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. Copyright © 1999 John Wiley & Sons, Ltd.

Physiology and pathophysiology of IGFBP-1 and IGFBP-2 – Consensus and dissent on metabolic control and malignant potential

“…In obese subjects without T2DM, IGFBP-2 levels were reduced and became further reduced in those patients that also had T2DM. As a point of interest, in T1DM subjects, IGFBP-2 was actually increased [57], as also reported by others in T1DM [58] and diabetic retinopathy [59], suggesting that T1DM and T2DM each have a unique impact on IGFBP-2 levels, perhaps related to differences in insulin sensitivity. Low circulating levels of IGFBP-2 have also been reported in lifestyle-related childhood obesity (with normal growth in spite of reduced GH secretion) and pre-pubertal obese subjects [60].…”

“…abnormal low IGFBP-2 leading to abnormal elevated free IGF-I) and in turn, IGFBP-2 contribution to maintenance of metabolic functions. A study by Frystyk et al [57], investigated potential alterations in the GH/IGF axis following overnight fasting in matched groups of lean subjects, obese subjects with or without T2DM, and subjects with T1DM. In obese subjects without T2DM, IGFBP-2 levels were reduced and became further reduced in those patients that also had T2DM.…”

Association of diabetes with mammographic breast density and breast cancer in the Minnesota breast cancer family study

“…There are few studies that have examined IGF-I levels in type II diabetes, but recent prospective epidemiologic studies suggest that higher IGF-I levels may actually lower diabetes risk [48,49]. One study that compared obese diabetics, obese non-diabetics, and lean controls, found that serum IGF-I were elevated among obese women with and without type II diabetes, although only the difference between non-diabetics and controls achieved statistical significance [50]. It is interesting to note that obesity increases risk of diabetes and post-menopausal breast cancer, but is inversely associated with density and pre-menopausal breast cancer.…”

Growth hormone receptor modulators

“…In contrast, high levels of GHBP are associated with hyperinsulinaemia and obesity, with GHBP falling significantly in the obese after weight loss, with normalization of insulin levels [84,85]. GHBP levels correlate significantly with fat mass, and because adipocytes express GHRs, it is possible that elevated GHBP levels simply reflect an increase in fat mass [84].…”