Elevated plasma insulin-like growth factor binding protein-1 levels in Type 1 (insulin-dependent) diabetic patients with peripheral neuropathy

Previous studies have suggested that nerve regeneration may be defective in patients with diabetic polyneuropathy. Since insulin-like growth factor I (IGF-I) has been shown to stimulate nerve regeneration, and IGF binding protein-1 is acutely regulated by plasma insulin we have investigated the relationships between plasma IGF-I. IGFBP-1, glucose and insulin in Type 1 (insulin-dependent) diabetic patients with peripheral polyneuropathy. Plasma samples were taken at hourly intervals over an 11-h period (08.00-19.00 hours) in order to characterise secretory profiles for 15 Type 1 diabetic patients (eight neuropathic and seven non-neuropathic) and eight non-diabetic control subjects. In the non-diabetic subjects, mean plasma IGF-I levels were stable throughout the 11-h period with a range of 97 μg/l-169 μg/l. In contrast, mean plasma IGFBP-1 levels declined steadily from a high level of 1.99 μg/l at 08.00 hours to approximately one half (0.86μg/1) at 15.00 hours. Comparison of areas under the curves revealed significant negative correlations between IGFBP-1 and glucose (-0.88, p = 0.01). IGFBP-1 and insulin (-0.75, p = 0.016), and IGFBP-1 and IGF-I (-0.68, p = 0.03). A significant positive correlation was found between insulin and IGF-I (+ 0.89, p = 0.001). The diabetic patients had markedly elevated plasma IGFBP-1 levels (area under curve, p = 0.01) and lower plasma IGF-1 levels (p = 0.033) even though these patients were hyperinsulinaemic throughout the study period. The neuropathic diabetic patients had grossly elevated IGFBP-1 levels (X̄ = 40 μg/l at 08.00 hours) which were significantly higher (area under curve, p = 0.05) than in patients without neuropathy (X̄ = 15 μg/l at 08.00 hours). However, plasma levels of insulin and IGF-I in neuropathic and non-neuropathic subjects were similar, suggesting that the regulation of IGFBP-1 is more resistant to insulin in the neuropathic patients. In contrast to the non-diabetic subjects comparison of area under curve values revealed no positive correlation between insulin and IGF-I or negative correlations between IGF-I and IGFBP-1, and IGFBP-1 and glucose. We conclude that in Type 1 diabetes the relationships between plasma glucose, insulin. IGF-I and IGFBP-1 are clearly abnormal, and these abnormalities are more pronounced in patients with peripheral neuropathy.