Circulating microRNAs Associated with Insulin Resistance in South Asian and European Adults with Type 2 Diabetes (T2D): A Systematic Review and Mapping of Ethnic Patterns

Type 2 diabetes (T2D) is a global crisis affecting 589 million adults, with South Asian populations particularly vulnerable, developing T2D earlier and at lower BMIs than Europeans. Insulin resistance, measured by HOMA-IR, is central to T2D pathogenesis. Circulating microRNAs are stable biomarkers implicated in insulin signalling, but no systematic review has compared their associations with insulin resistance across South Asians and Europeans. To identify microRNAs associated with HOMA-IR in adults with T2D and explore whether association patterns differ between South Asians and Europeans. A PRISMA-compliant systematic review searched six databases (PubMed, Embase, Web of Science, Scopus, bioRxiv, medRxiv). Eligible studies reported statistical associations between circulating serum/plasma microRNA and HOMA-IR in adults with T2D. Bias risks were assessed using an adapted domain-based tool. A qualitative synthesis was conducted because of the differences in methodology. The review was registered on the Open Science Framework (OSF). A total of 14 studies were included (9 European, 5 South Asian), reporting 29 associations across 21 microRNA species, with 12 reaching statistical significance (p < 0.05). The strongest finding was that miR-122 positively associated with log HOMA-IR in a large European prospective cohort. Co-directional associations for miR192 and miR-194 suggested a hepatic microRNA cluster in Europeans. The miR-29 family and miR-192 emerged as cross-ethnic signals. Associations reported in South Asian populations included miR-128 and miR-374a-5p. Circulating microRNAs showed consistent positive associations with HOMA-IR, supporting biomarker potential. Cross-ethnic comparison was not possible within the included studies, revealing a gap in the literature rather than true ethnic differences. Multi-ethnic, methodologically standardised studies are needed, prioritising miR-122, miR-192, the miR-29 family, miR-128, and miR-374a-5p.