Euglycemic diabetic ketoacidosis with gastrointestinal dysfunction following lung surgery in a patient on SGLT2 inhibitor: a case report

Introduction

Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are recommended for patients with type 2 diabetes mellitus (T2DM) complicated by chronic heart or kidney disease, due to their proven benefits in reducing cardio-renal events and mortality. However, SGLT2 inhibitors are associated with a rare but serious adverse effect: euglycemic diabetic ketoacidosis (EDKA) (1,2). EDKA is characterized by elevated blood or urine ketones with normal or mildly elevated blood glucose (BG) levels (typically 7–13 mmol/L) (3). The absence of significant hyperglycemia often leads to underrecognition or delayed diagnosis.

Patients using SGLT2 inhibitors are at significantly increased risk of developing EDKA during the perioperative period. Precipitating factors include fasting, dehydration, surgical stress, and infection. Surgical trauma promotes the release of stress hormones (e.g., epinephrine, cortisol) and inflammatory mediators, exacerbating insulin resistance and enhancing gluconeogenesis, glycogenolysis, and ketogenesis (4).

While perioperative EDKA has been reported in abdominal and obstetric surgeries, its occurrence after lung surgery—particularly when there is concurrent gastrointestinal (GI) dysfunction—is rare (3,5). Video-assisted thoracoscopic surgery (VATS) lobectomy may contribute to GI dysfunction through mechanism such as diaphragmatic irritation which can exacerbate ketogenesis in SGLT2i users.

This article reports a case of EDKA accompanied by GI dysfunction following lung surgery in a patient using an SGLT2 inhibitor, and discusses the underlying mechanisms and potential preventive strategies. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-245/rc).

Case presentation

A 42-year-old female was admitted for a “right upper lung nodule detected during a health checkup two years prior”. She had a 10-year history of T2DM, managed with oral metformin (1 g bid) and empagliflozin (10 mg qd), achieving suboptimal glycemic control (fasting BG: 7 mmol/L; postprandial glucose: 8 mmol/L). She denied other chronic diseases, specific occupational exposures, smoking, or alcohol use. Preoperative chest computed tomography (CT) revealed a 12 mm × 9 mm solid nodule in the right upper lobe (suspected early-stage lung cancer). Admission fasting BG was 6.29 mmol/L. No adjustments were made to her antidiabetic regimen preoperatively. She had no evidence of acidemia at the time of admission.

After 17 hours of fasting, the patient underwent an uneventful video-assisted thoracoscopic right upper lobectomy with systematic lymph node dissection under general anesthesia. Until postoperative day (POD)1, her oral intake was minimal, consisting only of small amounts of a liquid diet, resulting in inadequate caloric and carbohydrate intake. Postoperatively (days 0 and 1), vital signs were stable. She reported mild right lower abdominal pain, and chest tube drainage was <25 mL/day. A chest X-ray on POD2 morning showed good lung re-expansion (Figure 1). No evidence of infection was found (white blood cell 5.54×10⁹/L, C-reactive protein 2.91 mg/L). Perioperative hydration included 1,500 mL/day crystalloids, and analgesia followed standard protocol. However, that afternoon, she developed sudden dyspnea and worsening right lower abdominal pain, despite normal flatus and bowel movements. Heart rate was 130–150 bpm, and oxygen saturation was 99%. The chest drain was removed, but symptoms persisted. Fasting BG was 6.23 mmol/L. Esmolol hydrochloride (0.1 g/hour) was administered intravenously, reducing the heart rate to 100 bpm. Arterial blood gas (ABG) analysis revealed severe metabolic acidosis: pH 7.022, pO₂ 146.1 mmHg, pCO₂ 19.5 mmHg, HCO₃⁻ 4.9 mmol/L, base excess (BE) −24.4 mmol/L, anion gap (AG) 27.4 mmol/L, BG 6.23 mmol/L. Despite immediate infusion of 500 mL sodium bicarbonate (250 mL, 12.5 g), repeat ABG showed minimal improvement (pH 7.153), and abdominal pain persisted. Thoracoabdominal CT confirmed postoperative changes without effusion but with significant GI distension (Figure 1). Nasogastric tube (NGT) insertion for decompression yielded large amounts of gas and food residue, with little pain relief.

Figure 1 Postoperative chest X-ray showing good lung re-expansion and abdominal CT demonstrating significant gastrointestinal distension. CT, computed tomography.

On POD3, the diagnosis of EDKA was confirmed based on the characteristic metabolic profile. Urinalysis revealed significant ketonuria (80 mg/dL) and glycosuria (2,000 mg/dL), while laboratory results demonstrated severe ketosis (β-hydroxybutyrate 8.11 mmol/L) in the context of a normal glycated hemoglobin (HbA1c) (7.4%) and lactate level (1.81 mmol/L), solidifying the diagnosis. The NGT was removed. Fluid resuscitation was initiated with enteral nutrition reintroduced. HbA1c, beta-hydroxybutyrate (β-HB), and lactate levels were monitored, alongside 2-hourly capillary BG checks. To simultaneously address the ketoacidosis and the risk of hypoglycemia, a fixed-dose intravenous insulin regimen was initiated. This consisted of an admixture of 10 IU of human insulin in a solution of 1,000 mL 5% dextrose and 500 mL 0.9% saline, supplemented with 30 mL of 10% KCl. This protocol was designed to provide a continuous, low-dose insulin infusion to suppress ketogenesis while the dextrose served as a substrate to prevent hypoglycemia. Capillary BG was monitored at 2-hour intervals to ensure levels remained within a target range of 7–12 mmol/L.

