Research Article Details
| Article ID: | A47815 |
| PMID: | 31434650 |
| Source: | Diabetes Care |
| Title: | Acquired Generalized Lipodystrophy: A New Cause of Anti-PD-1 Immune-Related Diabetes. |
| 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. |
| DOI: | 10.2337/dc18-2535 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I06 | 811 | Lipodystrophy | A connective tissue disease that is characterized by marked reduction, absence, and/or the redistribution of adipose tissue. https://www.ncbi.nlm.nih.gov/pubmed/25690482, https://www.ncbi.nlm.nih.gov/pubmed/25833179 | disease of anatomical entity/ musculoskeletal system disease/ connective tissue disease | Details |