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Safety and Effectiveness of Sodium-Glucose Cotransporter 2 Inhibitor Combined with Medical Nutrition Therapy for Hyperglycemia in Acute Stroke: A Retrospective Study.

ABSTRACT: Hyperglycemia, a predictor of poor clinical outcomes in acute stroke, must be lowered safely and promptly. We investigated the safety and effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2is) combined with medical nutrition therapy in lowering blood glucose levels. This retrospective study included stroke patients admitted between 2014 and 2019, who (1) had glycated hemoglobin ≥6.5%, blood glucose level ≥ 11.1 mmol/L at admission, (2) took their diet and drugs orally during hospitalization, (3) underwent SGLT2is pharmacotherapy after admission, and (4) underwent a fasting blood glucose (FBG) test on day 7. Patients were provided with a moderate-carbohydrate diet combined with total energy restriction. We assessed the achievement of FBG < 7 mmol/L on day 7 and the need for sulfonylurea or a long-acting insulin analog (LIA) treatment during hospitalization, which carries a risk of hypoglycemia. Fifty-one patients met our inclusion criteria. Of them, 33 (64.7%) achieved the target FBG on day 7. Only eight patients were treated with a small dose of LIA; however, no patients required sulfonylurea. No dehydration occurred. SGLT2is combined with a moderate carbohydrate- and energy-restricted diet achieved the target FBG level safely, effectively, and promptly in mild stroke patients with oral ingestion.

SUBMITTER: Mori T

PROVIDER: S-EPMC8779243 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Safety and Effectiveness of Sodium-Glucose Cotransporter 2 Inhibitor Combined with Medical Nutrition Therapy for Hyperglycemia in Acute Stroke: A Retrospective Study.

Mori Takahisa T Yoshioka Kazuhiro K Tanno Yuhei Y Kasakura Shigen S

Metabolites 20211228 1

Hyperglycemia, a predictor of poor clinical outcomes in acute stroke, must be lowered safely and promptly. We investigated the safety and effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2is) combined with medical nutrition therapy in lowering blood glucose levels. This retrospective study included stroke patients admitted between 2014 and 2019, who (1) had glycated hemoglobin ≥6.5%, blood glucose level ≥ 11.1 mmol/L at admission, (2) took their diet and drugs orally during hospit ...[more]

PMID: 35050147

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Project description:BackgroundSGLT2 (sodium/glucose cotransporter 2) inhibitors exert robust cardioprotective effects against heart failure in patients with diabetes, and there is intense interest to identify the underlying molecular mechanisms that afford this protection. Because the induction of the late component of the cardiac sodium channel current (late-INa) is involved in the etiology of heart failure, we investigated whether these drugs inhibit late-INa.MethodsElectrophysiological, in silico molecular docking, molecular, calcium imaging, and whole heart perfusion techniques were used to address this question.ResultsThe SGLT2 inhibitor empagliflozin reduced late-INa in cardiomyocytes from mice with heart failure and in cardiac Nav1.5 sodium channels containing the long QT syndrome 3 mutations R1623Q or ΔKPQ. Empagliflozin, dapagliflozin, and canagliflozin are all potent and selective inhibitors of H2O2-induced late-INa (half maximal inhibitory concentration = 0.79, 0.58, and 1.26 µM, respectively) with little effect on peak sodium current. In mouse cardiomyocytes, empagliflozin reduced the incidence of spontaneous calcium transients induced by the late-INa activator veratridine in a similar manner to tetrodotoxin, ranolazine, and lidocaine. The putative binding sites for empagliflozin within Nav1.5 were investigated by simulations of empagliflozin docking to a three-dimensional homology model of human Nav1.5 and point mutagenic approaches. Our results indicate that empagliflozin binds to Nav1.5 in the same region as local anesthetics and ranolazine. In an acute model of myocardial injury, perfusion of isolated mouse hearts with empagliflozin or tetrodotoxin prevented activation of the cardiac NLRP3 (nuclear-binding domain-like receptor 3) inflammasome and improved functional recovery after ischemia.ConclusionsOur results provide evidence that late-INa may be an important molecular target in the heart for the SGLT2 inhibitors, contributing to their unexpected cardioprotective effects.

Dataset Information

Safety and Effectiveness of Sodium-Glucose Cotransporter 2 Inhibitor Combined with Medical Nutrition Therapy for Hyperglycemia in Acute Stroke: A Retrospective Study.

Publications

Safety and Effectiveness of Sodium-Glucose Cotransporter 2 Inhibitor Combined with Medical Nutrition Therapy for Hyperglycemia in Acute Stroke: A Retrospective Study.

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