RELATIONSHIP BETWEEN NONENZYMATIC GLYCOSYLATION AND CHANGES IN SERUM INSULIN-LIKE GROWTH-FACTOR-I (IGF-1) AND IGF-BINDING PROTEIN-3 LEVELS IN PATIENTS WITH TYPE-2 DIABETES-MELLITUS

The possible occurrence of increased non-enzymatic glycosylation of se rum insulin-like growth factor binding protein-3 (IGFBP-3) in vivo and the changes that would simultaneously occur in serum levels of IGFBP- 3 and insulin-like growth factor-1 (IGF-I) were investigated. We measu red levels of IGF-I and IGFBP-3 and the degree of glycation of total s erum protein and IGFBP-3, in serum samples obtained from patients with poorly controlled noninsulin-dependent diabetes (type 2) and from age -matched non-diabetic controls. Type 2 diabetic patients had significa ntly higher glycated serum protein (GlyP) levels. GlyP significantly c orrelated with age in the control (r = 0.315. P<0.05) but not in the t ype 2 diabetes group. Control and diabetic subjects had comparable ser um IGF-I levels and in both groups IGF-I levels tended to decrease wit h age (r = -0.567, P<0.001 and r = -0.465, P<0.05 for control and type 2 diabetic subjects, respectively). In the type 2 diabetes group, IGF -I levels showed a negative correlation with serum GlyP values (r = -0 .476, P<0.05). Type 2 dia betic and control patients had comparable se rum IGFBP-3 levels, which were significantly higher in diabetic patien ts in the older age subgroups. A negative correlation was found betwee n IGFBP-3 levels and age in the control (r = -0.705, P<0.001) and in t he type 2 diabetes groups (r = -0.463, P<0.05). A significant negative correlation was found between IGFBP-3 levels and GlyP in control (r = -0.449, P<0.002) but not in type 2 diabetic subjects. The mean glycat ed IGFBP-3 (GlyIGFBP-3) levels were higher in the oldest type 2 diabet ic patients. In these patients, GlyIGFBP-3 was negatively associated w ith IGF-I levels (r = -0.447, P<0.05). The IGF-I/IGFBP-3 molar ra tio was significantly reduced in the 46-60-year-old type 2 diabetic group, whereas the IGF-I/IGFBP-3 ratio was positively and significantly corr elated with GlyP levels only in the control group (r = 0.489, P<0.01). Our results show that: a) increased non-enzymatic glycosylation of IG FBP-3 occurs in vivo; and b) this effect is accompanied by an increase in IGFBP-3 levels. These results suggest that the IGF-I/IGFBP-3 syste m is another target for the metabolic derangements of type 2 diabetes. Its alterations might play a role in diabetic complications.