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Published in: International Journal of Emergency Medicine 1/2019

Open Access 01-12-2019 | Metabolic Acidosis | Case report

Euglycemic diabetic ketoacidosis associated with sodium-glucose cotransporter-2 inhibitor use: a case report and review of the literature

Authors: Alexis Diaz-Ramos, Wesley Eilbert, Diego Marquez

Published in: International Journal of Emergency Medicine | Issue 1/2019

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Abstract

Background

The sodium-glucose cotransporter-2 (SGLT2) inhibitors are the newest class of anti-hyperglycemic medications used in the treatment of diabetes mellitus. Their increasing use has been driven by their apparent cardiovascular and renal benefits. They have been associated with a small but significantly increased risk of diabetic ketoacidosis (DKA). Many of the cases of DKA associated with SGLT2 inhibitor use present with normal or minimally elevated serum glucose levels, often delaying the diagnosis.

Case presentation

A 44-year-old woman with diabetes mellitus presented to our emergency department complaining of 3 days of generalized weakness. The SGLT2 inhibitor canagliflozin had been added to her medication regimen 4 weeks earlier, and she had stopped using insulin 2 weeks prior to presentation. Laboratory evaluation revealed a metabolic acidosis with an elevated anion gap and the presence of serum acetone, despite a minimally elevated serum glucose of 163 mg/dL. The patient was treated for euglycemic DKA with intravenous infusions of insulin and dextrose, with resolution of her symptoms in 3 days.

