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Insulin resistance in children and adolescents

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Abstract

IR is hypothesized to be the important pathophysiologic link between adiposity and future development of type 2 diabetes and cardiovascular disease. A variety of methods for measuring IR have been validated in children, from the gold-standard hyperinsulinemic euglycemic clamp, to simple fasting measures based on fasting insulin and glucose levels. Studies have shown that there are a number of important risk factors for IR in children, including adiposity and visceral adiposity, race/ethnicity, puberty, a family history of type 2 diabetes, sex, and being small for gestational age or prematurity. However, obesity represents the critical risk factor for IR in children. Greater than 50% of obese adolescents in the US have IR. Formal assessment of IR in obese children may represent an important strategy for improving the efficacy of pharmacologic therapy for weight loss and chronic disease prevention.

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References

  1. Lebovitz HE. Insulin resistance: definition and consequences. Exp Clin Endocrinol Diabetes 2001;109(Suppl 2):S135–48.

    Article  PubMed  CAS  Google Scholar 

  2. Cruz ML, Shaibi GQ, Weigensberg MJ, Spruijt-Metz D, Ball GD, Goran MI. Pediatric obesity and insulin resistance: chronic disease risk and implications for treatment and prevention beyond body weight modification. Annu Rev Nutr 2005;25:435–68.

    Article  PubMed  CAS  Google Scholar 

  3. Warram JH, Martin BC, Krolewski AS, Soeldner JS, Kahn CR. Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. Ann Intern Med 1990;113(12):909–15.

    PubMed  CAS  Google Scholar 

  4. Lillioja S, Mott DM, Spraul M, Ferraro R, Foley JE, Ravussin E, et al. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. N Engl J Med 1993;329(27):1988–92.

    Article  PubMed  CAS  Google Scholar 

  5. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 1988;37(12):1595–607.

    Article  PubMed  CAS  Google Scholar 

  6. Grundy SM, Brewer HB, Cleeman JI, Smith SC, Lenfant C. Definition of metabolic syndrome: report of the national heart, lung, and blood institute/American heart association conference on scientific issues related to definition. Circulation 2004;109:433–8.

    Article  PubMed  Google Scholar 

  7. Sinha R, Fisch G, Teague B, Tamborlane WV, Banyas B, Allen K, et al. Prevalence of impaired glucose tolerance among children and adolescents with marked obesity. N Engl J Med 2002;346(11):802–10.

    Article  PubMed  CAS  Google Scholar 

  8. Gungor N, Hannon T, Libman I, Bacha F, Arslanian S. Type 2 diabetes mellitus in youth: the complete picture to date. Pediatr Clin North Am 2005;52(6):1579–609.

    Article  PubMed  Google Scholar 

  9. Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285(19):2486–97.

    Article  Google Scholar 

  10. Sinaiko AR, Steinberger J, Moran A, Hong CP, Prineas RJ, Jacobs DR, Jr. Influence of insulin resistance and body mass index at age 13 on systolic blood pressure, triglycerides, and high-density lipoprotein cholesterol at age 19. Hypertension 2006;48:730–6.

    Article  PubMed  CAS  Google Scholar 

  11. Weiss R. Insulin sensitivity and secretion: swaying the pendulum. J Pediatr 2006;148(1):3–4.

    Article  PubMed  Google Scholar 

  12. Haymond MW. Measuring insulin resistance: a task worth doing. But how? Pediatr Diabetes 2003;4(3):115–8.

    Article  PubMed  Google Scholar 

  13. American Diabetes Association. Type 2 diabetes in children and adolescents. Pediatrics 2000;105(3 Pt 1):671–80.

    Article  Google Scholar 

  14. Troiano RP, Flegal KM. Overweight prevalence among youth in the United States: why so many different numbers? Int J Obes Relat Metab Disord 1999;23(Suppl 2):S22–7.

    Article  PubMed  Google Scholar 

  15. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents, and adults, 1999–2002. JAMA 2004;291(23):2847–50.

    Article  PubMed  CAS  Google Scholar 

  16. Jones KL. Why test the children? Understanding insulin resistance, its complications, and its progression. Diabetes Care 2002;25(12):2350–1.

