Current Diabetes Reports

, Volume 13, Issue 1, pp 81–88

Etiology of Insulin Resistance in Youth with Type 2 Diabetes

  • Melanie Cree-Green
  • Taylor M. Triolo
  • Kristen J. Nadeau
Pediatric Type 2 Diabetes (PS Zeitler, Section Editor)

Abstract

Type 2 diabetes (T2DM), historically an adult disease, is now increasingly prevalent in obese youth. Poor diet and increased sedentary behavior contribute to the increasing rates of obesity in youth, yet not all obese children develop T2DM. In general, T2DM is characterized by both insulin resistance (IR) and pancreatic beta-cell insufficiency. In children, IR is related to elevated body mass index (BMI) and pubertal hormones, along with abnormal fat partitioning, elevated free fatty acids, inflammation, and/or mitochondrial dysfunction. Hyperglycemia and T2DM develop when the pancreas cannot match the increased insulin demands resulting from IR. Unique to youth, IR varies with stage of pubertal development, and some children may have resolution of hyperglycemia post-puberty once the IR of puberty resolves. Further understanding of IR, the progression to T2DM in youth, and later outcomes as adults will help direct future therapies and interventions for youth at risk.

Keywords

Type 2 diabetes Insulin resistance Pediatrics Obesity 

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    D'Adamo E, Caprio S. Type 2 diabetes in youth: epidemiology and pathophysiology. Diabetes Care. 2011;34 Suppl 2:S161–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Arslanian S, Suprasongsin C. Insulin sensitivity, lipids, and body composition in childhood: is "syndrome X" present? J Clin Endocrinol Metab. 1996;81(3):1058–62.PubMedCrossRefGoogle Scholar
  3. 3.
    Ogden C, Carroll M, Kit B, Flegal K. Prevalence of obesity in the United States, 2009–2010 NCHS data brief, no 82 Hyattsville. MD: National Center for Health Statistics; 2012.Google Scholar
  4. 4.
    Levy-Marchal C, Arslanian S, Cutfield W, Sinaiko A, Druet C, Marcovecchio ML, et al. Insulin resistance in children: consensus, perspective, and future directions. J Clin Endocrinol Metab. 2010;95(12):5189–98.PubMedCrossRefGoogle Scholar
  5. 5.
    Lee S, Bacha F, Gungor N, Arslanian S. Comparison of different definitions of pediatric metabolic syndrome: relation to abdominal adiposity, insulin resistance, adiponectin, and inflammatory biomarkers. J Pediatr. 2008;152(2):177–84.PubMedCrossRefGoogle Scholar
  6. 6.
    • Rhodes ET, Prosser LA, Hoerger TJ, Lieu T, Ludwig DS, Laffel LM. Estimated morbidity and mortality in adolescents and young adults diagnosed with Type 2 diabetes mellitus. Diabet Med. 2012;29(4):453–63. This is a statistical modeleing paper which evaluated the rate of development of adult type 2 co-morbities, and applied them to children who develop diabetes. The model predicts an estimated 15 year shorter life span, and complicatons developing in the 4 th decade of life.PubMedCrossRefGoogle Scholar
  7. 7.
    Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics. 2005;115(3):e290–6.PubMedCrossRefGoogle Scholar
  8. 8.
    •• Crume TL, Ogden L, Daniels S, Hamman RF, Norris JM, Dabelea D. The impact of in utero exposure to diabetes on childhood body mass index growth trajectories: the EPOCH study. J Pediatr. 2011;158(6):941–6. This is a longitudinal cohort ofUS children with detailed gestational information. Those with in utero exposure to diabetes had a greater BMI growth velocity through childhood, compared to those who were not exposed to maternal diabetes.PubMedCrossRefGoogle Scholar
  9. 9.
    Yeckel CW, Weiss R, Dziura J, Taksali SE, Dufour S, Burgert TS, et al. Validation of insulin sensitivity indices from oral glucose tolerance test parameters in obese children and adolescents. J Clin Endocrinol Metab. 2004;89(3):1096–101.PubMedCrossRefGoogle Scholar
  10. 10.
