Association of SIRT1 Gene Polymorphisms with Type 2 Diabetes Mellitus and its Complications: A Systematic Review and Meta-Analysis

Sirtuin 1 (SIRT1) is a metabolic regulator implicated in insulin signaling, inflammation, and mitochondrial function. Several SIRT1 gene polymorphisms have been linked to Type 2 Diabetes Mellitus (T2DM) and its complications, but existing data remain inconsistent. To systematically evaluate the association between SIRT1 gene polymorphisms and the risk of T2DM and related vascular complications. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines, we conducted a comprehensive literature search across PubMed, Scopus, Web of Science, and Google Scholar (up to June 2025). Eligible studies included observational designs examining SIRT1 polymorphisms in relation to T2DM and/or its complications. Data were synthesized using random-effects meta-analysis, and study quality was assessed via the Newcastle-Ottawa Scale. GRADE (Grading of Recommendations Assessment) methodology was used to evaluate certainty of evidence. Ten studies (n=6,424 participants) were included. The rs3818291 GA genotype was associated with increased CHD (Coronary Heart Disease) risk in T2DM patients (OR=1.70, 95% CI: 1.06-2.79), while rs16924934 GG conferred a 1.91-fold CHD risk. The rs3758391 T allele showed a significant association with T2DM risk (Odds ratio (OR)=1.78, 95% CI: 1.15-2.74). The rs12778366 C allele was protective against diabetic foot (OR=0.68, 95% CI: 0.52-0.90), and rs10823108 GA genotype was linked to diabetic nephropathy (OR=1.35, 95% CI: 1.07-1.70). Overall evidence was graded as moderate for key associations. SIRT1 gene polymorphisms, particularly rs3818291, rs16924934, and rs3758391, are significantly associated with T2DM and its vascular complications. These variants may serve as potential biomarkers for personalized diabetes risk assessment. Further large-scale, multi-ethnic studies are warranted to validate these findings and explore clinical applications.