ACHAIKI IATRIKI | 2024; 43(3):149–151
Case Report
Christos Sotiropoulos, Christos Konstantakis, Georgios Theocharis, Christos Triantos, Konstantinos Thomopoulos
Gastroenterology Department, University General Hospital of Patras, Patras, Greece
Received: 16 Feb 2024; Accepted: 08 Apr 2024
Corresponding author: Christos Sotiropoulos, Gastroenterology Department, University General Hospital of Patras, Patras, Greece; cr.sotiropoulos@hotmail.com
Key words: Euglycemic diabetic ketoacidosis (euDKA), post-ERCP cholangitis, SGLT-2 inhibitors
Abstract
Background: Euglycemic diabetic ketoacidosis (euDKA) is a rare yet serious side effect of SGLT-2 inhibitors. It is typically triggered by acute illness (such as infections), reduced food and fluid intake, decreased insulin doses, or alcohol consumption.
Case Presentation: We present a case of a 53-year-old patient, with a history of type 2 diabetes mellitus treated with Empagliflozin, who presented with abdominal pain and jaundice. Ultrasound revealed a dilated biliary tract and an ERCP identified a stenosis in the intrapancreatic segment of the bile duct. Histological analysis suggested adenocarcinoma and an abdominal CT scan showed a hypodense lesion in the head of the pancreas. Postoperatively, the patient developed euglycemic diabetic ketoacidosis and a Pseudomonas aeruginosa microbemia. Due to persistent fever, a follow-up CT scan was conducted, revealing a liver abscess, which was subsequently drained under CT guidance.
Conclusions: Euglycemic diabetic ketoacidosis is a rare but serious condition and its atypical presentation necessitates a high level of vigilance from physicians, as early detection and treatment are crucial for quickly and safely restoring acid-base balance.
INTRODUCTION
SGLT-2 inhibitors have gained great importance in recent years due to their cardioprotective and nephroprotective properties in patients with type 2 diabetes mellitus. A rare but serious side effect of SGLT-2 inhibitors is the euglycemic diabetic ketoacidosis (euDKA), which is usually triggered by acute disease, reduced food and fluid intake, reduced insulin doses, or alcohol consumption [1-4].
CASE PRESENTATION
We report a 53-year-old patient with a history of cholecystectomy, dyslipidemia and type 2 diabetes mellitus under treatment with Metformin 1000 mg 1×2 and Empagliflozin 25 mg 1×1, who was admitted to the hospital due to right upper quadrant abdominal pain with accompanying jaundice and the following laboratory test values: AST: 2338 U/l, ALT: 1508 U/l, γ-GT: 2020 U/l, ALP: 483 U/l, TBL: 2.65 mg/dl, DBL: 2 .22 mg/dl, Ca 19-9: 1181.86 U/ml. Physical examination showed no pathological signs, while intrahepatic and extrahepatic bile duct dilatations were revealed by abdominal U/S. The patient underwent ERCP (Figure 1A) where a stenosis in the intrapancreatic segment of the bile duct with prestenotic dilatation was revealed, a cytological smear was taken (histological examination: adenocarcinoma) and a fully covered metal stent of 6 cm length was inserted through the stenosis, while abdominal CT (Figure 1B) revealed a hypodense lesion (d. 3cm) in the head of the pancreas and portal vein thrombosis. Postoperatively (in the 1st 24-hours), the patient presented with febrile right upper quadrant abdominal pain, nausea, vomiting, lethargy, tachypnea and tachycardia with an accompanying increase in inflammatory markers and cholestatic enzymes, with normal serum glucose (Glu: 180 mg/dl). Blood cultures and arterial blood gasses were obtained where metabolic acidosis was found (pH: 7.21, HCO3: 13 mmol/l, Lac: 0.8 mmol/l) with an increased anion gap (25 mmol/l), while the general urine test analysis showed ketonuria (ketone > 43 mg/dl). The patient was administered intravenous antibiotic treatment for Gram (-) and anaerobic microbes and treatment of euglycemic diabetic ketoacidosis with an insulin pump with co-administration of glucose solution and intravenous administration of crystalline fluids and potassium replenishment. The SGLT-2 inhibitor was discontinued. The patient showed progressive improvement with gradual recovery of acidosis and anion gap with undetectable urinary ketones. Microbemia due to Pseudomonas aeruginosa was detected from the blood cultures, where the antibiotic treatment was modified based on the antibiogram; however, due to lack of apyrexia, an imaging re-evaluation with CT scan was performed, where a liver abscess was detected (Figure 1C). Eventually, liver abscess was treated with drainage under CT guidance (Figure 1D).
Figure 1. A. ERCP cholangiogram revealing a stenosis in the intrapancreatic segment of the common bile duct with prestonotic dilatation. B. Abdominal CT scan showing a hypodense lesion (d. 3cm) in the head of the pancreas and portal vein thrombosis. C. Liver abscess. D. Liver abscess drainage.
DISCUSSION
SGLT-2 inhibitors have become increasingly significant due to their cardiovascular and renal protective effects in diabetes [1]. In 2015, the US Food and Drug Administration (FDA) issued an official warning advising cautious use of SGLT-2 inhibitors due to the potential risk of euglycemic diabetic ketoacidosis (euDKA) [1]. While the introduction of SGLT-2 inhibitors in diabetic patients can lead to euDKA, the precise mechanism behind this phenomenon remains unclear [1]. Several contributing factors associated with SGLT-2 inhibitors in exacerbating euDKA include infections, acute pancreatitis, post-surgery recovery, malignancy, and reduced oral intake [1]. The primary hypothesized mechanism is outlined as follows [2]: SGLT-2 inhibitors induce significant glucosuria, lowering plasma glucose levels and stimulating glucagon secretion [2]. With glucose being the primary trigger for insulin release, plasma insulin levels decrease notably [2]. Conversely, plasma glucagon levels rise due to reduced insulin secretion and possibly decreased SGLT-2 mediated glucose transport into α-cells [2]. The diminished insulin to glucagon ratio triggers lipolysis and increases lipid oxidation, leading to ketoacidosis [2]. Insulin plays a pivotal role in regulating lipid metabolism [2]. Diabetic ketoacidosis is recognized as a contributor to hypertriglyceridemia [2]. Insulin deficiency prompts heightened lipolysis in adipose tissue, resulting in increased release of fatty acids [2]. Elevated free fatty acid delivery to the liver boosts very-low-density lipoprotein (VLDL) production [2]. Insulin deficiency also reduces lipoprotein lipase activity, which normally breaks down triglycerides in lipoproteins [2]. The combination of elevated serum VLDL and reduced lipoprotein lipase activity contributes to hypertriglyceridemia, further exacerbating ketoacidosis [2].
CONCLUSIONS
Euglycemic diabetic ketoacidosis is a rare but serious complication of SGLT-2 inhibitor administration, often with a multifactorial etiology. Its atypical appearance requires a high level of awareness from physicians as early recognition of this complication can quickly and safely restore acid-base balance.
Conflict of interest disclosure: None to declare.
Declaration of funding sources: None to declare.
Author Contributions: Christos Sotiropoulos, Christos Konstantakis, Georgios Theocharis: data collection & drafting of the article; Christos Triantos, Konstantinos Thomopoulos: drafting of the article & critical revision of the article for important intellectual content & final approval of the article. All authors read and approved the final manuscript.
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