Aline Franco da Rocha1, Paulo Sergio Pereira Junior2, Gabriela Simonetti Calefi3, Guilherme Figueiredo Marquezine4, Helena Kaminami Morimoto5, Tania Longo Mazzuco4, Eliana Cotta de Faria6, Mariana Ragassi Urbano7, Alexandre Jose Faria Carrilho8,9. 1. Post-graduation Program of Health Sciences, Londrina State University, Londrina, Brazil. 2. Undergraduate Physiotherapy Course, Londrina State University, Londrina, Brazil. 3. Undergraduate Medicine Course, Londrina State University, Londrina, Brazil. 4. Division of Endocrinology, Department of Internal Medicine, Londrina State University, Londrina, Brazil. 5. Department of Pathology, Clinical and Toxicological Analysis, Health Sciences Center, Londrina State University, Londrina, Brazil. 6. Lipids Laboratory, Department of Clinical Pathology, Faculty of Medical Sciences, State University of Campinas, Sao Paulo, Brazil. 7. Department of Statistics, Londrina State University, Londrina, Brazil. 8. Post-graduation Program of Health Sciences, Londrina State University, Londrina, Brazil. acarrilho@uel.br. 9. Division of Endocrinology, Department of Internal Medicine, Londrina State University, Londrina, Brazil. acarrilho@uel.br.
Abstract
PURPOSE:Sodium-glucose cotransporter 2 inhibitors increase glucagon secretion by pancreatic alpha cells and the susceptibility to ketoacidosis. On the other hand, growth hormone (GH) stimulates peripheral lipolysis and provides free fatty acids (FFA) for ketogenesis; however, it remains unresolved whether GH directly impacts hepatic ketogenesis. We aimed to investigate the role of physiologic GH levels in promoting ketogenesis in prediabetic or type 2 diabetic patients under empagliflozin treatment. METHODS:Sixteen patients (11 women, 5 men) with prediabetes or type 2 diabetes mellitus, aged 55.6 ± 4.7 years and with a mean BMI of 30.7 ± 4.8 kg/m2 and HbA1c 7.1 ± 1.6% (means ± SD), participated in this study. All of them were submitted to three mixed-meal tests: they received placebo at -60 min (test 1), and empagliflozin 25 mg (test 2, 21st day) and empagliflozin 25 mg plus pegvisomant 30 mg were administered subcutaneously 36 h before (test 3, 28th day). After test 1, all patients were instructed to take empagliflozin 25 mg daily. RESULTS: The empagliflozin treatment decreased the plasma concentrations of glucose by 14% (P < 0.01), FFA by 23% (P < 0.01), and the insulin/glucagon ratio by 26% (P < 0.01), and it increased β-hydroxybutyrate by 44% (P < 0.05). The GH receptor block by pegvisomant restored the plasma β-hydroxybutyrate to baseline levels. CONCLUSIONS: We conclude that GH has a direct effect on promoting the ketogenesis environment in patients treated with empagliflozin.
RCT Entities:
PURPOSE:Sodium-glucose cotransporter 2 inhibitors increase glucagon secretion by pancreatic alpha cells and the susceptibility to ketoacidosis. On the other hand, growth hormone (GH) stimulates peripheral lipolysis and provides free fatty acids (FFA) for ketogenesis; however, it remains unresolved whether GH directly impacts hepatic ketogenesis. We aimed to investigate the role of physiologic GH levels in promoting ketogenesis in prediabetic or type 2 diabeticpatients under empagliflozin treatment. METHODS: Sixteen patients (11 women, 5 men) with prediabetes or type 2 diabetes mellitus, aged 55.6 ± 4.7 years and with a mean BMI of 30.7 ± 4.8 kg/m2 and HbA1c 7.1 ± 1.6% (means ± SD), participated in this study. All of them were submitted to three mixed-meal tests: they received placebo at -60 min (test 1), and empagliflozin 25 mg (test 2, 21st day) and empagliflozin 25 mg plus pegvisomant 30 mg were administered subcutaneously 36 h before (test 3, 28th day). After test 1, all patients were instructed to take empagliflozin 25 mg daily. RESULTS: The empagliflozin treatment decreased the plasma concentrations of glucose by 14% (P < 0.01), FFA by 23% (P < 0.01), and the insulin/glucagon ratio by 26% (P < 0.01), and it increased β-hydroxybutyrate by 44% (P < 0.05). The GH receptor block by pegvisomant restored the plasma β-hydroxybutyrate to baseline levels. CONCLUSIONS: We conclude that GH has a direct effect on promoting the ketogenesis environment in patients treated with empagliflozin.
Authors: T Heise; E Seewaldt-Becker; S Macha; S Hantel; S Pinnetti; L Seman; H J Woerle Journal: Diabetes Obes Metab Date: 2013-02-17 Impact factor: 6.577
Authors: Louise Moller; Helene Norrelund; Niels Jessen; Allan Flyvbjerg; Steen B Pedersen; Bruce D Gaylinn; Jianhua Liu; Michael O Thorner; Niels Moller; Jens Otto Lunde Jorgensen Journal: J Clin Endocrinol Metab Date: 2009-10-09 Impact factor: 5.958