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Peer-reviewedCC BY-NCDiabetes, metabolic syndrome and obesity : targets and therapy

Circulating miRNA-21 and Biomarkers of Inflammation, Fibrosis, and Oxidative Stress in Adults with Type 2 Diabetes Mellitus: A Cross-Sectional Study.

  1. 1Division of Nephrology and Hypertension, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia - Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
  2. 2Division of Endocrinology, Metabolism, and Diabetes, Department of Internal Medicine, Faculty of Medicine Universitas Indonesia, Jakarta, Indonesia.

Abstract

Purpose

Chronic inflammation, oxidative stress, and fibrosis are interconnected drivers of complications in type 2 diabetes mellitus (T2DM) and may precede detectable changes in conventional clinical markers. MicroRNA-21 (miR-21) has been implicated in all three pathways, but its associations with representative biomarkers have rarely been examined simultaneously in a single T2DM population. We evaluated correlations between circulating miR-21 and serum tumor necrosis factor receptor-1 (TNFR1), transforming growth factor-beta 1 (TGF-β1), and 8-hydroxy-2'-deoxyguanosine (8-OHdG), and explored differences by albuminuria status.Patients and methods

This cross-sectional study was a secondary analysis of clinical data and archived serum from 54 adults with T2DM enrolled in the Bogor Non-Communicable Disease Risk Factor Cohort, Indonesia. Most participants had preserved kidney function (mean eGFR 76.9 ± 15.0 mL/min/1.73m²; 63.0% without albuminuria). Circulating miR-21 was quantified by quantitative real-time PCR; TNFR1, TGF-β1, and 8-OHdG were measured by ELISA. Independent associations were evaluated using multivariable linear regression adjusted for age, sex, BMI, HbA1c, LDL cholesterol, and eGFR. Bootstrap resampling and albuminuria-stratified analyses were performed.Results

Log2-transformed miR-21 correlated weakly with log2 TNFR1 (ρ = 0.273, P = 0.046) and remained independently associated with TNFR1 after adjustment (β = 0.061, 95% CI 0.001-0.122, P = 0.048). This borderline association was robust to bootstrap resampling and additional adjustment for diabetes duration and statin use. No independent associations were observed with TGF-β1 or 8-OHdG overall. Exploratory findings showed that miR-21 was associated with TGF-β1 among participants with albuminuria (β = 0.286, P = 0.038), but the interaction was not significant (P = 0.087).Conclusion

In this T2DM population with predominantly preserved kidney function, circulating miR-21 was associated with TNFR1, a marker of TNF-α-related inflammatory activity, but not with TGF-β1 or 8-OHdG. These exploratory findings, limited by the small sample, borderline statistical significance, and lack of multiplicity adjustment, require confirmation in larger prospective, multicenter studies.

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BibTeX
@article{nugroho2026circulating,
  title = {{Circulating miRNA-21 and Biomarkers of Inflammation, Fibrosis, and Oxidative Stress in Adults with Type 2 Diabetes Mellitus: A Cross-Sectional Study.}},
  author = {Pringgodigdo Nugroho and Angeline Tancherla and Em Yunir and Vika Wirdhani and Anandhara Indriani Khumaedi and Renny Ary Soetedjo and Muhammad Jalaluddin Rumi},
  journal = {Diabetes, metabolic syndrome and obesity : targets and therapy},
  year = {2026},
  month = oct,
  doi = {10.2147/dmso.s655723},
  url = {https://europepmc.org/article/MED/42921214},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Circulating miRNA-21 and Biomarkers of Inflammation, Fibrosis, and Oxidative Stress in Adults with Type 2 Diabetes Mellitus: A Cross-Sectional Study.
AU  - Pringgodigdo Nugroho
AU  - Angeline Tancherla
AU  - Em Yunir
AU  - Vika Wirdhani
AU  - Anandhara Indriani Khumaedi
AU  - Renny Ary Soetedjo
AU  - Muhammad Jalaluddin Rumi
PY  - 2026
DA  - 2026/10/19
JO  - Diabetes, metabolic syndrome and obesity : targets and therapy
DO  - 10.2147/dmso.s655723
UR  - https://europepmc.org/article/MED/42921214
AB  - Purpose  Chronic inflammation, oxidative stress, and fibrosis are interconnected drivers of complications in type 2 diabetes mellitus (T2DM) and may precede detectable changes in conventional clinical markers. MicroRNA-21 (miR-21) has been implicated in all three pathways, but its associations with representative biomarkers have rarely been examined simultaneously in a single T2DM population. We evaluated correlations between circulating miR-21 and serum tumor necrosis factor receptor-1 (TNFR1), transforming growth factor-beta 1 (TGF-β1), and 8-hydroxy-2'-deoxyguanosine (8-OHdG), and explored differences by albuminuria status.Patients and methods  This cross-sectional study was a secondary analysis of clinical data and archived serum from 54 adults with T2DM enrolled in the Bogor Non-Communicable Disease Risk Factor Cohort, Indonesia. Most participants had preserved kidney function (mean eGFR 76.9 ± 15.0 mL/min/1.73m²; 63.0% without albuminuria). Circulating miR-21 was quantified by quantitative real-time PCR; TNFR1, TGF-β1, and 8-OHdG were measured by ELISA. Independent associations were evaluated using multivariable linear regression adjusted for age, sex, BMI, HbA1c, LDL cholesterol, and eGFR. Bootstrap resampling and albuminuria-stratified analyses were performed.Results  Log2-transformed miR-21 correlated weakly with log2 TNFR1 (ρ = 0.273, P = 0.046) and remained independently associated with TNFR1 after adjustment (β = 0.061, 95% CI 0.001-0.122, P = 0.048). This borderline association was robust to bootstrap resampling and additional adjustment for diabetes duration and statin use. No independent associations were observed with TGF-β1 or 8-OHdG overall. Exploratory findings showed that miR-21 was associated with TGF-β1 among participants with albuminuria (β = 0.286, P = 0.038), but the interaction was not significant (P = 0.087).Conclusion  In this T2DM population with predominantly preserved kidney function, circulating miR-21 was associated with TNFR1, a marker of TNF-α-related inflammatory activity, but not with TGF-β1 or 8-OHdG. These exploratory findings, limited by the small sample, borderline statistical significance, and lack of multiplicity adjustment, require confirmation in larger prospective, multicenter studies.
SN  - 1178-7007
ER  -