Adiponectin and Leptin are Independently Associated with Insulin Sensitivity, but not with Insulin Secretion or Beta-cell Function in Overweight Hispanic Adolescents

Abstract

The aim of the study was to investigate the independent effects of leptin and adiponectin on insulin sensitivity as well as insulin secretion and beta-cell function in overweight Hispanic adolescents. Despite pubertal changes in hormone secretion, studies investigating the independent effect of both hormones on insulin sensitivity and beta-cell function in adolescents are lacking. In a cross-sectional study, 175 overweight Hispanic adolescent boys (n=101) and girls (n=74) with a family history of diabetes were recruited and insulin sensitivity (SI), acute insulin response to glucose (AIR), disposition index (DI), body composition, total serum adiponectin, and leptin were assessed. Over age, leptin significantly increased in girls but not in boys (p for age×gender interaction=0.005) while adiponectin was similar in boys and girls. Leptin was not correlated to adiponectin. Leptin (partial r=−0.180; p=0.019) and adiponectin (partial r=0.230; p=0.003) predicted SI independent of age, gender, body fat, lean body mass, and Tanner stage but together, they explained 5% of the unique variation in SI (p for R²-change<0.001). Leptin or adiponectin were not related to AIR or DI. With regard to SI, AIR, and DI, no significant gender, age, or Tanner stage interactions were observed suggesting similar effects of adiponectin and leptin among gender, age, and Tanner stages. Leptin and adiponectin were independently associated with SI, but not with insulin secretion or beta-cell function.

