Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Paper
  • Published:

Pubertal alterations in growth and body composition. VI. Pubertal insulin resistance: relation to adiposity, body fat distribution and hormone release

International Journal of Obesity volume 26, pages 701–709 (2002)Cite this article

Abstract

Objective: To investigate the independent influence of alterations in fat mass, body fat distribution and hormone release on pubertal increases in fasting serum insulin concentrations and on insulin resistance assessed by the homeostasis model (HOMA).

Design and Subjects: Cross-sectional investigation of pre- (n=11, n=8), mid- (n=10, n=11), and late-pubertal (n=10, n=11) boys and girls with normal body weight and growth velocity.

Measurements: Body composition (by a four-compartment model), abdominal fat distribution and mid-thigh interfascicular plus intermuscle (extramyocellular) fat (by magnetic resonance imaging), total body subcutaneous fat (by skinfolds), mean nocturnal growth hormone (GH) release and 06:00 h samples of serum insulin, sex steroids, leptin and insulin-like growth factor-I (IGF-I).

Results: Pubertal insulin resistance was suggested by greater (P<0.001) fasting serum insulin concentrations in the late-pubertal than pre- and mid-pubertal groups while serum glucose concentrations were unchanged and greater (P<0.001) HOMA values in late-pubertal than pre- and mid-pubertal youth. From univariate correlation fat mass was most related to HOMA (r=0.59, P<0.001). Two hierarchical regression models were developed to predict HOMA. In one approach, subject differences in sex, pubertal maturation, height and weight were held constant by adding these variables as a block in the first step of the model (r2=0.36). Sequential addition of fat mass (FM) increased r2 (r2(inc)remental=0.08, r2=0.44, P<0.05) as did the subsequent addition of a block of fat distribution variables (extramyocellular fat, abdominal visceral fat, and sum of skinfolds; r2inc=0.11, r2=0.55, P<0.05). Sequential addition of a block of hormone variables (serum IGF-I and log(10) leptin concentrations; r2inc=0.04, P>0.05) did not reliably improve r2 beyond the physical characteristic and adiposity variables. In a second model, differences in sex and pubertal maturation were again held constant (r2=0.25), but body size differences were accounted for using percentage fat data. Sequential addition of percentage body fat (r2(inc)remental=0.11, r2=0.36, P<0.05), then a block of fat distribution variables (percentage extramyocellular fat, percentage abdominal visceral fat, and percentage abdominal subcutaneous fat; r2inc=0.08, r2=0.44, P=0.058), and then a block of serum IGF-I and log(10) leptin concentrations (r2inc=0.07, r2=0.51, P<0.05) increased r2. Mean nocturnal GH release was not related to HOMA (r=−0.04, P=0.75) and therefore was not included in the hierarchical regression models.

Conclusion: Increases in insulin resistance at puberty were most related to FM. Accumulation of fat in the abdominal visceral, subcutaneous and muscular compartments may increase insulin resistance at puberty beyond that due to total body fat. Serum concentrations of leptin and IGF-I may further modulate HOMA beyond the effects of adiposity and fat distribution. However, the results are limited by the cross-sectional design and the use of HOMA rather than a criterion measure of insulin resistance.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Bloch CA, Clemons P, Sperling MA . Puberty decreases insulin sensitivity J Pediatr 1987 110: 481–487.

    Article  CAS  PubMed  Google Scholar 

  2. Moran A, Jacobs DR, Steinberger J, Hong C-P, Prineas R, Luepker R, Sinaiko AR . Insulin resistance during puberty. Results from clamp studies in 357 children Diabetes 1999 48: 2039–2044.

    Article  CAS  PubMed  Google Scholar 

  3. Potau N, Ibanez L, Rique S, Carrascosa A . Pubertal changes in insulin secretion and peripheral insulin sensitivity Horm Res 1997 48: 219–226.

    Article  CAS  PubMed  Google Scholar 

  4. Caprio S, Plewe G, Diamond MP, Simonson DC, Boulware SD, Sherwin RS, Tamborlane WV . Increased insulin secretion in puberty: a compensatory response to reductions in insulin sensitivity J Pediatr 1989 114: 963–967.

    Article  CAS  PubMed  Google Scholar 

  5. Dietz WH . Critical periods in childhood for the development of obesity Am J Clin Nutr 1994 59: 955–959.

    Article  CAS  PubMed  Google Scholar 

  6. Amiel SA, Caprio S, Sherwin RS, Plewe G, Haymond MW, Tamborlane WV . Insulin resistance of puberty: a defect restricted to peripheral glucose metabolism J Clin Endocrinol Metab 1991 72: 277–282.

