Endocrine Abstracts (2010) 24 OC1.5

Factors affecting changes in insulin sensitivity and insulin secretion during Growth Hormone treatment in children born small for gestational age

A Thankamony1, R B Jensen2, S O’Connell3, J M W Kirk4, M D C Donaldson5, Sten-A Ivarsson6, O Söder7, H Hoey3, A Juul2 & D B Dunger1

1Department of Paediatrics, University of Cambridge, Cambridge, UK; 2Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark; 3Department of Paediatrics, Trinity College, National Children’s Hospital, Dublin, Ireland; 4Birmingham Children’s Hospital, Birmingham, UK; 5Royal Hospital for Sick Children, Glasgow, UK; 6Department of Paediatrics, Malmö University Hospital, Malmö, Sweden; 7Karolinska University Hospital, Stockholm, Sweden.

Background: Individuals born Small for Gestational age (SGA) are at high risk of development of type 2 diabetes. Growth hormone (GH) therapy can also adversely affect glucose metabolism.

Aim: To explore the factors associated with changes in insulin sensitivity (IS) and insulin secretion during one year of GH treatment in children born SGA.

Methods: In the NESGAS clinical trial, we studied 82 (55♂) pre-pubertal children (age 3.9–9.9 years) born SGA who had failed to catch-up. Subjects underwent a short intravenous glucose tolerance test to measure acute insulin response (AIR), a marker of insulin secretion. HOMA was used to calculate IS and the disposition index gave an estimate of insulin secretion for the degree of IS. The measurements were repeated after 12 months of GH treatment (67 μg/kg/day).

Results: Following GH treatment, IS markedly decreased (209±117 vs 118±54 P<0.001). However, a compensatory rise in AIR (1455±813 vs 2431±1514, P<0.001) resulted in similar disposition index (3.07±1.69 vs 2.82±1.33, P=0.29). Fall in insulin sensitivity was related to increases in both IGF-I levels (r=−0.31, P=0.013) and height (r=−0.28, P=0.03). Rise in IGF-I levels predicted increases in AIR independent of height gains and changes in IS ((β=0.05 (CI: 0.01–0.09)). Furthermore, increases in the IGFI levels, not the height gains predicted AIR at one year of GH treatment, independent of IS (β=0.04 (0.02–0.07)). Birth weight, gender, age, and IGF-I levels and height before GH treatment were not related to changes in insulin sensitivity and insulin secretion.

Conclusion: We found that while markers of GH action were related to fall in IS during GH therapy, increases in IGFI levels were associated with improvement in insulin secretion. IGFI is a determinant of beta- cell function in animal models. Our findings suggest a role of IGFI response to GH, in modifying beta- cell function and glucose metabolism.