Insulin Sensitivity and the Insulin-Like Growth Factor System in Prepubertal Boys with Premature Adrenarche

Abstract

Girls with premature adrenarche (PA), similar to women with polycystic ovarian syndrome, display alterations in the IGF system, may have impaired insulin sensitivity, and demonstrate unfavorable lipid profiles. Girls with PA are also at increased risk for functional ovarian hyperandrogenism. Metabolic studies in boys with PA, however, are limited. The objective of this study was to determine whether boys with PA show alterations in insulin sensitivity and the IGF system. We studied an ethnically heterogeneous group of 19 prepubertal boys: 11 with PA (age, 8.2 +/- 0.7 yr; body mass index (BMI)-Z score, 1.8 +/- 1.1) and 8 controls (age, 7.9 +/- 0.8 yr; BMI-Z score, 1.2 +/- 1.0). Fasting levels of glucose, insulin, proinsulin (P(0)), hemoglobin A1c, testosterone, SHBG, delta4-androstenedione, dehydroepiandrosterone sulfate, LH, FSH, IGF-I, IGF-binding protein-1, IGF-binding protein-3, free IGF-I, and lipids were measured. Ten of 11 boys with PA and six of eight controls underwent standard oral glucose tolerance testing. The insulin response to this test was measured by the insulin area under the curve. Measures of insulin sensitivity were calculated as the fasting glucose to insulin ratio, quantitative insulin sensitivity check index, and composite insulin sensitivity index. All values were adjusted for BMI-Z score. Total IGF-I, P(0), ratio of P(0) and fasting insulin level, and log insulin area under the curve were higher, and SHBG was lower in the boys with PA, compared with controls. Decreased insulin sensitivity was suggested by decreased composite insulin sensitivity index. A trend toward greater triglycerides was observed in the boys with PA, compared with the controls. Prepubertal boys with PA show differences in the IGF system and decreased insulin sensitivity, independent of obesity, as observed in girls with PA. These findings suggest that both boys and girls with PA should be monitored for the development of insulin resistance and associated complications, including diabetes mellitus and cardiovascular disease.

Pubertal development in obese children and adolescents

“…SHBG is regulated by insulin and therefore hyperinsulinemia in obesity might be responsible for the decreased SHBG levels. [43][44][45] Obese girls had elevated mean testosterone levels between 10 and 14 years of age compared to reference values. The origin of testosterone production in girls might be adrenal and possibly also ovarian.…”

The pubertal transition in 179 healthy Danish children: associations between pubarche, adrenarche, gonadarche, and body composition

“…Some studies have implicated that girls with premature adrenarche seem to be at increased risk of ovarian hyperandrogenism, polycystic ovarian syndrome (12), insulin resistance, and metabolic syndrome (13,14). Therefore, we found it important to study the timing of gonadarche and pubarche and the possible associations with adrenal androgen levels and fat accumulation in healthy Danish children.…”

Premature adrenarche: novel lessons from early onset androgen excess

“…Later on, Ibanez et al (76) published a number of casecontrol studies in lean Spanish (Catalonian) girls with a history of PP that showed evidence of insulin resistance based on both fasting insulin levels and the insulin response to a standard oral glucose tolerance test (OGTT) (76)(77)(78)(79)(80). Interestingly, these observations could not be confirmed in boys from the same population (81) but similar findings were obtained in pre-pubertal boys with PA from North America (82). In PP girls from North America, an inverse correlation between insulin sensitivity and ACTH-stimulated D5-androgen precursors (17-hydroxypregnenolone, DHEA) has been found; however, the study population was not body mass index (BMI) matched (83).…”