Metabolic consequences of hepatic steatosis in overweight and obese adolescents

Brandy A Wicklow, Kristy D M Wittmeier, Andrea C MacIntosh, Elizabeth A C Sellers, Lawrence Ryner, Hacene Serrai, Heather J Dean, Jonathan M McGavock, Brandy A Wicklow, Kristy D M Wittmeier, Andrea C MacIntosh, Elizabeth A C Sellers, Lawrence Ryner, Hacene Serrai, Heather J Dean, Jonathan M McGavock

Abstract

Objective: To test the hypothesis that hepatic steatosis is associated with risk factors for type 2 diabetes in overweight and obese youth, mediated by cardiorespiratory fitness.

Research design and methods: This was a cross-sectional study comparing insulin sensitivity between 30 overweight and obese adolescents with hepatic steatosis, 68 overweight and obese adolescents without hepatic steatosis, and 11 healthy weight adolescents without hepatic steatosis. Cardiorespiratory fitness was determined by a graded maximal exercise test on a cycle ergometer. Secondary outcomes included presence of metabolic syndrome and glucose response to a 75-g oral glucose challenge.

Results: The presence of hepatic steatosis was associated with 55% lower insulin sensitivity (P = 0.02) and a twofold greater prevalence of metabolic syndrome (P = 0.001). Differences in insulin sensitivity (3.5 vs. 4.5 mU ⋅ kg(-1) ⋅ min(-1), P = 0.03), prevalence of metabolic syndrome (48 vs. 20%, P = 0.03), and glucose area under the curve (816 vs. 710, P = 0.04) remained between groups after matching for age, sex, and visceral fat. The association between hepatic steatosis and insulin sensitivity (β = -0.24, t = -2.29, P < 0.025), metabolic syndrome (β = -0.54, t = -5.8, P < 0.001), and glucose area under the curve (β = 0.33, t = 3.3, P < 0.001) was independent of visceral and whole-body adiposity. Cardiorespiratory fitness was not associated with hepatic steatosis, insulin sensitivity, or presence of metabolic syndrome.

Conclusions: Hepatic steatosis is associated with type 2 diabetes risk factors independent of cardiorespiratory fitness, whole-body adiposity, and visceral fat mass.

References

    1. Demerath EW, Reed D, Rogers N, et al. Visceral adiposity and its anatomical distribution as predictors of the metabolic syndrome and cardiometabolic risk factor levels. Am J Clin Nutr 2008;88:1263–1271
    1. Goran MI, Bergman RN, Gower BA. Influence of total vs. visceral fat on insulin action and secretion in African American and white children. Obes Res 2001;9:423–431
    1. McGavock J, Sellers E, Dean H. Physical activity for the prevention and management of youth-onset type 2 diabetes mellitus: focus on cardiovascular complications. Diab Vasc Dis Res 2007;4:305–310
    1. D’Adamo E, Cali AM, Weiss R, et al. Central role of fatty liver in the pathogenesis of insulin resistance in obese adolescents. Diabetes Care 2010;33:1817–1822
    1. Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook S. Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation 2008;118:277–283
    1. Mootha VK, Lindgren CM, Eriksson KF, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 2003;34:267–273
    1. Fabbrini E, Magkos F, Mohammed BS, et al. Intrahepatic fat, not visceral fat, is linked with metabolic complications of obesity. Proc Natl Acad Sci U S A 2009;106:15430–15435
    1. Haufe S, Engeli S, Budziarek P, et al. Cardiorespiratory fitness and insulin sensitivity in overweight or obese subjects may be linked through intrahepatic lipid content. Diabetes 2010;59:1640–1647
    1. Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 2000;320:1240–1243
    1. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee Canadian Diabetes Association 2008 clinical practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2008;32:S1–S201
    1. Young TK, Reading J, Elias B, O’Neil JD. Type 2 diabetes mellitus in Canada’s first nations: status of an epidemic in progress. CMAJ 2000;163:561–566
    1. Ball GD, Shaibi GQ, Cruz ML, Watkins MP, Weigensberg MJ, Goran MI. Insulin sensitivity, cardiorespiratory fitness, and physical activity in overweight Hispanic youth. Obes Res 2004;12:77–85
    1. Boston RC, Stefanovski D, Moate PJ, Sumner AE, Watanabe RM, Bergman RN. MINMOD Millennium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test. Diabetes Technol Ther 2003;5:1003–1015
    1. Jolliffe CJ, Janssen I. Development of age-specific adolescent metabolic syndrome criteria that are linked to the Adult Treatment Panel III and International Diabetes Federation criteria. J Am Coll Cardiol 2007;49:891–898
    1. Katzmarzyk PT. Waist circumference percentiles for Canadian youth 11-18y of age. Eur J Clin Nutr 2004;58:1011–1015
    1. Altman D. Practical Statistics for Medical Research London, Chapman & Hall, 1991
    1. McGavock JM, Lingvay I, Zib I, et al. Cardiac steatosis in diabetes mellitus: a 1H-magnetic resonance spectroscopy study. Circulation 2007;116:1170–1175
    1. Szczepaniak LS, Babcock EE, Schick F, et al. Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo. Am J Physiol 1999;276:E977–E989
    1. Provencher SW. Automatic quantitation of localized in vivo 1H spectra with LCModel. NMR Biomed 2001;14:260–264
    1. Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology 2004;40:1387–1395
    1. Zib I, Jacob AN, Lingvay I, et al. Effect of pioglitazone therapy on myocardial and hepatic steatosis in insulin-treated patients with type 2 diabetes. J Investig Med 2007;55:230–236
    1. McGavock JM, Mandic S, Vonder Muhll I, et al. Low cardiorespiratory fitness is associated with elevated C-reactive protein levels in women with type 2 diabetes. Diabetes Care 2004;27:320–325
    1. Taksali SE, Caprio S, Dziura J, et al. High visceral and low abdominal subcutaneous fat stores in the obese adolescent: a determinant of an adverse metabolic phenotype. Diabetes 2008;57:367–371
    1. Weiss R, Dufour S, Taksali SE, et al. Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning. Lancet 2003;362:951–957
    1. Burgert TS, Taksali SE, Dziura J, et al. Alanine aminotransferase levels and fatty liver in childhood obesity: associations with insulin resistance, adiponectin, and visceral fat. J Clin Endocrinol Metab 2006;91:4287–4294
    1. Deivanayagam S, Mohammed BS, Vitola BE, et al. Nonalcoholic fatty liver disease is associated with hepatic and skeletal muscle insulin resistance in overweight adolescents. Am J Clin Nutr 2008;88:257–262
    1. Larson-Meyer DE, Heilbronn LK, Redman LM, et al. Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects. Diabetes Care 2006;29:1337–1344

Source: PubMed

Спонсоры и соавторы

Заболевания

Медикаментозные вмешательства

Подписаться