Sodium-glucose co-transporter 2 inhibitors induced euglycemic diabetic ketoacidosis within four days of initiation

TO THE EDlTOR

With great interest,we read the recent article "Euglycemic diabetic ketoacidosis:A missed diagnosis" by Nasa

[1].The authors have described various factors that can potentiate euglycemic diabetic ketoacidosis(EDKA)in sodium-glucose co-transporter 2 inhibitor(SGLT2-i)use.There is a steady increase in EDKA reports secondary to SGLT2-i.Most of the articles mention a precipitating factor behind the development of EDKA in patients taking SGLT2-i.More extensive studies mention no or unknown precipitating factor in 16%-51% of cases[2,3].This creates a need to explore a possible direct link of SGLT2-i in the development of EDKA in an otherwise healthy patient with diabetes.Acute vascular events such as stroke are infrequent inciting events for EDKA in the setting of SGLT2-i use.

We recently encountered an interesting case of a patient with type 2 diabetes mellitus(T2DM)who was admitted with acute stroke and developed EDKA within 4 d of initiation of empagliflozin.

A 45-year-old woman presented with sudden onset left arm weakness and slurred speech with facial droop.Magnetic resonance imaging revealed a right basal ganglia acute infarction,in addition to left parietal subcortical microangiopathic changes.The patient had a history of breast carcinoma,treated with mastectomy and maintenance tamoxifen.She also had T2DM and was prescribed sitagliptin/metformin 50/1000 mg two tablets daily.However,the patient was non-compliant with the medication and was not checking her blood sugar regularly.

The patient was started on dual antiplatelet therapy(aspirin 100 mg and clopidogrel 75 mg once daily)after establishing the diagnosis of an acute stroke.Her HbA1c was 14%,confirming a poor control of her diabetes.To manage her poorly controlled diabetes mellitus,sitagliptin/metformin was continued,with the addition of insulin glargine 12 units at bedtime and empagliflozin 10 mg once daily.

Four days later,the patient developed vomiting and generalized fatigue.Arterial blood gas showed severe metabolic acidosis with a pH of 6.9 and bicarbonate level of 3 mEq/L(reference range:22-26 mEq/L).Serum B-hydroxy butyrate was higher than the reported threshold of 9.60 mmol/L(reference range:0.03-0.3).Her blood glucose level at the time was 10.3 mmol/L(reference range:3.3-5.5),and her urine dipstick showed +4 ketone.She was diagnosed with severe EDKA and was shifted to the medical intensive care unit for further management and treatment.

The patient was consequently shifted back to the care of the general medicine team,where her glycemic control was monitored closely.After ensuring the patient's fitness and stability,she was transferred to a physical and occupational therapy rehabilitation facility.

Our case highlights that in the presence of a precipitating factor,SGLT2-i drugs can cause an early and severe EDKA.We recommend that wherever other choices are available,initiation of SGLT2-i should be delayed until patients are otherwise healthy and not admitted with an acute event.SGLT2-i medications should ideally be started in an outpatient setting,and the patients should be counseled not to rely on blood glucose and seek immediate medical attention when experiencing symptoms of DKA.

Regular insulin infusion and intravenous fluids were initiated,and a right internal jugular line was inserted for monitoring and resuscitation.Her arterial blood gas was measured every 2 h,and serum ketones were measured daily.Forty-eight hours later,the patient's condition improved,and she started tolerating oral feed.Her ABG results showed significant improvement with the closure of the anion gap(Table 1).She was started on subcutaneous glargine 20 units daily and insulin as part 7 units three times a day.

Remarkably4, after weeks and weeks in the hospital, the little boy survived. His legs were extremely scarred by the vicious（） attack of the animal and, on his arms, were deep scratches where his mother s fingernails dug into his flesh in her effort to hang on to the son she loved.

FOOTNOTES

Razok A,Ata F,and Ahmed SMI wrote the letter;Al Mohanadi DHSH revised the letter.

Zhang H

American College of Physicians,03770816.

Qatar

Back home, George was at a loss. In deep winter, he could not do without a pair of gloves. If he bought cheap ones again, he would have to replace them very soon. If he bought a new leather pair, they would cost fifty dollars now. He was very upset that people no longer returned things they found on the road.

Almurtada Razok 0000-0001-9430-0220;Fateen Ata 0000-0001-7121-8574;Sara Mohamed Ibrahim Ahmed 0000-0003-4499-5006;Dabia Hamad S H Al Mohanadi 0000-0002-6967-6047.

This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers.It is distributed in accordance with the Creative Commons Attribution NonCommercial(CC BYNC 4.0)license,which permits others to distribute,remix,adapt,build upon this work non-commercially,and license their derivative works on different terms,provided the original work is properly cited and the use is noncommercial.See:https://creativecommons.org/Licenses/by-nc/4.0/

The authors have no actual or potential conflict of interest to declare.

Wang TQ

2. Woodcutter: Woodcutter was one of the lowliest, least paying occupations (Matthews 1962). Jack48 Zipes explores the tale as a story of triumph of the working or plebian class over the higher class. The family is ultimately victorious49 over poverty and the witch -- who like the richer and higher classes -- has more than enough storage of food and treasure that could be shared to lessen50 the suffering of the lower classes. The hatred51 which the peasantry felt for the aristocracy as hoarders and oppressors is represented by the killing52 of the witch (Zipes 1979). Return to place in story.

And the Porcelain Maiden agreed to follow him, and after having given up her clothes, the young man bought a small horse for her, which went like the wind

The second week of the game brought more amazing events. The garbage was taken out without anyone being asked. Someone even did two of Kelly’s hard math problems one night when she left her homework out on the table.

Zhang H

1 Nasa P,Chaudhary S,Shrivastava PK,Singh A.Euglycemic diabetic ketoacidosis:A missed diagnosis.

2021;12:514-523[PMID:33995841 DOI:10.4239/wjd.v12.i5.514]

2 Clark A,Mohammed AS,Raut A,Moore S,Houlden R,Awad S.Prevalence and Clinical Characteristics of Adults Presenting With Sodium-Glucose Cotransporter-2 Inhibitor-Associated Diabetic Ketoacidosis at a Canadian Academic Tertiary Care Hospital.

2021;45:214-219[PMID:33046401 DOI:10.1016/j.jcjd.2020.08.100]

3 Ata F,Yousaf Z,Khan AA,Razok A,Akram J,Ali EAH,Abdalhadi A,Ibrahim DA,Al Mohanadi DHSH,Danjuma MI.SGLT-2 inhibitors associated euglycemic and hyperglycemic DKA in a multicentric cohort.

2021;11:10293[PMID:33986421 DOI:10.1038/s41598-021-89752-w]