Speakers - DEWC2025

Abstract

Abstract:
The majority of morbidity and mortality caused by diabetes mellitus, including type 2 diabetes (T2DM), is due to vascular complications.  Apart from elevated levels of glucose, chronic low-grade inflammation has also become an important mediator of endothelial dysfunction and vascular disease. This conceptual paper forwards that dysregulated metabolism in diabetes subsequently activates inflammatory signals: mostly those from advanced glycation end-products, receptor for advanced glycation end-products and nuclear factor-kappa B that cause injury to endothelium and atherogenesis. We present the mechanistic rationale for this hypothesis, we summarily present evidence supporting it, and we point to future research directions that can lead to new therapeutic strategies for anti-inflammation in the care of the diabetic vasculature.
1. Introduction
More than 500 million people in the world are affected by diabetes mellitus and a major risk factor for cardiovascular disease. Things like heart problems, strokes and blood flow issues are linked to diabetes. It’s not just because blood sugar levels are high. It also has to do with body parts reacting badly to the sugars and other substances that the patient’s body makes on their own. Chronic inflammation in T2DM is increasingly considered a key factor contributing to endothelial dysfunction that may develop myriad vascular diseases.
2. Background and Rationale
The endothelium is a vital component in vascular homeostasis. Diabetes disrupts the balance whereby a state of persistent hyperglycemia and insulin resistance results in endothelial activation and damage. Growing evidence indicates that high blood sugar encourages AGE formation. Subsequently, AGEs attach to RAGE on endothelial cells. This process kicks off NF-κB activation. Furthermore, this activation triggers the release of pro-inflammatory cytokines, like TNF-α, IL-6, MCP-1.
This ongoing inflammation causes more oxidative stress, lowers nitric oxide (NO) availability, and raises the levels of vascular adhesion molecules like VCAM-1 and E-selectin. The function of the endothelium will be impaired and atherogenic plaque will develop.

3. Hypothesis
Our study hypothesizes that diabetes-hyperglycemia and insulin resistance in T2DM induce vascular inflammation by enhancing cytokine production and activating AGE-RAGE-NF-κB signaling pathways. Endothelial dysfunction and atherogenesis speed up due to this cascade.
4. Evidence Supporting the Hypothesis.
Many clinical and experimental studies support this mechanism. In patients with diabetes and vascular complication there are increased serum level of IL-6, TNF-α, CRP levels. Studies done on cells show high sugar levels excite NF-kB in inside of blood vessel cells. Studies with animals show that stopping RAGE or NF-\u03baB signaling helps with a lot of things. 
5. Research Directions.
To test and refine this hypothesis, future research should measure markers for inflammation and endothelial dysfunction in diabetic and non-diabetic individuals.
To use the cultures of endothelial cells and diabetic animal models to dissect the signalling pathways.
To check out the protective benefits against vascular damage provided by anti-inflammatory agents like Metformin and Statins in this research. 
To study how genes and other factors control RAGE and NF-κB in diabetes.
6. Implications for Therapy
If this hypothesis is validated, it indicates that anti-inflammatory intervention is needed for diabetic vascular disease. Therapies which reduce inflammation may help with glycemic control and add further protection against cardiovascular complications.
7. Conclusion
This model links metabolic and inflammatory pathway that links diabetes to vascular injury.  The hypothesis provides a basis for future studies aimed at reducing diabetic vascular disease burden by anti-inflammatory strategies based on the AGE-RAGE-NF-κB axis and the correlated cytokine responses.