Association of SIRT6 circulating levels with urinary and glycometabolic markers in pre-diabetes and diabetes

Aim The study is aimed to detect the expression of serum Sirtuin 6 (SIRT6) with different severities and urinary albumin creatinine ratios (UACR) in type 2 diabetes mellitus (T2DM) patients, thus exploring the association of SIRT6 together with glycolipid metabolism and urinary protein in the cross-sectional study. Methods T2DM patients (313 cases), pre-diabetic patients (102 cases), and healthy volunteers (100 cases) were selected. T2DM patients were divided into the normal albuminuria (103 cases, UACR < 30 mg/g), micro-albuminuria (106 cases, UACR 30-300 mg/g), and large amount of albuminuria group (104 cases, UACR > 300 mg/g) based on different UACR levels. The medical history was asked, biochemical indicators were detected, hematuria samples were taken, serum SIRT6 levels were detected, and detailed statistical analysis was conducted. Results FPG, 2 h-PG, HOMA-IR, HbA1c, and LDL-C increased, while ISI and HDL-C decreased with the aggravation of diabetic status (P < 0.05). HbA1c, UACR, TNF alpha, HIF1 alpha, and SIRT6 increased with UACR in T2DM patients (P < 0.05). Correlation analysis demonstrated that SIRT6 was significantly positively correlated with glycolipid metabolism in the whole samples, and correlated with UACR, TNF alpha, and HIF1 alpha in T2DM patients (P < 0.05). Ridge regression analysis showed that SIRT6 was a risk factor for both glycolipid metabolism and urinary protein (P < 0.05). Conclusion SIRT6 increases with biomarkers in glycolipid metabolism and urinary protein in different severities of diabetes and UACR, which is expected to be a potential biomarker for early prediction and diagnosis related to glycolipid metabolism disorders and related nephropathy. Trial number: ChiCTR2000039808.