The SGLT2 Inhibitor Empagliflozin Ameliorates the Inflammatory Profile in Type 2 Diabetic Patients and Promotes an Antioxidant Response in Leukocytes.

Francesca Iannantuoni,Victor M Victor,Noelia Diaz-Morales,Rosa Falcon,Susana Rovira-Llopis,Aranzazu M De Marañon,Zaida Abad-Jimenez,Antonio Hernandez-Mijares,Celia Bañuls

doi:10.3390/jcm8111814

Abstract

Sodium–glucose co-transporter 2 inhibitors (iSGLT2) have been linked to a considerable reduction in cardiovascular risk in patients with type 2 diabetes (T2D), but the precise molecular mechanisms are still elusive. We aimed to evaluate the effects of the iSGLT2 empagliflozin on systemic inflammation and its potential antioxidant properties. This is an observational, prospective follow-up study of a cohort of fifteen patients with T2D who received 10 mg/day of empagliflozin according to standard clinical care. Measures at baseline, 12 and 24 weeks were taken. Metabolic and anthropometric parameters were evaluated. Production of mitochondrial superoxide, glutathione content, and glutathione s-reductase and catalase mRNA levels were measured in leukocytes. Serum levels of myeloperoxidase, hs-CRP and IL-10 were determined. In addition to decreased body weight and reduced glucose and HbA1c levels, we observed a reduction in superoxide production in leukocytes of diabetic patients and increased glutathione content, prominently after 24 weeks of empagliflozin treatment. Leukocyte expression of glutathione s-reductase and catalase, and serum levels of IL-10 were enhanced at 24 weeks of empagliflozin treatment. Concomitantly, reduced hs-CRP and myeloperoxidase levels were seen. This study provides evidence of the antioxidant and anti-inflammatory properties of empagliflozin treatment in humans, which may contribute to its beneficial cardiovascular effects.

Highlights

Type 2 diabetes (T2D) is one of the most common chronic metabolic diseases, strongly associated with cardiovascular diseases, which account for up to 80% of deaths among the diabetic population, constituting a serious health problem [1,2,3]
The characteristic metabolic disturbances of T2D are insulin resistance, hyperglycaemia and altered lipid metabolism, which sustain a state of subacute chronic inflammation [4]
The systemic inflammation present in diabetic patients is mainly manifested by increased circulating pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNFα) or interleukin 1 beta (IL-1β), released by leukocytes [6]. These two main features of diabetes, namely, oxidative stress and chronic inflammation are of pivotal importance for diabetes-induced cardiovascular risk, and as such are key targets for therapy [7]

Summary

Introduction

Type 2 diabetes (T2D) is one of the most common chronic metabolic diseases, strongly associated with cardiovascular diseases, which account for up to 80% of deaths among the diabetic population, constituting a serious health problem [1,2,3]. These alterations lead to a shift in the balance between oxidants and antioxidants in favour of oxidants, such as superoxide, which is released mostly as a by-product of mitochondrial oxidative phosphorylation [5]. The systemic inflammation present in diabetic patients is mainly manifested by increased circulating pro-inflammatory cytokines, such as tumor necrosis factor alpha (TNFα) or interleukin 1 beta (IL-1β), released by leukocytes [6]. These two main features of diabetes, namely, oxidative stress and chronic inflammation are of pivotal importance for diabetes-induced cardiovascular risk, and as such are key targets for therapy [7]

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