Altered Patterns of Early Metabolic Decompensation in Type 1 Diabetes During Treatment with a SGLT2 Inhibitor: An Insulin Pump Suspension Study
Open accessAbstract
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 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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For patients with T1D using an SGLT2 inhibitor, if CSII is suspended, the rate of increase in BG (but not BHB) is lower than without the SGLT2 inhibitor.
“For patients with T1D who are using a sodium-glucose cotransporter-2 (SGLT2) inhibitor, if there is a suspension of continuous subcutaneous insulin infusion (CSII), then the rate of increase in BG (but not BHB) is lower than without the SGLT2 inhibitor.13,17”
From Time to Moderate and Severe Hyperglycemia and Ketonemia Following an Insulin Pump Occlusion (2024) · cites this paper as [13]
Using the average rate of increase from the study with the highest rate of increase of BG, it would take 4.7 or 6.8 hours to reach a BG level of 300 or 400 mg/dL, respectively, starting at a BG of 120 mg/dL.
“Using the average rate of increase from the study with the highest rate of increase of BG, it would take 4.7 or 6.8 hours to reach a BG level of 300 or 400 mg/dL, respectively (starting at a BG of 120 mg/dL).13”
From Time to Moderate and Severe Hyperglycemia and Ketonemia Following an Insulin Pump Occlusion (2024) · cites this paper as [13]
Cites
Miller, K. M., Foster, N. C., Beck, R. W., Bergenstal, R. M., DuBose, S. N., DiMeglio, L. A., Maahs, D. M., & Tamborlane, W. V. (2015) · Diabetes Care · doi:10.2337/dc15-0078 · Cited by 1,254 · see citing works
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Dandona, P., Mathieu, C., Phillip, M., Hansen, L., Tschöpe, D., Thorén, F., Xu, J., Langkilde, A. M., DEPICT-1 Investigators, Proietto, J., et al. (2018) · Diabetes Care · doi:10.2337/dc18-1087 · Cited by 243 · see citing works
Time to Moderate and Severe Hyperglycemia and Ketonemia Following an Insulin Pump Occlusion
Klonoff, D. C., Ayers, A. T., Ho, C. N., Fabris, C., Villa-Tamayo, M. F., Allen, E., Cengiz, E., Ekhlaspour, L., Wong, J. C., Heineman, L., et al. (2024) · Journal of Diabetes Science and Technology · doi:10.1177/19322968241280386 · Cited by 4 · see citing works
Self-citation
- Authors
- Patel, N. S., Van Name, M. A., Cengiz, E., Carria, L. R., Weinzimer, S. A., Tamborlane, W. V., & Sherr, J. L.
- Affiliations
- Yale University (US)
- Department of Pediatric Endocrinology, Yale School of Medicine, New Haven, Connecticut.
- Venue
- Diabetes Technology & Therapeutics
- Publisher
- SAGE Publications
- Published
- 2017-11
- Volume
- 19
- Issue
- 11
- Pages
- 618-622
- ISSN
- 1520-9156 (ISSN-L)
- 1557-8593
- PMC
- PMC5689123
- OpenAlex
- W2765549757
- Cited by
- 30
- References
- 1
- Citations by year
- 2025: 2 · 2024: 4 · 2022: 2 · 2021: 6 · 2020: 3 · 2019: 8 · 2018: 5
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Diabetes Technology & Therapeutics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Yale University (UL1 TR000142)
- Endocrine Fellows Foundation
- National Institutes of Health (UL1TR000142, DK-45735, UL1TR001863)
- National Institute of Diabetes and Digestive and Kidney Diseases (K12DK094714, P30DK045735)
- National Center for Advancing Translational Sciences
- Yale Center for Clinical Investigation, Yale School of Medicine (UL1TR000142)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
- Keywords
- type 1 diabetes, SGLT2 inhibitors, canagliflozin, diabetic ketoacidosis, ketogenesis, beta-hydroxybutyrate, free fatty acids, glucagon, plasma insulin, hyperglycemia
- MeSH terms
- Canagliflozin, Sodium-Glucose Transporter 2 Inhibitors, Adolescent, Adult, Blood Glucose, Diabetes Mellitus, Type 1, Fatty Acids, Nonesterified, Female, Glucagon, Humans, Hypoglycemic Agents, Insulin, Insulin Infusion Systems, Male, Middle Aged, Young Adult
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