Metformin Can Decrease Serum levels of 12(S)-Hydroxyeicosatetraenoic Acid in Adults with Type 2 Diabetes Mellitus and Diabetic Kidney Disease

Background: Type 2 diabetes mellitus (T2DM) often accompanies by diabetic kidney disease (DKD). The occurrence and progression of T2DM and DKD are closely related to the inflammatory response and oxidative stress triggered by metabolic abnormalities including hyperglycemia and dyslipidemia. 12(S)-HETE, a metabolite of arachidonic acid, is considered as a critical lipid mediator in inflammation and oxidative stress and is believed to play a role in the occurrence and progression of DKD. Metformin is widely used as an initial drug for T2DM, but its effect on diabetic kidney disease still remains to be elucidated. Therefore, this study aimed to evaluate the impact of metformin treatment on serum 12(S)-HETE level in T2DM patients combined with DKD. Methods: A total of 121 T2DM patients were enrolled, including 63 T2DM patients with DKD and 58 T2DM patients without DKD. Then the T2DM patients with DKD were divided into two groups based on the use of metformin. There were 33 patients in the metformin group and 30 patients in the non-metformin group. Renal function was assessed by measuring glomerular filtration rate and urinary albumin-to-creatinine ratio for all the patients. Serum 12(S)-HETE was extracted and quantified using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Spearman’s correlation analysis was utilized to assess the relationship between serum 12(S)-HETE level and relevant variables associated with T2DM combined with DKD. Results: We reported a significant elevation of serum 12(S)-HETE level in T2DM patients with DKD compared to T2DM patients without DKD ( P <0.05). Among T2DM patients combined with DKD, patients receiving metformin treatment showed significantly lower serum 12(S)-HETE level compared to patients receiving treatment without metformin ( P <0.05). Spearman’s correlation analysis showed that serum 12(S)-HETE level had moderate positive correlations with ACR (R=0.3878, P <0.0001) and uAER (R=0.3198, P =0.0007) of renal function, and showed a moderate positive correlation with LDL-C/HDL-C levels of serum lipids (R=-0.3030, P =0.0014). Conclusions: Metformin reduced serum 12(S)-HETE level in T2DM patients with DKD. The mechanism might be related to the improvement of the abnormal lipid metabolic state through metformin.