Journal
DIABETES
Volume 69, Issue 3, Pages 413-423Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db19-0942
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Funding
- National Institutes of Health [F31 DK117548, T32 DK108736, URL1TR001427, P01 AI42288, R01 DK106191]
- National Institute of Diabetes and Digestive and Kidney Diseases-supported Human Islet Research Network [RRID:SCR_014393, UC4 DK104216-01]
- Children's Miracle Network
- JDRF [3-SRA-2016-209-Q-R]
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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 beta-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.
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