Microvascular and macrovascular disease and risk for major peripheral arterial disease in patients with type 2 diabetes

Kamel Mohammedi, Mark Woodward, Yoichiro Hirakawa, Sophia Zoungas, Bryan Williams, Liu Lisheng, Anthony Rodgers, Giuseppe Mancia, Bruce Neal, Stephen Harrap, Michel Marre, John Chalmers, ADVANCE Collaborative Group

Research output: Contribution to journalArticlepeer-review

63 Citations (Scopus)


OBJECTIVE Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis in type 2 diabetes, but the relationship between other vascular diseases and PAD has been poorly investigated. We examined the impact of previousmicrovascular and macrovascular disease on the risk of major PAD in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS We analyzed 10,624 patients with type 2 diabetes free frombaselinemajor PAD in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) clinical trial. The primary composite outcome was major PAD defined as PAD-induced death, peripheral revascularization, lowerlimb amputation, or chronic ulceration. The secondary end points were the PAD components considered separately. RESULTS Major PAD occurred in 620 (5.8%) participants during 5 years of follow-up. Baseline microvascular and macrovascular disease were both associated with subsequent risk of major PAD after adjustment for age, sex, region of origin, and randomized treatments. However, only microvascular disease remained significantly associated with PAD after further adjustment for established risk factors. The highest risk was observed in participants with a history of macroalbuminuria (hazard ratio 1.91 [95% CI 1.38-2.64], P < 0.0001) and retinal photocoagulation therapy (1.60 [1.11-2.32], P = 0.01). Baseline microvascular disease was also associated with a higher risk of chronic lower-limb ulceration (2.07 [1.56-2.75], P < 0.0001) and amputation (1.59 [1.15-2.22], P = 0.006),whereas baselinemacrovascular disease was associatedwith a higher rate of angioplasty procedures (1.75 [1.13-2.73], P = 0.01). CONCLUSIONS Microvascular disease, particularly macroalbuminuria and retinal photocoagulation therapy, strongly predicts major PAD in patients with type 2 diabetes, but macrovascular disease does not.

Original languageEnglish
Pages (from-to)1796-1803
Number of pages8
JournalDiabetes Care
Issue number10
Publication statusPublished - 1 Oct 2016
Externally publishedYes


  • major peripheral arterial disease
  • microvascular and macrovascular disease
  • type 2 diabetes
  • manifestation of atherosclerosis


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