    Article  CAS  PubMed  Google Scholar 

  7. Caprio S, Hyman LD, Limb C, McCarthy S, Lange R, Sherwin RS, Shulman G, Tamborlane WV . Central adiposity and its metabolic correlates in obese adolescent girls Am J Physiol 1995 269: E118–E126.

    Article  CAS  PubMed  Google Scholar 

  8. Caprio S, Hyman LD, McCarthy S, Lange R, Bronson M, Tamborlane WV . Fat distribution and cardiovascular risk factors in obese adolescent girls: importance of the intrabdominal fat depot Am J Clin Nutr 1996 64: 12–17.

    Article  CAS  PubMed  Google Scholar 

  9. Caprio S, Tamborlane WV, Silver D, Robinson C, Leibel R, McCarthy S, Grozman A, Belous A, Maggs D, Sherwin RS . Hyperleptinemia: an early sign of juvenile obesity. Relations to body fat depots and insulin concentrations Am J Physiol 1996 271: E626–E630.

    CAS  PubMed  Google Scholar 

  10. Brambilla P, Manzoni P, Sironi S, Simone P, Del Maschio A, di Natale B, Chiumello G . Peripheral and abdominal adiposity in childhood obesity Int J Obes Relat Metab Disord 1994 18: 795–800.

    CAS  PubMed  Google Scholar 

  11. Goodpaster BH, Thaete FL, Simoneau JA, Kelley DE . Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat Diabetes 1997 46: 1579–1585.

    Article  CAS  PubMed  Google Scholar 

  12. Abate N, Garg A, Peshock RM, Stray-Gundersen J, Grundy S . Relationships of generalized and regional adiposity to insulin sensitivity in men J Clin Invest 1995 96: 88–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Pan DA, Lillioja S, Kriketos AD, Milner MR, Baur LA, Bogardus C, Jenkins AB, Storlein LH . Skeletal muscle triglyceride levels are inversely related to insulin action Diabetes 1997 46: 983–988.

    Article  CAS  PubMed  Google Scholar 

  14. Phillips DIW, Caddy S, Ilic V, Fielding BA, Frayn KN, Borthwick AC, Taylor R . Muscle triglyceride and muscle insulin sensitivity: evidence for a relationship in nondiabetic subjects Metabolism 1996 45: 947–950.

    Article  CAS  PubMed  Google Scholar 

  15. Simoneau JA, Colberg SR, Thaete FL, Kelley DE . Skeletal muscle glycolytic and oxidative enzyme capacities are determinants of insulin sensitivity and muscle composition in obese women FASEB J 1995 9: 273–278.

    Article  CAS  PubMed  Google Scholar 

  16. Storlien LH, Jenkins AB, Chrisholm DJ, Pascoe WS, Khouri S, Kraegen EW . Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and −3 fatty acids in muscle phospholipid Diabetes 1991 40: 280–289.

    Article  CAS  PubMed  Google Scholar 

  17. Caprio S, Bronson M, Sherwin RS, Rife F, Tamborlane WV . Co-existence of severe insulin resistance and hyperinsulinaemia in pre-adolescent obese children Diabtologia 1996 39: 1489–1497.

    Article  CAS  Google Scholar 

  18. DeFronzo RA, Tobin JD, Andres R . Glucose clamp technique: a method for quantifying insulin secretion and resistance Am J Physiol 1979 237: E214–E233.

    CAS  PubMed  Google Scholar 

  19. Shulman GI, Rothman DL, Jue T, Stein P, DeFronzo RA, Shulman RG . Quantitation of muscle glycogen synthesis in normal subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy New Engl J Med 1990 322: 223–228.

    Article  CAS  PubMed  Google Scholar 

  20. Fehmann H-C, Berghofer P, Brandhorst D, Brandhorst H, Hering B, Bretzel RG, Goke B . Leptin inhibition of insulin secretion from isolated human islets Acta Diabetol 1997 34: 249–252.

    Article  CAS  PubMed  Google Scholar 

  21. Roemmich JN, Clark PA, Berr S, Mai V, Mantzoros C, Weltman A, Flier JS, Rogol AD . Gender differences in leptin levels during puberty are related to the subcutaneous fat depot and sex steroids Am J Physiol 1998 275: E543–E551.

    CAS  PubMed  Google Scholar 

  22. Bareille P, Azcona C, Matthews DR, Conway GS, Stanhope R . Lipid profile, glucose tolerance, and insulin sensitivity after more than four years of growth hormone therapy in non-growth hormone deficient adolescents Clin Endocrinol 1999 51: 347–353.

