IGF-binding proteins in type-1 diabetes are more severely altered in the presence of complications

Ashok Kumar Sharma, Sharad B Purohit, Shruti Sharma, Shan Bai, Wenbo Zhi, Sithara Raju Ponny, Diane Hopkins, Leigh Steed, Bruce Bode, Stephen W. Anderson, Jin-Xiong She

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Article number2
JournalFrontiers in Endocrinology
Volume7
Issue numberJAN
DOIs
StatePublished - Jan 1 2016

Keywords

  • Diabetes mellitus
  • Diabetic complications
  • IGF-1
  • IGF-binding proteins
  • IGFBP
  • Insulin-like growth factor 1
  • Type 1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism

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