    Henderson M, Rabasa-Lhoret R, Bastard JP, Chiasson JL, Baillargeon JP, Hanley JA, et al. Measuring insulin sensitivity in youth: How do the different indices compare with the gold-standard method? Diabetes Metab. 2011;37(1):72–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Utzschneider KM, Prigeon RL, Faulenbach MV, Tong J, Carr DB, Boyko EJ, et al. Oral disposition index predicts the development of future diabetes above and beyond fasting and 2-h glucose levels. Diabetes Care. 2009;32(2):335–41.PubMedCrossRefGoogle Scholar
  12. 12.
    Jeffery AN, Metcalf BS, Hosking J, Streeter AJ, Voss LD, Wilkin TJ. Age Before Stage: Insulin Resistance Rises Before the Onset of Puberty: A 9-year longitudinal study (EarlyBird 26). Diabetes Care. 2012;35(3):536–41.PubMedCrossRefGoogle Scholar
  13. 13.
    Nadeau KJ, Zeitler PS, Bauer TA, Brown MS, Dorosz JL, Draznin B, et al. Insulin resistance in adolescents with type 2 diabetes is associated with impaired exercise capacity. J Clin Endocrinol Metab. 2009;94(10):3687–95.PubMedCrossRefGoogle Scholar
  14. 14.
    George L, Bacha F, Lee S, Tfayli H, Andreatta E, Arslanian S. Surrogate estimates of insulin sensitivity in obese youth along the spectrum of glucose tolerance from normal to prediabetes to diabetes. J Clin Endocrinol Metab. 2011;96(7):2136–45.PubMedCrossRefGoogle Scholar
  15. 15.
    Pacini G. The hyperbolic equilibrium between insulin sensitivity and secretion. Nutr Metab Cardiovasc Dis. 2006;16 Suppl 1:S22–7.PubMedCrossRefGoogle Scholar
  16. 16.
    •• Sjaarda LG, Bacha F, Lee S, Tfayli H, Andreatta E, Arslanian S. Oral disposition index in obese youth from normal to prediabetes to diabetes: relationship to clamp disposition index. J Pediatr. 2012;161(1):51–7. This was a prospectice study that examined the relationship between a hyper-insulinemic clamp, a hyperglycemic clamp and an OGTT. The disposition index from the OGTT was similar to that from the clamp in youth.PubMedCrossRefGoogle Scholar
  17. 17.
    Lyssenko V, Almgren P, Anevski D, Perfekt R, Lahti K, Nissen M, et al. Predictors of and longitudinal changes in insulin sensitivity and secretion preceding onset of type 2 diabetes. Diabetes. 2005;54(1):166–74.PubMedCrossRefGoogle Scholar
  18. 18.
    Schwartz B, Jacobs Jr DR, Moran A, Steinberger J, Hong CP, Sinaiko AR. Measurement of insulin sensitivity in children: comparison between the euglycemic-hyperinsulinemic clamp and surrogate measures. Diabetes Care. 2008;31(4):783–8.PubMedCrossRefGoogle Scholar
  19. 19.
    • Aradillas-Garcia C, Rodriguez-Moran M, Garay-Sevilla ME, Malacara JM, Rascon-Pacheco RA, Guerrero-Romero F. Distribution of the homeostasis model assessment of insulin resistance in Mexican children and adolescents. Eur J Endocrinol. 2012;166(2):301–6. This is a large cross-sectional study of mexican children of all ages and tanner stages, who under went fasting glucose and insulin to caclulate a HOMA score, and proposes age and pubertal based norms for insulin resistance.PubMedCrossRefGoogle Scholar
  20. 20.
    McLaughlin T, Abbasi F, Cheal K, Chu J, Lamendola C, Reaven G. Use of metabolic markers to identify overweight individuals who are insulin resistant. Ann Intern Med. 2003;139(10):802–9.PubMedGoogle Scholar
  21. 21.
    Dabelea D, D'Agostino Jr RB, Mason CC, West N, Hamman RF, Mayer-Davis EJ, et al. Development, validation and use of an insulin sensitivity score in youths with diabetes: the SEARCH for Diabetes in Youth study. Diabetologia. 2011;54(1):78–86.PubMedCrossRefGoogle Scholar
  22. 22.
