Osteoprotegerin, Soluble Receptor Activator of Nuclear Factor-κB Ligand, and Subclinical Atherosclerosis in Children and Adolescents with Type 1 Diabetes Mellitus

Abstract

Aims. To evaluate carotid intima-media thickness (cIMT) and biomarkers of the osteoprotegerin/receptor activator of nuclear factor-κB ligand (OPG/RANKL) system in type 1 diabetes (T1DM) children and adolescents and controls. Subjects and Methods. Fifty six T1DM patients (mean ± SD age: 12.0 ± 2.7 years, diabetes duration: 5.42 ± 2.87 years and HbA1c: 8.0 ± 1.5%) and 28 healthy matched controls, were studied with anthropometric and laboratory measurements, including serum OPG, soluble RANKL (sRANKL) and cIMT. Results. Anthropometric, laboratory, and cIMT measurements were similar between T1DM youngsters and controls. However patients with longer diabetes duration (>/7.0 years) had indicatively higher cIMT (cIMT = 0.49 vs 0.44 mm, P 0.072) and triglyceride levels than the rest of the patients (93.7 vs 64.6 mg/dl, P 0.025). Both in the total study population (β 0.418, P 0.027) and among T1DM patients separately (β 0.604, P 0.013), BMI was the only factor associated with cIMT. BMI was further associated with OPG in both groups (β −0.335, P 0.003 and β −0.356, P 0.008 respectively), while sRANKL levels were not associated with any factor. Conclusions. BMI was the strongest independent predictor of cIMT among the whole population, and especially in diabetics, suggesting a possible synergistic effect of diabetes and adiposity on atherosclerotic burden. BMI was overall strongly associated with circulating OPG, but the causes of this association remain unclear.

Serum Osteoprotegrin, Total Srankl and Their Determinants in Adolescents with Type 1 Diabetes

“…In our study,likewise Lambrinoudaki and Galluzzino significant correlation between OPG concentrations and disease duration has been observed [22,23]. This may suggest, that changes in the course of diabetes which influence/have an impact on OPG levels appear with time, which is in contradiction to Singh's observations [38].…”

“…There has been no significant difference in OPG concentrations between the study groups and the controls. Lambrinoudaki did not observe differences in OPG levels between the control group and those with type 1 diabetes when analyzing the OPG concentrationand endothelial dysfunction [22]. The values of OPG concentrations were neither significantly higher, nor significantly lower in our group.…”

“…HbA1c levels and OPG concentrations [22]. Rassmussen, in the group of adults with T1DMhas demonstrated the correlationbetween OPG and glycemic control, blood pressure, and cardiovascular mortality [34].…”

Subclinical Arterial Damage in Children and Adolescents with Type 1 Diabetes: A Systematic Review and Meta‐Analysis

“…Eight studies reported no difference in mean cIMT levels between the two groups (Table ). In patients with type 1diabetes, cIMT levels associated significantly with age in four studies, with blood pressure in four studies, with lipid levels in four studies, with HbA1c in three studies, and with disease duration in two studies (Table ). The random effects meta‐analysis showed that patients with type 1 diabetes had significantly higher cIMT levels compared with controls (mean difference [ d ]:0.03, 95% CI: 0.02‐0.04, P < .00001) (Figure ).…”

“…The studies were conducted in the United States, Turkey, Canada, Germany, Egypt, Austria, Poland, Estonia, Finland, Greece, Australia, Norway, Mexico, Sweden, Serbia, and the Netherlands between 2002 and 2017. Twenty studies included cIMT as outcome, 11,12,14,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] and four included carotid-femoral PWV as outcome. 13,14,36,37 The characteristics of all 23 studies used for the systematic review are summarized in Table 1.…”