Marta Murillo

Variability in adherence to rhGH treatment: Socioeconomic causes and effect on children's growth

BACKGROUND In children with growth disorders, mean final height is associated to poor adherence to Growth Hormone therapy. The primary goal of this study is to identify patients who do not adhere to GH therapy and determine the influence of adherence in response to the treatment. The role of serum IGF-I and influence of socio-economic factors on the therapeutic adherence will also be evaluated. METHODS 158 children under treatment with rhGH were included in the study. Age, gender, etiology, Tanner stage, duration of treatment, growth rate, IGF-I serum values, daily dose, and annual rhGH dose data were collected. Adherence to therapy was defined as moderate-to-poor when the patient had taken less than 92% of the prescribed medication. A subgroup of 106 patients completed a questionnaire to assess social and environmental effects. RESULTS Moderate-to-poor adherence to rhGH treatment was determined in 33.5% of study patients. A decrease in adherence was associated to treatment duration (p=0.001). A significant correlation was determined between adherence and height velocity (p=0.002) and IGF-I (p<0.0001) levels. Adherence rates were associated to the mothers educational level (p=0.007). CONCLUSION Poor adherence to GH therapy was observed in one-third of study patients, resulting in suboptimal growth. IGF-I levels can be helpful to identify patients with poor adherence to GH medication. Physicians should pay special attention to certain characteristics of the patient and their environment, and encourage desirable therapeutic compliance.

Remission Phase in Paediatric Type 1 Diabetes: New Understanding and Emerging Biomarkers

Type 1 diabetes (T1D) is a metabolic disease of unknown aetiology that results from the autoimmune destruction of the β-cells. Clinical onset with classic hyperglycaemic symptoms occurs much more frequently in children and young adults, when less than 30% of β-cells remain. Exogenous insulin administration is the only treatment for patients. However, due to glucose dysregulation, severe complications develop gradually. Recently, an increase in T1D incidence has been reported worldwide, especially in children. Shortly after diagnosis, T1D patients often experience partial remission called “honeymoon phase,” which lasts a few months, with minor requirements of exogenous insulin. In this stage, the remaining β-cells are still able to produce enough insulin to reduce the administration of exogenous insulin. A recovery of immunological tolerance to β-cell autoantigens could explain the regeneration attempt in this remission phase. This mini-review focuses on the remission phase in childhood T1D. Understanding this period and finding those peripheral biomarkers that are signs of immunoregulation or islet regeneration could contribute to the identification of patients with a better glycaemic prognosis and a lower risk of secondary complications. This remission phase could be a good checkpoint for the administration of future immunotherapies.

Measured free 25-hydroxyvitamin D in healthy children and relationship to total 25-hydroxyvitamin D, calculated free 25-hydroxyvitamin D and vitamin D binding protein

BACKGROUND vitamin D deficiency in children is still a global health problem. Measuring free 25-hydroxyvitamin D concentrations could provide a better estimate of the vitamin D status than total 25-hydroxyvitamin D (25(OH)D) levels. OBJECTIVE To assess the relationship between measured free vitamin D (m-f25(OH)D) and calculated free 25(OH)D (c-f25(OH)D), total 25(OH)D, intact parathyroid hormone (iPTH) and other markers of phosphocalcic metabolism. To establish serum m-f25(OH)D concentrations corresponding to a total 25(OH)D > 50 nmol/L which is accepted as vitamin D-sufficiency status in children. DESIGN Prospective cohort study. SETTING January and February 2017 in a Mediterranean population. PATIENTS healthy children. MEASUREMENTS m-f25(OH)D and vitamin D binding protein (VDBP) by ELISA. Free 25(OH)D was calculated using the formula described by Bikle. RESULTS m-f25(OH)D directly correlated with total 25(OH)D (r:0.804,p < .001), serum calcium (r:0.26,p:0.035), and c-f25(OH)D (r:0.553,p:0.016); and inversely with iPTH (r:-0.374, p:0.002), alkaline phosphatase (r:-0.28, p:0.026), and age (r:-0.289, p:0.018). Total 25(OH)D correlated with the same parameters as m-f25(OH)D except for serum calcium. However, c-f25(OH)D correlated only with total 25(OH)D and VDBP, both included in the calculation formula. Multiple regression analysis showed that m-f25(OH)D variations were independently explained by calcium (β:0.156, p:0.026) and total 25(OH)D (β:0.043, p < .001). The optimal m-f25(OH)D cut-off for discriminating between insufficient and sufficient total 25(OH)D was >9.8 pmol/L (Area Under Curve (AUC): 0.897 (95% confidence interval (CI): (0.798-0.958); p < .001; sensitivity:72.7% (95%CI: 49.8-89.3); specificity: 95.5% (95%CI: 84.5-99.4)). CONCLUSIONS Directly measured free vitamin D correlated better with markers of phosphocalcic metabolism than total 25(OH)D and c-f25(OH)D in a population of healthy children.