    Weiss R, Dufour S, Taksali SE, Tamborlane WV, Petersen KF, Bonadonna RC, 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(9388):951–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Petersen KF, Hendler R, Price T, Perseghin G, Rothman DL, Held N, et al. 13C/31P NMR studies on the mechanism of insulin resistance in obesity. Diabetes. 1998;47(3):381–6.PubMedCrossRefGoogle Scholar
  24. 24.
    Kim G, Caprio S. Diabetes and insulin resistance in pediatric obesity. Pediatr Clin North Am. 2011;58(6):1355–61. ix.PubMedCrossRefGoogle Scholar
  25. 25.
    Nadeau KJ, Ehlers LB, Zeitler PS, Love-Osborne K. Treatment of non-alcoholic fatty liver disease with metformin versus lifestyle intervention in insulin-resistant adolescents. Pediatr Diabetes. 2009;10(1):5–13.PubMedCrossRefGoogle Scholar
  26. 26.
    Love-Osborne KA, Nadeau KJ, Sheeder J, Fenton LZ, Zeitler P. Presence of the metabolic syndrome in obese adolescents predicts impaired glucose tolerance and nonalcoholic fatty liver disease. J Adolesc Health. 2008;42(6):543–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Bennett B, Larson-Meyer DE, Ravussin E, Volaufova J, Soros A, Cefalu WT, et al. Impaired insulin sensitivity and elevated ectopic fat in healthy obese vs. nonobese prepubertal children. Obesity (Silver Spring). 2012;20(2):371–5.CrossRefGoogle Scholar
  28. 28.
    Perseghin G, Bonfanti R, Magni S, Lattuada G, De Cobelli F, Canu T, et al. Insulin resistance and whole body energy homeostasis in obese adolescents with fatty liver disease. Am J Physiol Endocrinol Metab. 2006;291(4):E697–703.PubMedCrossRefGoogle Scholar
  29. 29.
    Cali AM, Man CD, Cobelli C, Dziura J, Seyal A, Shaw M, et al. Primary defects in beta-cell function further exacerbated by worsening of insulin resistance mark the development of impaired glucose tolerance in obese adolescents. Diabetes Care. 2009;32(3):456–61.PubMedCrossRefGoogle Scholar
  30. 30.
    Turrens JF. Mitochondrial formation of reactive oxygen species. J Physiol. 2003;552(Pt 2):335–44.PubMedCrossRefGoogle Scholar
  31. 31.
    Cree MG, Wolfe RR. Postburn trauma insulin resistance and fat metabolism. Am J Physiol Endocrinol Metab. 2008;294(1):E1–9.PubMedCrossRefGoogle Scholar
  32. 32.
    Reinehr T, Kiess W, Andler W. Insulin sensitivity indices of glucose and free fatty acid metabolism in obese children and adolescents in relation to serum lipids. Metabolism. 2005;54(3):397–402.PubMedCrossRefGoogle Scholar
  33. 33.
    Kelley DE, He J, Menshikova EV, Ritov VB. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes. 2002;51(10):2944–50.PubMedCrossRefGoogle Scholar
  34. 34.
    Fleischman A, Kron M, Systrom DM, Hrovat M, Grinspoon SK. Mitochondrial function and insulin resistance in overweight and normal-weight children. J Clin Endocrinol Metab. 2009;94(12):4923–30.PubMedCrossRefGoogle Scholar
  35. 35.
    Morino K, Petersen KF, Dufour S, Befroy D, Frattini J, Shatzkes N, et al. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J Clin Invest. 2005;115(12):3587–93.PubMedCrossRefGoogle Scholar
  36. 36.
    Cook JS, Hoffman RP, Stene MA, Hansen JR. Effects of maturational stage on insulin sensitivity during puberty. J Clin Endocrinol Metab. 1993;77(3):725–30.PubMedCrossRefGoogle Scholar
  37. 37.
    Roemmich JN, Clark PA, Lusk M, Friel A, Weltman A, Epstein LH, et al. Pubertal alterations in growth and body composition. VI. Pubertal insulin resistance: relation to adiposity, body fat distribution and hormone release. Int J Obes Relat Metab Disord. 2002;26(5):701–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Guercio G, Rivarola MA, Chaler E, Maceiras M, Belgorosky A. Relationship between the growth hormone/insulin-like growth factor-I axis, insulin sensitivity, and adrenal androgens in normal prepubertal and pubertal girls. J Clin Endocrinol Metab. 2003;88(3):1389–93.PubMedCrossRefGoogle Scholar
  39. 39.
