Kidney Week

Abstract: PO1009

Empagliflozin Is Associated with Increased Plasma Lipid Metabolites in Type 1 Diabetes

Session Information

• Diabetic Kidney Disease: Clinical - 2
  October 22, 2020 | Location: On-Demand
  Abstract Time: 10:00 AM - 12:00 PM

Category: Diabetic Kidney Disease

• 602 Diabetic Kidney Disease: Clinical

Authors

• Liu, Hongyan, Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada

Hongyan Liu,

• Lovblom, Leif Erik, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

Leif Erik Lovblom,

• Lytvyn, Yuliya, Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada

Yuliya Lytvyn,

• Ye, Hongping, Center for Renal Precise Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, United States

Hongping Ye,

• Montemayor, Daniel, Center for Renal Precise Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, United States

Daniel Montemayor,

• Scarr, Daniel, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

Daniel Scarr,

• Perkins, Bruce A., Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada

Bruce A. Perkins,

• Sharma, Kumar, Center for Renal Precise Medicine, Division of Nephrology, Department of Medicine, University of Texas Health San Antonio, San Antonio, Texas, United States

Kumar Sharma,

• Cherney, David, Division of Nephrology, Department of Medicine, University Health Network, Toronto, Ontario, Canada

David Cherney,

Background

Sodium glucose cotransporter-2 (SGLT2) inhibition reduces the risk of cardiorenal complications in people with diabetes, possibly by altering energy substrate pathways. It has been hypothesized that SGLT2 inhibitors improve mitochondrial efficiency and may induce a shift towards increased lipid utilization as an energy substrate. In this exploratory, post-hoc analysis, we investigated the effects of SGLT2 inhibition on plasma lipid and tricarboxylic acid (TCA) cycle metabolites in patients with type 1 diabetes (T1D).

Methods

In the ATIRMA trial (NCT01392560), patients with T1D were assessed under clamped euglycemia and hyperglycemia at baseline and after 8 weeks of empagliflozin treatment. Plasma samples from the ATIRMA trial were analyzed for lipid and TCA cycle metabolites using the ZipChip method.

Results

Of the 15 lipid metabolites, 5 increased during clamped euglycemia in response to empagliflozin (Figure) while 1 increased after treatment during clamped hyperglycemia. Of the 3 TCA cycle metabolites, 2 increased during clamped euglycemia in response to empagliflozin. None of the metabolites decreased significantly after empagliflozin treatment.

Conclusion

In patients with T1D, SGLT2 inhibition increased plasma TCA cycle metabolite levels, suggesting an impact on mitochondrial function. Lipid metabolite levels were also increased after SGLT2 inhibition, suggesting a possible increase in beta oxidation. Further work is needed to determine if these changes contribute to cardiorenal protection with SGLT2 inhibitors.

Figure Plasma concentrations of (A.) 2-ketoglutaric acid, (B.) succinic acid, (C.) arachidonic acid, (D.) α-lanolenic acid, (E.) ethylmalonic acid, (F.) linoleic acid, and (G.) oleic acid during clamped euglycemia and hyperglycemia at baseline and post 8 weeks treatment with empagliflozin. Data shown are medians ± Q₁/Q3. Succinic acid levels significantly increased after treatment during clamped euglycemia.