    Article  PubMed  Google Scholar 

  17. Arslanian SA. Clamp techniques in paediatrics: what have we learned? Horm Res 2005;64(Suppl 3):16–24.

    Article  PubMed  CAS  Google Scholar 

  18. Wallace TM, Matthews DR. The assessment of insulin resistance in man. Diabet Med 2002;19(7):527–34.

    Article  PubMed  CAS  Google Scholar 

  19. Bergman RN, Prager R, Volund A, Olefsky JM. Equivalence of the insulin sensitivity index in man derived by the minimal model method and the euglycemic glucose clamp. J Clin Invest 1987;79(3):790–800.

    PubMed  CAS  Google Scholar 

  20. Bergman RN. Minimal model: perspective from 2005. Horm Res 2005;64(Suppl 3):8–15.

    Article  PubMed  CAS  Google Scholar 

  21. Bergman RN, Ider YZ, Bowden CR, Cobelli C. Quantitative estimation of insulin sensitivity. Am J Physiol 1979;236(6):E667–77.

    PubMed  CAS  Google Scholar 

  22. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999;22(9):1462–70.

    Article  PubMed  CAS  Google Scholar 

  23. Soonthornpun S, Setasuban W, Thamprasit A, Chayanunnukul W, Rattarasarn C, Geater A. Novel insulin sensitivity index derived from oral glucose tolerance test. J Clin Endocrinol Metab 2003;88(3):1019–23.

    Article  PubMed  CAS  Google Scholar 

  24. 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.

    Article  PubMed  CAS  Google Scholar 

  25. Cutfield WS, Hofman PL. Simple fasting methods to assess insulin sensitivity in childhood. Horm Res 2005;64(Suppl 3):25–31.

    Article  PubMed  CAS  Google Scholar 

  26. Gungor N, Saad R, Janosky J, Arslanian S. Validation of surrogate estimates of insulin sensitivity and insulin secretion in children and adolescents. J Pediatr 2004;144(1):47–55.

    Article  PubMed  CAS  Google Scholar 

  27. Conwell LS, Trost SG, Brown WJ, Batch JA. Indexes of insulin resistance and secretion in obese children and adolescents: a validation study. Diabetes Care 2004;27(2):314–9.

    Article  PubMed  Google Scholar 

  28. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28(7):412–9.

    Article  PubMed  CAS  Google Scholar 

  29. Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C. Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 2005;115(4):e500–3.

    Article  PubMed  Google Scholar 

  30. Uwaifo GI, Fallon EM, Chin J, Elberg J, Parikh SJ, Yanovski JA. Indices of insulin action, disposal, and secretion derived from fasting samples and clamps in normal glucose-tolerant black and white children. Diabetes Care 2002;25(11):2081–7.

    Article  PubMed  CAS  Google Scholar 

  31. Quon MJ. Limitations of the fasting glucose to insulin ratio as an index of insulin sensitivity. J Clin Endocrinol Metab 2001;86(10):4615–7.

    Article  PubMed  CAS  Google Scholar 

  32. Saad R, Gungor N, Arslanian S. Progression from normal glucose tolerance to type 2 diabetes in a young girl: longitudinal changes in insulin sensitivity and secretion assessed by the clamp technique and surrogate estimates. Pediatr Diabetes 2005;6(2):95–9.

    Article  PubMed  Google Scholar 

  33. Goran MI, Ball GD, Cruz ML. Obesity and risk of type 2 diabetes and cardiovascular disease in children and adolescents. J Clin Endocrinol Metab 2003;88(4):1417–27.

    Article  PubMed  CAS  Google Scholar 

  34. 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.

    Article  PubMed  CAS  Google Scholar 

  35. 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(4):215–9.

    Article  PubMed  CAS  Google Scholar 

  36. Gutin B, Islam S, Manos T, Cucuzzo N, Smith C, Stachura ME. Relation of percentage of body fat and maximal aerobic capacity to risk factors for atherosclerosis and diabetes in black and white seven- to eleven-year-old children. J Pediatr 1994;125(6 Pt 1):847–52.

    PubMed  CAS  Google Scholar 

  37. 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.

    Article  PubMed  CAS  Google Scholar 

  38. Sinaiko AR, Jacobs DR, Jr., Steinberger J, Moran A, Luepker R, Rocchini AP, et al. Insulin resistance syndrome in childhood: associations of the euglycemic insulin clamp and fasting insulin with fatness and other risk factors. J Pediatr 2001;139(5):700–7.

