Association of osteoprotegerin with peripheral artery disease in patients with type 2 diabetes

Abstract

Background: Osteoprotegerin plays a critical role in the pathogenesis of atherosclerosis. Elevated osteoprotegerin concentrations have been reported in microvascular complications of diabetes. Patients with diabetes are at increased risk of macrovascular complications, particularly peripheral artery disease (PAD).

Aim: To investigate the association between osteoprotegerin concentration and PAD in diabetes.

Methods: In a cross-sectional setting, patients with type 2 diabetes for>5 years and no apparent diabetic foot ulcer were recruited. Patients underwent colour Doppler ultrasonography of lower limbs and were designated PAD+ if arterial narrowing was detected. Ankle-brachial index (ABI) was measured. Serum osteoprotegerin concentrations were determined.

Results: Ninety-eight patients (47 PAD+, 51 PAD-) were recruited. Osteoprotegerin concentrations (median [interquartile range]) were significantly higher in PAD+ versus PAD- patients (0.80 [0.50-1.95] ng/mL vs 0.30 [0.25-0.40] ng/mL; P<0.001). In logistic regression, log-osteoprotegerin was a predictor of PAD in univariate and multivariable analyses. In the final multivariable model, adjusting for age, sex, body mass index, smoking, hypertension, glycaemic control, lipid profile, renal function and C-reactive protein, one standard deviation increase in log-osteoprotegerin was associated with a more than twofold increase in the risk of having PAD (odds ratio 2.26, 95% confidence interval 1.50-3.40). In PAD+ patients, osteoprotegerin was a significant predictor of disease severity, determined by ABI and percentage of vessel occlusion in univariate and multivariable models.

Conclusions: Osteoprotegerin concentrations are increased in patients with diabetes and PAD. Osteoprotegerin is an independent predictor of the presence and severity of PAD in diabetic patients.

Keywords: Ankle-brachial index; Artériopathie oblitérante des membres inférieurs; Diabète de type 2; Index de pression systolique; Index de sévérité; Osteoprotegerin; Ostéoprotégérine; Peripheral vascular diseases/diagnosis; Severity of Illness Index; Type 2 diabetes mellitus.