Circulating MicroRNAs as Predictors of Beta Cell Function in Youth-Onset Type 2 Diabetes: The TODAY study
Document Type
Journal Article
Publication Date
5-30-2024
Journal
The Journal of clinical endocrinology and metabolism
DOI
10.1210/clinem/dgae376
Keywords
Beta Cell Function; Youth-onset Type 2 Diabetes; miRNA
Abstract
AIMS: In the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study, an intervention trial followed by an observational phase, half the participants reached the primary outcome (HbA1c ≥ 8% for at least 6 months) within 4 years which was associated with a decrease in C-peptide oral disposition index (oDI). We aimed to identify circulating miRNA species associated with decline in beta cell function. METHODS: Following a preliminary survey of select participants using nCounter Human v3 miRNA Panel (NanoString Technologies), polymerase chain reaction analyses were carried out for 17 miRNAs from 365 participants from samples at baseline, 24, 60, 96, and 120 months. RESULTS: Using a backward selection approach, four baseline miRNA log2 fold changes independently predicted treatment failure; however, baseline HbA1c was higher in those with treatment failure. Three baseline miRNA log2 fold changes remained significant predictors of this C-peptide oDI decline ≥20% (p < 0.05). Increased levels of miRNA-155 (OR:1.2, 95%CI:1.1-1.4) and miRNA-130b (OR:1.3, 95%CI: 1.0-1.7) were associated with oDI decline, while decreased levels of miRNA-126 (OR:0.6, 95%CI: 0.4-0.8) were associated with oDI decline. miRNA-122 was negatively correlated with C-peptide oDI at baseline and 24-months (R = 0.22, p < 0.01 and R = 0.19, p < 0.01, respectively), and positively correlated with proinsulin, at baseline, 24-, and 60- months (R = 0.26, p < 0.01, R = 0.26, p < 0.01, R = 0.18, p < 0.01, respectively). CONCLUSIONS: The miRNA species associated with beta cell function are associated with alterations in cellular metabolism and apoptosis, suggesting that differences in baseline abundance may serve as circulating markers of beta cell dysfunction and provide potential mechanistic insights into the aggressive nature of youth-onset type 2 diabetes.
APA Citation
Redling, Dakota; Bialak, Shannon; El Ghormli, Laure; Chernausek, Steven D.; Jones, Kenneth; and Tryggestad, Jeanie B., "Circulating MicroRNAs as Predictors of Beta Cell Function in Youth-Onset Type 2 Diabetes: The TODAY study" (2024). GW Authored Works. Paper 4869.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/4869
Department
Biostatistics and Bioinformatics