Conclusions

The SGLT2 inhibitors are a novel class of anti-hyperglycemic medications that are being used with increasing frequency in the treatment of diabetes mellitus. They are associated with a small but significantly increased risk of DKA. Many of the patients presenting with DKA associated with SGLT2 inhibitor use will have normal or minimally elevated serum glucose levels. This unusual presentation of DKA can be diagnostically challenging.
Literature
1.
go back to reference Kitabachi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crisis in adults with diabetes. Diabetes Care. 2009;32:1335–43.CrossRef Kitabachi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crisis in adults with diabetes. Diabetes Care. 2009;32:1335–43.CrossRef
3.
go back to reference Modi A, Agrawal A, Morgan F. Euglycemic ketoacidosis: a review. Curr Diabetes Rev. 2017;13(13):315–21.CrossRefPubMed Modi A, Agrawal A, Morgan F. Euglycemic ketoacidosis: a review. Curr Diabetes Rev. 2017;13(13):315–21.CrossRefPubMed
9.
go back to reference Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, et al. Consensus statement by the American Association of Clinical Endocrinologist and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2019 executive summary. Endocr Pract. 2019;25:69–100.CrossRefPubMed Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, et al. Consensus statement by the American Association of Clinical Endocrinologist and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2019 executive summary. Endocr Pract. 2019;25:69–100.CrossRefPubMed
10.
go back to reference Goldenberg RM, Berard LD, Cheng AYY, Gilbert JD, Verma S, Woo VC, et al. SGLT2 inhibitor - associated diabetic ketoacidosis: clinical review and recommendations for prevention and diagnosis. Clin Ther. 2016;38:2654–64.CrossRefPubMed Goldenberg RM, Berard LD, Cheng AYY, Gilbert JD, Verma S, Woo VC, et al. SGLT2 inhibitor - associated diabetic ketoacidosis: clinical review and recommendations for prevention and diagnosis. Clin Ther. 2016;38:2654–64.CrossRefPubMed
11.
go back to reference Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca MP, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019;393:31–9.CrossRefPubMed Zelniker TA, Wiviott SD, Raz I, Im K, Goodrich EL, Bonaca MP, et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet. 2019;393:31–9.CrossRefPubMed
12.
go back to reference Wu JH, Foote C, Blomster J, Toyama T, Perkovic V, Sundstrom J, et al. Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2016;4:411–9.CrossRefPubMed Wu JH, Foote C, Blomster J, Toyama T, Perkovic V, Sundstrom J, et al. Effects of sodium-glucose cotransporter-2 inhibitors on cardiovascular events, death, and major safety outcomes in adults with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2016;4:411–9.CrossRefPubMed
13.
go back to reference Whalen K, Miller S, Onge ES. The role of sodium-glucose co-transporter 2 inhibitors in the treatment of type 2 diabetes. Clin Ther. 2015;37:1150–66.CrossRefPubMed Whalen K, Miller S, Onge ES. The role of sodium-glucose co-transporter 2 inhibitors in the treatment of type 2 diabetes. Clin Ther. 2015;37:1150–66.CrossRefPubMed
14.
go back to reference Bonner C, Kerr-Conte J, Gmyr V, Queniat G, Moerman E, Thevenet J, et al. Inhibition of glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat Med. 2015;21:512–7.CrossRefPubMed Bonner C, Kerr-Conte J, Gmyr V, Queniat G, Moerman E, Thevenet J, et al. Inhibition of glucose transporter SGLT2 with dapagliflozin in pancreatic alpha cells triggers glucagon secretion. Nat Med. 2015;21:512–7.CrossRefPubMed
15.
go back to reference Henry RR, Thakkar P, Tong C, Polidori D, Alba M. Efficacy and safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to insulin in patients with type I diabetes. Diabetes Care. 2015;38:2258–65.CrossRefPubMed Henry RR, Thakkar P, Tong C, Polidori D, Alba M. Efficacy and safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to insulin in patients with type I diabetes. Diabetes Care. 2015;38:2258–65.CrossRefPubMed
16.
go back to reference Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–28.CrossRef Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–28.CrossRef
17.
go back to reference Erondu N, Desai M, Ways K, Meininger G. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care. 2015;38:1680–6.CrossRefPubMedPubMedCentral Erondu N, Desai M, Ways K, Meininger G. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care. 2015;38:1680–6.CrossRefPubMedPubMedCentral
18.
go back to reference Dizon S, Keely EJ, Malcolm J, Arnaout A. Insights into the recognition and management of SGLT2-inhibitor-associated ketoacidosis: it’s not just euglycemic diabetic ketoacidosis. Can J Diabetes. 2017;41:499–503.CrossRefPubMed Dizon S, Keely EJ, Malcolm J, Arnaout A. Insights into the recognition and management of SGLT2-inhibitor-associated ketoacidosis: it’s not just euglycemic diabetic ketoacidosis. Can J Diabetes. 2017;41:499–503.CrossRefPubMed
19.
go back to reference Fadini GP, Bonora BM, Avogaro A. SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA adverse event reporting system. Diabetologia. 2017;60:1385–9.CrossRefPubMed Fadini GP, Bonora BM, Avogaro A. SGLT2 inhibitors and diabetic ketoacidosis: data from the FDA adverse event reporting system. Diabetologia. 2017;60:1385–9.CrossRefPubMed
20.
go back to reference Misaghian-Xanthos N, Shariff AI, Mekala K, Fearrington LR, Setji TL, Aloi JA, et al. Sodium-glucose transporter 2 inhibitors and diabetic ketoacidosis: a case series from three academic institutions. Diabetes Care. 2017;40:e65–6.CrossRefPubMedPubMedCentral Misaghian-Xanthos N, Shariff AI, Mekala K, Fearrington LR, Setji TL, Aloi JA, et al. Sodium-glucose transporter 2 inhibitors and diabetic ketoacidosis: a case series from three academic institutions. Diabetes Care. 2017;40:e65–6.CrossRefPubMedPubMedCentral
21.
go back to reference Handelsman Y, Henry RR, Bloomgarden ZT, Dagogo-Jack S, Defronzo RA, Einhorn D, et al. American Association of Clinical Endocrinologists and American College of Endocrinology position paper on the association of SGLT-2 inhibitors and diabetic ketoacidosis. Endocr Pract. 2016;22:753–62.CrossRefPubMed Handelsman Y, Henry RR, Bloomgarden ZT, Dagogo-Jack S, Defronzo RA, Einhorn D, et al. American Association of Clinical Endocrinologists and American College of Endocrinology position paper on the association of SGLT-2 inhibitors and diabetic ketoacidosis. Endocr Pract. 2016;22:753–62.CrossRefPubMed
22.
go back to reference Burke KR, Schumacher CA, Harpe SE. SGLT2 inhibitors: a systematic review of diabetic ketoacidosis and related risk factors in the primary literature. Pharmacotherapy. 2017;37:187–94.CrossRefPubMed Burke KR, Schumacher CA, Harpe SE. SGLT2 inhibitors: a systematic review of diabetic ketoacidosis and related risk factors in the primary literature. Pharmacotherapy. 2017;37:187–94.CrossRefPubMed
24.
go back to reference Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsh IB. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015;38:1687–93.CrossRefPubMedPubMedCentral Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsh IB. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care. 2015;38:1687–93.CrossRefPubMedPubMedCentral
25.
go back to reference Ogawa W, Sakaguchi K. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. J Diabetes Investig. 2016;7:135–8.CrossRefPubMed Ogawa W, Sakaguchi K. Euglycemic diabetic ketoacidosis induced by SGLT2 inhibitors: possible mechanism and contributing factors. J Diabetes Investig. 2016;7:135–8.CrossRefPubMed
26.
go back to reference Jenkins D, Close CF, Krentz AJ, Nattrass M, Wright AD. Euglycemic diabetic ketoacidosis: does it exist? Acta Diabetol. 1993;30:251–3.CrossRefPubMed Jenkins D, Close CF, Krentz AJ, Nattrass M, Wright AD. Euglycemic diabetic ketoacidosis: does it exist? Acta Diabetol. 1993;30:251–3.CrossRefPubMed
27.
go back to reference Benoit SR, Zhang Y, Giess LS, Gregg EW, Albright A. Trends in diabetic ketoacidosis hospitalizations and in-house mortality – United States, 2000-2014. MMWR Morb Mortal Wkly Rep. 2018;67:362–5.CrossRefPubMedPubMedCentral Benoit SR, Zhang Y, Giess LS, Gregg EW, Albright A. Trends in diabetic ketoacidosis hospitalizations and in-house mortality – United States, 2000-2014. MMWR Morb Mortal Wkly Rep. 2018;67:362–5.CrossRefPubMedPubMedCentral
Metadata
Title
Euglycemic diabetic ketoacidosis associated with sodium-glucose cotransporter-2 inhibitor use: a case report and review of the literature
Authors
Alexis Diaz-Ramos
Wesley Eilbert
Diego Marquez
Publication date
01-12-2019
Publisher
Springer Berlin Heidelberg
Published in
International Journal of Emergency Medicine / Issue 1/2019
Print ISSN: 1865-1372
Electronic ISSN: 1865-1380
DOI
https://doi.org/10.1186/s12245-019-0240-0

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