    Travers SH, Jeffers BW, Bloch CA, Hill JO, Eckel RH. Gender and Tanner stage differences in body composition and insulin sensitivity in early pubertal children. J Clin Endocrinol Metab. 1995;80(1):172–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Wilson AJ, Prapavessis H, Jung ME, Cramp AG, Vascotto J, Lenhardt L, et al. Lifestyle modification and metformin as long-term treatment options for obese adolescents: study protocol. BMC Public Health. 2009;9:434.PubMedCrossRefGoogle Scholar
  41. 41.
    Modan M, Karasik A, Halkin H, Fuchs Z, Lusky A, Shitrit A, et al. Effect of past and concurrent body mass index on prevalence of glucose intolerance and type 2 (non-insulin-dependent) diabetes and on insulin response. The Israel study of glucose intolerance, obesity and hypertension. Diabetologia. 1986;29(2):82–9.PubMedCrossRefGoogle Scholar
  42. 42.
    Sakurai Y, Teruya K, Shimada N, Umeda T, Tanaka H, Muto T, et al. Association between duration of obesity and risk of non-insulin-dependent diabetes mellitus. The Sotetsu Study. Am J Epidemiol. 1999;149(3):256–60.PubMedCrossRefGoogle Scholar
  43. 43.
    Everhart JE, Pettitt DJ, Bennett PH, Knowler WC. Duration of obesity increases the incidence of NIDDM. Diabetes. 1992;41(2):235–40.PubMedCrossRefGoogle Scholar
  44. 44.
    Lee JM, Gebremariam A, Vijan S, Gurney JG. Excess body mass index-years, a measure of degree and duration of excess weight, and risk for incident diabetes. Arch Pediatr Adolesc Med. 2012;166(1):42–8.PubMedGoogle Scholar
  45. 45.
    Dietz WH. Health consequences of obesity in youth: childhood predictors of adult disease. Pediatrics. 1998;101(3 Pt 2):518–25.PubMedGoogle Scholar
  46. 46.
    Brotman LM, Dawson-McClure S, Huang KY, Theise R, Kamboukos D, Wang J, et al. Early childhood family intervention and long-term obesity prevention among high-risk minority youth. Pediatrics. 2012;129(3):e621–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Kimm SY, Glynn NW, Kriska AM, Fitzgerald SL, Aaron DJ, Similo SL, et al. Longitudinal changes in physical activity in a biracial cohort during adolescence. Med Sci Sports Exerc. 2000;32(8):1445–54.PubMedCrossRefGoogle Scholar
  48. 48.
    Fagot-Campagna A. Emergence of type 2 diabetes mellitus in children: epidemiological evidence. J Pediatr Endocrinol Metab. 2000;13 Suppl 6:1395–402.PubMedGoogle Scholar
  49. 49.
    Urakami T, Habu M, Kuwabara R, Komiya K, Nagano N, Suzuki J, et al. Insulin resistance at diagnosis in Japanese children with type 2 diabetes mellitus. Pediatr Int. 2012;54(4):516–9.PubMedCrossRefGoogle Scholar
  50. 50.
    Wei M, Gibbons LW, Mitchell TL, Kampert JB, Lee CD, Blair SN. The association between cardiorespiratory fitness and impaired fasting glucose and type 2 diabetes mellitus in men. Ann Intern Med. 1999;130(2):89–96.PubMedGoogle Scholar
  51. 51.
    Laaksonen DE, Lindstrom J, Lakka TA, Eriksson JG, Niskanen L, Wikstrom K, et al. Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study. Diabetes. 2005;54(1):158–65.PubMedCrossRefGoogle Scholar
  52. 52.
    • Henderson M, Gray-Donald K, Mathieu ME, Barnett TA, Hanley JA, O'Loughlin J, et al. How are physical activity, fitness, and sedentary behavior associated with insulin sensitivity in children? Diabetes Care. 2012;35(6):1272–8. This was a prospective cohort study examine physcial fitness, percent body fat, and activity in children with 1 obese parent. Moderate to vigorous activity and sedentary behaviors were associated with percent body fat and insulin sensitivity.PubMedCrossRefGoogle Scholar
  53. 53.