    Article  CAS  Google Scholar 

  23. Amiel SA, Sherwin RS, Simonson DC, Lauritano AA, Tamborlane WV . Impaired insulin action in puberty New Engl J Med 1986 315: 215–219.

    Article  CAS  PubMed  Google Scholar 

  24. Cook JS, Hoffman RP, Stene MA, Hansen JR . Effects of maturational stage on insulin sensitivity during puberty J Clin Endocrinol Metab 1993 77: 725–730.

    CAS  PubMed  Google Scholar 

  25. Caprio S . Insulin: the other anabolic hormone of puberty Acta Paediatr 1999 433 (Suppl): 84–87.

    Article  Google Scholar 

  26. 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: 412–419.

    Article  CAS  PubMed  Google Scholar 

  27. Tanner JM . Growth at adolescence Blackwell Scientific: Oxford 1962.

    Google Scholar 

  28. Roemmich JN, Clark PA, Mai V, Berr S, Weltman A, Veldhuis JD, Rogol AD . Alterations in growth and body composition during puberty: III. Influence of maturation, gender, body composition, fat distribution, aerobic fitness, and energy expenditure on nocturnal growth hormone release during puberty J Clin Endocrinol Metab 1998 83: 1440–1447.

    CAS  PubMed  Google Scholar 

  29. Veldhuis JD, Johnson ML . Cluster analysis: a simple, versatile, and robust algorithm for endocrine detection Am J Physiol 1986 250: E486–E493.

    Article  CAS  PubMed  Google Scholar 

  30. Lohman TG . Advances in body composition assessment Human Kinetics: Champaign, IL 1992.

    Google Scholar 

  31. Roemmich JN, Clark PA, Weltman A, Rogol AD . Alterations in growth and body composition during puberty: I. Comparison among 2-, 3- and 4-compartment models of body composition J Appl Physiol 1997 83: 927–935.

    Article  CAS  PubMed  Google Scholar 

  32. Harrison GG, Buskirk ER, Lindsay Carter JE, Johnston FE, Lohman TG, Pollack ML, Roche AF, Wilmore JH . 1988 Skinfold thicknesses and measurement technique. In: Lohman TG, Roche AF, Martorell R (eds) Anthropometric standardization reference manual Human Kinetics: Champaign, IL 1988 55–70.

    Google Scholar 

  33. Radziuk J . Insulin sensitivity and its measurement: structural commonalities among the methods J Clin Endocrinol Metab 2000 85: 4426–4433.

    CAS  PubMed  Google Scholar 

  34. Petrie JR, Morris AD, Dorrian CA, Small M, Connell JM . Specific insulin assays, insulin sensitivity and blood pressure Q J Med 1997 90: 465–475.

    Article  CAS  Google Scholar 

  35. Gower BA, Nagy TR, Goran MI . Visceral fat, insulin sensitivity, and lipids in prepubertal children Diabetes 1999 48: 1515–1521.

    Article  CAS  PubMed  Google Scholar 

  36. Arslanian S, Suprasongsin C . Insulin sensitivity, lipids, and body composition in childhood: is ‘syndrome X’ present? J Clin Endocrinol Metab 1996 81: 1058–1062.

    Article  CAS  PubMed  Google Scholar 

  37. Jiang X, Srinivasan SR, Berenson GS . Relation of obesity to insulin secretion and clearance in adolescents: the Bogalusa Heart Study Int J Obes Relat Metab Disord 1996 20: 951–956.

    CAS  PubMed  Google Scholar 

  38. Radetti G, Ghizzoni L, Paganini C, Iughetti L, Caselli G, Bernasconi S . Insulin pulsatility in obese and normal prepubertal children Horm Res 1998 50: 78–82.

    CAS  PubMed  Google Scholar 

  39. Smith CP, Dunger DB, Williams AJK, Taylor AM, Perry LA, Gale EAM, Preece MA, Savage MO . Relationship between insulin, insulin-like growth factor I, and dehydroepiandrosterone sulfate concentrations during childhood, puberty, and adult life J Clin Endocrinol Metab 1989 68: 932–937.

    Article  CAS  PubMed  Google Scholar 

  40. Pouliot M-C, Despres J-P, Lemieux S, Moorjani S, Bouchard C, Tremblay A, Nadeau A, Lupien PJ . Waist circumference and abdominal sagittal diameter: best simple anthropometric indexes of abdominal visceral adipose tissue accumulation and related cardiovascular risk in men and women Am J Cardiol 1994 73: 460–468.

