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

To evaluate the effects of obesity and impaired glucose tolerance on insulin sensitivity, we performed a euglycaemic-hyperinsulinemic clamp at about 350 pmol l-1, combined with 3H-glucose infusion, in 14 obese patients, BMI 36.5 +/- 1.2 and in 12 matched controls, BMI 23.9 +/- 0.4. Six obese patients had normal glucose tolerance (oNGT), and eight had impaired glucose tolerance (oIGT). The ability of insulin to inhibit lipolysis in isolated adipocytes was also studied. Insulin-mediated glucose utilization was more severely impaired in oIGT than in oNGT with respect to the controls (621 +/- 51 vs. 897 +/- 83 vs. 1298 +/- 55 mumol m-2 min-1, P < 0.001). Plasma glycerol was higher in oIGT than in oNGT and in the controls, both fasting (238 +/- 12 vs. 179 +/- 14 vs. 112 +/- 8 mumol l-1, P < 0.001) and during the clamp (175 +/- 21 vs. 120 +/- 12 vs. 36 +/- 6 mumol l-1, P < 0.001). The correlation between glucose utilization and the percent reduction of plasma glycerol during the clamp was significant in the study group as a whole (r = 0.809, P = 0.0001), and in each of the groups separately (oIGT: r = 0.929, P = 0.002; oNGT: r = 0.943, P = 0.036; controls: r = 0.902, P = 0.0001). Inhibition by insulin of noradrenaline-stimulated lipolysis in isolated adipocytes was more severely impaired in oIGT than in oNGT compared with the controls (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The glucoregulatory and antilipolytic actions of insulin in abdominal obesity with normal or impaired glucose tolerance: an in vivo and in vitro study. 147 41

Type 2 diabetes is a familial disease, but recent analysis of nuclear families indicates it is unlikely to be due to a single dominant gene with high penetrance and that it could be polygenic. Insulin resistance is a major feature, with obesity being a major determinant. Beta cell deficiency is a sine qua non of Type 2 diabetes. It is possible that obesity, insulin resistance independent from obesity and impaired beta cell function are independently inherited factors. None of these can be said to be 'primary' as diabetes usually results from the interaction of several geometric and environmental factors. This makes linkage analysis of Type 2 diabetes of uncertain benefit, since heterogeneity can occur within a pedigree. The only mutation so far discovered is of glucokinase producing maturity-onset diabetes of the young, that has a clearly defined and unusual phenotype. Identification of genes that cause classical Type 2 diabetes is likely to come from population association studies, molecular scanning techniques and direct sequencing of candidate genes rather than linkage analysis.
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PMID:Type II diabetes: search for primary defects. 148 47

Non insulin-dependent diabetes is often associated with obesity and always with some degree of insulin resistance. First choice treatment consists of appropriate and sometimes hypocaloric diet and oral hypoglycemic agents. Using insulin becomes mandatory in patients with associated pathology or at risk of metabolic imbalance. Insulin administration must be discussed in each individual case when it aims at a long-term improvement of blood glucose control, taking into account the lack of consensus on this point and the potential drawbacks of insulin therapy, notably weight increase and risk of hypoglycaemia.
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PMID:[Insulin in type 2 diabetes. Why, when, how?]. 149 37

We tested the hypothesis that hypercorticosteronemia causes the hypercholesterolemia in young developing "fatty" rats. Obesity induced increases in corticosterone. Insulin, glucose, body weight, average daily food intake, plasma triglyceride, plasma phospholipids, liver weight, liver triglyceride, various adipose tissue parameters, and liver hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase activity were all ameliorated by adrenalectomy. Adrenalectomy exacerbated the hypercholesterolemia in obese animals and induced it in lean rats. Changes or lack of change in hepatic microsomal cholesterol, HMG-CoA reductase, and 7 alpha-hydroxylase, combined with the adrenalectomy-induced curtailment of tissue storage of cholesterol in adipose tissue, all contribute to the hypercholesterolemia caused by adrenalectomy. We suggest a mechanism whereby this may be related to elevated hepatic very low-density lipoprotein secretion rates. The elevated HMG-CoA reductase activity in obese rats results from the lower liver microsomal free cholesterol content. We conclude that the absence of glucocorticoids does not directly reduce plasma cholesterol in obese Zucker rats. The surprising elevation of cholesterol by adrenalectomy is due to other prevailing mechanisms in liver and adipose tissue, which curtail their capacity to store cholesterol.
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PMID:Is there a role for the adrenals in the development of hypercholesterolemia in Zucker fatty rats? 151 9