    Group TS, Zeitler P, Hirst K, Pyle L, Linder B, Copeland K, et al. A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med. 2012;366(24):2247–56.CrossRefGoogle Scholar
  54. 54.
    Centers for Disease Control and Prevention. Trends in intake of energy and macronutrients--United States, 1971–2000. MMWR Morb Mortal Wkly Rep. 2004;53(4):80–2.Google Scholar
  55. 55.
    Esmaillzadeh A, Kimiagar M, Mehrabi Y, Azadbakht L, Hu FB, Willett WC. Dietary patterns, insulin resistance, and prevalence of the metabolic syndrome in women. Am J Clin Nutr. 2007;85(3):910–8.PubMedGoogle Scholar
  56. 56.
    Esmaillzadeh A, Kimiagar M, Mehrabi Y, Azadbakht L, Hu FB, Willett WC. Fruit and vegetable intakes, C-reactive protein, and the metabolic syndrome. Am J Clin Nutr. 2006;84(6):1489–97.PubMedGoogle Scholar
  57. 57.
    Sahyoun NR, Jacques PF, Zhang XL, Juan W, McKeown NM. Whole-grain intake is inversely associated with the metabolic syndrome and mortality in older adults. Am J Clin Nutr. 2006;83(1):124–31.PubMedGoogle Scholar
  58. 58.
    Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, et al. Effect of a mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA. 2004;292(12):1440–6.PubMedCrossRefGoogle Scholar
  59. 59.
    Dorgan JF, Liu L, Barton BA, Deshmukh S, Snetselaar LG, Van Horn L, et al. Adolescent diet and metabolic syndrome in young women: results of the Dietary Intervention Study in Children (DISC) follow-up study. J Clin Endocrinol Metab. 2011;96(12):E1999–2008.PubMedCrossRefGoogle Scholar
  60. 60.
    Willi SM, Martin K, Datko FM, Brant BP. Treatment of type 2 diabetes in childhood using a very-low-calorie diet. Diabetes Care. 2004;27(2):348–53.PubMedCrossRefGoogle Scholar
  61. 61.
    Gillman MW, Rifas-Shiman S, Berkey CS, Field AE, Colditz GA. Maternal gestational diabetes, birth weight, and adolescent obesity. Pediatrics. 2003;111(3):e221–6.PubMedCrossRefGoogle Scholar
  62. 62.
    Brumbaugh DE, Cree-Green M, Alston M, Hoffman MC, Reynolds RM, Friedman JE, et al. Maternal pre-pregnancy BMI influences hepatic fat storage in neonates. J Dev Orig Health Dis. 2011;2(S1):S35–150.CrossRefGoogle Scholar
  63. 63.
    Borgono CA, Hamilton JK, Ye C, Hanley AJ, Connelly PW, Sermer M, et al. Determinants of insulin resistance in infants at age 1 year: impact of gestational diabetes mellitus. Diabetes Care. 2012;35(8):1795–7.PubMedCrossRefGoogle Scholar
  64. 64.
    Crume TL, Bahr TM, Mayer-Davis EJ, Hamman RF, Scherzinger AL, Stamm E, et al. Selective protection against extremes in childhood body size, abdominal fat deposition, and fat patterning in breastfed children. Arch Pediatr Adolesc Med. 2012;166(5):437–43.PubMedCrossRefGoogle Scholar
  65. 65.
    Defronzo RA. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes. 2009;58(4):773–95.PubMedCrossRefGoogle Scholar
  66. 66.
    Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature. 2006;444(7121):840–6.PubMedCrossRefGoogle Scholar
  67. 67.
    Brufani C, Ciampalini P, Grossi A, Fiori R, Fintini D, Tozzi A, et al. Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy. Pediatr Diabetes. 2010;11(1):47–54.PubMedCrossRefGoogle Scholar
  68. 68.
    Weiss R, Caprio S, Trombetta M, Taksali SE, Tamborlane WV, Bonadonna R. Beta-cell function across the spectrum of glucose tolerance in obese youth. Diabetes. 2005;54(6):1735–43.PubMedCrossRefGoogle Scholar
  69. 69.
