Fasting insulin sensitivity and post-oral glucose hyperinsulinaemia related to cardiovascular risk factors in adolescents with precocious pubarche

OBJECTIVE Adolescents and young women with a history of precocious pubarche (PP, appearance of pubic hair before 8 years) exhibit hyperlipidaemia, and ovarian hyperandrogenism, indicating increased risk of coronary heart disease in the long term. The aim of this study was to determine the relative contribution of fasting insulin sensitivity, and post oral glucose tolerance test (OGTT) measures of insulin secretion to metabolic risk markers of adult disease. PATIENTS AND DESIGN We have analysed data from 51 young women presenting with isolated PP (age range, 5.9-19.0 years) in early, mid and late puberty and 68 puberty-matched controls (age range, 6.2-16.8 years). Body composition data from a further 67 girls with PP are also presented. MEASUREMENTS The homeostasis model of assessment insulin sensitivity index (HOMA Si) based on fasting glucose and insulin measurements and MSI120 based on insulin levels over the first 120 min following standard oral glucose load were selected as measures of fasting insulin sensitivity and 0-120-min insulinaemia, respectively. ISI30 was used as an index of insulin secretion 30 min following oral glucose load. RESULTS The physiological decrease in fasting insulin sensitivity, 30-min insulin secretion and 0-120-min insulinaemia during puberty were exaggerated in PP girls. The relationship between fasting insulin sensitivity and 0-120-min insulinaemia was similar in PP girls and in controls but at each level of fasting insulin sensitivity the PP girls had a higher level of insulin secretion in response to an oral glucose load (P < 0.001). Fasting insulin sensitivity and 0-120 minute insulinaemia but not 30-min insulin secretion were strongly related to known cardiovascular risk factors. In a multivariate model incorporating fasting insulin sensitivity, 0-120-min insulinaemia, pubertal stage and body mass index (BMI) SDS as covariates, 0-120-min insulinaemia was strongly associated with elevated free androgen index, total cholesterol and truncal fat mass (P < 0.001) whereas fasting insulin sensitivity was associated only with reduced free androgen index (P < 0.02). CONCLUSIONS Chronic exposure to insulin as reflected by 0-120 min hyperinsulinaemia, rather than 30 min insulin secretion, or fasting insulin senstivity, was most closely related cardiovascular disease risk in girls with PP.