Enhanced insulin sensitivity in prepubertal children with constitutional delay of growth and development.

OBJECTIVE: To test the hypothesis that prepubertal children with presumed constitutional delay of growth and development (CDGD) have enhanced insulin sensitivity and, therefore, insulin sensitivity is associated with later onset of puberty. STUDY DESIGN: Twenty-one prepubertal children with presumed CDGD and 23 prepubertal control children, underwent a frequently sampled intravenous glucose tolerance test to evaluate insulin sensitivity and other markers of insulin, glucose, and growth regulation. RESULTS: Children in the CDGD group were shorter and leaner than control subjects. Children with presumed CDGD were 40% more insulin sensitive (17.0 x 10(-4) min(-1)/[mU/L] versus 12.1 x 10(-4) min(-1)/[mU/L]; P = .0006) and had reduced acute insulin response, thus maintaining euglycemia (216 mU/L versus 330 mU/L; P = .02) compared with control subjects. In addition, the CDGD group had lower serum insulin-like growth factor binding protein 3 levels (3333 ng/mL versus 3775 ng/mL; P = .0004) and a trend toward lower serum insulin-like growth factor-II levels (794 ng/mL versus 911 ng/mL; P = .06). CONCLUSION: Prepubertal children with presumed CDGD have enhanced insulin sensitivity, supporting the hypothesis that insulin sensitivity is associated with timing of puberty. It may signify long-term biological advantages with lower risk of metabolic syndrome and malignancy.

Insulin resistance in healthy prepubertal twins.

OBJECTIVES: To evaluate insulin sensitivity (S(I)) in prepubertal twins and to examine the relation to reduced birth weight, prematurity, and peroxisome proliferator-activated receptor-gamma (PPAR gamma) polymorphism. STUDY DESIGN: Fifty twins (birth weight SDS, -0.7 +/- 0.2; gestation, 33.5 +/- 0.5 weeks; and body mass index SDS, -0.04 +/- 0.2) were studied at 8.2 +/- 0.3 years. S(I) was measured by Bergman's minimal model from a 90 minutes frequently sampled intravenous glucose test. Twenty control children (height SDS, -1.7 +/- 0.3; birth weight SDS, -0.3 +/- 0.2; and gestation of 39.2 +/- 0.7 weeks) were also evaluated at 7.0 +/- 0.4 years. The PPAR gamma T-variant polymorphism was evaluated in 41 twins. Values are expressed as mean +/- SEM, or 95% confidence intervals. RESULTS: S(I) was reduced in twins compared with control subjects, (12.7 [11-15] versus 23.0 [16.8-31.4] 10(-4) min(-1) microU/mL, respectively, P=.005). The reduction in S(I) was independent of prematurity and birth weight and zygosity (P<.0001). There was no difference in S(I), even in twin pairs with >20% difference in birth weight (P=.9). The PPAR gamma heterozygote T-variant polymorphism was present in 7 of 41, with a further reduction in S(I) (P=.03) and a later gestation (P=.03). These twins also had increased fat mass (P=.02) but with similar fat free mass (P=.14). CONCLUSIONS: Twin children, independent of prematurity or birth weight, had a marked reduction in S(I). To use twins as a model to study the fetal origins of adult diseases for glucose homeostasis is not valid.

Reduced insulin sensitivity during growth hormone therapy for short children born small for gestational age.

OBJECTIVES: To examine the influence of recombinant human growth hormone (rhGH) therapy on insulin sensitivity in short children born small for gestational age (SGA). STUDY DESIGN: Twelve short (height standard deviation score, -3.2 +/- 0.1) non-GH-deficient children SGA (7 boys/5 girls) were studied at 9.3 +/- 1.0 years of age. The insulin sensitivity index was measured with Bergman's minimal model before (11 children) and during (12 children) rhGH therapy (21 +/- 6 months) administered daily at 20 IU/m(2) per week. No child had a change in pubertal status during the study. In addition, 5 children who remained prepubertal had insulin sensitivity remeasured 3 months after rhGH therapy was suspended. RESULTS: With rhGH therapy, insulin sensitivity fell 44% +/- 10% (P =.018), with a compensatory rise in the acute insulin response of 123% +/- 59% (P <.009). Reassessment of insulin sensitivity in 5 children (3 boys/2 girls) 3 months after suspension of rhGH occurred at 9.9 +/- 0.7 years. Insulin sensitivity remained unchanged after rhGH therapy was stopped: 31.6 (20.5-42.3) before treatment, 11.5 (5.7-24.4) with treatment, and 10.7 (6.2-16.9) 10(-4). min(-1) microU/mL after treatment. CONCLUSIONS: Children SGA are known to have reduced insulin sensitivity. There was a further reduction in insulin sensitivity with rhGH therapy that did not recover 3 months after rhGH therapy was stopped.