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

• Published in: Diabetes (New York, N.Y.) Vol. 69; no. 3; pp. 413 - 423
• Main Authors: Shapiro, Melanie R., Wasserfall, Clive H., McGrail, Sean M., Posgai, Amanda L., Bacher, Rhonda, Muir, Andrew, Haller, Michael J., Schatz, Desmond A., Wesley, Johnna D., von Herrath, Matthias, Hagopian, William A., Speake, Cate, Atkinson, Mark A., Brusko, Todd M.
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.03.2020
• Subjects: Adolescent; Adult; Autoantibodies; Autoantibodies - immunology; Beta cells; Bioavailability; Biological activity; Child; Cohort Studies; Cross-Sectional Studies; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - diagnosis; Diabetes Mellitus, Type 1 - immunology; Diabetes Mellitus, Type 1 - metabolism; Diagnosis; Disease Progression; Female; Glucose metabolism; Humans; Insulin; Insulin-Like Growth Factor Binding Proteins - metabolism; Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Insulin-like growth factor II; Insulin-Like Growth Factor II - metabolism; Insulin-like growth factor-binding protein 1; Insulin-like growth factors; Male; Medical diagnosis; Pathophysiology; Prediabetic State - immunology; Prediabetic State - metabolism; Time Factors; Young Adult
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db19-0942

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.