Insulin binding to erythrocytes (IB) and serum immunoreactive insulin concentration (IRI) were measured and relationships between these parameters and body mass index (BMI) were investigated in obese children and age matched controls with normal body weight. IRI was increased and IB was decreased significantly in the obese group compared to data of the controls. The decreased IB was due to a decrease in insulin receptor number since it was not accompanied by alteration of half maximal inhibition dose (ID50). Strong negative correlations were found between BMI and IB and between IRI and IB while a positive association was seen between BMI and IRI. These results prove an interrelationship between weight excess, hyperinsulinism and insulin resistance in childhood obesity.
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PMID:[Insulin resistance in childhood obesity]. 152 85

Lactate metabolism is altered in obesity. Increasing obesity is associated with increased blood lactate levels after an overnight fast. In contrast, we have recently shown a marked decrease in the capacity for acute lactate generation in obese subjects following an oral glucose load, which we postulated might be linked to altered insulin sensitivity. In the present study, we systematically analyzed the relationship between insulin sensitivity (the Sensitivity Index [SI] derived using the minimal model), body mass index (BMI), and glucose, insulin, and lactate levels in the basal state and following intravenous (IV) glucose and insulin administration in lean and obese subjects. The results showed that SI and BMI were inversely related, as expected. Insulin sensitivity was more tightly associated with glucose, insulin, and lactate levels (both basal and integrated) than obesity per se. A significant inverse relationship was found between SI and basal lactate levels (r = -.56). Moreover, a significant and positive relationship was found between SI and incremental lactate area under the curve (reflecting acute lactate production) (r = .41). In a multiple regression analysis to separate the independent effects of obesity (BMI) and insulin sensitivity, after adjusting for age, sex, and race, SI accounted for 34% of the variance in basal lactate and 24% of the variance in incremental lactate area. Obesity independently accounted for 10% of the variance in basal lactate and 11% of the variance in incremental lactate area, neither of which were statistically significant. We conclude that elevations in basal lactate are associated with the development of insulin resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Insulin resistance in obesity is associated with elevated basal lactate levels and diminished lactate appearance following intravenous glucose and insulin. 153 40

In an attempt to determine the principles of diet management in obese pregnant women, the association between maternal weight gain during pregnancy (Group I; weight reduction, Group II; +0-4 kg, Group III; +5-9 kg, Group IV; +10 kg-) and the incidence of the complications was investigated in 151 obese pregnant women. Studies on glucose tolerance and insulin binding to erythrocytes were also undertaken. 1) In Group I, the incidences of C/S, forceps delivery, prolonged labor and complication of PIH were lower than those of other groups. There were no heavy-for-dates and light-for-dates babies in Group I, differing from the other three groups. 2) Plasma levels of glucose and insulin were high in obese pregnant women on 75 g OGTT in the second trimester. The binding sites of insulin to erythrocytes were significantly decreased in obese pregnant women. In conclusion, the risks of pregnancy complicated by obesity were high. Insulin resistance was a characteristic of obese pregnant women. The results of this study suggested that the nutritional requirements for very obese pregnant women should be restricted to maintaining the same weight or losing weight during the course of pregnancy to minimize maternal and perinatal risks.
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PMID:[Studies of diet management and insulin resistance in obese pregnant women]. 154 76

Altered lipoprotein composition may be a better predictor of cardiovascular disease than modestly increased serum lipid concentrations, although possible interactions between lipoprotein composition, obesity, and insulinemia have not been fully elucidated. Therefore, we investigated the association between different measures of insulinemia and lipoproteins in 297 healthy Caucasian men (body mass index [BMI] less than 27 in 233, greater than 27 [obese] in 64) and 295 healthy Caucasian women (BMI less than 25 in 198, greater than 25 [obese] in 97). Associations observed in both obese and nonobese men and women were between increasing tertiles of most insulin measures and serum triglyceride concentrations (p = 0.079-0.004) and the ratio of low density lipoprotein to high density lipoprotein cholesterol (p = 0.094-0.008). Graded reductions in the high density lipoprotein cholesterol to apolipoprotein A-I ratio were also recorded in obese women, with increasing tertiles of fasting (p = 0.014-0.007) and postglucose load (p = 0.001) serum insulin levels, after correcting for BMI and triglyceride concentrations. Less marked graded increases in the triglyceride to apolipoprotein B ratios were recorded in obese women with increasing tertiles of fasting (p = 0.001-0.006) and postglucose challenge (p = 0.081) insulinemic measures. In men with normal or slightly elevated cholesterol levels (fasting serum cholesterol less than 6.5 mmol/l), hyperapobetalipoproteinemia was recorded with increasing tertiles of insulinemia (p = 0.006, correcting for BMI and triglyceride concentrations), as well as in subjects with hypertriglyceridemia (fasting serum triglycerides greater than 1.70 mmol/l) (p = 0.004, correcting for BMI and age). Hyperinsulinemia and insulin resistance are associated with altered lipoprotein composition in obese women, presumably reflecting a complex interplay between sex hormones, body mass, and insulin action. Insulin resistance appears to be more associated with apolipoprotein B concentrations in men. The hyperinsulinemic nondiabetic subject may be at increased risk of cardiovascular disease because of altered concentrations of apolipoprotein concentrations and lipoprotein composition.
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PMID:Relation between insulinemia, body mass index, and lipoprotein composition in healthy, nondiabetic men and women. 154 96