    Article  PubMed  CAS  Google Scholar 

  39. Lee JM, Okumura MJ, Davis MM, Herman WH, Gurney JG. Prevalence and determinants of insulin resistance among U.S. adolescents: a population based study. Diabetes Care 2006;29(11):2427–32.

    Article  PubMed  Google Scholar 

  40. Boyko EJ, Leonetti DL, Bergstrom RW, Newell-Morris L, Fujimoto WY. Low insulin secretion and high fasting insulin and C-peptide levels predict increased visceral adiposity. 5-year follow-up among initially nondiabetic Japanese-American men. Diabetes 1996;45(8):1010.

    Article  PubMed  CAS  Google Scholar 

  41. Kelley DE, Thaete FL, Troost F, Huwe T, Goodpaster BH. Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance. Am J Physiol Endocrinol Metab 2000;278(5):E941–8.

    PubMed  CAS  Google Scholar 

  42. 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(8):423–31.

    PubMed  CAS  Google Scholar 

  43. Bacha F, Saad R, Gungor N, Janosky J, Arslanian SA. Obesity, regional fat distribution, and syndrome X in obese black versus white adolescents: race differential in diabetogenic and atherogenic risk factors. J Clin Endocrinol Metab 2003;88(6):2534–40.

    Article  PubMed  CAS  Google Scholar 

  44. Cruz ML, Bergman RN, Goran MI. Unique effect of visceral fat on insulin sensitivity in obese Hispanic children with a family history of type 2 diabetes. Diabetes Care 2002;25(9):1631–6.

    Article  PubMed  Google Scholar 

  45. Svec F, Nastasi K, Hilton C, Bao W, Srinivasan SR, Berenson GS. Black–white contrasts in insulin levels during pubertal development. The Bogalusa heart study. Diabetes 1992;41(3):313–7.

    Article  PubMed  CAS  Google Scholar 

  46. Arslanian S, Suprasongsin C, Janosky JE. Insulin secretion and sensitivity in black versus white prepubertal healthy children. J Clin Endocrinol Metab 1997;82(6):1923–7.

    Article  PubMed  CAS  Google Scholar 

  47. Arslanian S, Suprasongsin C. Differences in the in vivo insulin secretion and sensitivity of healthy black versus white adolescents. J Pediatr 1996;129(3):440–3.

    Article  PubMed  CAS  Google Scholar 

  48. Goran MI, Bergman RN, Cruz ML, Watanabe R. Insulin resistance and associated compensatory responses in African-American and Hispanic children. Diabetes Care 2002;25 (12):2184–90.

    Article  PubMed  CAS  Google Scholar 

  49. Lindquist CH, Gower BA, Goran MI. Role of dietary factors in ethnic differences in early risk of cardiovascular disease and type 2 diabetes. Am J Clin Nutr 2000;71(3):725–32.

    PubMed  CAS  Google Scholar 

  50. Ku CY, Gower BA, Hunter GR, Goran MI. Racial differences in insulin secretion and sensitivity in prepubertal children: role of physical fitness and physical activity. Obes Res 2000;8 (7):506–15.

    Article  PubMed  CAS  Google Scholar 

  51. Gower BA, Fernandez JR, Beasley TM, Shriver MD, Goran MI. Using genetic admixture to explain racial differences in insulin-related phenotypes. Diabetes 2003;52(4):1047–51.

    Article  PubMed  CAS  Google Scholar 

  52. Arslanian SA, Kalhan SC. Protein turnover during puberty in normal children. Am J Physiol 1996;270(1 Pt 1):E79–84.

    PubMed  CAS  Google Scholar 

  53. Moran A, Jacobs DR, Jr., Steinberger J, Hong CP, Prineas R, Luepker R, et al. Insulin resistance during puberty: results from clamp studies in 357 children. Diabetes 1999;48(10):2039–44.

    Article  PubMed  CAS  Google Scholar 

  54. Caprio S, Cline G, Boulware S, Permanente C, Shulman GI, Sherwin RS, et al. Effects of puberty and diabetes on metabolism of insulin-sensitive fuels. Am J Physiol 1994;266(6 Pt 1):E885–91.

