Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes during Treatment with a SGLT2 Inhibitor: An Insulin Pump Suspension Study

Neha Patel, Michelle A. Van Name, Eda Cengiz, Lori R. Carria, Stuart A. Weinzimer, William V. Tamborlane, Jennifer L. Sherr

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)618-622
Number of pages5
JournalDiabetes Technology and Therapeutics
Volume19
Issue number11
DOIs
StatePublished - Nov 1 2017

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Type 1 Diabetes Mellitus
Suspensions
Insulin
Sodium-Glucose Transport Proteins
Glucose
Glucagon
Nonesterified Fatty Acids
Diabetic Ketoacidosis
Therapeutics
Hydroxybutyrates
Canagliflozin

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Medical Laboratory Technology

Cite this

Patel, Neha ; Van Name, Michelle A. ; Cengiz, Eda ; Carria, Lori R. ; Weinzimer, Stuart A. ; Tamborlane, William V. ; Sherr, Jennifer L. / Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes during Treatment with a SGLT2 Inhibitor : An Insulin Pump Suspension Study. In: Diabetes Technology and Therapeutics. 2017 ; Vol. 19, No. 11. pp. 618-622.
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abstract = "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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Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes during Treatment with a SGLT2 Inhibitor : An Insulin Pump Suspension Study. / Patel, Neha; Van Name, Michelle A.; Cengiz, Eda; Carria, Lori R.; Weinzimer, Stuart A.; Tamborlane, William V.; Sherr, Jennifer L.

In: Diabetes Technology and Therapeutics, Vol. 19, No. 11, 01.11.2017, p. 618-622.

Research output: Contribution to journalArticle

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

AU - Van Name, Michelle A.

AU - Cengiz, Eda

AU - Carria, Lori R.

AU - Weinzimer, Stuart A.

AU - Tamborlane, William V.

AU - Sherr, Jennifer L.

PY - 2017/11/1

Y1 - 2017/11/1

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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