This study aims to (1) analyze the clinical characteristics and risk factors of patients with type 2 diabetes and comorbid depression and (2) explore the association between SIRT1 gene single-nucleotide polymorphism sites and this comorbidity. A total of 450 type 2 diabetes patients hospitalized in the General Medicine Department at The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology from July 2022 to September 2023, and 300 healthy individuals from the physical examination department were selected as study subjects. Both groups were assessed using general information surveys and questionnaires. Statistical analyses were performed to compare clinical indicators across 3 groups: individuals with only type 2 diabetes, those with comorbid depression, and healthy controls. The age, gender, disease duration, marital status, income and drug expenditure, employment status, fasting blood glucose level, fasting insulin level difference, insulin resistance index difference, glycated hemoglobin, high-density lipoprotein level, and HCY difference among the 3 groups of patients were risk factors for type 2 diabetes comorbid depression patients. The SIRT1 mRNA level was significantly reduced in type 2 diabetes comorbid depression patients. The SIRT1 gene had 3 sites: rs12415800, rs3758391, and rs932658, which were related to the patient's type 2 diabetes comorbid depression. They were the additive model and dominant model of rs12415800 and rs3758391, respectively. In addition, the GTGGT haplotype composed of rs12415800-rs932658-rs7895833-rs2273773-rs1467568 and the AGACT haplotype composed of rs3758391-rs932658-rs33957861-rs3818292-rs1467568 were significantly associated with type 2 diabetes comorbid depression. Numerous factors influence the presence of depression in patients with type 2 diabetes, with the SIRT1 gene playing a significant role, serving as a potential biomarker for this comorbidity.
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