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)

Amylin, a 37-amino acid polypeptide, has been identified as the major protein component of pancreatic amyloid deposits in patients with non-insulin-dependent (type II) diabetes mellitus. Amylin is stored and released together with insulin and has been proposed to play a major role in the pathogenesis of type II diabetes. To compare amylin release and its proportion to insulin secretion under different metabolic conditions, oral and intravenous glucose tolerance tests (OGTT and IVGTT, respectively) were performed in healthy, lean control subjects, obese patients with normal and impaired glucose tolerance (NGT and IGT, respectively), and obese type II diabetic patients. Compared with control subjects, basal and stimulated amylin secretion during OGTT was significantly higher in obese patients with NGT and IGT but not in type II diabetic patients. The integrated amylin response was significantly higher in obese patients with NGT than lean control subjects and type II diabetic patients matched for degree of obesity. The amylin-insulin ratio decreased slightly in obese subjects with NGT and IGT and significantly in type II diabetic patients. Amylin secretion was significantly stimulated during IVGTT in control subjects and obese patients with NGT and IGT but not in type II diabetic patients. These findings suggest that amylin is physiologically released by pancreatic beta-cells in a constant ratio to insulin in nondiabetic subjects. Glucose-stimulated amylin secretion is increased in obese subjects with NGT and IGT. In type II diabetes mellitus, amylin secretion relative to that of insulin is decreased, and amylin is not stimulated by IVGTT.
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PMID:Decrease of stimulated amylin release precedes impairment of insulin secretion in type II diabetes. 175 2

The incidence of impaired glucose tolerance (IGT) in obese juvenile has not yet been well defined. Glycemic and insulin responses to OGTT were evaluated in 398 obese juveniles (and 70 healthy control subjects) to investigate possible correlations with age, body mass index (BMI) and obesity duration. Subjects were subdivided into two groups according to OGTT results: obese with normal glucose tolerance (OB-NGT) and obese with impaired glucose tolerance (OB-IGT). IGT was found in 11% of subjects but no correlations were observed in relation to age, BMI and obesity duration. There was no difference in the glycemic response to OGTT in terms of the biological parameters examined. Insulin plasma levels were twice as high in OB-NGT in comparison to control subjects and OB-NGT. Basal insulinemia increased with BMI in OB-IGT but not in OB-NGT.
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PMID:[Impaired glucose tolerance in obesity in children and adolescents]. 206 6

To elucidate the metabolism of islet amyloid polypeptide (IAPP) with respect to a possible renal elimination we investigated IAPP levels in 20 lean, nondiabetic patients with renal failure maintained on chronic hemodialysis (HD) and in 20 healthy controls. The basal levels of IAPP were significantly higher in uremic patients than in controls (15.1 +/- 3.2 vs. 3.2 +/- 0.2 pM, P < 0.001) suggesting renal excretion of IAPP. To investigate the impact of chronically elevated levels of endogenous IAPP on insulin secretion and insulin sensitivity, a frequently sampled intravenous glucose tolerance test (FSIGT) was performed in a subset of patients on hemodialysis and in age-matched healthy controls (C) and obese patients with normal (NGT) and with impaired glucose tolerance (IGT). Insulin sensitivity index (SI) was 8.7 +/- 1.5 in C (P < 0.05 vs. NGT, P < 0.01 vs. IGT), 5.4 +/- 0.9 in HD (P < 0.05 vs. IGT), 3.1 +/- 1.0 in NGT, and 2.0 +/- 0.5 in IGT. First phase insulin secretion was increased in patients on HD compared with those of several control groups. The results of this study therefore indicate a renal route of metabolism of IAPP. Increased endogenous circulating IAPP levels over a long period of time do not lead to a decrease in insulin release in patients on HD and do not cause the insulin resistance commonly seen in obesity and diabetes. Increased levels of circulating IAPP therefore are not likely to be a pathogenetic factor in the development of non-insulin-dependent diabetes mellitus (NIDDM).
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PMID:Increased levels of circulating islet amyloid polypeptide in patients with chronic renal failure have no effect on insulin secretion. 796 50

