Relationship between non-enzymatic glycosylation and changes in serum insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 levels in patients with type 2 diabetes mellitus

Abstract

The possible occurrence of increased non-enzymatic glycosylation of serum 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 measured levels of IGF-I and IGFBP-3 and the degree of glycation of total serum 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 significantly higher glycated serum protein (GlyP) levels. GlyP significantly correlated with age in the control (r = 0.315, P < 0.05) but not in the type 2 diabetes group. Control and diabetic subjects had comparable serum IGF-I levels and in both groups IGF-I levels tended to decrease with 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 diabetic and control patients had comparable serum IGFBP-3 levels, which were significantly higher in diabetic patients in the older age subgroups. A negative correlation was found between IGFBP-3 levels and age in the control (r = -0.705, P < 0.001) and in the 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 glycated IGFBP-3 (GlyIGFBP-3) levels were higher in the oldest type 2 diabetic patients. In these patients, GlyIGFBP-3 was negatively associated with IGF-I levels (r = -0.447, P < 0.05). The IGF-I/IGFBP-3 molar ratio was significantly reduced in the 46-60-year-old type 2 diabetic group, whereas the IGF-I/IGFBP-3 ratio was positively and significantly correlated with GlyP levels only in the control group (r = 0.489, P < 0.01). Our results show that: a) increased non-enzymatic glycosylation of IGFBP-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 system is another target for the metabolic derangements of type 2 diabetes. Its alterations might play a role in diabetic complications.

Association of serum levels of IGF-I and IGFBP-1 with renal function in patients with type 2 diabetes mellitus

“…age and treatment with insulin) had the most significant impact on the serum IGF-I level. Specifically, serum IGF-I levels measured in type 2 diabetic patients were found to be decreasing with advancing age similar to a previous study by Cortizo et al [18]. Moreover, a lower level of IGF-I was observed in diabetic patients being treated with insulin than in those who were being treated with OAD.…”

Lack of relationship between glycemic control and bone mineral density in type 2 diabetes mellitus

“…Thus, it is possible that the association of DM with osteopenia represents one more aspect of the heterogeneity of this disorder. Type 2 DM is associated with obesity, hyperandrogenism, elevation of estrogen levels, normal IGFI, and frequently hyperinsulinemia, (15,31,32), which are factors that protect against the loss of bone mass. In contrast, type 1 DM is associated with insulinopenia, weight loss, low IGFI levels (15), and frequently with amenorrhea and hypoestrogenism, which are associated with osteopenia.…”

Posttranslational modifications of the insulin-like growth factor-binding protein 3 in patients with type 2 diabetes mellitus assessed by affinity chromatography

“…Naturally occurring isoforms of IGFBP-3 of approximately 40-45 kDa differ in the amount and the site of saccharide binding. In patients with DM a glycated IGFBP-3 was detected [9], and it was postulated to have an increased number of IGF-binding sites [12]. Increased proteolytic activity against IGFBP-3 was measured in these patients [13] and it seems to be related to glycosylation and/or glycation status [14].…”

“…Homologous peptides, insulin-like growth factors (IGFs), besides having glucose-lowering potential, have been suggested to play an important role in the progression of diabetic complications [9]. In the circulation, IGFs are bound to the IGF-binding proteins (IGFBPs) and 1-5% is free and physiologically active [10].…”