp. Insulin-stimulated glucose utilization was significantly decreased in both PCO groups whether expressed per kilogram total weight (P less than .001) or per kilogram fat free mass (P less than .001) or when divided by the steady-state plasma insulin (l) level (M/l, P less than .001). There was residual HGP in 4 of 15 obese PCO, 0 of 11 obese normal, 2 of 10 nonobese PCO, and 0 of 8 nonobese normal women. The metabolic clearance rate of insulin did not differ in the four groups. We conclude that 1) PCO women have significant insulin resistance that is independent of obesity, changes in body composition, and impairment of glucose tolerance, 2) PCO and obesity have a synergistic deleterious effect on glucose tolerance, 3) hyperinsulinemia in PCO is not the result of decreased insulin clearance, and 4) PCO is associated with a unique disorder of insulin action.
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PMID:Profound peripheral insulin resistance, independent of obesity, in polycystic ovary syndrome. 267 Jun 45

NIDDM is the predominant form of diabetes mellitus in all populations, almost exclusively so in some. Its prevalence varies enormously, with particularly high rates in populations whose lifestyle has drastically changed since World War II. Epidemiologic data from the developed countries of Europe and North America are not adequate to determine whether their incidence rates have also increased. Genetic factors are clearly implicated in the etiology of NIDDM, but their location and mode of expression remain to be determined. The two variables most strongly related to the incidence of NIDDM are age and degree of obesity, although there is emerging evidence of an independent association with fat distribution. Whether the nature of the habitual diet and the degree of physical activity influence the incidence of NIDDM remains uncertain and should be further researched. Cardiovascular disease is strongly associated with NIDDM in most populations, but there are between-population differences in the degree of association and the relative excess in the two sexes. There is increasing evidence, in particular for coronary heart disease, that increased risk precedes the onset of hyperglycemia; the implication of this is that NIDDM and atherosclerosis share common antecedents. The specific complications of NIDDM--eye and renal disease--are important causes of morbidity and mortality and for those populations, often relatively poor, in which NIDDM is already or is becoming very common will pose substantial problems in provision of health care.
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PMID:Epidemiology and public health aspects of non-insulin-dependent diabetes mellitus. 268 May 53


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