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

Diabetes Care. 2019 Oct;42(10):2008-2010. doi: 10.2337/dc18-2535. Epub 2019 Aug 21.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / adverse effects*
  • Diabetes Mellitus, Type 1 / chemically induced*
  • Diabetes Mellitus, Type 1 / immunology
  • Female
  • Humans
  • Lipodystrophy / chemically induced*
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Middle Aged
  • Neoplasm Metastasis
  • Nivolumab / adverse effects*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / immunology
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology

Substances

  • Antineoplastic Agents
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab