Insulin secretion and sensitivity in GH deficient children at the end of rhGH therapy and after 1 year of follow-up: influences of d3GH receptor polymorphism on metabolic parameters
V. Agarla, F. Prodam, S. Savastio, A. Petri, C. Balossini, R. Ricotti, G. Genoni, G. Aimaretti, G. Bona & S. Bellone
Introduction: A rise in serum insulin levels during GH therapy is reported. Insulin resistance is a risk factor for type 2 diabetes, atherosclerosis, dyslipidemia, and hypertension. Few data describe insulin secretion and sensitivity after the end of GH therapy in children.
Methods: Aim of our study was to evaluate changes in insulin secretion and sensitivity in 24 children with isolated GHD at 3 times: i) during the last year of therapy (T0); ii) 6 months (T6) and iii) 12 months (T12) after stopped therapy. We measured glucose and insulin levels at fasting and after an oral glucose tolerance test (OGTT). Insulin resistance and sensitivity were estimated with classical indexes. Disposition index (DI) and insulinogenic index (INS) were also evaluated. The presence (Del) or absence (Ndel) of exon 3 deletion in the GH receptor was investigated (GHD: 4 Del, 16 Ndel). They were compared with 30 healthy puberty matched subjects.
Results: No subjects showed dysglycemia or hypertension. Fasting insulin, insulin and glucose levels at each point after OGTT were progressively lower at T6 and T12 compared to T0 (P<0.001). HOMA-IR and HOMA2 indexes were higher, and Matsuda and QUICKI indexes were lower at T0 respect to T6 and T12 (P<0.01). All the metabolic parameters were similar to controls at T12. INS and DI progressively decreased unexpectedly only in GHD Ndel arriving to values lower at T12 than NW (P<0.05). No alterations were found in GHD Del.
Conclusions: Insulin sensitivity decreased during rhGH therapy without the onset of dysglycemia and was associated with a compensatory insulin secretion and a reduction in DI only in GHD Ndel. Insulin and glucose secretion progressively restored after stopping treatment being similar to controls in the next 12 months. The presence or absence of exon 3 deletion, could affect some metabolic effects of rhGH in GHD children.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.