Abstract

Background/ObjectiveClosed-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 ReportA 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. DiscussionVolume 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. ConclusionPatients 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.

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