    PubMed  CAS  Google Scholar 

  55. Goran MI, Gower BA. Longitudinal study on pubertal insulin resistance. Diabetes 2001;50(11):2444–50.

    Article  PubMed  CAS  Google Scholar 

  56. Ball GD, Huang TT, Gower BA, Cruz ML, Shaibi GQ, Weigensberg MJ, et al. Longitudinal changes in insulin sensitivity, insulin secretion, and beta-cell function during puberty. J Pediatr 2006;148(1):16–22.

    Article  PubMed  CAS  Google Scholar 

  57. Hoffman RP, Vicini P, Sivitz WI, Cobelli C. Pubertal adolescent male–female differences in insulin sensitivity and glucose effectiveness determined by the one compartment minimal model. Pediatr Res 2000;48(3):384–8.

    Article  PubMed  CAS  Google Scholar 

  58. 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.

    Article  PubMed  CAS  Google Scholar 

  59. Ishikawa M, Pruneda ML, Adams-Huet B, Raskin P. Obesity-independent hyperinsulinemia in nondiabetic first-degree relatives of individuals with type 2 diabetes. Diabetes 1998;47(5):788–92.

    Article  PubMed  CAS  Google Scholar 

  60. Leslie RD, Volkmann HP, Poncher M, Hanning I, Orskov H, Alberti KG. Metabolic abnormalities in children of non-insulin dependent diabetics. Br Med J (Clin Res Ed) 1986;293(6551):840–2.

    Article  CAS  Google Scholar 

  61. Arslanian SA, Bacha F, Saad R, Gungor N. Family history of type 2 diabetes is associated with decreased insulin sensitivity and an impaired balance between insulin sensitivity and insulin secretion in white youth. Diabetes Care 2005;28(1):115–9.

    Article  PubMed  Google Scholar 

  62. Danadian K, Balasekaran G, Lewy V, Meza MP, Robertson R, Arslanian SA. Insulin sensitivity in African-American children with and without family history of type 2 diabetes. Diabetes Care 1999;22(8):1325–9.

    Article  PubMed  CAS  Google Scholar 

  63. Goran MI, Coronges K, Bergman RN, Cruz ML, Gower BA. Influence of family history of type 2 diabetes on insulin sensitivity in prepubertal children. J Clin Endocrinol Metab 2003;88(1):192–5.

    Article  PubMed  CAS  Google Scholar 

  64. Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia 1993;36(1):62–7.

    Article  PubMed  CAS  Google Scholar 

  65. Lee PA, Chernausek SD, Hokken-Koelega AC, Czernichow P. International small for gestational age advisory board consensus development conference statement: management of short children born small for gestational age, April 24–October 1, 2001. Pediatrics 2003;111(6 Pt 1):1253–61.

    Article  PubMed  Google Scholar 

  66. Hofman PL, Cutfield WS, Robinson EM, Bergman RN, Menon RK, Sperling MA, et al. Insulin resistance in short children with intrauterine growth retardation. J Clin Endocrinol Metab 1997;82(2):402–6.

    Article  PubMed  CAS  Google Scholar 

  67. Veening MA, Van Weissenbruch MM, Delemarre-Van De Waal HA. Glucose tolerance, insulin sensitivity, and insulin secretion in children born small for gestational age. J Clin Endocrinol Metab 2002;87(10):4657–61.

    Article  PubMed  CAS  Google Scholar 

  68. Hofman PL, Regan F, Jackson WE, Jefferies C, Knight DB, Robinson EM, et al. Premature birth and later insulin resistance. N Engl J Med 2004;351(21):2179–86.

    Article  PubMed  CAS  Google Scholar 

  69. American Diabetes Association. Consensus development conference on insulin resistance. 5–6 November 1997. Diabetes Care 1998;21(2):310–4.

    Google Scholar 

  70. Lustig RH, Mietus-Snyder ML, Bacchetti P, Lazar AA, Velasquez-Mieyer PA, Christensen ML. Insulin dynamics predict body mass index and z-score response to insulin suppression or sensitization pharmacotherapy in obese children. J Pediatr 2006;148(1):23–9.

    Article  PubMed  CAS  Google Scholar 

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Lee, J.M. Insulin resistance in children and adolescents. Rev Endocr Metab Disord 7, 141–147 (2006). https://doi.org/10.1007/s11154-006-9019-8

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