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

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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