SAT-671 - Severe Insulin Resistance in A Case of Partial Lipodystrophy Significantly Improved by Tirzepatide

Background:
Lipodystrophy comprises a group of rare genetic or acquired disorders characterized by selective loss of adipose tissue. Impaired lipid storage leads to ectopic fat accumulation and severe insulin resistance, predisposing affected patients to multiple metabolic complications. Therapeutic options remain limited, and many patients experience progressive metabolic deterioration despite conventional therapy.
Clinical

Case:
A 44-year-old woman with a 26-year history of type 2 diabetes mellitus was referred to the clinic for further evaluation of long-standing metabolic disease. Her medical history was notable for recurrent pancreatitis, severe hypertriglyceridemia with chylomicronemia syndrome, coronary artery disease requiring coronary artery bypass grafting, and significant insulin resistance needing 1,200 units of insulin daily. Glycemic control remained poor over the years despite adherence to lifestyle interventions and treatment with multiple antihyperglycemic agents, including metformin, thiazolidinediones, SGLT2 inhibitors, and high doses of insulin. Physical examination revealed characteristic features of partial lipodystrophy, including disproportionate loss of adipose tissue in the lower extremities with relative central fat accumulation and marked acanthosis nigricans. Laboratory evaluation demonstrated persistent hyperglycemia, markedly elevated triglycerides of 1440 mg/dL, and creatine phosphokinase levels of 617 U/L. Secondary causes of insulin resistance, including Cushing syndrome, were excluded. Fasting leptin was 27 ng/mL. Body composition analysis using Dual-Energy X-ray Absorptiometry showed an increased trunk-to-lower-limb fat ratio of 1.16. Genetic testing for common forms of partial lipodystrophy, including LMNA and PPARG mutations, was negative. The patient was diagnosed with partial lipodystrophy based on physical examination, body composition analysis, and the severity of metabolic abnormalities. Tirzepatide was started at 2.5 mg weekly and titrated to 5 mg after one month. Over five months of therapy, the patient experienced substantial metabolic improvement without any side effects. Hemoglobin A1c decreased from 11.7% to 7.2%, triglyceride levels normalized to 126 mg/dL, and total daily insulin requirements decreased to 160 units per day, representing an 87% reduction. Levels of creatine phosphokinase also decreased to 161 U/L.

Conclusion:
This case adds to the growing body of evidence supporting the potential benefit of incretin-based therapies in patients with partial lipodystrophy and severe insulin resistance. The marked metabolic improvements observed with tirzepatide underscore the need for systematic studies to better define its therapeutic role in this high-risk population.

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