Case Report: Resolution of severe hypertriglyceridemia and cessation of exogenous insulin during ketogenic-range therapeutic carbohydrate reduction, insulin deprescribing, and tirzepatide

Severe hypertriglyceridemia [sHTG; triglycerides ≥500 mg/dL (SI: ≥5.65 mmol/L)] is conventionally managed with dietary fat restriction, but in insulin-resistant type 2 diabetes mellitus (T2DM) low-fat diets may increase carbohydrate intake and worsen dysglycemia. A 51-year-old woman with persistent sHTG, five episodes of pancreatitis, T2DM requiring 210 units of insulin daily, and a body mass index of 27.5 kg/m 2 was evaluated. Despite two decades of low-fat counseling and multidrug therapy, fasting triglycerides were 860 mg/dL (SI: 9.71 mmol/L), hemoglobin A1c 7.1% (SI: 54 mmol/mol), glucose management indicator (GMI) 8.3%, and continuous glucose monitoring (CGM) time in range (TIR) 35%. She was prescribed therapeutic carbohydrate reduction (TCR), a whole-food eating pattern delivered as a written food list designed to provide fewer than 20 g/day of carbohydrate (approximately 5% of energy, within the ketogenic range); intake was not quantified and ketones were not measured. A chylomicronemia gene panel identified no pathogenic variants, consistent with probable multifactorial chylomicronemia syndrome (MCS). At 1 month, after initiation of carbohydrate reduction with concurrent CGM-guided reduction of insulin from 210 to 20 units/day, with no other medication change and before tirzepatide, triglycerides had fallen 49.5% to 434 mg/dL (SI: 4.90 mmol/L), GMI to 7.1%, and TIR had risen to 74%. This brought triglycerides below the level at which endocrinology, cardiology, and the treating clinician had, by individualized judgment, deferred incretin therapy, and tirzepatide 2.5 mg was initiated. At 5 months triglycerides were 162 mg/dL (SI: 1.83 mmol/L), hemoglobin A1c 6.1% (SI: 43 mmol/mol), body weight had fallen 18%, and exogenous insulin had been discontinued. At 9 months she remained free of exogenous insulin, with triglycerides 172 mg/dL (SI: 1.94 mmol/L) and hemoglobin A1c 6.1% (SI: 43 mmol/mol). The first-month triglyceride reduction occurred during ketogenic-range TCR with concurrent insulin reduction; later improvements occurred during continued TCR, insulin cessation, weight loss, and tirzepatide, and the contributions of these components cannot be separated. In selected patients with probable MCS and insulin-resistant T2DM, supervised ketogenic-range TCR may be considered when low-fat counseling has not achieved sustained control and may permit reconsideration of therapies deferred by individualized judgment for pancreatitis risk.