Secondary Prevention of Diabetes Type 1 with Oral Calcitriol and Analogs, the PRECAL Study

Author:

Papadimitriou Dimitrios T.12ORCID,Dermitzaki Eleni2,Christopoulos Panagiotis1ORCID,Papagianni Maria34ORCID,Kleanthous Kleanthis2ORCID,Marakaki Chrysanthi2,Papadimitriou Anastasios5ORCID,Mastorakos George1ORCID

Affiliation:

1. Second Department of Obstetrics and Gynecology, Aretaieion University Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece

2. Department of Pediatric-Adolescent Endocrinology and Diabetes, Athens Medical Center, 15125 Marousi, Greece

3. Department of Nutrition and Dietetics, University of Thessaly, 42132 Trikala, Greece

4. Unit of Endocrinology, Diabetes and Metabolism, Third Department of Pediatrics, Aristotle University of Thessaloniki, Hippokrateion Hospital of Thessaloniki, 54642 Thessaloniki, Greece

5. Pediatric Endocrinology Unit, Attikon University Hospital, National and Kapodistrian University of Athens, 12462 Haidari, Greece

Abstract

Screening for Type 1 Diabetes (T1D, incidence 1:300) with T1D autoantibodies (T1Ab) at ages 2 and 6, while sensitive, lacks a preventive strategy. Cholecalciferol 2000 IU daily since birth reduced T1D by 80% at 1 year. T1D-associated T1Ab negativized within 0.6 years with oral calcitriol in 12 children. To further investigate secondary prevention of T1D with calcitriol and its less calcemic analog, paricalcitol, we initiated a prospective interventional non-randomized clinical trial, the PRECAL study (ISRCTN17354692). In total, 50 high-risk children were included: 44 were positive for T1Ab, and 6 had predisposing for T1D HLA genotypes. Nine T1Ab+ patients had variable impaired glucose tolerance (IGT), four had pre-T1D (3 T1Ab+, 1 HLA+), nine had T1Ab+ new-onset T1D not requiring insulin at diagnosis. T1Ab, thyroid/anti-transglutaminase Abs, glucose/calcium metabolism were determined prior and q3–6 months on calcitriol, 0.05 mcg/Kg/day, or paricalcitol 1–4 mcg × 1–3 times/day p.o. while on cholecalciferol repletion. Available data on 42 (7 dropouts, 1 follow-up < 3 months) patients included: all 26 without pre-T1D/T1D followed for 3.06 (0.5–10) years negativized T1Ab (15 +IAA, 3 IA2, 4 ICA, 2 +GAD, 1 +IAA/+GAD, 1 +ICA/+GAD) within 0.57 (0.32–1.3) years or did not develop to T1D (5 +HLA, follow-up 3 (1–4) years). From four pre-T1D cases, one negativized T1Ab (follow-up 1 year), one +HLA did not progress to T1D (follow-up 3.3 years) and two +T1Ab patients developed T1D in 6 months/3 years. Three out of nine T1D cases progressed immediately to overt disease, six underwent complete remission for 1 year (1 month–2 years). Five +T1Ab patients relapsed and negativized again after resuming therapy. Four (aged <3 years) negativized anti-TPO/TG, and two anti-transglutaminase-IgA. Eight presented mild hypercalciuria/hypercalcemia, resolving with dose titration/discontinuation. Secondary prevention of T1D with calcitriol and paricalcitol seems possible and reasonably safe, if started soon enough after seroconversion.

Publisher

MDPI AG

Subject

Pediatrics, Perinatology and Child Health

Reference98 articles.

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