Endocrine Abstracts (2007) 13 S49

The use of insulin sensitisers in the adolescent

David Dunger


Addenbrooke’s Hospital, Cambridge, United Kingdom.


Normal pubertal development is characterised by a decline in insulin sensitivity resulting from the effects of elevated growth hormone levels on peripheral glucose uptake in muscle. The increased glucose availability for other tissues leads to protein sparing, contributing to the anabolism of puberty. Insulin also has an important role in the regulation of the tempo of puberty through its actions on SHBG and IGFBP-1 which, in part, determine the bioavailability of sex steroids and IGF-I: a mechanism whereby the nutritional status can accelerate or put a ‘brake’ on the tempo of pubertal development. Subjects born small for gestational age (SGA) who show rapid postnatal weight gain, are at increased risk of insulin resistance, obesity, and early pubertal development. The high insulin levels during puberty may accelerate maturation leading to reductions in adult stature. Metformin has been shown to slow pubertal development, and may even lead to gains in final height. The abnormal body composition of these children, demonstrated by increased fat mass and reduced lean body mass, which is associated with adverse cardiovascular risk profiles, can also be reversed with insulin sensitisation.

In girls, the sequence of low birth weight, catch up growth, may lead to exaggerated adrenarche and precocious pubarche, with risks for the subsequent development of ovarian hyperandrogenism. This may be prevented by early intervention with Metformin. In post-menarchal subjects with ovarian hyperandrogenism, the addition of low-dose Flutamide to Metformin therapy may be more effective in preventing progression to PCOS. It is still to be determined whether insulin sensitisation during puberty in subjects at risk will result in permanent protection. Whereas, early studies with Metformin and Flutamide suggested that signs and symptoms recur with cessation of therapy, in a recent study of younger SGA children, early Metformin therapy resulted in continued benefits after treatment was stopped.

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