Peripheral Artery Disease in Diabetes
Summary: This open-access mini-review highlights peripheral artery disease (PAD) in type 2 diabetes as a distinct, aggressive entity characterized by diffuse distal arterial involvement, medial arterial calcification (MAC), microvascular dysfunction, neuropathy, and a pro-thromboinflammatory milieu. PAD prevalence in T2D ranges from 12.5%–22% (more than twofold higher than the general population), with faster progression to chronic limb-threatening ischemia (CLTI), foot ulcers, infection, and amputation. MAC doubles amputation risk in diabetic foot ulcers and quadruples it with concurrent chronic kidney disease. Pathophysiology involves hyperglycemia-driven oxidative stress, endothelial dysfunction, AGE-RAGE signaling, platelet hyperreactivity, and impaired fibrinolysis. Diagnostic challenges include unreliable ankle-brachial index (ABI) due to non-compressible vessels; toe-brachial index (TBI), transcutaneous oxygen pressure (TcPO2), and skin perfusion pressure (SPP) are recommended. Management focuses on metabolic optimization, supervised exercise, antithrombotics, revascularization, and emerging agents such as GLP-1 receptor agonists (e.g., semaglutide improving walking distance) and lipid-lowering therapies that reduce ulceration/gangrene.
Key Highlights:
- PAD prevalence 12.5%–22% in T2D; MAC doubles DFU amputation risk (4x with CKD)
- Distinct features: distal diffuse disease, microvascular rarefaction, masked symptoms due to neuropathy
- Improved diagnostics: prefer TBI, TcPO2, SPP over ABI for wound healing prediction
- Emerging therapies: GLP-1 RAs (semaglutide), SGLT2i, PCSK9 inhibitors, and regenerative approaches
- Authors: Sheena Amin, Eri Fukaya, Anand Athavale
Keywords: peripheral artery disease diabetes, diabetic foot ulcer amputation, medial arterial calcification, Sheena Amin