Euglycemic diabetic ketoacidosis following sleeve gastrectomy in a patient with type 2 diabetes on a sodium-glucose co-transporter 2 inhibitor: a case report and call for practice guidelines

Introduction

Background

Sodium-glucose co-transporter 2 inhibitors (SGLT2is) belong to a relatively new oral glucose-lowering class of medications. They inhibit glucose reabsorption in the renal proximal convoluted tubules, promoting glucosuria. This has been shown to cause a glycated hemoglobin (A1C) reduction of 0.8–1% on average (1). Over the past decade, these agents have gained popularity with more evidence showing cardiorenal benefits, including reduction in major adverse cardiovascular events, preservation of nephron function in chronic kidney disease, and reduction in hospitalizations in patients with type 2 diabetes (T2D) and heart failure (HF) (2).

These advantages, in addition to their modest weight-loss effects, make SGLT2is an attractive choice for lowering glucose levels in patients with T2D and obesity (3).

Despite being rare in T2D, diabetic ketoacidosis (DKA), which usually occurs in the absence of insulin in type 1 diabetes (T1D), has been reported in T2D, especially in patients taking SGLT2is, prompting the release of a Food and Drug Administration (FDA) warning in 2015 (4).

This entity presents a diagnostic challenge owing to the absence of one of the elements of the classical DKA triad—significant hyperglycemia, and the non-specificity of symptomatology. However, the other two elements of this triad, metabolic acidosis and ketonemia, are present. DKA requires fast recognition and treatment, as it is a serious and potentially fatal condition, with mortality rates of 0.65–3.3% (5).

Typical DKA presents with symptoms of hyperglycemia, such as polyuria and polydipsia; other nonspecific symptoms, such as nausea, vomiting, abdominal pain, dyspnea, and confusion; or symptoms of precipitating factors, such as infection and major cardiovascular events (6). Therefore, a high index of suspicion should be raised if any of these symptoms are present in a patient with T1D and ketosis-prone T2D in the event of precipitants, such as acute illness, excessive physical exertion, and recent major surgery. Healthcare providers should assess for acidosis (pH <7.3 and/or bicarbonate <18 mmol/L), ketonemia or ketonuria (β-hydroxybutyrate concentration ≥3 mmol/L or urine ketone strip ≥2+), and hyperglycemia (serum glucose ≥11 mmol/L or prior history of diabetes) in typical DKA. However, serum glucose is likely to be lower in the context of SGLT2i; hence it causes euglycemic DKA (eDKA) (7,8).

T2D, a common comorbidity of obesity, is a prevalent background condition in patients undergoing bariatric surgery. Many of these patients are on SGLT2is, which increases the risk of eDKA (3).

Rationale and knowledge gap

Few cases of bariatric surgery-related DKA have been described in the literature, calling for more efforts to address this preventable life-threatening condition in such an increasingly prevalent surgical intervention (9-12). However, this has not been reflected in the current bariatric surgery literature and guidelines in the form of clear guidance to clinicians (13-15).

Objective

This report presents a case of eDKA following a laparoscopic sleeve gastrectomy (LSG) in a patient with T2D on an SGLT2i and discusses the implications for perioperative diabetes management. This case raises awareness and calls for better perioperative medication guidelines. This article is presented in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-232/rc).

Case presentation

A 62-year-old woman with T2D and severe obesity was referred to the bariatric surgery clinic for evaluation of candidacy for LSG. Her body mass index at the time of the initial evaluation was 55 kg/m². She also had severe obesity complications, including a history of poorly controlled T2D, gastroesophageal reflux disease, degenerative joint disease of the spine, and obstructive sleep apnea.

She had a history of more than 30 years of poorly controlled T2D with difficulty in controlling blood glycemia despite multiple oral anti-hyperglycemic medications, insulin, and lifestyle efforts.

Most recently, prior to the LSG, she was referred to the endocrinology clinic for preoperative diabetes control because her A1C was 14%. Over the following 18 months, she aggressively lowered A1C to 7.1%, a month prior to the procedure with insulin degludec 40 IU at bedtime and prandial insulin aspart 40 IU. On admission, the patient underwent an uneventful LSG. Throughout her 2-day post-operative hospital stay, her home insulin regimen was completely stopped. She was placed on a fast-acting insulin sliding scale and required no insulin injections, with in-house serum glucose readings of 3.9–8.9 mmol/L. The patient tolerated a liquid diet, with mild nausea and minimal surgical site pain, which was controlled using oral analgesics. Otherwise, she felt well, ambulated, and voided as expected for safe discharge. For diabetes management, she was discharged on metformin 500 mg twice daily and empagliflozin 25 mg daily on post-operative day (POD) 2 and instructed to discontinue all insulin medications.

