Circulating levels of free insulin-like growth factors in obese subjects: the impact of type 2 diabetes.
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.
Frystyk
J
J
Institute of Experimental Clinical Research, Medical Research Laboratories and Medical Department M, Aarhus University Hospital, Aarhus, Denmark. jan@frystyk.dk
Skjaerbaek
C
C
Vestbo
E
E
Fisker
S
S
Orskov
H
H
D000704:Analysis of Variance; D015992:Body Mass Index; D001835:Body Weight; D003920:Diabetes Mellitus / Q000097:blood*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood*; D012016:Reference Values; D012044:Regression Analysis
D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II