Reduced insulin-like growth factor binding protein-1 (IGFBP-1) levels correlate with increased cardiovascular risk in noninsulin dependent diabetes mellitus (NIDDM)

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Abstract

IGF-I and -II levels are altered in patients with atherogenic lipid profiles and may contribute to the development of macrovascular disease in NIDDM. We examined cardiovascular risk factors, IGF-I, IGF-II and IGFBP-1 in 74 NIDDM patients analysed as a whole group and according to treatment type. IGF-I was not significantly associated with cardiovascular risk factors but IGF-II levels correlated positively with total and LDL cholesterol most markedly in the diet treated group (0.72, p<0.01 and 0.76, p<0.01 respectively). In the whole group reduced IGFBP-1 levels were significantly associated with factors known to increase cardiovascular risk: i.e. low HDL cholesterol (0.31, p<0.01) and elevated blood pressure (-0.35, p<0.01), BMI (-0.37, p<0.01), insulin (-0.29, p<0.01) and proinsulin (-0.24, p<0.01). In the treatment groups IGFBP-1 was lower in patients on diet alone (n=11, 42.6+/-11.6 mu g/l) and sulphonylurea+insulin (n=39, 53.2+/-7.6 mu g/l) relative to insulin treatment (n=24, 103.0+/-19, 7 mu g/l, p<0.05). The lower levels of IGFBP-1 were not due to a significant change in phosphorylation status from the highly phosphorylated circulating form since lesser and non-phosphorylated variants were undetectable in 53/74 patients. Multiple regression analysis revealed the best predictors of IGFBP-1 were BMI and MAP (R(2) = 0.2. p<0.001) and for blood pressure, IGFBP-1 and age (R(2) = 0.47, p<0.001). These findings indicate that in NIDDM patients low IGFBP-1 levels are associated with multiple factors predisposing to atherogenesis.

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