Objective: To investigate the possible contribution of plasma cortisol and growth hormone (GH) as reflected by insulin-like growth factor-I (IGF-I)/insulin-like growth factor-binding protein-3 (IGFBP-3) on insulin action in short-statured children. Methods: In this study, insulin resistance (HOMA) was determined in 34 normal short-statured (age 9.4 ± 3.5 years) and in 19 GH-deficient children (age 10.4 ± 2.2 years). HOMA was examined in relation to fasting plasma cortisol, IGF-I, IGFBP-3 and in addition to birthweight and body mass index (BMI). Results: Birthweight was not correlated to insulin resistance. In GH-deficient children, BMI was significantly augmented and was associated with HOMA (p < 0.02). In both groups of patients, fasting plasma cortisol was related to HOMA (normal: r = 0.295, p < 0.05, GH-deficient: r = 0.495, p < 0.02). Only in normal short-statured children IGF-I (r = 0.338, p < 0.03) and IGFBP-3 (r = 0.493, p < 0.002) were associated with insulin resistance. Conclusion: The results indicated that at a young age cortisol contributed to insulin resistance in short-statured children. In normal short-statured children HOMA was associated with IGF-I and IGFBP-3. Possibly GH, a known cause of insulin resistance, contributed to HOMA as IGF-I and IGFBP-3 do not mediate insulin resistance but reflect growth hormone secretion. The results in GH-deficient children supported this conclusion as in the absence of GH insulin resistance was not associated with IGF-I/IGFBP-3.

1.
Hales CN, Barker DJ, Clark PM, Cox LJ, Fall, Osmond C, Winter PD: Fetal and infant growth and impaired glucose tolerance at age 64. BMJ 1991;303:1019–1022.
2.
Phipps K, Barker DJ, Hales CN, Fall CH, Osmond C, Clark PM: Fetal growth and impaired glucose tolerance in men and women. Diabetologia 1993;36:225–228.
3.
Phillips DIW: Birth weight and the future development of diabetes. Diabetes Care 1998;21(suppl 2)B150–B155.
4.
Barker DJ: Mothers, Babies and Health in Later Life. Edinburgh, Churchill Livingstone, 1998.
5.
Poulsen P, Vaag AA, Kyvik KO, Moller-Jensen D, Beck-Nielsen H: Low birth weight is associated with NIDDM in discordant monozygotic and dizygotic twin pairs. 1997;40:439–446.
6.
Baird J, Osmond C, MacGregor A, Snieder H, Hales CN, Philipps DIW: Testing the fetal origin hypothesis in twins: The Birmingham Twin Study. Diabetologia 2001;44:3–39.
7.
Poulsen P, Vaag AA, Kyvik KO, Beck-Nielsen H: Genetic versus environmental aetiology of the metabolic syndrome among male and female twins. Diabetologia 2001;44:537–543.
8.
Bo S, Cavallo-Perin P, Ciccone G, Scaglione L, Pagano G: The metabolic syndrome in twins: A consequence of low birth weight or of being a twin? Exp Clin Endocrinol Diabetes 2001;109:135–140.
9.
Whincup PH, Cook DG, Adshead E, Taylor SJC, Walker M, Papacosta O, Albert KGM: Childhood size is more strongly related than size at birth to glucose and insulin levels in 10- to 11-year-old children. Diabetologia 1997;40:319–326.
10.
Hales CN, Barker DJ: Type II (non-insulin-dependent) diabetes mellitus: The thrifty phenotye hypothesis. Diabetologia 1992;35:595–601.
11.
Philipps DI: Insulin resistance as a programmed response to fetal undernutrition. Diabetologia 1996;39:1119–1122.
12.
Hattersley AT, Took JE: The fetal insulin hypothesis: An alternative explanation of the association of low birthweight with diabetes and vascular disease. Lancet 1999;353:789–1792.
13.
Stolk RP, Lamberts SWJ, de Jong FH, Pols HAP, Grobbee DE: Gender differences in the associations between cortisol and insulin sensitivity in healthy subjects. J Endocrinol 1996;149:313–318.
14.
Filipovsky J, Ducimetiere P, Eschwege E, Richard JL, Rosselin G, Claude JR: The relationship of blood pressure with glucose, insulin, heart rate, free fatty acids and plasma cortisol levels according to degree of obesity in middle-aged men. J Hypertens 1996;14:229–235.
15.
Philipps DIW, Barker DJP, Fall CHD, Seckl JR, Whorwood CB, Wood PJ, Walker BR: Elevated plasma cortisol concentrations: A link between low birthweight and the insulin resistance syndrome. J Clin Endocrinol Metab 1998;83:757–760.
16.
Bloch CA, Clemonts P, Sperling MA: Puberty decreases insulin sensitivity. J Pediatr 1987;110:481–487.
17.
Caprio S, Plewe G, Diamond MP, Simonson DC, Boulware SD, Sherwin RS, Tomberlane WV: Increased insulin secretion in puberty: A compensatory response to reductions in insulin sensitivity. J Pediatr 1989;114:963–967.
18.
Prader A, Budliger H: Körpermasse, Wachstumsgeschwindigkeit und Knochenalter gesunder Kinder in den ersten zwölf Jahren (Longitudinale Wachstumsstudie Zürich). Helv Paediatr Acta 1977;suppl 37:1–44.
19.
Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC: Homeostasis model assessment: Insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–419.
20.
Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Järvinen H, Van Haften T, Renn W, Gerich J: Use of oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care 2000;23:295–301.
21.
DeFronzo RA, Tobin JD, Andres R: Glucose clamp technique: A method for quantifying insulin secretion and resistance. Am J Physiol 1979;237:E214–E223.
22.
Moller DE, Flier JS: Insulin resistance mechanisms, syndromes, and implications. N Engl J Med 1991;325:938–948.
23.
Bonora E, Tagher G, Alberiche M, Bonadonna RC, Sadggiani F, Zenere MB, Moauni T, Muggeo M: Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity. Diabetes Care 2000;23:57–63.
24.
Heinze E, Horn T, Wabitsch M, Wudy S, Sorgo W, Homoki J: Bestimmung von Insulinresistenz und Insulinsensitivität bei Kindern und Jugendlichen. Monatsschr Kinderheilkd 2002;150:1095–1100.
25.
Levitt NS, Lambert EV, Woods D, Hales CN, Andrew R, Seckl JR: Impaired glucose tolerance and elevated blood pressure in low birth weight, nonobese, young South African adults: Early programming of cortisol axis. J Clin Endocrnol Metab 2000;85:4611–4618.
26.
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.
27.
Rizza RA, Mandarino LJ, Gerich JE: Effects of growth hormone on insulin action in man. Diabetes 1982;31:663–669.
28.
Amiel SA, Sherwin RS, Simonson DC, Lauritano AA, Tomberlane WV: Impaired insulin action in puberty: A contributing factor to poor glycemic control in adolescents with diabetes. N Engl J Med 1986;315:215–219.
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