    Article  CAS  PubMed  Google Scholar 

  41. Gower BA, Nagy TR, Trowbridge CA, Dezenberg C, Goran MI . Fat distribution and insulin response in prepubertal African American and white children Am J Clin Nutr 1998 67: 821–827.

    Article  CAS  PubMed  Google Scholar 

  42. Boden G, Lebed B, Schatz M, Homko C, Lemieu S . Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance of healthy subjects Diabetes 2001 50: 1612–1617.

    Article  CAS  PubMed  Google Scholar 

  43. Perseghin G, Scifo P, De Cobelli F, Pagliato E, Battezzati A, Arcelloni C, Vanzulli A, Testolin G, Pozza G, Del Maschio A, Luzi L . Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H–13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents Diabetes 2001 48: 1600–1606.

    Article  Google Scholar 

  44. Arslanian SA, Heil BV, Becker DJ, Drash AL . Sexual dimorphism in insulin sensitivity in adolescents with insulin-dependent diabetes mellitus J Clin Endocrinol Metab 1991 72: 920–926.

    Article  CAS  PubMed  Google Scholar 

  45. Heptulla RA, Boulware SD, Caprio S, Silver D, Sherwin RS, Tamborlane WV . Decreased insulin sensitivity and compensatory hyperinsulinemia after hormone treatment in children with short stature J Clin Endocrinol Metab 1997 82: 3234–3238.

    CAS  PubMed  Google Scholar 

  46. Seminara S, Merello G, Masi S, Filpo A, La Cauza F, D'Onghia G, Martelli E, Loche S . Effect of long-term growth hormone treatment on carbohydrate metabolism in children with growth hormone deficiency Clin Endocrinol 1998 49: 125–130.

    Article  CAS  Google Scholar 

  47. Travers SH, Jeffers BW, Blocj 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: 172–178.

    CAS  PubMed  Google Scholar 

  48. Clemmons DR, Moses AC, McKay MJ, Sommer A, Rosen DM, Ruckle J . The combination of insulin-like growth factor I and insulin-like growth factor binding protein-3 reduces insulin requirements in insulin-dependent type 1 diabetes: evidence of in vivo biological activity J Clin Endocrinol Metab 2000 85: 1518–1524.

    CAS  PubMed  Google Scholar 

  49. Schwartz MW, Baskin DG, Kaiyala KJ, Woods SC . Model for the regulation of energy balance and adiposity by the central nervous system Am J Clin Nutr 1999 69: 584–596.

    Article  CAS  PubMed  Google Scholar 

  50. 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.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors are indebted to Ms Sandra Jackson and the nursing staff at the University of Virginia General Clinical Research Center who provided patient care and Katy Nash, MS and Catherine DeGood for study coordination. We thank Bret Goodpaster PhD for his insightful suggestions on an earlier version of this paper. We acknowledge the subjects for their enthusiasm for the research program. This work was supported in part by grants from the National Institutes of Health HD 32631 (ADR), General Clinical Research Center grants MO1 RR00847 (University of Virginia), the Genentech Foundation for Growth and Development (PAC), and the University of Virginia Children's Medical Center (JNR).

Author information

Author notes

  1. JN Roemmich: Present address of: JN Roemmich is currently with the Department of Pediatrics, Division of Behavioral Medicine, State University of New York at Buffalo; PA Clark is with the Department of Pediatrics, Division of Endocrinology, University of Louisville; and AD Rogol is with Insmed Pharmaceuticals Inc., Richmond, VA, USA.

Authors and Affiliations

  1. Department of Pediatrics, Division of Endocrinology, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA

    JN Roemmich, PA Clark, M Lusk, A Friel & AD Rogol

  2. Department of Human Services, Curry School of Education, University of Virginia, Charlottesville, Virginia, USA

    A Weltman

  3. Department of Medicine, Division of Endocrinology and Metabolism, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA

    A Weltman

  4. Department of Pediatrics, Division of Behavioral Medicine, University at Buffalo, School of Medicine and Biomedical Sciences, Buffalo, New York, USA

    LH Epstein

  5. Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville, Virginia, USA

    AD Rogol

Authors
  1. JN Roemmich
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. PA Clark
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M Lusk
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A Friel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Weltman
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. LH Epstein
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. AD Rogol
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to JN Roemmich.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Roemmich, J., Clark, P., 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 26, 701–709 (2002). https://doi.org/10.1038/sj.ijo.0801975

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0801975

Keywords

This article is cited by

Search

Advanced search

Quick links