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Insulin Resistance of Puberty

  • Pediatric Type 2 Diabetes (PS Zeitler, Section Editor)
  • Published:
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Abstract

Puberty is a time of considerable metabolic and hormonal change. Notably, puberty is associated with a marked decrease in insulin sensitivity, on par with that seen during pregnancy. In otherwise healthy youth, there is a nadir in insulin sensitivity in mid-puberty, and then it recovers at puberty completion. However, there is evidence that insulin resistance (IR) does not resolve in youth who are obese going into puberty and may result in increased cardiometabolic risk. Little is known about the underlying pathophysiology of IR in puberty, and how it might contribute to increased disease risk (e.g., type 2 diabetes). In this review, we have outlined what is known about the IR in puberty in terms of pattern, potential underlying mechanisms and other mediating factors. We also outline other potentially related metabolic changes that occur during puberty, and effects of underlying insulin resistant states (e.g., obesity) on pubertal changes in insulin sensitivity.

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References

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

  1. Amiel SA, Sherwin RS, Simonson DC, et al. 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  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  3. Hannon TS, Janosky J, Arslanian SA. Longitudinal study of physiologic insulin resistance and metabolic changes of puberty. Pediatr Res. 2006;60(6):759–63.

    Article  CAS  PubMed  Google Scholar 

  4. Bloch CA, Clemons P, Sperling MA. Puberty decreases insulin sensitivity. J Pediatr. 1987;110(3):481–7.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. Travers SH, Jeffers BW, Eckel RH. Insulin resistance during puberty and future fat accumulation. J Clin Endocrinol Metab. 2002;87(8):3814–8.

    Article  CAS  PubMed  Google Scholar 

  7. Caprio S, Plewe G, Diamond MP, et al. Increased insulin secretion in puberty: a compensatory response to reductions in insulin sensitivity. J Pediatr. 1989;114(6):963–7.

    Article  CAS  PubMed  Google Scholar 

  8. 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(1):16–22 [see comment].

    Article  CAS  PubMed  Google Scholar 

  9. Hoffman RP, Vicini P, Sivitz WI, et al. 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  CAS  PubMed  Google Scholar 

  10. Reinehr T, Wolters B, Knop C, et al. Strong impact of pubertal status on metabolic health in obese children: a longitudinal study. J Clin Endocrinol Metab. 2014:jc20142674. The first longitudinal study to demonstrate a significant impact of puberty on cardiometabolic risk in obese youth.

  11. Copeland KC, Zeitler P, Geffner M, et al. Characteristics of adolescents and youth with recent-onset type 2 diabetes: the TODAY cohort at baseline. J Clin Endocrinol Metab. 2011;96(1):159–67.

    Article  CAS  PubMed  Google Scholar 

  12. Dabelea D, Bell RA, D’Agostino Jr RB, et al. Incidence of diabetes in youth in the United States. JAMA. 2007;297(24):2716–24.

    Article  PubMed  Google Scholar 

  13. Guzzaloni G, Grugni G, Mazzilli G, et al. Comparison between beta-cell function and insulin resistance indexes in prepubertal and pubertal obese children. Metabolism. 2002;51(8):1011–6.

    Article  CAS  PubMed  Google Scholar 

  14. Roemmich JN, Clark PA, Lusk M, 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.

    Article  CAS  PubMed  Google Scholar 

  15. Amiel SA, Caprio S, Sherwin RS, et al. Insulin resistance of puberty: a defect restricted to peripheral glucose metabolism. J Clin Endocrinol Metab. 1991;72(2):277–82.

    Article  CAS  PubMed  Google Scholar 

  16. Arslanian SA, Kalhan SC. Correlations between fatty acid and glucose metabolism. Potential explanation of insulin resistance of puberty. Diabetes. 1994;43(7):908–14.

    Article  CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  18. Dai S, Labarthe DR, Grunbaum JA, et al. Longitudinal analysis of changes in indices of obesity from age 8 years to age 18 years. Project HeartBeat! Am J Epidemiol. 2002;156(8):720–9.

    Article  PubMed  Google Scholar 

  19. Travers SH, Jeffers BW, Bloch CA, et al. Gender and Tanner stage differences in body composition and insulin sensitivity in early pubertal children. J Clin Endocrinol Metab. 1995;80(1):172–8.

    CAS  PubMed  Google Scholar 

  20. Altwaijri YA, Day RS, Harrist RB, et al. Sexual maturation affects diet-blood total cholesterol association in children: Project HeartBeat! Am J Prev Med. 2009;37(1 Suppl):S65–70.

