FREE AND TOTAL INSULIN-LIKE-GROWTH-FACTOR-I (IGF-I), IGF-BINDING PROTEIN-1 (IGFBP-1), AND IGFBP-3 AND THEIR RELATIONSHIPS TO THE PRESENCE OF DIABETIC-RETINOPATHY AND GLOMERULAR HYPERFILTRATION IN INSULIN-DEPENDENT DIABETES-MELLITUS

The existing literature on serum insulin-like growth factor I (IGF-I) levels in insulin-dependent diabetes mellitus (IDDM) is conflicting. F ree IGF-I may have greater physiological and clinical relevance than t otal IGF-I. Recently, a validated method has been developed to measure free IGF-I levels in the circulation. Serum free and total IGF-I, IGF -binding protein-1 (IGFBP-1), and IGFBP-3 levels were measured in 56 i nsulin-treated IDDM patients and 52 healthy sex- and age-matched contr ols. Diabetic retinopathy was established by direct fundoscopy. In 54 IDDM patients, the glomerular filtration rate (GFR) and effective rena l plasma flow were calculated from the clearance rate of [I-125]iothal amate and [I-131]iodohippurate sodium. Fasting free IGF-I, total IGF-I , and IGFBP-3 levels were significantly lower in IDDM patients than in age-and sex-matched healthy controls (free IGF-I, P < 0.005; total IG F-I, P < 0.001; IGFBP-3, P = 0.001), whereas IGFBP-1 levels were highe r (P < 0.001). In IDDM subjects, decreases in free IGF-I, total IGF-I, and IGFBP-3 levels with age were observed (free IGF-I, r = -0.27 and P = 0.05; total IGF-I, r = -0.52 and P < 0.001; IGFBP-3, r = -0.37 and P = 0.005). Free IGF-I was inversely related to fasting glucose in ID DM subjects (r = -0.35; P = 0.01), whereas the relationship between to tal IGF-I and fasting glucose did not reach significance (r = -0.27; P = 0.06). Age-adjusted free IGF I levels were significantly higher (P < 0.05) in IDDM subjects with retinopathy than in subjects without ret inopathy after adjustment for age. Total IGF-I and IGFBP-3 levels were positively related to GFR (total IGF-I, r = 0.35 and P < 0.05; IGFBP- 3, r = 0.28 and P < 0.05). Both of these differences lost significance after adjustment for age. Free IGF-I, total IGF-I, and IGFBP-3 levels were lower and IGFBP-1 levels were higher in insulin-treated IDDM sub jects compared to those in age-and sex-matched controls. Free IGF-I, t otal IGF-I, and IGFBP-3 levels decreased significantly with age in IDD M subjects. Age-adjusted free IGF-I levels in subjects with diabetic r etinopathy were higher than those in subjects without diabetic retinop athy. Total IGF-I and IGFBP-3 levels were positively related to GFR in IDDM subjects, but these relations were lost after adjustment for age . Measurement of serum free IGF-I levels in IDDM subjects did not have clear advantages compared to that of total IGF-I, IGFBP-1, and IGFBP- 3 levels. Serum IGF-I and IGFBPs reflect their tissue concentrations t o a various degree. Consequently, extrapolations concerning the pathog enetic role of the IGF/IGFBP system in the development of diabetic com plications at the tissue level remain speculative.