Below-knee arterial calcification in type 2 diabetes: association with receptor activator of nuclear factor κB ligand, osteoprotegerin, and neuropathy

J Clin Endocrinol Metab. 2014 Nov;99(11):4250-8. doi: 10.1210/jc.2014-1047. Epub 2014 Jul 11.

Abstract

Context: Calcification of the arterial wall in diabetes contributes to the arterial occlusive process occurring below the knee. The osteoprotegerin (OPG)/receptor activator of nuclear factor κB ligand (RANKL) system is suspected to be involved in the calcification process.

Objective: The aim of the study was to investigate whether there is a link between arterial calcification in type 2 diabetes and 1) conventional cardiovascular risk factors, 2) serum RANKL and OPG levels, and 3) neuropathy.

Patients and methods: We objectively scored, in a cross-sectional study, infrapopliteal vascular calcification using computed tomography scanning in 198 patients with type 2 diabetes, a high cardiovascular risk, and a glomerular filtration rate >30 mL/min. Color duplex ultrasonography was performed to assess peripheral arterial occlusive disease, and mediacalcosis. Peripheral neuropathy was defined by a neuropathy disability score >6. RANKL and OPG were measured in the serum by routine chemistry.

Results: Below-knee arterial calcification was associated with arterial occlusive disease. In multivariate logistic regression analysis, the variables significantly and independently associated with the calcification score were age (odds ratio [OR] = 1.08; 95% confidence interval [CI] = 1.04-1.13; P < .0001), male gender (OR = 3.53; 95% CI = 1.54-8.08; P = .003), previous cardiovascular disease (OR = 2.78; 95% CI = 1.39-5.59; P = .005), and neuropathy disability score (per 1 point, OR = 1.21; 95% CI = 1.05-1.38; P = .006). The association with ln OPG, significantly associated with calcification score in univariate analysis (OR = 3.14; 95% CI = 1.05-9.40; P = .045), was no longer significant in multivariate analysis. RANKL and OPG/RANKL were not significantly associated with the calcification score.

Conclusions: Below-knee arterial calcification severity is clearly correlated with peripheral neuropathy severity and with several usual cardiovascular risk factors, but not with serum RANKL level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arterial Occlusive Diseases / blood
  • Arterial Occlusive Diseases / etiology*
  • Arterial Occlusive Diseases / pathology
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / pathology
  • Diabetic Neuropathies / blood
  • Diabetic Neuropathies / etiology*
  • Diabetic Neuropathies / pathology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Osteoprotegerin / blood*
  • RANK Ligand / blood*
  • Severity of Illness Index
  • Vascular Calcification / blood
  • Vascular Calcification / etiology*
  • Vascular Calcification / pathology

Substances

  • Osteoprotegerin
  • RANK Ligand