Carotid intima media thickness and associations with serum osteoprotegerin and s-RANKL in children and adolescents with type 1 diabetes mellitus with increased risk for endothelial dysfunction

J Pediatr Endocrinol Metab. 2018 Nov 27;31(11):1169-1177. doi: 10.1515/jpem-2018-0147.

Abstract

Background Although carotid intima media thickness (CIMT) is an established marker of endothelial dysfunction, limited data exist on relative laboratory biomarkers in youngsters with type 1 diabetes mellitus (T1DM). Our aim was to study CIMT and the biomarkers of the osteoprotegerin (OPG)/RANKL system in young T1DM patients and controls, and also in subgroups of patients with increased risk for endothelial dysfunction, such as those with overweight/obesity, poor metabolic control or the presence of microalbuminuria. Methods CIMT and OPG/RANKL of 56 T1DM children and adolescents were compared to 28 healthy controls. Results Anthropometric, laboratory, CIMT and OPG/RANKL measurements were similar between patients and controls. Overweight/obese patients had greater CIMT than the normal weight ones (0.50 vs. 0.44 mm, p=0.001). Microalbuminuric patients had greater CIMT (0.49 vs. 0.44 mm, p=0.035) than the normoalbuminuric ones, with no difference in terms of OPG/RANKL. In the microalbuminuric group, OPG (r=-0.90, p=0.036) and RANKL (r=-0.92, p=0.024) were significantly negatively associated with CIMT. Following linear regression analysis, in the total patients group, microalbuminuria was the only factor significantly associated with CIMT (beta±SE: 0.050±0.021, p=0.035), body mass index (BMI)-z-scores were negatively associated with OPG (beta±SE: -0.25±0.12, p=0.05), while in the microalbuminuric group, CIMT was negatively associated with OPG (beta±SE: -0.070±0.019, p=0.036). During the forward stepwise procedure, microalbuminuria and age were the only variables negatively associated with RANKL (b=-0.334, p=0.034, b=-35.95, p=0.013, respectively). Conclusions In T1DM pediatric patients, overweight/obesity and microalbuminuria were associated with greater CIMT and with impaired OPG/RANKL levels, as biochemical indices of calcification of the atherosclerotic plaque.

Keywords: OPG/RANKL; childhood diabetes; endothelial dysfunction; microalbuminuria; obesity.

MeSH terms

  • Adolescent
  • Biomarkers / blood
  • Blood Glucose
  • Body Mass Index
  • Carotid Intima-Media Thickness*
  • Child
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / diagnostic imaging*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Endothelium, Vascular / diagnostic imaging*
  • Endothelium, Vascular / physiopathology
  • Female
  • Humans
  • Male
  • Osteoprotegerin / blood*
  • Overweight / blood
  • Overweight / diagnostic imaging*
  • Overweight / physiopathology
  • RANK Ligand / blood*
  • Ultrasonography

Substances

  • Biomarkers
  • Blood Glucose
  • Osteoprotegerin
  • RANK Ligand