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

• Type of Material: Article
• Authors: Melanie R Shapiro, University of Florida; Clive H Wasserfall, University of Florida; Sean M McGrail, University of Florida; Amanda L Posgai, University of Florida; Rhonda Bacher, University of Florida; Andrew Muir, Emory University; Michael J Haller, University of Florida; Desmond A Schatz, University of Florida; Johnna D Wesley, Novo Nordisk Res Ctr; Matthias von Herrath, Novo Nordisk Res Ctr; William A Hagopian, Pacific Northwest Res Inst; Cate Speake, Virginia Mason; Mark A Atkinson, University of Florida; Todd M Brusko, University of Florida
• Language: English
• Date: 2020-03-01
• Publisher: AMER DIABETES ASSOC
• Publication Version: Final Published Version
• Copyright Statement: © 2019 by the American Diabetes Association.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.2337/db19-0942
• Title of Journal or Parent Work: DIABETES
• Volume: 69
• Issue: 3
• Start Page: 413
• End Page: 423
• Grant/Funding Information: Project support was provided by grants from the National Institutes of Health (F31 DK117548 to M.R.S., T32 DK108736 to M.A.A., Clinical and Translational Science Award URL1TR001427 to D.A.S., P01 AI42288 to M.A.A. and T.M.B., and R01 DK106191 to T.M.B.), the National Institute of Diabetes and Digestive and Kidney Diseases–supported Human Islet Research Network (RRID:SCR_014393, hirnetwork.org [UC4 DK104216-01 to D.A.S.]), the Children’s Miracle Network (to M.R.S. and M.J.H.), and JDRF (3-SRA-2016-209-Q-R to C.S.).
• Keywords: AGE; HORMONE; BETA-CELL FUNCTION; FACTOR AXIS; Endocrinology & Metabolism; Science & Technology; PANCREAS; AUTOANTIBODIES; FACTOR-I; Life Sciences & Biomedicine; PROGRESSION; RISK; IGF-I
• Research Categories: Health Sciences, Immunology; Health Sciences, Medicine and Surgery; Health Sciences, Pathology

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)1 compared with AAb2 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 AAb1 cohort monthly for a year. IGF1 and IGF2 showed longitudinal stability in single AAb1 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.