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Euglycemic ketosis in patients with type 2 diabetes on SGLT2-inhibitor therapy—an emerging problem and solutions offered by diabetes technology

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Abstract

Diabetic ketoacidosis is an infrequent but life-threatening acute complication of diabetes, affecting predominantly patients with type 1 diabetes, children, and pregnant women, where ketosis is usually associated with marked hyperglycemia. Recently, an increasing number of cases have been reported of euglycemic diabetic ketoacidosis in patients with type 2 diabetes receiving sodium-glucose cotransporter 2 inhibitor treatment in routine practice. There is a minor, but not negligible diabetic ketoacidosis risk associated with this drug class, which was not seen in randomized clinical trials. However, sodium-glucose cotransporter2 inhibitors increase the risk of ketosis by increasing glucagon secretion in the pancreas and decreasing the renal excretion of 3-hydroxybutyrate and acetoacetate. When used in addition to insulin, any insulin dose reduction required to avoid hypoglycemia may lead to insufficient suppression of lipolysis and ketogenesis. sodium-glucose cotransporter2 inhibitor-induced loss of urinary glucose encourages euglycemia. Normo-glycemic or near-normoglycemic diabetic ketoacidosis represents a major threat to the health and well-being of a patient, because it may occur undetected and without any indicative hyperglycemia. In consequence, patients on sodium-glucose cotransporter2 inhibitors are recommended to perform regular blood ketone tests since they are not alerted to incipient diabetic ketoacidosis by glucose testing alone. This option is offered by several blood glucose meters that can also measure ketones with a separate ketone strip or in one case by an automatic parallel ketone assessment from the same strip. The need for extra testing and the associated costs may be a barrier to patient acceptance of this risk mitigation procedure. However, patients who are at risk for euglycemic diabetic ketoacidosis when being treated with sodium-glucose cotransporter2 inhibitors should be specially advised to monitor blood ketone levels on a regular basis.

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Abbreviations

AACE:

American Association of Clinical Endocrinologists

ACE:

American College of Endocrinology

ß-OHB:

- ß-hydroxybutyrate

DKA:

Diabetic ketoacidosis

SGLT2:

Sodium-glucose cotransporter 2

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Acknowledgements

A.P. has received research grants, speaker fees, and travel support from Abbott Diabetes Care, Inside Biometrics, Menarini Diagnostics, and Nova Diabetes Care.

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Authors and Affiliations

  1. Pfützner Science & Health Institute, Mainz, UK

    A. Pfützner

  2. Mills Peninsula Healthcare Services, San Mateo, USA

    D. Klonoff

  3. Science & Co, Düsseldorf, UK

    L. Heinemann

  4. Department of Endocrinology, Clinical Institute, Aalborg University, Aalborg University Hospital, Aalborg, UK

    N. Ejskjaer

  5. Division of Diabetes and Nutritional Sciences, King’s College London, Guy’s Hospital, London, UK

    J. Pickup

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  1. A. Pfützner
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  2. D. Klonoff
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Pfützner, A., Klonoff, D., Heinemann, L. et al. Euglycemic ketosis in patients with type 2 diabetes on SGLT2-inhibitor therapy—an emerging problem and solutions offered by diabetes technology. Endocrine 56, 212–216 (2017). https://doi.org/10.1007/s12020-017-1264-y

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