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

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 disea...

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Published inDiabetes care Vol. 42; no. 10; pp. 2008 - 2010
Main Authors Jehl, Alexandre, Cugnet-Anceau, Christine, Vigouroux, Corinne, Legeay, Anne L, Dalle, Stéphane, Harou, Olivier, Marchand, Lucien, Lascols, Olivier, Caussy, Cyrielle, Thivolet, Charles, Laville, Martine, Disse, Emmanuel
Format Journal Article
LanguageEnglish
Published United States American Diabetes Association 01.10.2019
Subjects
Adipose tissue
Antibodies
Apoptosis
Biopsy
CD8 antigen
Cell death
Complications
Cytotoxicity
Diabetes
Diabetes mellitus
Diabetes mellitus (insulin dependent)
Fibrosis
Hyperglycemia
Hypertriglyceridemia
Immune checkpoint
Immunotherapy
Insulin
Insulin resistance
Leptin
Life Sciences
Lipodystrophy
Lymphocytes
Lymphocytes T
Melanoma
Metastases
Monoclonal antibodies
PD-1 protein
Research design
Targeted cancer therapy
Therapy
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Summary: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. We describe the first reported case of AGL induced by immune checkpoint therapy. 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. 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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ISSN:0149-5992
1935-5548
0149-5992
DOI:10.2337/dc18-2535