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

Alexandre Jehl1,2,3, Christine Cugnet-Anceau1,2,3,4, Corinne Vigouroux1,5,6

  • 1French Network of Rare Diseases of Insulin Secretion and Insulin Sensitivity (PRISIS) and FIRENDO Network, Paris and Lyon, France.

Diabetes Care
|August 23, 2019
PubMed
Abstract

Insights

Immune checkpoint therapy, specifically anti-PD-1 antibodies, can cause acquired generalized lipodystrophy (AGL). This rare condition leads to severe insulin resistance and related complications.

Area of Science:

  • Immunology
  • Endocrinology
  • Oncology

Background:

  • Anti-programmed cell death-1 (anti-PD-1) antibodies are a revolutionary cancer therapy.
  • These therapies can cause immune-related adverse events, including endocrine disorders like type 1 diabetes.
  • Acquired generalized lipodystrophy (AGL) is a rare, immune-mediated condition causing adipose tissue loss and insulin resistance.

Observation:

  • A patient with metastatic melanoma treated with nivolumab developed AGL.
  • The patient presented with hyperglycemia, hypertriglyceridemia, nonalcoholic steatohepatitis, and rapid loss of subcutaneous adipose tissue.
  • Biopsy showed adipose tissue with CD8+ T cell infiltration and fibrosis.

Findings:

  • This case represents the first report of AGL induced by immune checkpoint therapy.
  • The patient experienced severe insulin resistance and undetectable leptin levels.
  • The findings link AGL to anti-PD-1 therapy.

Implications:

  • AGL is a newly identified immune-related adverse event associated with anti-PD-1 therapy.
  • This condition can lead to significant insulin resistance and associated complications.
  • Awareness of AGL is crucial for managing patients undergoing immune checkpoint therapy.

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