We analysed the data of 395 nondiabetic obese (BMI 25-42.2, impaired glucose tolerance, IGT, 257 and normal glucose tolerance, NGT, 138) and 482 nonobese subjects (BMI 15.9-24.9, IGT 170 and NGT 312). The blood pressure, plasma glucose, insulin, triglyceride and total cholesterol in obese were higher than that in nonobese, while HDL-c level was lower after controlling for age and sex (P < 0.001). This difference remained to be significant even after the adjustment of age, sex, insulin and 2-hours plasma glucose. Therefore, it was suggested that obesity was easy of access to coronary heart disease risk factors independent of hyperglycemia and hyperinsulinemia.
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PMID:[Relationship between obesity and risk factors of coronary heart disease in nondiabetics]. 813 57

This review describes recent studies which have assessed early metabolic alterations in IGT. Several studies showed decreases in the initial insulin release in response to glucose without significant changes in insulin sensitivity in IGT. Fasting plasma proinsulin-like molecules were higher and the pulsatile insulin secretion was altered too. On the other hand, several studies has proposed that insulin resistance develops first. They have demonstrated that absolute day-long plasma insulin concentrations in response to glucose are not lower than normal and glucose metabolism is impaired. These results are still inconclusive. The physiological role of the initial insulin secretion may be clarified, while the effects of the subtle differences in age, obesity, fat distribution, and ethnic groups between IGT and NGT on insulin resistance may be differentiated.
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PMID:[Insulin release kinetics and insulin sensitivity in impaired glucose tolerance]. 891 24

The study was performed to determine plasma levels of proinsulin (PI) and specific insulin (SI) in normoglycemic (NGT) Asian Indians and to assess the effect of obesity and impaired glucose tolerance (IGT) on these concentrations. Blood samples from 151 adult nondiabetic South Indian subjects were collected during an epidemiological survey of diabetes. Plasma SI and PI levels were measured in fasting and 30-minute and 120-minute samples of a glucose tolerance test (World Health Organization criteria) using monospecific antibodies. The total insulin (TI) level was also measured by the nonspecific assay. The molar ratio of PI to SI (PI/SI) was calculated. Correlations of the peptides with anthropometry, serum lipids, and blood pressure (BP) were studied by univariate and multivariate analyses. Comparisons were also made in NGT versus IGT groups. As expected, TI values were higher than SI values, but the patterns of response were similar for both. SI and PI responses in NGT were similar to the values found in Mexican-Americans who had a higher body mass index (BMI). Asian Indians were thus found to have a high SI response despite a low BMI. Obesity and IGT produced an increased response of both PI and SI, with normal PI/SI ratios thus showing an absence of hyperproinsulinemia in either condition. Fasting PI showed a strong association with serum triglycerides, and proinsulin at 120 minutes was associated with cholesterol. None of the peptides showed a correlation with BP. Using specific assays for insulin and PI, it is shown that Asian Indians with NGT have a hyperinsulinemic response despite a low BMI. Obesity and mild hyperglycemia in IGT produce a simultaneous increase in PI and SI with no alteration in the PI/SI ratio.
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PMID:Specific insulin and proinsulin concentrations in nondiabetic South Indians. 947 76

We evaluated dietary habits as risk factor for glucose intolerance in a high risk population of Japanese-Brazilians enrolled in a study on the prevalence of diabetes (DM). Based on oral glucose tolerance test and WHO criteria, 331 had normal tolerance (NGT), 88 impaired tolerance (IGT) and 83 had type 2 DM (51 self-reported, 32 newly diagnosed diabetics). Clinical, laboratory and dietary data, assessed by food frequency questionnaire (FFQ), were compared between the NGT group and another composed of IGT and newly diagnosed DM (disturbed glucose tolerance or DGT group). Associations of total energy intake and nutrient intakes with glucose intolerance were analyzed by logistic regression. Also, subjects with NGT and DGT entered into separate models of multiple linear regression including BMI as the dependent variable, and total energy intake or each nutrient as independent variables. DGT group showed higher waist-to-hip ratio, blood pressure, plasma glucose and insulin levels and worse lipid profile. Total energy intake, macronutrients, fibers, alcohol and saturated fat intakes did not differ between groups; DGT was not associated with any nutrient intake in multivariate analyses. BMI of the subjects with DGT but not with NGT was associated with protein and cholesterol intakes in linear regression analysis. Our findings did not support an association between nutritional factors and glucose intolerance even in subjects who are unaware of their DGT, using FFQ to reflect current habits. However, we suggest that protein and cholesterol intakes may be markers of increased BMI. Despite assuming that obesity and insulin resistance precedes DM, FFQ may not be useful in the assessment of unfavorable dietary patterns among subjects at risk for glucose intolerance, such as Japanese-Brazilians with elevated BMI.
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PMID:Dietary patterns in a high-risk population for glucose intolerance. Japanese-Brazilian Diabetes Study Group. 1077 35

