Advanced glycosylation end products (AGEs), insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 (IGFBP-3) in patients with type 2 diabetes mellitus.

Abstract

Advanced glycosylation end product (AGE) formation is a major mechanism for the development of complications in diabetes, and the possible roles of insulin-like growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) are not clearly established. We examined the associations of AGEs, free IGF-I and IGFBP-3 in Type 2 diabetes mellitus (DM) patients under diverse conditions. In a cross-sectional design we studied 110 subjects (67 women and 43 men): non-diabetic controls in group 1, (n = 15) and diabetes patients as follows: group 2, without complications (n = 25); group 3, with chronic complications (n = 25); group 4, with acute or chronic infections (n = 24); group 5, hospitalized for reasons unrelated to diabetes (n = 9); group 6, with end-stage renal disease (ESRD) (n = 12). AGEs were determined by a spectrofluorometric method (HPLC). Insulin and IGFBP-3 were measured by RIA and free IGF-1 with an IRMA method. AGEs were 13-fold higher in patients with ESRD (p<0.001), and lower in healthy individuals. Free IGF-1 was lower in the patients with complications (p = 0.017), with infections (p = 0.006) and hospitalized (p = 0.04). IGFBP-3 was higher in hospitalized patients (p=0.017). AGEs were associated with free IGF-1 (r = 0.41, p = 0.04) in the group with complications, and with HbA(1c) (r = -0.90, p = 0.002) in hospitalized patients. In the total group, free IGF-1 (r = -0.25, p = 0.008), and IGFBP-3 (r = -0.22, p = 0.021) were associated with HbA(1c). We concluded that AGEs were markedly increased in diabetic patients with ESRD, IGF-1 was decreased in patients with infections and hospitalized, and was negatively associated with HbA(1c). IGFBP-3 was increased in hospitalized patients, with higher levels in patients with long bone fractures. A complex interaction of humoral factors may participate in the acceleration of complications of diabetes.