Insulin-Like Growth Factor Dysregulation Both Preceding and Following Type 1 Diabetes Diagnosis.

Abstract

Insulin-like growth factors (IGFs), specifically IGF1 and IGF2, promote glucose metabolism, with their availability regulated by IGF-binding proteins (IGFBPs). We hypothesized that IGF1 and IGF2 levels, or their bioavailability, are reduced during type 1 diabetes development. Total serum IGF1, IGF2, and IGFBP1-7 levels were measured in an age-matched, cross-sectional cohort at varying stages of progression to type 1 diabetes. IGF1 and IGF2 levels were significantly lower in autoantibody (AAb)+ compared with AAb- relatives of subjects with type 1 diabetes. Most high-affinity IGFBPs were unchanged in individuals with pre-type 1 diabetes, suggesting that total IGF levels may reflect bioactivity. We also measured serum IGFs from a cohort of fasted subjects with type 1 diabetes. IGF1 levels significantly decreased with disease duration, in parallel with declining β-cell function. Additionally, plasma IGF levels were assessed in an AAb+ cohort monthly for a year. IGF1 and IGF2 showed longitudinal stability in single AAb+ subjects, but IGF1 levels decreased over time in subjects with multiple AAb and those who progressed to type 1 diabetes, particularly postdiagnosis. In sum, IGFs are dysregulated both before and after the clinical diagnosis of type 1 diabetes and may serve as novel biomarkers to improve disease prediction.

• Authors: Melanie R Shapiro, Clive H Wasserfall, Sean M McGrail, Amanda L Posgai, Rhonda Bacher, Andrew Muir, Michael J Haller, Desmond A Schatz, Johnna D Wesley, Matthias von Herrath, William A Hagopian, Cate Speake, Mark A Atkinson, Todd M Brusko
• Journal: Diabetes (Diabetes) Vol. 69 Issue 3 Pg. 413-423 (03 2020) ISSN: 1939-327X [Electronic] United States
• PMID: 31826866 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 by the American Diabetes Association.

Chemical References

• Autoantibodies
• IGF1 protein, human
• IGF2 protein, human
• Insulin-Like Growth Factor Binding Proteins
• Insulin-Like Growth Factor I
• Insulin-Like Growth Factor II

Topics

• Adolescent
• Adult
• Autoantibodies (immunology)
• Child
• Cohort Studies
• Cross-Sectional Studies
• Diabetes Mellitus, Type 1 (diagnosis, immunology, metabolism)
• Disease Progression
• Female
• Humans
• Insulin-Like Growth Factor Binding Proteins (metabolism)
• Insulin-Like Growth Factor I (metabolism)
• Insulin-Like Growth Factor II (metabolism)
• Male
• Prediabetic State (immunology, metabolism)
• Time Factors
• Young Adult