Insulin-like growth factor binding proteins (IGFBPs) in serum and urine and IGFBP-2 protease activity in patients with insulin-dependent diabetes mellitus

Diabetes mellitus and glucose dysregulation have significant effects on the circulating level of insulin-like growth factor-I (IGF-I) and IGF binding proteins (IGFBPs), In the present study, serum and urine IGFBP (IGFBP-1, -2 , and -3) and serum IGF-I and -II levels were measured by radioimmunoassay (RIA) in 27 patients with type 1 diabetes aged 9 to 48 years compared with 9 healthy subjects aged 10 to 28 years. The patients were divided into 3 gr oups according to the amount of albumin excreted in 24 hours. The macroalbu minuria group (>500 mg/24 h) had elevated serum IGFBP-1 and -2 and decrease d IGF-I levels (P < .01 v normal controls). Serum IGFBP-3 and IGF-II were n ot different among the patient groups and controls (P > .05), The mean urin ary IGFBP-1 was decreased in all 3 patient groups compared with the control s (P < .05). Urinary IGFBP-2 and IGFBP-3 were increased in patients with ma croalbuminuria. Immunoblot analysis showed increased low-molecular-weight f ragments of urinary IGFBP-2 in the poorly controlled diabetics, and direct evidence for increased urinary IGFBP-2 proteolytic activity could be demons trated in both the microalbuminuric and macroalbuminuric groups. Low-molecu lar-weight fragments of urinary IGFBP-3 were also increased in both the mic roalbuminuric and macroalbuminuric groups, In conclusion, alterations of IG FBPs in urine and serum are related to metabolic control in diabetic patien ts, and there is an increase of urinary IGFBP-2 protease activity in poorly controlled diabetics. The changes in serum IGFBP concentrations (eg, incre ases in IGFBP-1 and IGFBP-2) may lead to alterations in the availability of IGF-I to peripheral tissues. Copyright (C) 2000 by W.B. Saunders Company.