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Review
. 2024 Nov;18(6):1472-1479.
doi: 10.1177/19322968241280386. Epub 2024 Sep 6.

Time to Moderate and Severe Hyperglycemia and Ketonemia Following an Insulin Pump Occlusion

David C Klonoff  1 , Alessandra T Ayers  2 , Cindy N Ho  2 , Chiara Fabris  3 , María Fernanda Villa-Tamayo  3 , Eleanor Allen  4 , Eda Cengiz  4 , Laya Ekhlaspour  4 , Jenise C Wong  4 , Lutz Heineman  5 , Michael A Kohn  6
Affiliations
Review

Time to Moderate and Severe Hyperglycemia and Ketonemia Following an Insulin Pump Occlusion

David C Klonoff et al. J Diabetes Sci Technol. 2024 Nov.

Erratum in

Abstract

Introduction: Insulin pump therapy can be adversely affected by interruption of insulin flow, leading to a rise in blood glucose (BG) and subsequently of blood beta-hydroxybutyrate (BHB) ketone levels.

Methods: We performed a PubMed search for English language reports (January 1982 to July 2024) estimating the rate of rise in BG and/or BHB after ≥ 60 minutes of interruption of continuous subcutaneous insulin infusion (CSII) in persons with type 1 diabetes (PwT1D). We also simulated the rise in BG in a virtual population of 100 adults with T1D following suspension of continuous subcutaneous insulin infusion.

Results: We identified eight relevant studies where BG and BHB (seven of these eight studies) were measured following suspension of CSII as a model for occlusion. After 60 minutes post-suspension, the mean extracted rates of rise averaged 0.62 mg/dL/min (37 mg/dL/h) for BG and 0.0038 mmol/L/min (0.20 mmol/L/h) for BHB. Mean estimated time to moderately/severely elevated BG (300/400 mg/dL) or BHB (1.6/3.0 mmol/L) was, respectively, 5.8/8.5 and 8.0/14.2 hours. The simulation model predicted moderately/severely elevated BG (300/400 mg/dL) after 9.25/12, 6.75/8.75, and 4.75/5.75 hours in the virtual subjects post-interruption with small (5th percentile), medium (50th percentile), and large (95th percentile) hyperglycemic changes.

Discussion: Clinical studies and a simulation model similarly predicted that, following CSII interruption, moderate/severe hyperglycemia can occur within 5-9/6-14 hours, and clinical studies predicted that moderate/severe ketonemia can occur within 7-12/13-21 hours. Patients and clinicians should be aware of this timing when considering the risks of developing metabolic complications after insulin pump occlusion.

Keywords: hyperglycemia; insulin pump; ketoacidosis; occlusion; suspension.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: D.C.K. is a consultant for Afon, Embecta, GlucoTrack, Lifecare, Novo, Samsung, and Thirdwayv. C. N. H. has nothing to disclose. A.T.A. has nothing to disclose. C.F. reports receiving research support from Novo Nordisk A/S and Dexcom, Inc handled by the University of Virginia, and patent royalties from Novo Nordisk A/S and Dexcom, Inc handled by the University of Virginia’s Licensing and Ventures Group. M.F.V.-T. reports receiving patent royalties from Dexcom, Inc handled by the University of Virginia’s Licensing and Ventures Group. E.A. has nothing to disclose. E.C. has served on the scientific advisory board of Novo Nordisk, Eli Lilly, MannKind, Arecor, Portal Insulin, Provention Bio, Tandem, and Ypsomed. L.E. receives salary support from NIDDK; has received research support from JDRF, Medtronic, MannKind, and Abbot and has served on the advisory board of Diabetes Center Berne, Sequel, and Medtronic. She has received consulting fees from Jaeb, Tandem Diabetes Care, and Ypsomed and has received honorarium fees from Medtronic and Insulet. J.C.W. has received research support from Dexcom, Inc and Tandem Diabetes Care. L.H. is a shareholder of the Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany, Science Consulting in Diabetes GmbH Düsseldorf, and diateam GmbH, Bad Mergentheim, and Düsseldorf. L.H. is a consultant for several companies that are developing novel diagnostic and therapeutic options for diabetes treatment. M.A.K. has nothing to disclose.

Figures

Figure 1.
Figure 1.
Flow diagram for the systematic review of clinical studies presenting the rate of rise in BG and/or BHB after interruption of a subcutaneous insulin infusion in PwT1D (Generated by Covidence and then modified.). Abbreviations: BG, blood glucose; BHB, beta-hydroxybutyrate; CGM, continuous glucose monitor; PwT1D, persons with type 1 diabetes.
Figure 2.
Figure 2.
Simulated BG responses to interruption of insulin infusion in 100 virtual PwT1D. This figure was generated from the UVA/Padova Type 1 Diabetes Simulator. For this simulation, basal insulin was completely suspended at time 0 (when pump delivery failed) and maintained at 0 U/h over the remaining course of the simulations. Colors are assigned at random. Abbreviations: BG, blood glucose; PwT1D, persons with type 1 diabetes.
See this image and copyright information in PMC

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