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Abstract: PO1484

SGLT2-Mediated Changes in Urinary Handling of Ketones in Type 1 Diabetes

Session Information

Category: Fluid, Electrolyte, and Acid-Base Disorders

  • 902 Fluid, Electrolyte, and Acid-Base Disorders: Clinical

Authors

  • Scarr, Daniel, Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada
  • Lovblom, Leif Erik, Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada
  • Montemayor, Daniel, Center for Renal Precision Medicine (CRPM), Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, United States
  • Ye, Hongping, Center for Renal Precision Medicine (CRPM), Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, United States
  • Liu, Hongyan, Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • Lytvyn, Yuliya, Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • Sharma, Kumar, Center for Renal Precision Medicine (CRPM), Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, United States
  • Cherney, David, Division of Nephrology, Department of Medicine, University Health Network, University of Toronto, Toronto, Ontario, Canada
  • Perkins, Bruce A., Lunenfeld-Tanenbaum Research Institute, Toronto, Ontario, Canada
Background

Adjunctive therapy with sodium glucose co-transporter 2 (SGLT2) inhibitors have demonstrated clinically meaningful metabolic benefits in type 1 diabetes (T1D), but also represent a component cause of diabetic ketoacidosis. In this post-hoc analysis we examined SGLT2-mediated changes in ketone concentrations during clamped euglycemia and hyperglycemia in people with T1D.

Methods

T1D participants enrolled in the ATIRMA trial (NCT01392560) underwent measurement of plasma and urine beta-hydroxybutrate (BHB) and acetoacetate (AA) at baseline and after 8 weeks of empagliflozin 25 mg QD using a novel ZipChip Method developed at the CRPM, during both clamped euglycemia (4-6 mmol/L) and hyperglycemia (9-11 mmol/L).

Results

Forty participants (50% female), aged 24±5 years, HbA1c 8.0±0.9% with diabetes duration of 17.5±7 years, were enrolled. Median [IQR] plasma BHB at baseline was 0.05 [0.02-0.16] mmol/L during euglycemia and 0.06 [0.02-0.17] mmol/L during hyperglycemia. Plasma BHB significantly increased after treatment during both euglycemia (0.20 [0.09-0.40] mmol/L) and hyperglycemia (0.21[0.05-0.40] mmol/L), p<0.05 for both comparisons. Urine BHB at baseline was 1.9 [1.2-4.3] µmol/mmol creatinine during euglycemia and was 3.7 [1.7-10.0] µmol/mmol creatinine during hyperglycemia. Urine BHB significantly increased after treatment during euglycemia (4.1 [1.8-9.7] umol/mmol creatinine), p<0.01. Results were similar for AA.

Conclusion

In people with T1D, ketones were detectable in plasma and urine at baseline during clamped euglycemia and hyperglycemia and ketone concentrations significantly increased after 8 weeks of SGLT2 inhibition under the same study conditions. Further work is needed to establish factors associated with SGLT2-mediated changes in urinary handling of ketones and ketogenesis in people with T1D, which may assist in ketoacidosis prevention strategies.

Funding

  • Commercial Support