She presented to the bariatric surgery clinic on POD 7 with generalized fatigue for 5 days, nausea, vomiting after any oral intake, abdominal pain, constipation, progressive dizziness, and blurred vision. However, the patient denied having abdominal distention, melena, or hematochezia. She noticed concentrated urine but had no change in urine color or smell. She was hemodynamically stable, except for tachypnea (22 breaths per minute). She looked ill and dehydrated but had a normal mental state exam, and abdominal examinations revealed well-healing surgical wounds and mild tenderness without distension or signs of peritonitis. She had severe metabolic acidosis detected on point-of-care venous blood gas (VBG) testing, which prompted a decision to send her to the emergency department.

Upon hospital evaluation, the surgical team requested imaging studies, including a fluoroscopic Gastrografin study, followed by computed tomography (CT) of the abdomen and pelvis. The initial imaging study demonstrated an unobstructed flow of contrast through the gastric sleeve without evidence of leakage or obstruction, while the CT confirmed the absence of surgical complications.

The patient’s blood tests revealed a normal serum sodium of 140 mmol/L, chloride of 105 mmol/L, and hypokalemia with potassium at 2.9 mmol/L (normal: 3.5–5.0 mmol/L). Blood urea nitrogen was 2.5 mmol/L (2.5–7.1 mmol/L), while creatinine was initially 98 µmol/L (her baseline was in the 40 s). VBGs consistently demonstrated a high anion gap metabolic acidosis, with an initial pH of 7.15, bicarbonate of 10 mmol/L, pCO₂ of 21.5 mmHg, and an anion gap of 20 (normal: 8–12). Lactate level was normal (1.3 mmol/L). The urine dipstick test was strongly positive for ketones (+3) and glucose (+3). Blood glucose levels remained between 5.4 and 9 mmol/L. A complete blood count was unremarkable with a white cell count of 9.5×10⁹/L, hemoglobin of 146 g/L, and platelets of 314×10⁹/L. Liver function tests were within acceptable limits, and lipase was 113 U/L and not consistent with pancreatitis.

The patient was admitted to a step-down unit under the care of a general medical team. The endocrinology team was consulted, and a diagnosis of eDKA was made. The potential etiology was the initiation of SGLT2is in a high-risk post-bariatric surgery state with decreased oral intake and insulin deficiency. The culprit medication was discontinued, and the patient received appropriate treatment with hydration and intravenous insulin therapy, in addition to electrolyte correction. She was discharged after 2 days with normalization of blood markers, improvement of symptoms, and tolerance of oral intake. She resumed a lower basal-bolus insulin regimen with close follow-up and endocrinology appointments. After 3 months, during her endocrinology visit, she felt well and was able to successfully advance her diet; she lost 10 kg, and her A1C level decreased to 6.1% on 1,000 mg metformin twice a day and 30 IU insulin degludec. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Key findings

This report presents a case of early post-LSG eDKA following the initiation of SGLT2i and discontinuation of insulin in a normoglycemic patient with long-standing T2D.

Explanations of findings

Perioperative eDKA, specifically post-bariatric surgery, tends to be multifactorial and requires a multidisciplinary approach for management and prevention. This patient probably had underlying partial insulinopenia evident by a long-term history of T2D, poor glycemic control, and a high insulin requirement preoperatively. Therefore, eDKA was likely triggered by a combination of premature insulin withdrawal plus superimposed addition of SGLT2i. Other factors that affect bariatric surgery patients, particularly those at higher risk for DKA, include catabolism and physiological stress responses from extended caloric restriction, and the tendency for hypovolemia in the context of expected decreased oral intake (7). SGLT2is may contribute to the complexity of eDKA via three mechanisms. First, they suppress insulin release, stimulate glucagon release in the absence of hepatic glycogen storage, and induce glucosuria, all of which promote the formation of ketone bodies. Second, by directly acting on pancreatic α-cells, these agents further stimulate glucagon secretion. Third, they may enhance ketone reabsorption in the nephrons. Additionally, increased urinary glucose excretion may prevent hyperglycemia and suppress gluconeogenesis and subsequent ketogenesis (16).

