Central adiposity and its metabolic correlates in obese adolescent girls.

To establish whether alterations in insulin action and secretion and their relationship to body fat distribution occur early in the course of developing obesity, we studied 14 obese adolescent girls [13.2 +/- 0.7 yr, body mass index (BMI) 32 +/- 1.4], 16 nonobese young women (24.0 +/- 0.6 yr, BMI 21.0 +/- 0.9). Insulin action was assessed by a sequential two-step (8 and 40 mU,m-2.min-1) euglycemic insulin clamp in combination with [1-13C]glucose and indirect calorimetry. Insulin secretion was determined by the hyperglycemic clamp technique (6.9 mmol/l). Magnetic resonance imaging was used to quantify visceral and subcutaneous abdominal fat depots. In obese girls, an impairment in glucose disposal was present with both insulin doses; at the higher dose, rates of glucose uptake were reduced by 30% in nonobese girls (240 +/- 30 vs. 340 +/- 19 mg.m-2.min-1, P < 0.05) and by an additional 29% (170 +/- 17 mg.m-2.min-1, P < 0.05) in obese girls. Insulin infusion failed to stimulate glucose oxidation and to suppress lipid oxidation only in obese girls. Suppression of free fatty acid levels, but not hepatic glucose production, was decreased in obese girls compared with controls. Fasting and glucose-stimulated insulin responses were greater in obese than in nonobese adolescents, who, in turn, had greater responses than lean women. In obese girls, visceral fat, but neither waist-to-hip circumference ratio nor subcutaneous fat, was highly correlated with basal insulin secretion (r = 0.89, P < 0.001), stimulated insulin secretion (r = 0.61, P < 0.05), and insulin resistance (r = -0.87, P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

[1]  P. Bougnères,et al.  Early Changes in Postprandial Insulin Secretion, Not in Insulin Sensitivity, Characterize Juvenile Obesity , 1994, Diabetes.

[2]  Roland Bramlet,et al.  Radioactive and Stable Isotope Tracers in Biomedicine , 1993 .

[3]  J. Lancaster,et al.  Total Body Fat Content and Fat Topography Are Associated Differently With In Vivo Glucose Metabolism in Nonobese and Obese Nondiabetic Women , 1992, Diabetes.

[4]  Darrell M. Wilson,et al.  Standardized percentile curves of body-mass index for children and adolescents. , 1991, American journal of diseases of children.

[5]  P. Björntorp "Portal" adipose tissue as a generator of risk factors for cardiovascular disease and diabetes. , 1990, Arteriosclerosis.

[6]  L. Groop,et al.  Obesity and insulin resistance in humans: a dose-response study. , 1990, Metabolism: clinical and experimental.

[7]  S. Haffner,et al.  Incidence of Type II Diabetes in Mexican Americans Predicted by Fasting Insulin and Glucose Levels, Obesity, and Body-Fat Distribution , 1990, Diabetes.

[8]  F. Lönnqvist,et al.  Mechanisms underlying regional differences in lipolysis in human adipose tissue. , 1989, The Journal of clinical investigation.

[9]  L. Groop,et al.  Glucose and free fatty acid metabolism in non-insulin-dependent diabetes mellitus. Evidence for multiple sites of insulin resistance. , 1989, The Journal of clinical investigation.

[10]  W. Tamborlane,et al.  Increased insulin secretion in puberty: a compensatory response to reductions in insulin sensitivity. , 1989, The Journal of pediatrics.

[11]  W. Totty,et al.  Measurement of fat distribution by magnetic resonance imaging. , 1989, Investigative radiology.

[12]  P. Björntorp,et al.  Metabolism of adipose tissue in intraabdominal depots of nonobese men and women. , 1989, Metabolism: clinical and experimental.

[13]  P. Bougnères,et al.  Increased Basal Glucose Production and Utilization in Children With Recent Obesity Versus Adults With Long-Term Obesity , 1989, Diabetes.

[14]  W. Tamborlane,et al.  Oxidative fuel metabolism during mild hypoglycemia: critical role of free fatty acids. , 1989, The American journal of physiology.

[15]  A N Peiris,et al.  Biology of regional body fat distribution: relationship to non-insulin-dependent diabetes mellitus. , 1989, Diabetes/metabolism reviews.

[16]  R. DeFronzo,et al.  Metabolic basis of obesity and noninsulin-dependent diabetes mellitus. , 1988, Diabetes/metabolism reviews.

[17]  G. Reaven Role of Insulin Resistance in Human Disease , 1988, Diabetes.

[18]  L. Mandarino,et al.  Effects of insulin infusion on human skeletal muscle pyruvate dehydrogenase, phosphofructokinase, and glycogen synthase. Evidence for their role in oxidative and nonoxidative glucose metabolism. , 1987, The Journal of clinical investigation.

[19]  R N Bergman,et al.  Estimation of Endogenous Glucose Production During Hyperinsulinemic-Euglycemic Glucose Clamps: Comparison of Unlabeled and Labeled Exogenous Glucose Infusates , 1987, Diabetes.

[20]  J. Foley,et al.  Comparison of body composition, adipocyte size, and glucose and insulin concentrations in Pima Indian and Caucasian children. , 1987, Metabolism: clinical and experimental.

[21]  W H Dietz,et al.  Increasing pediatric obesity in the United States. , 1987, American journal of diseases of children.

[22]  R. DeFronzo,et al.  Regulation of hepatic glucose metabolism in humans. , 1987, Diabetes/metabolism reviews.

[23]  R. Mueller,et al.  Splanchnic insulin metabolism in obesity. Influence of body fat distribution. , 1986, The Journal of clinical investigation.

[24]  P. Björntorp,et al.  Reduced hepatic insulin clearance in rats with dietary-induced obesity. , 1986, Metabolism: clinical and experimental.

[25]  A. Kissebah,et al.  Relationship between skeletal muscle insulin resistance, insulin-mediated glucose disposal, and insulin binding. Effects of obesity and body fat topography. , 1984, The Journal of clinical investigation.

[26]  S. Lillioja,et al.  Correlation between muscle glycogen synthase activity and in vivo insulin action in man. , 1984, The Journal of clinical investigation.

[27]  P. Arner,et al.  Differences at the Receptor and Postreceptor Levels Between Human Omental and Subcutaneous Adipose Tissue in the Action of Insulin on Lipolysis , 1983, Diabetes.

[28]  A. Rosenbloom,et al.  Age-adjusted Analysis of Insulin Responses During Normal and Abnormal Glucose Tolerance Tests in Children and Adolescents , 1975, Diabetes.

[29]  M. Novak COLORIMETRIC ULTRAMICRO METHOD FOR THE DETERMINATION OF FREE FATTY ACIDS. , 1965, Journal of lipid research.