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[Preprint]. 2024 Jan 16:rs.3.rs-3846347.
doi: 10.21203/rs.3.rs-3846347/v1.

MicroRNAs Associated with Metformin Treatment in the Diabetes Prevention Program

Kimberly A Lewis  1 , Benjamin Stroebel  1 , Li Zhang  1 , Bradley Aouizerat  2 , Aras Mattis  1 , Elena Flowers  1
Affiliations

MicroRNAs Associated with Metformin Treatment in the Diabetes Prevention Program

Kimberly A Lewis et al. Res Sq. .

Update in

Abstract

The Diabetes Prevention Program (DPP) randomized controlled trial demonstrated that metformin treatment reduced progression to type 2 diabetes (T2D) by 31% compared to placebo in adults with prediabetes. Circulating micro-ribonucleic acids (miRs) are promising biomarkers of T2D risk, but little is known about their associations with metformin regimens for T2D risk reduction. We compared the change in 24 circulating miRs from baseline to 2 years in a subset from DPP metformin intervention (n = 50) and placebo (n = 50) groups using Wilcoxon signed rank tests. Spearman's correlations were used to evaluate associations between miR change and baseline clinical characteristics. Multiple linear regression was used to adjust for covariates. The sample was 73% female, 17% Black, 13% Hispanic, and 50 ± 11 years. Participants were obese, normotensive, prediabetic, and dyslipidemic. Change in 12 miR levels from baseline to 2 years was significantly different in the metformin group compared with placebo after adjusting for multiple comparisons: six (let-7c-5p, miR-151a-3p, miR-17-5p, miR-20b-5p, miR-29b-3p, and miR-93-5p) were significantly upregulated and six (miR-130b-3p, miR-22-3p, miR-222-3p, miR-320a-3p, miR-320c, miR-92a-3p) were significantly downregulated in the metformin group. These miRs help to explain how metformin is linked to T2D risk reduction, which may lead to novel biomarkers, therapeutics, and precision-health strategies.

Keywords: diabetes prevention program; epigenetics; metformin; microRNA; post-transcriptional regulation; type 2 diabetes.

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Conflict of interest statement

Additional Declarations: The authors declare no competing interests

Figures

Figure 1
Figure 1
Box Plots of Mean Change in MicroRNA Expression Level by Treatment Group for MicroRNAs Significant After Adjustment for Multiple Comparisons Note: MiR-93a--5p was borderline statistically significant after adjusting for multiple comparisons (FDR=0.059).
Figure 2
Figure 2
Correlation plot featuring only miRNAs significant after adjustment for multiple comparisons and baseline clinical characteristics. Cells with p > 0.05 are omitted. Color coding represents the spearman’s rank correlation coefficient.
See this image and copyright information in PMC

References

    1. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2020. Atlanta, GA: Centers for Disease Control and Prevention, U.S. Dept of Health and Human Services; 2020.
    1. Aroda VR, Knowler WC, Crandall JP, Perreault L, Edelstein SL, Jeffries SL, Molitch ME, Pi-Sunyer X, Darwin C, Heckman-Stoddard BM, Temprosa M, Kahn SE, Nathan DM; Diabetes Prevention Program Research Group. Metformin for diabetes prevention: insights gained from the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study. Diabetologia. 2017;60(9):1601–1611. doi: 10.1007/s00125-017-4361-9 - DOI - PMC - PubMed
    1. Diabetes Prevention Program Research Group. Long-term Effects of Metformin on Diabetes Prevention: Identification of Subgroups That Benefited Most in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study. Diabetes Care. 2019;42(4):601–608. doi: 10.2337/dc18-1970 - DOI - PMC - PubMed
    1. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393–403. doi: 10.1056/NEJMoa012512 - DOI - PMC - PubMed
    1. Madsen KS, Chi Y, Metzendorf MI, Richter B, Hemmingsen B. Metformin for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus. Cochrane Database Syst Rev. 2019;12(12):CD008558. Published 2019 Dec 3. doi: 10.1002/14651858.CD008558.pub2 - DOI - PMC - PubMed

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