Combined GH and IGF1 therapy
D B Dunger
Epidemiological studies indicate that low circulating concentrations of IGF1 are associated with increased adult risk for the development of type 2 diabetes (T2D) and the metabolic syndrome (MS). Although comparable epidemiological data relating to GH concentrations are lacking, GH deficiency (GHD) is associated with many of the features of the MS and increased T2D risk. These data indicate that reduced activity of the GH/IGF1 axis is a risk factor for MS yet IGF1 and GH have contrasting effects on metabolism. IGF1 is an insulin sensitisor and low levels are associated with insulin resistance. Although it has little direct effect on lipid metabolism, low IGF1 conditions are commonly associated with hyperinsulinaemia which is associated with visceral fat accumulation. GH has potent lipolytic actions and it is an insulin antagonist: GHD being associated with visceral adiposity and insulin resistance. Both GH and IGF1 may have important roles in the maintenance of beta cell mass and insulin secretion. Thus, there is a clear rational for combined GH and IGF1 therapy in these subjects.
rhIGF1 therapy has been shown to improve insulin sensitivity in subjects with T1D and T2D and there are preliminary data to indicate it could improve glucose tolerance in subjects with MS. Low dose GH therapy has been explored in adult subjects with the MS and it leads to reductions in visceral adiposity but with variable effects on insulin sensitivity and other elements of the MS. Elevations in FFA and ectopic deposition may be a limiting factor. Combined GH/IGF1 therapy appears attractive as it could lead to reduction in visceral fat whilst maintaining insulin sensitivity: both agents having the potential to improve beta cell function. There are limited animal data but human studies should be encouraged. Such studies will need to take particular care to identify potential benefits of normalisation of the GH/IGF1 axis and avoid perceived risks relating to excess GH/IGF1 activity and cancer risk.