Insulin-like growth factor binding protein-1 in NIDDM: relationship with the insulin resistance syndrome.
OBJECTIVE
In order to examine the role of insulin-like growth factors in the pathogenesis of accelerated macrovascular disease in noninsulin-dependent diabetes mellitus (NIDDM), we investigated the relationship between the insulin resistance syndrome and the IGF axis.


METHODS
Cross-sectional analysis of the relationship between insulin resistance syndrome variables and concentrations of IGF-1, IGF-2, IGFBP-1 and IGFBP-3 in 80 subjects with NIDDM.


RESULTS
After correcting for age, sex and body mass index, concentrations of IGFBP-1, correlated with those of HDL-cholesterol (r = 0.40; P < 0.001), triglycerides (r = -0.24; P = 0.04), insulin (r = -0.39; P < 0.001), intact proinsulin (r = -0.32; P = 0.006), des 31,32 proinsulin (r = -0.40; P = 0.001), and with insulin sensitivity (r = 0.38; P = 0.001) and PAI-1 activity (r = -0.24; P = 0.05); IGF-1 levels only correlated with those of HDL-cholesterol (r = -0.33; P = 0.005), and this was not explained by IGFBP-1 or insulin sensitivity. With additional correction for insulin, concentrations of IGFBP-1 still correlated with HDL-cholesterol (r = 0.40; P < 0.001), but not those of triglycerides or PAI-1 activity. There were no significant relationships between levels of IGF-2 and any of the variables investigated, and IGFBP-3 levels only correlated with those of total cholesterol (r = 0.24, P = 0.04).


CONCLUSIONS
In NIDDM, concentrations of IGFBP-1 are related to those of insulin, insulin sensitivity, serum lipoproteins and PAI-1 activity. The relationship between concentrations of IGFBP-1 and HDL-cholesterol is not explained by insulin. Concentrations of IGF-1 are linked to HDL-cholesterol, and this is not explained by levels of IGFBP-1. IGFBP-1 concentrations were related to PAI-1 activity, and this may be explained by insulin, which regulates the production of IGFBP-1 and PAI-1.
Mohamed-Ali
V
V
Centre For Diabetes and Cardiovascular Risk, University College London Medical School, UK. vmohamed@med.ucl.ac.uk
Pinkney
J H
JH
Panahloo
A
A
Cwyfan-Hughes
S
S
Holly
J M
JM
Yudkin
J S
JS
D000704:Analysis of Variance; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011384:Proinsulin / Q000097:blood; D011498:Protein Precursors / Q000097:blood; D012044:Regression Analysis
D008076:Cholesterol, HDL; D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D017395:Plasminogen Activator Inhibitor 1; D011498:Protein Precursors; C070703:proinsulin, des(31,32)-; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D011384:Proinsulin; D002784:Cholesterol