ESPE Abstracts

Type 1 diabetes (T1D) hits about 1:300 with rising incidence affecting increasingly younger children. Population screening at ages 2-6yrs with T1D associated autoantibodies (T1Ab) has been recently proven sensitive. While potential treatments to prevent or delay T1D are currently in development, a population based cost-effective preventive strategy is still lacking. Hence, 2000IU cholecalciferol daily in a large birth cohort study published in 2001 reduced by 80% the risk of T1D in 1yr. A pilot clinical trial in 2013, demonstrated negativation of T1Ab within 0.6(0.4-2.1)yrs under oral calcitriol. In a prospective interventional non-randomized clinical trial, the PRECAL study (ISRCTN17354692). Between 2010-2022, 50 children (26 boys, 24 girls) aged 0.65-16.37yrs identified as at high risk for T1D were included: 44 with +T1Abs (Insulin auto-antibodies, IAA; anti-tyrosinase abs, IA2, anti-glutamic decarboxylase abs, GAD; islet auto-abs, ICA; anti-Zn8 if available) and 6 with negative T1Abs but predisposing HLA A DQ DR haplotypes/genotypes. Nine had varied impaired glucose tolerance (IGT) (T1Ab+), 4 pre-T1D (3 T1Ab+ and 1 HLA+), and 9 new-onset T1D (T1Ab+). Serum T1Ab levels and fasting plasma glucose, HbA1c, c-peptide, Ca (tolerated ≤11.5 mg/dl), P, ALP, Ca/Cr 2-hr urine morning sample, 25(OH)D, 1-25(OH)2D with renal ultrasound in cases with hypercalcemia/hypercalciuria (tolerated ≤50%, or at the upper normal for age) were determined before and q3-6 months after initiation of calcitriol (0.05 mcg/Kg/day) 0.25-0.5 x 1-3/day or its synthetic analogue, paricalcitol (thrice the calcitriol dose) 1-4 mg x 1-3/day p.o. under cholecalciferol repletion. Measurements are given as median and range. Available data on 42 (7 dropouts, 1 follow-up <3m). All 26 without pre-T1D/T1D followed 3.06(0.5-10)yrs negativized T1Abs (15IAA, 3IA2, 4ICA, 2GAD, 1IAA/GAD, 1ICA/GAD) within 0.57(0.32-1.3)yrs or did not progress to T1D [5 +HLA, follow-up 3(1-4)yrs]. From 4 pre-T1D, 1 negativized T1Abs (follow-up 1yr), 1 with +HLA did not progress to T1D (follow-up 3.3yrs) and 2 with +T1Ab developed T1D in 6m/3yrs. Three out of 8 children with T1D progressed immediately to overt disease, 5 showed complete remission for 1yr (1m-2yrs). Five with +T1Ab relapsed and negativized again after resuming therapy. Four (<3yrs) negativized anti-TPO/TG, and two anti-transglutaminase-IgA. Eight presented mild hypercalciuria/hypercalcemia, resolving with dose titration/discontinuation. Calcitriol, and paricalcitol were 100% effective and reasonably safe in negativizing T1Abs in healthy children, possibly preventing T1D, at least if started soon enough after seroconversion.