Age, female sex, and obesity are well-known risk factors for gallstones; in contrast the possible role of type 2 diabetes mellitus (type-2 DM) is controversial. One reason for this discrepancy might be that type 2 DM is often accompanied by obesity. Therefore, the aim of this study was to evaluate the importance of obesity and of type 2 DM, separately and together, as risk factors for gallstones. In all, 203 obese patients with normal glucose tolerance (obese NGT), 446 obese patients with type 2 DM (obese type 2 DM), 269 lean patients with type 2 DM (lean type 2 DM) and 250 lean subjects with a normal glucose tolerance (lean NGT) were evaluated by ultrasonography for the presence of gallstones. At univariate analysis patients with gallstones (177) were older and were more frequently affected by both obesity and type 2 DM, and had higher triglycerides and fasting blood glucose levels. At multiple logistic regression analysis, only age and obesity, both in the presence or in absence of type 2 DM, were strongly associated with gallstones (P < 0.001); diabetes alone had a lower level of statistical significance (P = 0.07). These data suggest that obesity is a stronger risk factor for gallstones than type 2 DM.
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PMID:Association of obesity and type II diabetes mellitus as a risk factor for gallstones. 1111 74

A G-to-A (UCSNP-43) polymorphism of the calpain-10 gene was significantly associated with type 2 diabetes (DM) in Mexican-American, and was postulated, together with a T-to-C (UCSNP-44) polymorphism, as a risk factor for DM. We examined the association of these genotypes with DM in Japanese. Eighty-one subjects with DM and 81 non-diabetic subjects (NGT) were recruited. The number of subjects with genotypes UCSNP-43 G/G, G/A and A/A were 76, 5 and 0, respectively, for the DM and NGT groups. The number of subjects with genotypes UCSNP-44 T/T, T/C and C/C were 66, 14 and 1 for the DM group and 64, 17 and 0 for the NGT group. There was no difference between the groups in terms of frequency of any genotype combinations. No association between the genotypes and DM was observed. We next examined the differences between the genotypes or genotype combinations in terms of the traits related to DM, obesity, hypertension and dyslipidemia. No differences were observed between the genotypes UCSNP43 G/G and G/A, between UCSNP-44 T/T and the others, or between the genotype combination UCSNP-43 G/G and UCSNP-44 T/T and the others, except that the individuals with the genotype combination had significantly increased serum cholesterol levels (212.6 +/- 34.3 vs. 198.5 +/- 29.9, P=0.020). The genotype combination might be a risk factor, not for DM, obesity and hypertension, but for increased serum cholesterol.
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PMID:Calpain 10 gene polymorphisms are related, not to type 2 diabetes, but to increased serum cholesterol in Japanese. 1189 Oct 23

