Linking SIRT1 gene variation and protein levels to the pathophysiology of type 2 diabetes

Sirtuin 1 (SIRT1), an NAD⁺-dependent deacetylase, is involved in glucose homeostasis, insulin signaling, and inflammatory regulation, making it a potential molecular target in type 2 diabetes mellitus (T2DM). This case-control study investigated the association between serum SIRT1 levels, the SIRT1 promoter polymorphism rs7895833, and metabolic parameters in 150 patients with T2DM and 150 age- and sex-matched healthy controls. Serum SIRT1 concentrations were measured by ELISA, and rs7895833 genotyping was performed using allele-specific PCR. Clinical and biochemical variables were also assessed. Serum SIRT1 levels were significantly lower in patients with T2DM than in controls (p < 0.001) and showed significant inverse correlations with fasting plasma glucose (p = 0.001) and HbA1c (p < 0.001). Genotypic analysis revealed a significant difference in the distribution of the rs7895833 AG genotype between the two groups (p = 0.03), and under the overdominant model (AG vs. AA + GG), the heterozygous AG genotype was significantly associated with T2DM risk (OR = 1.81, p = 0.011), whereas no significant association was found between SIRT1 genotypes and circulating SIRT1 levels. These findings suggest that reduced SIRT1 is associated with hyperglycemia and poor glycemic control in T2DM. Overall, SIRT1 may serve as a potential biomarker and molecular mediator in T2DM pathogenesis. This study provides original data from a Middle Eastern population and may help inform future mechanistic and comparative studies.