adiponectin - leptin - insulin sensitivity - beta-cell function

References

• 1 Weiss R, Taksali SE, Caprio S. Development of type 2 diabetes in children and adolescents.  Curr Diab Rep. 2006;  6 182-187
• 2 Goran MI, Bergman RN, Cruz ML, Watanabe R. Insulin resistance and associated compensatory responses in African-American and Hispanic children.  Diabetes Care. 2002;  25 2184-2190
• 3 Goran MI, Bergman RN, Avila Q. et al . Impaired glucose tolerance and reduced beta-cell function in overweight Latino children with a positive family history for type 2 diabetes.  J Clin Endocrinol Metab. 2004;  89 207-212
• 4 Weigensberg MJ, Ball GD, Shaibi GQ, Cruz ML, Goran MI. Decreased beta-cell function in overweight Latino children with impaired fasting glucose.  Diabetes Care. 2005;  28 2519-2524
• 5 Amiel SA, Sherwin RS, Simonson DC, Lauritano AA, Tamborlane WV. Impaired insulin action in puberty. A contributing factor to poor glycemic control in adolescents with diabetes.  N Engl J Med. 1986;  315 215-219
• 6 Goran MI, Gower BA. Longitudinal study on pubertal insulin resistance.  Diabetes. 2001;  50 2444-2450
• 7 Ball GD, Huang TT, Gower BA. et al . Longitudinal changes in insulin sensitivity, insulin secretion, and beta-cell function during puberty.  J Pediatr. 2006;  148 16-22
• 8 Ball GD, Weigensberg MJ, Cruz ML. et al . Insulin sensitivity, insulin secretion and beta-cell function during puberty in overweight Hispanic children with a family history of type 2 diabetes.  Int J Obes (Lond). 2005;  29 1471-1477
• 9 Goran MI, Shaibi GQ, Weigensberg MJ, Davis JN, Cruz ML. Deterioration of insulin sensitivity and beta-cell function in overweight Hispanic children during pubertal transition: A longitudinal assessment.  Int J Pediatr Obes. 2006;  1 139-145
• 10 Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism.  Nature. 2001;  414 799-806
• 11 Zhang Y, Scarpace PJ. The role of leptin in leptin resistance and obesity.  Physiol Behav. 2006;  88 249-256
• 12 Friedman JM. The function of leptin in nutrition, weight, and physiology.  Nutr Rev. 2002;  60 S1-S14 , ; discussion S68–S84, S85–S87
• 13 Steinberger J, Steffen L, Jacobs  Jr  DR. et al . Relation of leptin to insulin resistance syndrome in children.  Obes Res. 2003;  11 1124-1130
• 14 Yamauchi T, Kamon J, Minokoshi Y. et al . Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase.  Nat Med. 2002;  8 1288-1295
• 15 Matsubara M, Maruoka S, Katayose S. Inverse relationship between plasma adiponectin and leptin concentrations in normal-weight and obese women.  Eur J Endocrinol. 2002;  147 173-180
• 16 Huypens P, Quartier E. Adiponectin expression is paradoxically increased in gold-thioglucose-induced obesity.  Horm Metab Res. 2006;  38 486-490
• 17 Thamer C, Haap M, Heller E. et al . Beta cell function, insulin resistance and plasma adiponectin concentrations are predictors for the change of postprandial glucose in non-diabetic subjects at risk for type 2 diabetes.  Horm Metab Res. 2006;  38 178-182
• 18 Emilsson V, Liu YL, Cawthorne MA, Morton NM, Davenport M. Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion.  Diabetes. 1997;  46 313-316
• 19 Cases JA, Gabriely I, Ma XH. et al . Physiological increase in plasma leptin markedly inhibits insulin secretion in vivo.  Diabetes. 2001;  50 348-352
• 20 Bacha F, Saad R, Gungor N, Arslanian SA. Adiponectin in youth: relationship to visceral adiposity, insulin sensitivity, and beta-cell function.  Diabetes Care. 2004;  27 547-552
• 21 Staiger K, Stefan N, Staiger H. et al . Adiponectin is functionally active in human islets but does not affect insulin secretory function or beta-cell lipoapoptosis.  J Clin Endocrinol Metab. 2005;  90 6707-6713
• 22 Leclercq-Meyer V, Malaisse WJ. Failure of human and mouse leptin to affect insulin, glucagon and somatostatin secretion by the perfused rat pancreas at physiological glucose concentration.  Mol Cell Endocrinol. 1998;  141 111-118
• 23 Khan A, Narangoda S, Ahren B. et al . Long-term leptin treatment of ob/ob mice improves glucose-induced insulin secretion.  Int J Obes Relat Metab Disord. 2001;  25 816-821
• 24 Wauters M, Considine RV, Yudkin JS. et al . Leptin levels in type 2 diabetes: associations with measures of insulin resistance and insulin secretion.  Horm Metab Res. 2003;  35 92-96
• 25 Pardini VC, Victoria IM, Rocha SM. et al . Leptin levels, beta-cell function, and insulin sensitivity in families with congenital and acquired generalized lipoatropic diabetes.  J Clin Endocrinol Metab. 1998;  83 503-508
• 26 Cruz ML, Weigensberg MJ, Huang TT. et al . The metabolic syndrome in overweight Hispanic youth and the role of insulin sensitivity.  J Clin Endocrinol Metab. 2004;  89 108-113
• 27 Centers for Disease Control and Prevention. CDC growth Charts. In: U.S. Department of Health and Human Services CfDCaP ed. National Center for Health Statistics 2000
• 28 American Diabetes Association . Type 2 diabetes in children and adolescents.  Pediatrics. 2000;  105 671-680
• 29 Marshall WA, Tanner JM. Growth and physiological development during adolescence.  Annu Rev Med. 1968;  19 283-300
• 30 Bottner A, Kratzsch J, Muller G. et al . Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels.  J Clin Endocrinol Metab. 2004;  89 4053-4061
• 31 Rattarasarn C. Physiological and pathophysiological regulation of regional adipose tissue in the development of insulin resistance and type 2 diabetes.  Acta Physiol (Oxf). 2006;  186 87-101
• 32 Vikram NK, Misra A, Pandey RM, Dwivedi M, Luthra K. Adiponectin, insulin resistance, and C-reactive protein in postpubertal Asian Indian adolescents.  Metabolism. 2004;  53 1336-1341
• 33 Arslanian S, Suprasongsin C, Kalhan SC. et al . Plasma leptin in children: relationship to puberty, gender, body composition, insulin sensitivity, and energy expenditure.  Metabolism. 1998;  47 309-312
• 34 Huang KC, Lin RC, Kormas N. et al . Plasma leptin is associated with insulin resistance independent of age, body mass index, fat mass, lipids, and pubertal development in nondiabetic adolescents.  Int J Obes Relat Metab Disord. 2004;  28 470-475
• 35 Stefan N, Vozarova B, Funahashi T. et al . Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans.  Diabetes. 2002;  51 1884-1888
• 36 Ceddia RB. Direct metabolic regulation in skeletal muscle and fat tissue by leptin: implications for glucose and fatty acids homeostasis.  Int J Obes (Lond). 2005;  29 1175-1183
• 37 Perez C, Fernandez-Galaz C, Fernandez-Agullo T. et al . Leptin impairs insulin signaling in rat adipocytes.  Diabetes. 2004;  53 347-353
• 38 Seufert J, Kieffer TJ, Leech CA. et al . Leptin suppression of insulin secretion and gene expression in human pancreatic islets: implications for the development of adipogenic diabetes mellitus.  J Clin Endocrinol Metab. 1999;  84 670-676
• 39 Seufert J. Leptin effects on pancreatic beta-cell gene expression and function.  Diabetes. 2004;  53 ((Suppl 1)) S152-S158
• 40 Kieffer TJ, Habener JF. The adipoinsular axis: effects of leptin on pancreatic beta-cells.  Am J Physiol Endocrinol Metab. 2000;  278 E1-E14
• 41 Kratzsch J, Lammert A, Bottner A. et al . Circulating soluble leptin receptor and free leptin index during childhood, puberty, and adolescence.  J Clin Endocrinol Metab. 2002;  87 4587-4594
• 42 Kennedy A, Gettys TW, Watson P. et al . The metabolic significance of leptin in humans: gender-based differences in relationship to adiposity, insulin sensitivity, and energy expenditure.  J Clin Endocrinol Metab. 1997;  82 1293-1300
• 43 Nagy TR, Gower BA, Trowbridge CA. et al . Effects of gender, ethnicity, body composition, and fat distribution on serum leptin concentrations in children.  J Clin Endocrinol Metab. 1997;  82 2148-2152

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