Comparison with similar research

Existing cases of DKA following LSG share similar diagnostic challenges, underscoring the need for clearer guidelines. Table 1 shows the characteristics of this patient, in comparison with previously reported patients (9,17). The four patients shared baseline conditions, including T2D, insulin use, and severe obesity (class III obesity), which indicated severe insulin resistance and low pancreatic cell reserve. All patients presented with DKA post LSG within the first 30 days and required hospital admission to a high level of care (i.e., intensive care unit or stepdown medical unit). Nausea and vomiting were by far the most common presenting symptoms. These are considered “expected” post-bariatric surgery complaints, contributing to delays in presentation and diagnosis. In the present case, SGLT2is were introduced to the patient regimen for the first time post-surgery, causing eDKA with normoglycemia. Notably, SGLT2is were never stopped in case two and were discontinued 1 week pre-surgery in case three. In the latter two cases, SGLT2is partially masked hyperglycemia, but at different levels. Case one is an example of classic DKA in which the three components of the classic DKA triad, including marked hyperglycemia, were present. Proactive measurements of serum ketone levels, bicarbonate concentrations, and the anion gap in patients taking SGLT2is for acute illness or physiological stress may be reasonable for the early detection of eDKA (7). In all these cases, insulin omission was the main culprit, highlighting the need for physician and patient education regarding early post-operative insulin management in T2D. Patient and physician fear of hypoglycemia caused by decreased oral intake may promote premature and excessive reduction in insulin dosage.

Implications and actions needed

In a broader scope, the use of SGLT2is in hospitalized patients, a similar high-risk group, for inpatient glycemic control has been discouraged due to the increased risk of DKA, hypovolemia, and genitourinary infections. Current guidelines favor insulin or dipeptidyl peptidase-4 inhibitors in such population. However, emerging evidence suggests potential advantages of initiating SGLT2is for patients during hospitalization in the setting of HF (18). The current perioperative guidelines, including bariatric surgery, lack consistent recommendations on management of SGLT2is (13,15,19). Preoperatively, multiple international professional societies advise withholding SGLT2is for at least 3 days while others recommend stopping only the day before (19). Another ongoing controversy is the value of using ketone-based risk stratification preoperatively to assess risk of eDKA in such patients (19). This divergence highlights the need for standardized perioperative algorithms. The Canadian Adult Obesity Clinical Practice Guidelines released in 2020 state that SGLT2is should be discontinued while on a very low-calorie diet in preparation for bariatric surgery, when it is done for the purpose of decreasing liver volume, usually 2 weeks prior to surgery. However, they do not make further recommendations for the post-operative management of SGLT2is in this case or pre-operative and post-operative management in other case scenarios (15). The American Association of Clinical Endocrinologists/American College of Endocrinology; The Obesity Society; American Society for Metabolic and Bariatric Surgery; Obesity Medicine Association; and the American Society of Anesthesiologists collaborative guidelines in 2019 have given grade D recommendations for stopping SGLT2is and insulin secretagogues in immediate post-operative patients (13). A more cautious approach has been recommended by experts in the field who advocate that SGLT2is should only be postoperatively restarted if oral intake is stable; insulin needs are defined; and the risks of catabolism, hypovolemia, and ketosis have resolved, which usually coincides with the progression to solid foods at 4–6 weeks post-bariatric surgery (7).

Strengths and limitations

This case adds to the limited literature on eDKA after bariatric surgery, particularly when SGLT2is are introduced early in the postoperative period. The strength of this case lies in raising awareness of a preventable complication and offering practical recommendations for perioperative diabetes management. However, as a single case, it cannot quantify risk. Larger studies and formal guidelines are needed to guide safe practice in this setting.

Conclusions

Incorporating perioperative endocrinology involvement in managing every bariatric surgery patient with diabetes who is on insulin and/or SGLT2is is suggested, along with postoperative routine monitoring of anion gap and ketones. In addition, surgical care teams should be educated about eDKA in this context, and current perioperative diabetes management guidelines on SGLT2i management, particularly in bariatric surgery, should be reassessed.

Acknowledgments

None.

Footnote

Reporting Checklist: The author has completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-232/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-232/prf

Funding: None.

Conflicts of Interest: The author has completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-232/coif). The author has no conflicts of interest to declare.

Ethical Statement: The author is accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Written informed consent was obtained from the patient for the publication of this case report. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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