Review of miRNA associations with high-risk diabetes profiles in midlife women

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medRxiv Published April 28, 2026 Medically reviewed April 28, 2026 Study authors: Longoria, K. D.; Stroebel, B.; Gadgil, M.; Perez, N.; Lewis, K. A.; Weiss, S. J.; Flowers, E. DOI ↗ By Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

Key Takeaway

Note miR-320a/c and race associations with high-risk diabetes profiles in midlife women.

This publication is a review of an observational study conducted within the Diabetes Prevention Program. The scope focuses on microRNAs (miRs) as potential markers for risk stratification in women during midlife, specifically ages 40 to 64 years. The sample size included 603 participants. The study compared a high-risk profile assignment against a low-risk profile comparator.

Key findings indicate that MiR-320a and miR-320c were associated with increased odds of high-risk profile assignment. Additionally, the PC3 cluster, which is a co-expression cluster enriched for miRs belonging to the miR-320 family, was significantly associated with increased odds. Black race demonstrated at least threefold higher odds compared to other races. These associations were determined via logistic regression models. A false discovery rate of q less than 0.05 was used to control for multiple comparisons.

The authors acknowledge that sex- and age-specific studies on phenotypic and mechanistic factors underlying risk for co-occurrence are limited. The review does not report adverse events, discontinuations, or tolerability data. Mechanisms that may underlie risk and potential therapeutic targets are not fully elucidated in this work.

Practice relevance emphasizes the potential utility of integrated, multidimensional approaches for risk stratification. Clinicians should interpret these findings cautiously as associations rather than causal relationships, given the observational nature of the data.

Study Details

Sample sizen = 603

EvidenceLevel 5

PublishedApr 2026

View Original Abstract ↓

Introduction The bidirectional relationship between depression and type 2 diabetes (T2D) is well-established. Women are disproportionately affected by their co-occurrence, particularly during midlife, yet sex- and age-specific studies on phenotypic and mechanistic factors underlying risk for their co-occurrence are limited. The purpose of this study was to identify combined risk profiles (i.e., depression, T2D) in women during midlife and to determine if microRNAs (miRs) that are associated with high-risk profiles provide mechanistic insights into multimorbidity. Materials and Methods This study included baseline data from women during midlife (ages 40-64 years) who participated in the Diabetes Prevention Program (DPP) (n = 603). Unsupervised k-means clustering was used to identify multimorbid risk profiles. Clinical characteristics included for risk profiling included Beck Depression Inventory (BDI-I), age, BMI, waist circumference, triglycerides, high HDL, FBG, and HbA1c. Associations between risk profiles and individual miRs and principal components of co-expressed miRs were determined via logistic regression models adjusted for participant race and ethnicity. False discovery rate (q< 0.05) was used to control for multiple comparisons. Results Two distinct profiles were identified, with the high-risk profile characterized by younger age yet higher adiposity, glycemic biomarkers, and depression symptom burden compared to the low-risk profile. MiR-320a and miR-320c were associated with increased odds of high-risk profile assignment, and a co-expression cluster enriched for miRs belonging to the miR-320 family (PC3) was significantly associated with increased odds of high-risk profile assignment. Across all models, Black race demonstrated at least threefold higher odds of high-risk profile assignment. Discussion These findings highlight distinct multimorbid risk profiles in women during midlife, emphasizing the potential utility of integrated, multidimensional approaches for risk stratification. Findings also revealed mechanisms that may underly risk for co-occurrence of T2D and depression in women during midlife and potential therapeutic targets for prevention and treatment.