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.

AIR, Acute insulin response, antiGAD, Glutamic acid decarboxylase antibody, BIA, Bioelectrical impedance analyzer, BMI, Body mass index, CDGD, Constitutional delay of growth and development, DHEAS, Dehydroepiandrosterone sulfate, DI, Disposition index, FFA, Free fatty acids, FSIGT, Frequently sampled intravenous glucose tolerance test, GnRH, Gonadotropin releasing hormone, HDL, High-density lipoprotein cholesterol, IA2, Islet antigen 2 antibody, IGFBP1, Insulin like growth factor binding protein 1, IGFBP2, Insulin like growth factor binding protein 2, IGFBP3, Insulin like growth factor binding protein 3, IGF-I, Insulin-like growth factor I, IGF-II, Insulin-like growth factor II, IL-6, Interleukin-6, Kg, Glucose disposal coefficient, LDL, Low-density lipoprotein cholesterol, MPH, Mid-parental height, SDS, Standard deviation scores, Sg, Glucose effectiveness, S_I, Insulin sensitivity