Insulin-like growth factor binding protein-1 in NIDDM: Relationship with the insulin resistance syndrome

Abstract

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. DESIGN: 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.