Diabetic retinopathy is associated with decreased serum levels of free IGF-I and changes of IGF-binding proteins

In patients with diabetic retinopathy, elevated serum levels of total circu lating insulin-like growth factor-1 (IGF-I) have been implicated as an impo rtant mediator of the disease. There is no study, however, measuring free I GF-1 levels in patients with diabetic retinopathy which mediate the biologi cal effects of IGF-I and are modulated by a complex system of six specific IGF binding proteins (IGFBPs) and several IGFBP proteases. To address the role of free IGF-I, we performed a cross-sectional study in 159 diabetes patients, among them 99 individuals with retinopathy (RP+; dia betes type 1/type 2: 41/58) and 60 without retinopathy (RP-; diabetes type 1/type 2: 22/38) and 110 age-matched healthy control subjects. Serum levels of both free and total IGF-I and IGFB-1 to -6 were determined by specific immunoassays. Free IGF-I levels were significantly lower in RP+ patients (1.1 +/- 0.1 ng/ ml) than in RP- patients (3.22 +/- 0.3 ng/ml, P<0.005). In contrast, RP+ pa tients showed higher serum levels of total IGF-1 (139.7 +/- 5.8 ng/ml) than RP- patients (116.3 +/- 8 ng/ml, P<0.05 vs RP+), which is consistent with previous reports. Type 1 diabetic patients with retinopathy showed signific antly higher levels of IGFBP-1 but lower levels of IGFBP-2, -3 and -6 than type 1 patients without retinopathy, Type 2 patients with retinopathy showe d lower levels of IGFBP-3 and -6, IGFBP-4 and -5 levels were not different between subgroups. Linear regression analysis revealed that free IGF-I leve ls correlated positively with IGFBP-3 and negatively with IGFBP-1. Furtherm ore, free IGF-I levels correlated negatively with HbA1c values, indicating that poor glycaemic control may contribute to a decreased IGF-I bioavailabi lity. In summary, type 1 as well as type 2 diabetics with retinopathy showed mark edly decreased levels of free IGF-1 which correlated with complex alteratio ns in IGFBPs and glycaemic control. (C) 2000 Harcourt Publishers Ltd.