Insulin-Like Growth Factor-1 and Its Binding Proteins, IGFBP-1 and IGFBP-3, in Adolescents with Type-1 Diabetes mellitus and Microalbuminuria

Abstract

Background/Aims: Numerous clinical and experimental studies suggest that growth factors may contribute to the development of diabetic microvascular complications. The aim of the study was to test the hypothesis that in adolescents with type-1 diabetes mellitus and microalbuminuria (MA) there are specific disorders of serum insulin-like growth factor-1 (IGF-1) and concentrations of its binding proteins, IGFBP-1 and IGFBP-3, that could be of importance in the pathogenesis of microvascular diabetic complications. Methods: 25 adolescents with MA, 24 adolescents with diabetes without complications, and 17 controls were examined. There were no differences with regard to age, puberty stage, HbA1c and body mass index between the groups examined. Two of the patients in the first group also had diabetic retinopathy. Serum fasting concentrations of IGF-1 and overnight urine albumin concentrations were measured by radioimmunoassay, IGFBP-1 and IGFBP-3 concentrations by immunoradiometric assay and HbA1c by high-performance liquid chromatography methods. Diabetic patients were examined by an experienced ophthalmologist and neurologist. The data were analyzed using Kruskal-Wallis ANOVA and multiple regression analysis. Results: Significantly lower IGF-1 concentrations were found in adolescents with diabetes and MA compared to diabetic patients without complications and healthy contemporaries. IGFBP-1 concentrations were significantly higher and IGFBP-3 concentrations were statistically lower in diabetic patients with MA than in patients without complications. Conclusions: The IGF-IGFBP system is deranged in adolescents with type-1 diabetes mellitus and MA. Our results suggest the participation of circulating IGFBP-1 in the origin of diabetic complications. It could be also possible that IGFBP-3 takes part in the protection from them.

Insulin-Like Growth Factor Binding Proteins in Autoimmune Diseases

“…It's also a biomarker for diabetic retinopathy in T1DM but not T2DM patients (54). Serum IGFBP2 levels were also reported as an increased biomarker in T1DM (53, 55). In a recent study, Zhi et al used a proteomic approach to identify IGFBP2 as a potential diagnostic biomarker for T1DM (56).…”

“…Besides being a diagnostic marker, serum IGFBP1 level was a good indicator of complications related to T1DM. In T1DM patients complicated with microalbuminuria, serum IGFBP1 level has been reported to be significantly increased (53). It's also a biomarker for diabetic retinopathy in T1DM but not T2DM patients (54).…”

Differential control of muscle mass in type 1 and type 2 diabetes mellitus

“…However, studies performed in murine models show that alterations in other signaling pathways can also contribute to this loss. First, circulating IGF-1 levels are reduced in type 1 diabetes patients [97,98]. IGF-1 is an anabolic factor for skeletal muscle and is involved in the regulation of skeletal muscle mass [99].…”

Immunological Risk Factors for the Development and Progression of Diabetic Retinopathy

“…Interestingly, the same group of children had raised VEGF levels in serum and the longer the duration of the disease, the higher were the levels (with maximum levels in patients with diabetes for over 10 years) (Chiarelli et al, 2000;Santilli et al, 2001;Peczyńska et al 2004;Zorena et al, 2009). Also much lower IGF-I concentrations were found in adolescents with microangiopathy compared to diabetic patients without complications and healthy children (Wedrychowicz et al, 2005). However, IGFBP-1 levels in serum were much higher whereas IGFBP-3 were lower in patients with microangiopathy compared to those without complications.…”