Circulating levels of free insulin-like growth factors in obese subjects: the impact of Type 2 diabetes

Abstract

BACKGROUND: Obese subjects show major abnormalities in the growth hormone (GH)/insulin-like growth factor (IGF) system. Furthermore, they are prone to develop Type 2 diabetes, but the impact of diabetes plus obesity on the GH/IGF system remains unknown. METHODS: We compared overnight fasting serum levels of free and total (extractable) IGF-I and -II, IGF-binding protein (IGFBP) -1, -2 and -3, and the high affinity GH-binding protein (GHBP) in matched groups of lean subjects (n=26) and obese subjects without (n=24) and with (n=29) Type 2 diabetes. Two groups (n=7) of healthy and Type 1 diabetic subjects were also studied. RESULTS: Non-diabetic obese subjects had increased free IGF-I and -II, total IGF-II, IGFBP-3 and GHBP, reduced IGFBP-1 and -2 (p<0.05), but normal total IGF-I, when compared to lean subjects. In obese Type 2 diabetics free IGF-I was insignificantly reduced by 9% (p=0.3), when compared to non-diabetic obese subjects. However, the concentration was not significantly elevated when compared to that of lean controls (p=0.13). Also IGFBP-1 and total IGF-I were normal in obese Type 2 diabetics, whereas free and total IGF-II and IGFBP-3 remained elevated to a similar extent as in simple obesity (p<0.05). In contrast, GHBP was further increased and IGFBP-2 further reduced in obese Type 2 diabetics (p<0.05). In Type 1 diabetics total IGF-I and -II, and IGFBP-3 were normal. In contrast, free IGF-I and -II and GHBP were markedly reduced, whereas IGFBP-1 and -2 were increased (p<0.05). CONCLUSIONS: Simple obesity was associated with marked changes in the GH/IGF system. Many of these abnormalities were unaffected by the concomitant presence of Type 2 diabetes (total IGF-I, free and total IGF-II and IGFBP-3). However, some changes became accentuated (GHBP and IGFBP-2), while others (free IGF-I and IGFBP-1) were no longer present. Notably, the impact of Type 1 diabetes on the GH/IGF system was clearly different from that of Type 2 diabetes.