Background: The increased risk for development of type 2 diabetes mellitus (T2DM) in adults with growth hormone deficiency (GHD) has been attributed to insulin resistance arising from increased visceral fat accumulation and the putative effects of low insulin-like growth factor I (IGF-I) levels on pancreatic β-cell mass and insulin secretion. Failure of GH replacement to reverse these abnormalities may reflect nonphysiological GH replacement or inability of the β-cell to recover. Methods and Results: We have demonstrated in normal subjects and in those with GHD that very low doses of GH can improve postabsorptive insulin sensitivity in direct relation to increased free IGF-I, reduce fasting glucose levels and potentially improve β-cell secretory capacity. Conclusions: These low doses of GH should prevent the development of T2DM in adult subjects, but this needs to be confirmed by long-term studies.

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