Following the initiation of intravenous insulin and dextrose therapy, the patient’s symptoms (including palpitations and abdominal pain) resolved. By POD5, the patient was alert, well, and symptom-free. Repeat ABG and urinalysis were normal (pH 7.479, pO₂ 126 mmHg, pCO₂ 35.1 mmHg, AG 19.73 mmol/L, BG 7.8 mmol/L, normal potassium and bicarbonate levels; Figure 2). The patient was discharged.

Figure 2 Dynamic changes in key metabolic parameters during hospitalization. The patient’s SGLT2i was discontinued on the day before surgery and was not resumed. The line graph illustrates the trends of serum HCO₃⁻ (mmol/L), BG (mmol/L), AG (mmol/L), and arterial pH from POD2 to POD7. Key clinical milestones are annotated, including the confirmation of EDKA, removal of the NGT, and initiation of fluid resuscitation. AG, anion gap; BG, blood glucose; EDKA, euglycemic diabetic ketoacidosis; HCO₃⁻, bicarbonate; NGT, nasogastric tube; POD, postoperative day; SGLT2i, sodium-glucose cotransporter-2 inhibitor.

The patient was followed up 3 months after discharge. She had recovered well with no reported complications. Her BG levels and other metabolic indicators were normal without recurrence.

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 and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

Diabetic ketoacidosis (DKA) is a complication of both type 1 and type 2 diabetes mellitus, characterized by severe metabolic derangement in carbohydrate, fat, and protein metabolism due to insulin deficiency and inappropriate elevation of counterregulatory hormones. Its classic features include hyperglycemia, ketonemia/ketonuria, and metabolic acidosis. The American Diabetes Association (ADA) diagnostic criteria require hyperglycemia (BG >13.9 mmol/L), acidosis (arterial pH <7.3, serum bicarbonate <15 mEq/L), and ketosis (moderate ketonuria or ketonemia) (6). This patient presented with acidosis and ketonuria without significant hyperglycemia, consistent with EDKA.

Common causes of EDKA include SGLT2i use, pregnancy, and prolonged fasting (7). While SGLT2is offer cardiovascular and renal protective benefits (8,9), they inhibit renal glucose reabsorption via SGLT2 transporters in the proximal tubule, promoting glycosuria and weight loss, but also enhancing insulin sensitivity (10). This mechanism leads to osmotic diuresis, volume contraction, reduced BG, enhanced lipolysis, increased glucagon/insulin ratio, and ultimately, elevated ketogenesis (10-12).

EDKA specifically associated with SGLT2i use in the perioperative period is termed SGLT2i-associated perioperative ketoacidosis (SAPKA) (3). A cohort study of 2,183 surgeries estimated SAPKA incidence at 0.17% for elective and 1.1% for emergency procedures, highlighting its rarity in elective settings and potential for misdiagnosis (13).

This patient underwent elective VATS lobectomy while taking an SGLT2i. The combination of preoperative fasting and markedly inadequate postoperative oral intake (only minimal liquid diet on POD1) likely depleted glycogen stores, triggering lipolysis and ketogenesis despite euglycemia, precipitating EDKA. A critical observation in this case was the possible association between postoperative GI distension (confirmed by CT) and EDKA development. Anesthesia and surgical trauma directly suppress GI motility, impairing carbohydrate absorption and depleting hepatic glycogen. Concomitant SGLT2i use exacerbated volume depletion via osmotic diuresis, further suppressing insulin and elevating glucagon. This created a vicious cycle of “malabsorption-hypovolemia-insulin resistance”, culminating in ketoacidosis. Non-specific symptoms like abdominal distension and pain are easily mistaken for routine postoperative issues; this case underscores the danger, as diagnosis was delayed until severe acidosis (pH 7.0) occurred (14,15). Crucially, mechanical decompression via NGT alleviated distension but failed to halt ketogenesis, emphasizing the necessity of metabolic intervention.

Based on this case, we recommend for surgical patients on SGLT2i:

• Discontinue SGLT2i 3–4 days preoperatively, substituting with alternative agents or insulin pump therapy tailored to the patient (16).
• Routinely monitor urine ketones perioperatively. Positive ketones warrant immediate ABG analysis to assess for ketoacidosis.
• Encourage adequate carbohydrate intake postoperatively to minimize lipolysis and ketogenesis.
• For patients with poor oral intake, administer dextrose-containing intravenous fluids with insulin and potassium, closely monitoring cardiac function.
• Consider EDKA promptly in patients with GI symptoms (abdominal pain, nausea, vomiting), ensuring metabolic intervention accompanies symptomatic treatment.

Conclusions

This case highlights the diagnostic challenge of EDKA in postoperative patients on SGLT2 inhibitors, particularly when masked by GI symptoms. It underscores the critical importance of prompt metabolic intervention with dextrose, insulin, and fluids, as isolated symptomatic management is ineffective. This report emphasizes the necessity of preoperative drug cessation and heightened clinical vigilance to prevent this serious complication.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-245/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-245/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-245/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are 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 and accompanying images. 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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