A controlled study of medial arterial calcification of legs: Implications for diabetic polyneuropathy

Background: Diabetes mellitus (DM) is associated with an increased prevalence of peripheral arterial disease and medial arterial calcification (MAC), possibly related to prevalence and severity of diabetic polyneuropathy (DPN). Objective: To assess the prevalence, risk covariates, and implication of MAC in a controlled study of healthy subjects and patients with DM. Design: Masked evaluation of radiographs. Setting: Olmsted County, Minnesota. Patients: Ambulatory volunteers with DM from the Rochester Diabetic Neuropathy Study cohort (n = 260) and matched healthy subjects from the Rochester Diabetic Neuropathy Study-Healthy Subject cohort (n = 221). Methods: Patients and controls underwent standard radiographs of distal legs and feet from January 1, 1995, through December 31, 2002. The radiographs were independently read by masked, experienced radiologists for vessel calcification. Medial arterial calcification prevalence, risk covariates, correlation with peripheral arterial disease, and implication for distal, length-dependent sensorimotor polyneuropathy (DSPN) were studied. Results: Of 481 study participants, MAC was found in 66 (13.7%): 55 of 260 (21.2%) in patients with DM and 11 of 221 (5.0%) in healthy subjects (P≲λτ∀.001). Interrater agreement of MAC was 94.1% (≲καππα∀ coefficient of 0.7). Medial arterial calcification was significantly associated with DSPN (P≲λτ∀.001). In stepwise logistic regression analysis, the significant risk covariates for MAC were advancing age, male sex, DM, and stage of microvessel disease (retinopathy). Conclusions: Medial arterial calcification of legs was approximately 4 times as prevalent in population-representative ambulatory persons with DM as in healthy subjects. Advancing age, male sex, DM, and retinopathy were the significant risk covariates for MAC of legs. Medial arterial calcification of legs, although significantly associated with DSPN, was not a useful surrogate marker of DSPN. Also, MAC was not shown to be a risk covariate for late worsening of DSPN, although other lines of evidence suggest that peripheral arterial disease may worsen DSPN.