Perioperative diabetic ketoacidosis associated with sodium-glucose co-transporter-2 inhibitors: a systematic review

Abstract

Background: Perioperative diabetic ketoacidosis (DKA) with near-normal blood glucose concentrations, termed euglycaemic ketoacidosis (EDKA), is an adverse effect associated with sodium-glucose co-transporter-2 inhibitors (SGLT2i). Guidelines are still evolving concerning the perioperative management of patients on SGLT2i. We performed a systematic review of published reports of DKA from SGLT2i in the surgical setting to understand better the clinical presentation and characteristics of SGLT2i-associated DKA. Methods: We searched PubMed, Embase, and ProQuest for reports of perioperative DKA involving SGLT2i up to January 2019. Results: Forty-two reports of EDKA and five cases of hyperglycaemic diabetic ketoacidosis (HDKA) were identified from 33 publications. Canagliflozin was implicated in 26 cases. Presentation time varied from a few hours up to 6 weeks after operation. Precipitating factors may include diabetes medication changes, diet modifications, and intercurrent illnesses. There were 13 cases (12 EDKA and one HDKA) of bariatric surgery, 10 of them noted very-low-calorie diet regimes as a precipitating factor. No precise association between interruption of SGLT2i and the occurrence of DKA could be identified. Seven patients required mechanical ventilation, and acute kidney injury was noted in five. Five cases needed imaging to rule out anastomotic leak and pulmonary embolism, all of them revealed negative findings. Outcome data were available in 32 cases, all of them recovered completely. Conclusions: EDKA is likely to be under-recognised because of its atypical presentation and may delay the diagnosis. Understanding this clinical entity, vigilance towards monitoring plasma/capillary ketones helps in early identification and assists in the management.

Scientific evidence underlying contraindications to the ketogenic diet: An update

“…Since the introduction of the glucose lowering class of drugs sodiumglucose cotransporter-2 inhibitors (SGLT2-i), several reports have been published regarding the risk of euglycaemic diabetic ketoacidosis (DKA) in those consuming HFKDs while on SGLT-2 treatment for type 2 diabetes [15][16][17][18][19]. SGLT2-i increase glucose urinary excretion by inhibiting the sodium and glucose reuptake in the kidney.…”

Periprocedural Euglycemic Diabetic Ketoacidosis Associated With Sodium–Glucose Cotransporter 2 Inhibitor Therapy During Colonoscopy

“…In contrast to reports in other settings, colonoscopy patients were systemically well ( 4 ). Patients presenting for colonoscopy have many of the same precipitating factors (e.g., very-low-calorie diet, volume depletion, reduced insulin administration/secretion) as those observed in bariatric surgery patients ( 5 ). It appears that bowel preparation increases EDKA risk, while the colonoscopy procedure itself may not.…”

Role of Canagliflozin on function of CD34+ endothelial progenitor cells (EPC) in patients with type 2 diabetes

“…Lastly, we wanted to examine any possible differences in ketone bodies between placebo and low dose canagli ozin as the latter has been shown to cause euglycemic ketosis [47], however at this dose we did not note any signi cant difference in serum ketone body levels. There are reports of canagli ozin in uencing mitochondrial function via AMPK-Sirt1-Pgc-1α signalling pathway [48] however we did not note any signi cant differences in NAD: NADH ratio, however it will be worthwhile to investigate into these effects at higher doses.…”