Low Circulating Levels of Insulin-Like Growth Factor Binding Protein-1 (IGFBP-1) Are Closely Associated With the Presence of Macrovascular Disease and

The IGF system is increasingly implicated in the devel-opment of cardiovascular disease. The effects of circu-lating IGFs on the vasculature are largely modulated by IGFBPs, which control their access to cell-surface IGF receptors. IGFBP-1 has been proposed as the acute regulator of IGF bioavailability because of its metabolic regulation by glucoregulatory hormones. Posttransla-tional phosphorylation of IGFBP-1 significantly in-creases its affinity for IGF-I and therefore represents a further mechanism for controlling IGF bioavailability. We have therefore examined the IGF system and IGFBP-1 phosphorylation status, using specifically de-veloped immunoassays, in a cohort of 160 extensively characterized type 2 diabetic subjects on two occasions 12 months apart. Total IGFBP-1 (tIGFBP-1), which i