    Article  PubMed  Google Scholar 

  21. Morrison JA, Laskarzewski PM, Rauh JL, et al. Lipids, lipoproteins, and sexual maturation during adolescence: the Princeton maturation study. Metabolism. 1979;28(6):641–9.

    Article  CAS  PubMed  Google Scholar 

  22. Porkka KV, Viikari JS, Ronnemaa T, et al. Age and gender specific serum lipid and apolipoprotein fractiles of Finnish children and young adults. The Cardiovascular Risk in Young Finns Study. Acta Paediatr. 1994;83(8):838–48.

    Article  CAS  PubMed  Google Scholar 

  23. Tell GS, Mittelmark MB, Vellar OD. Cholesterol, high density lipoprotein cholesterol and triglycerides during puberty: the Oslo Youth Study. Am J Epidemiol. 1985;122(5):750–61.

    CAS  PubMed  Google Scholar 

  24. Garcia-Mayor RV, Andrade MA, Rios M, et al. Serum leptin levels in normal children: relationship to age, gender, body mass index, pituitary-gonadal hormones, and pubertal stage. J Clin Endocrinol Metab. 1997;82(9):2849–55.

    CAS  PubMed  Google Scholar 

  25. Ahmed ML, Ong KK, Morrell DJ, et al. Longitudinal study of leptin concentrations during puberty: sex differences and relationship to changes in body composition. J Clin Endocrinol Metab. 1999;84(3):899–905.

    CAS  PubMed  Google Scholar 

  26. 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(3):309–12.

    Article  CAS  PubMed  Google Scholar 

  27. Blum WF, Englaro P, Hanitsch S, et al. Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone. J Clin Endocrinol Metab. 1997;82(9):2904–10.

    CAS  PubMed  Google Scholar 

  28. Andersen KK, Frystyk J, Wolthers OD, et al. Gender differences of oligomers and total adiponectin during puberty: a cross-sectional study of 859 Danish school children. J Clin Endocrinol Metab. 2007;92(5):1857–62.

    Article  CAS  PubMed  Google Scholar 

  29. 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(8):4053–61.

    Article  PubMed  Google Scholar 

  30. Tsou PL, Jiang YD, Chang CC, et al. Sex-related differences between adiponectin and insulin resistance in schoolchildren. Diabetes Care. 2004;27(2):308–13.

    Article  CAS  PubMed  Google Scholar 

  31. Xu L, Li M, Yin J, et al. Change of Body composition and adipokines and their relationship with insulin resistance across pubertal development in obese and nonobese Chinese children: the BCAMS study. Int J Endocrinol. 2012;2012:389108.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Luna AM, Wilson DM, Wibbelsman CJ, et al. Somatomedins in adolescence: a cross-sectional study of the effect of puberty on plasma insulin-like growth factor I and II levels. J Clin Endocrinol Metab. 1983;57(2):268–71.

    Article  CAS  PubMed  Google Scholar 

  33. Caprio S, Boulware D, Tamborlane V. Growth hormone and insulin interactions. Horm Res. 1992;38 Suppl 2:47–9.

    Article  CAS  PubMed  Google Scholar 

  34. Vijayakumar A, Yakar S, Leroith D. The intricate role of growth hormone in metabolism. Front Endocrinol. 2011;2:32.

    Article  Google Scholar 

  35. Saenger P. Metabolic consequences of growth hormone treatment in paediatric practice. Horm Res. 2000;53 Suppl 1:60–9.

    CAS  PubMed  Google Scholar 

  36. Barbour LA, Mizanoor Rahman S, Gurevich I, et al. Increased P85alpha is a potent negative regulator of skeletal muscle insulin signaling and induces in vivo insulin resistance associated with growth hormone excess. J Biol Chem. 2005;280(45):37489–94.

    Article  CAS  PubMed  Google Scholar 

  37. del Rincon JP, Iida K, Gaylinn BD, et al. Growth hormone regulation of p85alpha expression and phosphoinositide 3-kinase activity in adipose tissue: mechanism for growth hormone-mediated insulin resistance. Diabetes. 2007;56(6):1638–46.

    Article  PubMed  Google Scholar 

  38. Caprio S. Insulin: the other anabolic hormone of puberty. Acta Paediatr Suppl. 1999;88(433):84–7.

    Article  CAS  PubMed  Google Scholar 

  39. Guercio G, Rivarola MA, Chaler E, et al. Relationship between the GH/IGF-I axis, insulin sensitivity, and adrenal androgens in normal prepubertal and pubertal boys. J Clin Endocrinol Metab. 2002;87(3):1162–9.

    Article  CAS  PubMed  Google Scholar 

  40. Moran A, Jacobs Jr DR, Steinberger J, et al. Association between the insulin resistance of puberty and the insulin-like growth factor-I/growth hormone axis. J Clin Endocrinol Metab. 2002;87(10):4817–20.