Insulin secretion rates can be accurately estimated from plasma C-peptide levels with a two-compartment model for C-peptide distribution and degradation. In previous studies, the kinetic parameters of C-peptide clearance were derived in each subject from the decay curve observed after bolus intravenous injection of biosynthetic human C-peptide. To determine whether standard parameters for C-peptide clearance could be defined and used to calculate insulin secretion without obtaining a decay curve in each subject, we analyzed 200 decay curves of biosynthetic human C-peptide obtained in normal, obese, and non-insulin-dependent diabetes mellitus subjects studied in our laboratory. This analysis showed that the volume of distribution and kinetic parameters of C-peptide distribution and metabolism vary by less than 30% in a population highly heterogeneous in terms of age, sex, degree of obesity, and degree of glucose tolerance. The volume of distribution correlated with the degree of obesity as quantified by body surface area (BSA). This dependence of C-peptide distribution volume on BSA was more marked in men than in women. The long half-life was slightly longer in elderly subjects than in younger adults. When effects of BSA, sex, and age were taken into account, the parameters of C-peptide kinetics were very similar in normal, obese, and diabetic subjects. Based on these findings, a simple procedure to derive standard parameters for C-peptide clearance taking into account degree of obesity, sex, and age was defined. These standard parameters resulted in estimations of mean insulin secretion rates, which differed in each subject by only 10-12% from those obtained with individual parameters. The approach of using standard rather than individual parameters did not systematically underestimate or overestimate insulin secretion so that group values for the fasting secretion rate, the mean 24-h secretion rate, and the number and the amplitude of secretory pulses obtained with standard parameters differed by only 1-2% from the values obtained with individual parameters. Furthermore, the accuracy of measurements based on standard parameters was not different from that associated with replicate determinations of the parameters of C-peptide clearance in the same subject. We conclude that it is possible to estimate insulin secretion rates from plasma C-peptide levels with standard parameters for C-peptide clearance rather than individually derived parameters without significant loss of accuracy.
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PMID:Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance. 155 97

We measured the degree of association between obesity, blood pressure, insulin resistance, and insulin secretion in 72 male and female obese hypertensive, obese nonhypertensive, and normal weight control subjects. Baseline weight, body mass index, percent body fat, waist/hip ratio, and systolic and diastolic blood pressures were obtained. Insulin sensitivity was assessed according to Bergman's minimal model. Twelve-hour urinary c-peptide was measured after a standard liquid meal. Insulin action was inversely associated with blood pressure status, obesity status, and age. Meal-stimulated c-peptide excretion significantly correlated with systolic blood pressure and percent fat but not with body mass index or age. Multivariate regression analysis indicated that, of the measures of body composition, percent fat and waist/hip ratio had the strongest correlation with insulin action either alone or in combination with c-peptide excretion. Obese hypertensive patients had an index of insulin action (10(-4).min-1/[microunits/ml]) of 1.34 +/- 0.19, which was significantly (p less than 0.003) lower than in the obese nonhypertensive patients (index, 2.26 +/- 0.10) or the nonobese subjects (index, 5.41 +/- 0.26, p less than 0.001). Meal-stimulated c-peptide excretion (nmol/kg lean body mass) was increased only in the obese hypertensive group (0.32 +/- 0.01) and was significantly higher (p less than 0.001) than in the obese nonhypertensive (0.16 +/- 0.01) or the nonobese subjects (0.14 +/- 0.01). These results support the hypothesis that abnormalities in blood pressure regulation, insulin-stimulated glucose uptake, and insulin secretion coexist.
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PMID:Insulin resistance versus insulin secretion in the hypertension of obesity. 155 70


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