A new review published in Genes & Diseases identifies trained immunity — a long-lasting adaptation of the innate immune system — as a key mechanism in diabetes and its complications.
Here is a summary of the press release:
What is trained immunity?
It’s a form of immune memory where innate immune cells like monocytes and macrophages undergo lasting changes after exposure to metabolic stress or inflammation. They become primed to react more aggressively to future triggers, creating a state of chronic, low-grade inflammation that can persist even after blood sugar normalizes.
What triggers it in diabetes?
The review found that common diabetes-related factors can activate these pathways, including:
- Hyperglycemia (high blood sugar)
- Obesity
- Lipid abnormalities
- Changes in the gut microbiome
Why it matters for disease progression:
This sustained inflammatory response can:
- Promote insulin resistance
- Impair insulin-producing beta cell function
- Accelerate tissue damage
Beyond diabetes itself, trained immunity may help explain major complications, including atherosclerosis and cardiovascular disease, diabetic kidney disease, delayed wound healing, tissue fibrosis, and vascular dysfunction.
New treatment opportunities:
The authors suggest future therapies should target the immune mechanism itself, not just blood glucose. Promising directions highlighted include:
- Targeting inflammatory pathways like the NLRP3 inflammasome
- Modifying cellular metabolism (immunometabolism)
- Improving gut microbial balance through diet and microbiome-focused therapies
- Exploring vaccination strategies that reprogram immune responses
The overall shift is from viewing diabetes as purely a metabolic disorder to understanding it as a disease with a persistent innate immune component — opening new avenues for prevention and treatment of its long-term complications.