Microvascular and Macrovascular Disease and Risk for Major Peripheral Arterial Disease in Patients With Type 2 Diabetes

Diabetes Care. 2016 Oct;39(10):1796-803. doi: 10.2337/dc16-0588. Epub 2016 Jul 25.

Abstract

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 previous microvascular 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 from baseline major 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, lower-limb 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 baseline macrovascular disease was associated with 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.

Trial registration: ClinicalTrials.gov NCT00145925.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Drug Combinations
  • Endpoint Determination
  • Female
  • Follow-Up Studies
  • Gliclazide / administration & dosage
  • Glycated Hemoglobin / metabolism
  • Humans
  • Indapamide / administration & dosage
  • Male
  • Middle Aged
  • Perindopril / administration & dosage
  • Peripheral Arterial Disease / complications*
  • Proportional Hazards Models
  • Risk Factors

Substances

  • Blood Glucose
  • Drug Combinations
  • Glycated Hemoglobin A
  • indapamide, perindopril drug combination
  • Indapamide
  • Gliclazide
  • Perindopril

Associated data

  • ClinicalTrials.gov/NCT00145925