AUTHOR=Sharma Ashok , Purohit Sharad , Sharma Shruti , Bai Shan , Zhi Wenbo , Ponny Sithara Raju , Hopkins Diane , Steed Leigh , Bode Bruce , Anderson Stephen W. , She Jin-Xiong TITLE=IGF-Binding Proteins in Type-1 Diabetes Are More Severely Altered in the Presence of Complications JOURNAL=Frontiers in Endocrinology VOLUME=7 YEAR=2016 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2016.00002 DOI=10.3389/fendo.2016.00002 ISSN=1664-2392 ABSTRACT=Aims

Reduced levels of free and total insulin-like growth factor 1 (IGF-I) have been observed in type-1 diabetes (T1D) patients. The bioavailability of IGF-I from the circulation to the target cells is controlled by multifunctional IGF-binding proteins (IGFBPs). The aim of this study was to profile serum IGFBPs in T1D and its complications.

Design

We measured the IGFBP levels in 3662 patient serum samples from our ongoing Phenome and Genome of Diabetes Autoimmunity (PAGODA) study. IGFBP levels of four different groups of T1D patients (with 0, 1, 2, and ≥3 complications) were compared with healthy controls.

Results

Three serum IGFBPs (IGFBP-1, -2, and -6) are significantly higher in T1D patients, and these alterations are greater in the presence of diabetic complications. IGFBP-3 is lower in patients with diabetic complications. Analyses using quintiles revealed that risk of T1D complications increases with increasing concentrations of IGFBP-2 (fifth quintile ORs: 18–60, p < 10−26), IGFBP-1 (fifth quintile ORs: 8–20, p < 10−15), and IGFBP-6 (fifth quintile ORs: 3–148, p < 10−3). IGFBP-3 has a negative association with T1D complications (fifth quintile ORs: 0.12–0.25, p < 10−5).

Conclusion

We found that elevated serum levels of IGFBP-1, -2, and -6 were associated with T1D, and its complications and IGFBP-3 level was found to be decreased in T1D with complications. Given the known role of these IGFBPs, the overall impact of these alterations suggests a negative effect on IGF signaling.