TY - JOUR
T1 - Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes during Treatment with a SGLT2 Inhibitor
T2 - An Insulin Pump Suspension Study
AU - Patel, Neha S.
AU - Van Name, Michelle A.
AU - Cengiz, Eda
AU - Carria, Lori R.
AU - Weinzimer, Stuart A.
AU - Tamborlane, William V.
AU - Sherr, Jennifer L.
N1 - Funding Information:
The authors thank the participants and their families, the healthcare professionals, and staff of the Yale Children’s Diabetes Clinic, the Yale Center for Clinical Investigation, and the dedicated nursing staff of the Hospital Research Unit, whose support and participation made this project possible. Funding: This publication was made possible through the support of grants from the Endocrine Fellows Foundation, Juvenile Diabetes Research Foundation (5-ECR-2014-112-A-N), and the National Institutes of Health (K12-DK-094714, UL1TR000142, P30 DK45735).
Publisher Copyright:
© 2017, Mary Ann Liebert, Inc.
PY - 2017/11
Y1 - 2017/11
N2 - Background: Enthusiasm for the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as an adjunctive treatment in type 1 diabetes (T1D) has been offset by the possible increased risk of diabetic ketoacidosis (DKA). Since pump-treated T1D patients are susceptible to DKA due to infusion site problems, this study was undertaken to assess how treatment with SGLT2i affects patterns of early metabolic decompensation following suspension of basal insulin. Methods: Ten T1D participants (age 19-35 years, duration 10 ± 8 years, A1c 7.4% ± 0.8%) underwent overnight pump suspension studies before and after treatment with canagliflozin (CANA). On both nights, basal insulin was suspended at 3 AM and plasma glucose (PG), β-hydroxybutyrate (BHB), free fatty acids (FFA), plasma insulin (PI), and glucagon were measured. Studies were terminated 6 h after suspension or if PG rose to >350 mg/dL or BHB >2.5 mmol/L. Results: PI levels at the start of suspension were reduced by 30% after CANA treatment (44 ± 11 uU/mL vs. 31 ± 10 uU/mL, P < 0.01), but baseline PG, BHB, FFA, and glucagon levels were not significantly different. During the suspension, PG rose from 104 ± 10 to 301 ± 21 mg/dL before treatment, but only from 109 ± 8 to 195 ± 14 mg/dL after treatment (P = 0.002 vs. pretreatment values). On the other hand, CANA treatment did not significantly affect the magnitude of increases in FFA, BHB, and glucagon levels during the suspension study. Conclusion: These data indicate that SGLT2i do not accelerate the rate of ketogenesis following the interruption of basal insulin infusion in T1D. Rather, the failure of patients to promptly recognize early metabolic decompensation relates to the much more gradual rise in PG levels.
AB - Background: Enthusiasm for the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) as an adjunctive treatment in type 1 diabetes (T1D) has been offset by the possible increased risk of diabetic ketoacidosis (DKA). Since pump-treated T1D patients are susceptible to DKA due to infusion site problems, this study was undertaken to assess how treatment with SGLT2i affects patterns of early metabolic decompensation following suspension of basal insulin. Methods: Ten T1D participants (age 19-35 years, duration 10 ± 8 years, A1c 7.4% ± 0.8%) underwent overnight pump suspension studies before and after treatment with canagliflozin (CANA). On both nights, basal insulin was suspended at 3 AM and plasma glucose (PG), β-hydroxybutyrate (BHB), free fatty acids (FFA), plasma insulin (PI), and glucagon were measured. Studies were terminated 6 h after suspension or if PG rose to >350 mg/dL or BHB >2.5 mmol/L. Results: PI levels at the start of suspension were reduced by 30% after CANA treatment (44 ± 11 uU/mL vs. 31 ± 10 uU/mL, P < 0.01), but baseline PG, BHB, FFA, and glucagon levels were not significantly different. During the suspension, PG rose from 104 ± 10 to 301 ± 21 mg/dL before treatment, but only from 109 ± 8 to 195 ± 14 mg/dL after treatment (P = 0.002 vs. pretreatment values). On the other hand, CANA treatment did not significantly affect the magnitude of increases in FFA, BHB, and glucagon levels during the suspension study. Conclusion: These data indicate that SGLT2i do not accelerate the rate of ketogenesis following the interruption of basal insulin infusion in T1D. Rather, the failure of patients to promptly recognize early metabolic decompensation relates to the much more gradual rise in PG levels.
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U2 - 10.1089/dia.2017.0267
DO - 10.1089/dia.2017.0267
M3 - Article
C2 - 29068709
AN - SCOPUS:85034081535
SN - 1520-9156
VL - 19
SP - 618
EP - 622
JO - Diabetes Technology and Therapeutics
JF - Diabetes Technology and Therapeutics
IS - 11
ER -