    •• Kleber M, Lass N, Papcke S, Wabitsch M, Reinehr T. One-year follow-up of untreated obese white children and adolescents with impaired glucose tolerance: high conversion rate to normal glucose tolerance. Diabet Med. 2010;27(5):516–21. 79 children with IGT were examined with an OGTT at baseline and a year later. A year later, 66% had convered to NGT, 33% were still IGT, and one had progressed to T2DM.PubMedCrossRefGoogle Scholar
  70. 70.
    Gungor N, Arslanian S. Progressive beta cell failure in type 2 diabetes mellitus of youth. J Pediatr. 2004;144(5):656–9.PubMedCrossRefGoogle Scholar
  71. 71.
    Lyssenko V, Jonsson A, Almgren P, Pulizzi N, Isomaa B, Tuomi T, et al. Clinical risk factors, DNA variants, and the development of type 2 diabetes. N Engl J Med. 2008;359(21):2220–32.PubMedCrossRefGoogle Scholar
  72. 72.
    Salgin B, Ong KK, Thankamony A, Emmett P, Wareham NJ, Dunger DB. Higher fasting plasma free Fatty Acid levels are associated with lower insulin secretion in children and adults and a higher incidence of type 2 diabetes. J Clin Endocrinol Metab. 2012;97(9):3302–9.PubMedCrossRefGoogle Scholar
  73. 73.
    Pozzilli P, Guglielmi C, Caprio S, Buzzetti R. Obesity, autoimmunity, and double diabetes in youth. Diabetes Care. 2011;34 Suppl 2:S166–70.PubMedCrossRefGoogle Scholar
  74. 74.
    Taha D, Umpaichitra V, Banerji MA, Castells S. Type 2 diabetes mellitus in African-American adolescents: impaired beta-cell function in the face of severe insulin resistance. J Pediatr Endocrinol Metab. 2006;19(2):135–42.PubMedCrossRefGoogle Scholar
  75. 75.
    Burns SF, Bacha F, Lee SJ, Tfayli H, Gungor N, Arslanian SA. Declining beta-cell function relative to insulin sensitivity with escalating OGTT 2-h glucose concentrations in the nondiabetic through the diabetic range in overweight youth. Diabetes Care. 2011;34(9):2033–40.PubMedCrossRefGoogle Scholar
  76. 76.
    Tfayli H, Lee SJ, Bacha F, Arslanian S. One-hour plasma glucose concentration during the OGTT: what does it tell about beta-cell function relative to insulin sensitivity in overweight/obese children? Pediatr Diabetes. 2011;12(6):572–9.PubMedGoogle Scholar
  77. 77.
    • Giannini C, Weiss R, Cali A, Bonadonna R, Santoro N, Pierpont B, et al. Evidence for early defects in insulin sensitivity and secretion before the onset of glucose dysregulation in obese youths: a longitudinal study. Diabetes. 2012;61(3):606–14. 60 obese children who were NGT with an OGTT and a hyperinsulinemic clamp are baseline were restudied 2 years later, and found to have a decline in beta cell function, prior to the development of hyperglycemia.PubMedCrossRefGoogle Scholar
  78. 78.
    Nowicka P, Santoro N, Liu H, Lartaud D, Shaw MM, Goldberg R, et al. Utility of hemoglobin A(1c) for diagnosing prediabetes and diabetes in obese children and adolescents. Diabetes Care. 2011;34(6):1306–11.PubMedCrossRefGoogle Scholar
  79. 79.
    Weiss R, Taksali SE, Tamborlane WV, Burgert TS, Savoye M, Caprio S. Predictors of changes in glucose tolerance status in obese youth. Diabetes Care. 2005;28(4):902–9.PubMedCrossRefGoogle Scholar
  80. 80.
    Kleber M, deSousa G, Papcke S, Wabitsch M, Reinehr T. Impaired glucose tolerance in obese white children and adolescents: three to five year follow-up in untreated patients. Exp Clin Endocrinol Diabetes. 2011;119(3):172–6.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  • Melanie Cree-Green
    • 1
  • Taylor M. Triolo
    • 1
  • Kristen J. Nadeau
    • 1
  1. 1.Division of Endocrinology, Department of PediatricsUniversity of Colorado Denver and the Children’s Hospital ColoradoAuroraUSA

Personalised recommendations