Snowhite_et_al._Supplemental_Material.pdf (413.64 kB)
Download fileBaseline Assessment of Circulating microRNAs Near Diagnosis of Type 1 Diabetes Predicts Future Stimulated Insulin Secretion
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posted on 2020-12-04, 17:21 authored by Isaac Snowhite, Ricardo Pastori, Jay Sosenko, Shari Messinger Cayetano, Alberto PuglieseType 1 diabetes is an autoimmune disease resulting
in severely impaired insulin secretion. We
investigated whether circulating microRNAs (miRNAs) are associated with residual
insulin secretion at diagnosis and predict the severity of its future decline. We
studied 53 newly diagnosed subjects enrolled in placebo groups of TrialNet
clinical trials. We measured serum levels of 2,083 miRNAs using RNAseq
technology, in fasting samples from the baseline visit (<100 days from
diagnosis), during which residual insulin secretion was measured with a mixed
meal tolerance test (MMTT). Area under the curve (AUC) C-peptide and peak
C-peptide were stratified by quartiles of expression of 31 miRNAs. After
adjustment for baseline C-peptide, age, BMI and sex, baseline levels of miR-3187-3p,
miR-4302, and the miRNA combination of miR-3187-3p/miR-103a-3p predicted
differences in MMTT C-peptide AUC/peak levels at the 12-month visit; the
combination miR-3187-3p/miR-4723-5p predicted proportions of subjects
above/below the 200 pmol/L clinical trial eligibility threshold at the 12-month
visit. Thus, miRNA assessment at
baseline identifies associations with C-peptide and stratifies subjects for future
severity of C-peptide loss after 1 year. We suggest that miRNAs may be useful
in predicting future C-peptide decline for improved subject stratification in
clinical trials.