Even small increases in the frequency of thrombotic disease in users of OCs have general health impact because of their widespread use, which is currently expanding to potential risk groups. The present investigations were launched to study the effects of OCs containing 20-40 micrograms of EE combined with the latest developed gonane progestogens on biochemical risk markers within metabolic systems involved in the development of arterial thrombotic disease. The studies included evaluation of carbohydrate and lipid metabolism as well as the haemostatic system and were performed in non-diabetic women and in women with IDDM, who are prone to the development of arterial thrombosis. In the evaluation of the carbohydrate metabolism in non-diabetic women, we found no effect on fasting glucose or insulin and no effect on the insulin response to oral glucose in women using monophasic OCs containing EE combined with DSG or GST. This contrasts the evaluation of triphasic OCs containing EE combined with GST or NGT, which increased fasting insulin and reduced insulin sensitivity without affecting the glucose-effectiveness or the beta-cell function. Impaired glucose tolerance developed in 10% of the women after 6 months. These finding suggest that OCs are able to induce a state of insulin resistance, which should be considered in the prescription for women with potential disturbed insulin sensitivity or reduced beta-cell secretory capacity e.g. women with ovarian hyperandrogenism, obesity, previous GDM or perimenopausal women. We found no change in glycaemic control in 22 women with well-regulated IDDM treated with a monophasic combination of EE and GST for one year and none of the women developed microalbuminuria during treatment. In the women with diabetes we observed an increase in fasting levels of triglycerides, a decrease in LDL-cholesterol, and unchanged concentrations of total cholesterol and HDL-cholesterol during treatment. In non-diabetic women treated with the same compound or an OC containing EE and DSG we found similar changes in triglycerides and total cholesterol, but increased levels of HDL-cholesterol and unchanged LDL-cholesterol concentrations. In the women with IDDM there was a negative correlation between daily insulin requirement and HDL-cholesterol before and during treatment, but no other statistically significant correlation between estimates of glycaemic control and lipids and lipoproteins were observed. In the non-diabetic women, changes in the haemostatic system included an increase in the procoagulant factors fibrinogen and Factor VIIc; the concentration of active t-PA increased, mainly because of decreased inhibition by PAI-1. The ratio between molecular markers of the activity of the coagulation system and the efficacy of fibrinolysis was unchanged. This was also found in the women with IDDM, who showed evidence of increased fibrin formation and an attenuated fibrinolytic response during treatment. The regulation of the t-PA/PAI system was studied in non-diabetic women in order to elucidate if the effects of OCs are caused by a direct effect on synthesis or clearance of these variables or if they are secondary to changed insulin sensitivity, as described in individuals with atherosclerosis. We found no indications that insulin resistance is involved in the regulation of t-PA and PAI-1 antigen levels, neither before nor during intake of OCs. We showed, however, that the decreased t-PA antigen concentration observed in OC users is caused by reduced synthesis outside the splanchnic circulation. The studies indicate that low-dose OCs containing newer gonane progestogens are able to induce insulin resistance and to impair glucose tolerance. Lipoproteins were not adversely influenced by the OCs neither in the diabetic nor the non-diabetic women; on the contrary, there was a tendency towards increased plasma levels of HDL-cholesterol and decreased LDL-cholesterol which are associated with a decreased risk of atherosclerosis. The changes observed within the haemostatic system were in accordance with a maintained balance between coagulation and fibrinolysis although the rate of fibrin formation may be increased in the women with IDDM. Irrespective of OC use, the interrelationships between metabolic systems in young non-diabetic women are different from those reported in individuals with atherosclerosis or insulin resistance. The effects of OCs on the t-PA/PAI system seem to be mediated by a direct effect on the vessel wall and not by changes in the hepatic clearance. The present findings were obtained in diabetic women without vascular complications, so the conclusion that women with IDDM can use OCs without metabolic alterations of known clinical significance is therefore restricted to those without evidence of diseased vessels. When evaluating the results obtained in the non-diabetic women, it should be remembered that women with recognised risk factors were excluded. The results may therefore be of limited value when evaluating the risk of arterial thrombosis in predisposed populations. In healthy individuals, the present integrated evaluation of biochemical markers does not indicate an increased risk of arterial thrombosis during use of low-dose OCs containing newer gonane progestogens; thus, the findings are in accordance with the recent epidemiological studies on these compounds. The application of relevant biochemical markers facilitate the understanding of the non-reproductive effects of sex steroids which have increasing importance because of their expanding use, not only as contraceptives, but also in the treatment of benign gynaecological disorders, as hormone replacement therapy and as prophylactic agents against specific degenerative conditions. Moreover, they may prove to be helpful in the future identification of women, who have increased susceptibility to the metabolic effects of sex steroids due to genetic predisposition.
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PMID:Pharmacodynamic effects of oral contraceptive steroids on biochemical markers for arterial thrombosis. Studies in non-diabetic women and in women with insulin-dependent diabetes mellitus. 1189 23


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