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

Daniel Scarr, Erik Lovblom, Hongping Ye, Hongyan Liu, Abdulmohsen Bakhsh, Natasha J. Verhoeff, Thomas M.S. Wolever, Patrick R. Lawler, Kumar Sharma, David Z.I. Cherney, Bruce A. Perkins

Producción científica: Articlerevisión exhaustiva

Resumen

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.

Idioma originalEnglish (US)
Número de artículo111031
PublicaciónDiabetes Research and Clinical Practice
Volumen207
DOI
EstadoPublished - ene 2024

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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