Persisting effects on fasting glucose levels and insulin sensitivity after 6 months of discontinuation of a very low-dose GH therapy in adults with severe GH deficiency.

OBJECTIVE: We recently reported that, in contrast to the standard GH (SGH) replacement dose titrated to normalize serum IGF-I levels, 12-month treatment with a fixed low GH dose (LGH) (0.1 mg/day) decreased fasting glucose levels and improved insulin sensitivity with little effect on body composition in severely GH-deficient adults. In this study, we have subsequently examined the effects after 6 months of discontinuation of these variable GH doses (LGH: n = 8; fixed dose 0.10 mg/day and SGH: n = 8; mean dose 0.50 mg/day) on glucose metabolism, body composition and other surrogate cardiovascular risk markers.

METHODS: Fasting insulin sensitivity using the homeostasis model assessment, and body composition using dual-energy X-ray absorptiometry scans were assessed at baseline, after 12 months of therapy (month 12) and after 6 months following discontinuation of therapy (month 18).

RESULTS: At month 12, the LGH decreased fasting glucose levels and improved insulin sensitivity without altering body composition, whereas the SGH improved body composition without modifying insulin sensitivity. Six months after discontinuation of the LGH treatment (month 18), fasting glucose levels remained decreased and the enhanced insulin sensitivity persisted. In contrast, after discontinuation of SGH treatment (month 18), body composition reverted to baseline without changes in either fasting glucose levels or insulin sensitivity. CONCLUSION In contrast to the SGH, the LGH induces effects on fasting glucose levels and insulin sensitivity, which persist after 6 months of discontinuation of therapy. The exact molecular mechanisms are unclear but may involve the modulation of hepatic and muscle insulin sensitivity, possibly by altering insulin and IGF-I receptor responsiveness and/or density.