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Acquired Generalized Lipodystrophy: A New Cause of Anti-PD-1 Immune-Related Diabetes

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Jehl, A. | Cugnet-Anceau, C. | Vigouroux, C. | Legeay, A. L. | Dalle, S. | Harou, O. | Marchand, L. | Lascols, O. | Caussy, C. | Thivolet, C. | Laville, M. | Disse, E.

Edité par CCSD ; American Diabetes Association -

International audience. OBJECTIVE: Anti-programmed cell death-1 (anti-PD-1) antibodies have revolutionized advanced cancer therapy. Anti-PD-1 therapy is responsible for immune-related adverse events, with frequent endocrine manifestations, including acute-onset type 1 diabetes. Acquired generalized lipodystrophy (AGL) is a rare disease, believed to be immune mediated, characterized by loss of adipose tissue and insulin resistance-associated complications. RESEARCH DESIGN AND METHODS: We describe the first reported case of AGL induced by immune checkpoint therapy. RESULTS: A 62-year-old woman with metastatic melanoma treated with nivolumab was referred for major hyperglycemia, hypertriglyceridemia, and nonalcoholic steatohepatitis. She had presented with a rapidly progressive generalized loss of subcutaneous adipose tissue. Diabetes was associated with severe insulin resistance and undetectable plasma leptin. Subcutaneous biopsy revealed atrophic adipose tissue infiltrated with cytotoxic CD8(+) T lymphocytes and fibrosis. CONCLUSIONS: AGL is an additional immune-related adverse event of anti-PD-1 therapy that leads to severe insulin resistance-associated complications.

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