Diabetic Ketoacidosis in a Patient With Type I Diabetes Treated With a Closed-Loop Sensor-Augmented Insulin Infusion System.

Background/objective: Closed-loop insulin infusion systems (CLSs) such as Tandem t:slim with Control-IQ (t:slim CIQ) improve glycemic control and decrease diabetic ketoacidosis (DKA) risk in type 1 diabetes mellitus (T1DM). We report a case of CLS failure, likely from tirzepatide-induced volume depletion, leading to DKA.

Case Report: A 36-year-old woman with T1DM on t:slim CIQ CLS was prescribed tirzepatide for weight loss. Three months later, 4 days after the last tirzepatide injection, she presented with worsening nausea, vomiting, 50-lbs weight loss, minimal oral intake for 3 days, and positive urine ketone result. Her heart rate was 137 beats/min and respiratory rate was 35 breaths/min, and she had Kussmaul breathing, with dry oral mucosa indicating volume depletion. Laboratory examination showed a fingerstick glucose level of 289 mg/dL, serum glucose level of 322 mg/dL, bicarbonate level of 12 mmol/L, and anion gap of 21 mmol/L confirming high-anion-gap metabolic acidosis, suggesting DKA. A concurrent continuous glucose monitor (CGM) reading was 40 mg/dL. The CLS and CGM were removed. DKA resolved within 72 hours (serum glucose level of 143 mg/dL, anion gap of 8 mmol/L, bicarbonate level of 24 mmol/L) on intravenous insulin and fluids. The CLS and CGM were restarted with good glycemic control. Tirzepatide was discontinued to avoid future episodes of volume depletion.

Discussion: Volume depletion affects interstitial fluid glucose levels due to compensatory mechanisms. This may result in CLS failure due to CGM dependence on interstitial glucose measurements, precipitating DKA.

Conclusion: Patients on CLS therapy should be cautioned against CLS failure in volume-depleted states with interstitial glucose-level changes. A back-up plan with multiple daily insulin injections should be discussed.