Experimental compound may prevent diabetes complications independent of blood sugar control
An experimental drug compound shows promise for preventing and treating certain complications of diabetes — including slow wound healing and excessive inflammation — and appears to act independently of blood glucose control, according to a new study in mice and human cells published in Cell Chemical Biology.
What the researchers found
The research team, led by Dr. Ann Marie Schmidt at NYU Langone and structural biologist Alexander Shekhtman at SUNY Albany, focused on a cell-surface receptor called RAGE (receptor for advanced glycation end products) and its intracellular partner DIAPH1. Advanced glycation end products (AGEs) accumulate with age and more rapidly in chronic conditions such as diabetes, activating RAGE and triggering inflammatory and damaging cellular responses.
“The complications of diabetes — which really are the issues that make people sick, that reduce their lifespan, and that just make them unwell — are only partly mitigated by tight control of the blood sugar,” said Dr. Ann Marie Schmidt.
The team built detailed structural models of how RAGE and DIAPH1 interact and screened roughly 58,000 small molecules to find compounds that block that interaction. An analogue of an initially identified candidate, chosen for a better safety profile, was tested in both human cells and mouse models.
Key results
- In human cells from people with type 1 diabetes, the compound blocked the RAGE–DIAPH1 interaction and reduced inflammatory signaling.
- In diabetic mice, topical application of the compound to skin wounds reduced inflammation and accelerated healing.
- Oral dosing reduced inflammation in a separate mouse model of allergic inflammation, though oral dosing was not tested in diabetic mice in this study.
Implications and next steps
The findings suggest that targeting the RAGE–DIAPH1 interaction could limit or prevent complications of diabetes that are not fully controlled by glucose management alone. However, the authors and external commentators emphasize that extensive additional animal testing is required before human trials can begin.
If ultimately approved, researchers suggest such a therapy would likely be most beneficial when started early after a diabetes diagnosis and used alongside tight blood glucose control to minimize the buildup of AGEs and the resulting harmful cascade.
Experts also note potential broader applications: RAGE has been implicated in inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD), where disrupting RAGE–DIAPH1 signaling might also prove useful.
Limitations: The current results are preclinical (cells and animal models). Safety, dosing, and efficacy in humans remain unknown and require further study.
This article presents research findings and is not medical advice.
