Ketone production and excretion even during mild hyperglycemia and the impact of sodium-glucose co-transporter inhibition in type 1 diabetes.

Autor: Scarr D; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada., Lovblom E; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada., Ye H; Center for Renal Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, TX, United States., Liu H; Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada., Bakhsh A; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Kidney & Pancreas Health Centre, Organ Transplant Centre of Excellence, King Faisal Specialist Hospital & Research Centre, Riyadh, Kingdom of Saudi Arabia; Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada., Verhoeff NJ; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada., Wolever TMS; Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada., Lawler PR; McGill University Health Centre, Montreal, Canada; The Peter Munk Cardiac Centre at University Health Network, University of Toronto, Canada., Sharma K; Center for Renal Precision Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, TX, United States., Cherney DZI; Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada., Perkins BA; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; Division of Endocrinology and Metabolism, Department of Medicine, University of Toronto, Toronto, Ontario, Canada. Electronic address: Bruce.Perkins@sinaihealth.ca.
Jazyk: angličtina
Zdroj: Diabetes research and clinical practice [Diabetes Res Clin Pract] 2024 Jan; Vol. 207, pp. 111031. Date of Electronic Publication: 2023 Nov 28.
DOI: 10.1016/j.diabres.2023.111031
Abstrakt: Aims: We aimed to determine if ketone production and excretion are increased even at mild fasting hyperglycemia in type 1 diabetes (T1D) and if these are modified by ketoacidosis risk factors, including sodium-glucose co-transporter inhibition (SGLTi) and female sex.
Methods: In secondary analysis of an 8-week single-arm open-label trial of empagliflozin (NCT01392560) we evaluated ketone concentrations during extended fasting and clamped euglycemia (4-6 mmol/L) and mild hyperglycemia (9-11 mmol/L) prior to and after treatment. Plasma and urine beta-hydroxybutyrate (BHB) concentrations and fractional excretion were analyzed by metabolomic analysis.
Results: Forty participants (50 % female), aged 24 ± 5 years, HbA1c 8.0 ± 0.9 % (64 ± 0.08 mmol/mol) with T1D duration of 17.5 ± 7 years, were studied. Increased BHB production even during mild hyperglycemia (median urine 6.3[3.5-13.6] vs. 3.5[2.2-7.0] µmol/mmol creatinine during euglycemia, p < 0.001) was compensated by increased fractional excretion (0.9 % [0.3-1.6] vs. 0.4 % [0.2-0.9], p < 0.001). SGLTi increased production and attenuated the increased BHB fractional excretion (decreased to 0.3 % during mild hyperglycemia, p < 0.001), resulting in higher plasma concentrations (increased to 0.21 [0.05-0.40] mmol/L, p < 0.001), particularly in females (interaction p < 0.001).
Conclusions: Even mild hyperglycemia is associated with greater ketone production, compensated by urinary excretion, in T1D. However, SGLTi exaggerates production and partially reduces compensatory excretion, particularly in women.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: B.A.P. has received honoraria for educational events from Medtronic, Novo Nordisk, Sanofi, Insulet and Abbott. His research institute has received funding from BMO Bank of Montreal and Novo Nordisk for research Support. He has served as an advisor to Boehringer Ingelheim, Sanofi, Insulet and Abbott. D.Z.I.C has received honoraria from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon and Novo-Nordisk and has received operational funding for clinical trials from Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring and Novo-Nordisk. The remaining authors have no conflicts of interest to declare.
(Copyright © 2023. Published by Elsevier B.V.)
Databáze: MEDLINE
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