    Article  CAS  PubMed  Google Scholar 

  41. Travers SH, Labarta JI, Gargosky SE, et al. Insulin-like growth factor binding protein-I levels are strongly associated with insulin sensitivity and obesity in early pubertal children. J Clin Endocrinol Metab. 1998;83(6):1935–9.

    CAS  PubMed  Google Scholar 

  42. 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(12):1471–7.

    Article  CAS  Google Scholar 

  43. Pinhas-Hamiel O, Lerner-Geva L, Copperman NM, et al. Lipid and insulin levels in obese children: changes with age and puberty. Obesity (Silver Spring). 2007;15(11):2825–31.

    Article  CAS  Google Scholar 

  44. 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(1):207–12.

    Article  CAS  PubMed  Google Scholar 

  45. Kelly LA, Lane CJ, Weigensberg MJ, et al. Pubertal changes of insulin sensitivity, acute insulin response, and beta-cell function in overweight Latino youth. J Pediatr. 2011;158(3):442–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Burns SF, Bacha F, Lee SJ, et al. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Giannini C, Weiss R, Cali A, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Sjaarda LG, Bacha F, Lee S, et al. Oral disposition index in obese youth from normal to prediabetes to diabetes: relationship to clamp disposition index. J Pediatr. 2012;161(1):51–7.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Reinehr T, Toschke AM. Onset of puberty and cardiovascular risk factors in untreated obese children and adolescents: a 1-year follow-up study. Arch Pediatr Adolesc Med. 2009;163(8):709–15.

    Article  PubMed  Google Scholar 

  50. Agirbasli M, Agaoglu NB, Orak N, Caglioz H, Ocek T, Poci N, et al. Sex hormones and metabolic syndrome in children and adolescents. Metabolism. 2009;58(9):1256–62.

    Article  CAS  PubMed  Google Scholar 

  51. Basterfield L, Adamson AJ, Frary JK, et al. Longitudinal study of physical activity and sedentary behavior in children. Pediatrics. 2011;127(1):e24–30.

    Article  PubMed  Google Scholar 

  52. Nader PR, Bradley RH, Houts RM, et al. Moderate-to-vigorous physical activity from ages 9 to 15 years. JAMA. 2008;300(3):295–305.

    Article  CAS  PubMed  Google Scholar 

  53. Craggs C, Corder K, van Sluijs EM, et al. Determinants of change in physical activity in children and adolescents: a systematic review. Am J Prev Med. 2011;40(6):645–58.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Davis CL, Pollock NK, Waller JL, et al. Exercise dose and diabetes risk in overweight and obese children: a randomized controlled trial. JAMA. 2012;308:1103–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Nassis GP, Papantakou K, Skenderi K, et al. Aerobic exercise training improves insulin sensitivity without changes in body weight, body fat, adiponectin, and inflammatory markers in overweight and obese girls. Metabolism. 2005;54:1472–9.

    Article  CAS  PubMed  Google Scholar 

  56. Schmitz KH, Jacobs Jr DR, Hong CP, et al. Association of physical activity with insulin sensitivity in children. Int J Obes Relat Metab Disord. 2002;26(10):1310–6.

    Article  CAS  PubMed  Google Scholar 

  57. Nadeau KJ, Zeitler PS, Bauer TA, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Regensteiner JG, Bauer TA, Reusch JE. Rosiglitazone improves exercise capacity in individuals with type 2 diabetes. Diabetes Care. 2005;28(12):2877–83.

    Article  CAS  PubMed  Google Scholar 

  59. Marshall WA, Tanner JM. Variations in pattern of pubertal changes in girls. Arch Dis Child. 1969;44(235):291–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Marshall WA, Tanner JM. Variations in the pattern of pubertal changes in boys. Arch Dis Child. 1970;45(239):13–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Pediatric Endocrinology, University of Colorado School of Medicine, Children’s Hospital Colorado School of Medicine, 13123 E 16th Ave, B265, Aurora, CO, 80045, USA

    Megan M. Kelsey & Philip S. Zeitler

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  1. Megan M. Kelsey
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  2. Philip S. Zeitler
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Correspondence to Megan M. Kelsey.

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Megan M. Kelsey and Philip S. Zeitler declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors (other than previously published studies that are referenced within).

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This article is part of the Topical Collection on Pediatric Type 2 Diabetes

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Kelsey, M.M., Zeitler, P.S. Insulin Resistance of Puberty. Curr Diab Rep 16, 64 (2016). https://doi.org/10.1007/s11892-016-0751-5

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