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Circulating MicroRNAs as Predictors of Beta Cell Function in Youth-onset Type 2 Diabetes: The TODAY Study
Dakota Redling1, Shannon Bialak1, Laure El Ghormli2
1University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
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 [hemoglobin A1c (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 microRNA (miRNA) species associated with a 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, 4 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 < .05). Increased levels of miRNA-155 [odds ratio (OR): 1.2, 95% confidence interval (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: .4-.8) were associated with oDI decline. miRNA-122 was negatively correlated with C-peptide oDI at baseline and 24 months (R = 0.22, P < .01 and R = 0.19, P < .01, respectively) and positively correlated with proinsulin at baseline, 24, and 60 months (R = 0.26, P < 0.01, R = 0.26, P < .01, R = 0.18, P < .01, respectively).
Conclusion:
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.
Insights
Specific microRNAs (miRNAs) are linked to declining beta cell function in youth with type 2 diabetes. These circulating miRNAs may indicate early dysfunction and aggressive disease progression.
Area of Science:
- Endocrinology
- Molecular Biology
- Genetics
Background:
- Type 2 diabetes in adolescents is often aggressive, with many experiencing poor glycemic control.
- The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study revealed significant beta cell dysfunction in participants.
- Identifying biomarkers for early beta cell decline is crucial for understanding disease progression.
Purpose of the Study:
- To identify circulating microRNAs (miRNAs) associated with a decline in beta cell function in adolescents with type 2 diabetes.
- To explore the relationship between specific miRNAs and treatment failure in the TODAY study cohort.
Main Methods:
- Analysis of 17 miRNAs from 365 participants in the TODAY study using NanoString nCounter Human v3 miRNA Panel and polymerase chain reaction.
- Longitudinal sample collection at baseline, 24, 60, 96, and 120 months.
- Statistical analysis using backward selection to identify predictive miRNAs for beta cell function decline.
Main Results:
- Three baseline miRNAs significantly predicted a decline in C-peptide oral disposition index (oDI).
- Increased levels of miRNA-155 and miRNA-130b were associated with oDI decline.
- Decreased levels of miRNA-126 and altered levels of miRNA-122 were correlated with reduced beta cell function and increased proinsulin.
Conclusions:
- Specific circulating miRNAs are associated with beta cell dysfunction in youth-onset type 2 diabetes.
- These miRNAs may serve as biomarkers for early detection of beta cell decline.
- Findings suggest miRNAs play a role in the cellular mechanisms underlying aggressive youth-onset type 2 diabetes.
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