Circulating Receptor Activator of Nuclear Factor kB Ligand and triglycerides are associated with progression of lower limb arterial calcification in type 2 diabetes: a prospective, observational cohort study

Cardiovasc Diabetol. 2020 Sep 18;19(1):140. doi: 10.1186/s12933-020-01122-4.

Abstract

Background: Lower limb arterial calcification is a frequent, underestimated but serious complication of diabetes. The DIACART study is a prospective cohort study designed to evaluate the determinants of the progression of lower limb arterial calcification in 198 patients with type 2 diabetes.

Methods: Lower limb arterial calcification scores were determined by computed tomography at baseline and after a mean follow up of 31.20 ± 3.86 months. Serum RANKL (Receptor Activator of Nuclear factor kB Ligand) and bone remodeling, inflammatory and metabolic parameters were measured at baseline. The predictive effect of these markers on calcification progression was analyzed by a multivariate linear regression model.

Results: At baseline, mean ± SD and median lower limb arterial calcification scores were, 2364 ± 5613 and 527 respectively and at the end of the study, 3739 ± 6886 and 1355 respectively. Using multivariate analysis, the progression of lower limb arterial log calcification score was found to be associated with (β coefficient [slope], 95% CI, p-value) baseline log(calcification score) (1.02, 1.00-1.04, p < 0.001), triglycerides (0.11, 0.03-0.20, p = 0.007), log(RANKL) (0.07, 0.02-0.11, p = 0.016), previous ischemic cardiomyopathy (0.36, 0.15-0.57, p = 0.001), statin use (0.39, 0.06-0.72, p = 0.023) and duration of follow up (0.04, 0.01-0.06, p = 0.004).

Conclusion: In patients with type 2 diabetes, lower limb arterial calcification is frequent and can progress rapidly. Circulating RANKL and triglycerides are independently associated with this progression. These results open new therapeutic perspectives in peripheral diabetic calcifying arteriopathy. Trial registration NCT02431234.

Keywords: Arterial calcification; Biomarkers; Calcium score; Mediacalcosis; Peripheral artery disease; Type 2 diabetes.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetic Angiopathies / blood*
  • Diabetic Angiopathies / diagnostic imaging
  • Diabetic Angiopathies / epidemiology
  • Disease Progression
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Lower Extremity / blood supply*
  • Male
  • Middle Aged
  • Myocardial Ischemia / epidemiology
  • Prospective Studies
  • RANK Ligand / blood*
  • Tomography, X-Ray Computed
  • Triglycerides / blood*
  • Vascular Calcification / blood*
  • Vascular Calcification / diagnostic imaging
  • Vascular Calcification / epidemiology

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • RANK Ligand
  • TNFSF11 protein, human
  • Triglycerides

Associated data

  • ClinicalTrials.gov/NCT02431234