Abstract
Abstract Background and Aims Recent evidences has shown that sodium-glucose co-transporter 2 (SGLT2) inhibitors improve cardiovascular and renal outcomes of type 2 diabetes mellitus (T2DM) patients. However, the mechanisms by which SGLT2 inhibitors improve clinical outcomes are unclear. Mitochondrial dysfunction plays a principal role in the pathophysiology of T2DM and its complications. We hypothesized empagliflozin, an SGLT2 inhibitor improves mitochondrial dysfunction in T2DM patients. Method We prospectively recruited healthy volunteers (n = 22) and SGLT2 naïve T2DM patients (n = 21). Copy numbers of urinary and serum mitochondrial DNA (mtDNA) nicotinamide adenine dinucleotide dehydrogenase subunit-1 (mtND-1) and cytochrome-c oxidase 3 (mtCOX-3) were measured using quantitative polymerase chain reaction in healthy volunteers and T2DM patients at baseline and in T2DM patients after 3 months of treatment with empagliflozin (10 mg, n = 17 or 25 mg, n = 4). Results Patients with T2DM were older than healthy volunteers and had higher body mass index and systolic blood pressure, but lower estimated glomerular filtration rate. Urinary mtND-1 and mtCOX-3 copy numbers were significantly higher in the T2DM group than in healthy volunteers. Urinary mtDNA copy numbers were correlated with diabetes duration (8.74 ± 7.60 years, r = 0.54, P = 0.01 for mtND-1, r = 0.50, P = 0.02 for mtCOX-3). Urinary copy numbers of mtND-1 and mtCOX-3 decreased after empagliflozin treatment. The amount of reduction of urinary mtDNA copy number did not differ according to empagliflozin dose (P = 0.897 for mtND-1, P = 0.462 for mtCOX-3). Conclusion In this study, we found that T2DM is associated with elevated urinary mtND-1 and mtCOX-3 copy numbers. Empagliflozin reduces the elevated urinary mtND-1 and mtCOX-3 copy numbers in patients with T2DM. Our results suggest that empagliflozin could attenuate mitochondrial damage in the kidney cells of T2DM patients.
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