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

Dimitrios T Papadimitriou1,2, Eleni Dermitzaki2, Panagiotis Christopoulos1

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

Children (Basel, Switzerland)
|May 27, 2023
PubMed

Insights

Secondary prevention of Type 1 Diabetes (T1D) is possible with calcitriol and paricalcitol in high-risk children. Early intervention after autoantibody positivity shows promise in preventing or delaying T1D onset and achieving remission.

Area of Science:

  • Endocrinology
  • Immunology
  • Pediatrics

Background:

  • Type 1 Diabetes (T1D) screening identifies at-risk children, but lacks effective preventive strategies.
  • Cholecalciferol has shown potential in reducing T1D incidence, and calcitriol has been observed to negativize T1D autoantibodies.
  • Further investigation into calcitriol and its analog paricalcitol for secondary T1D prevention is warranted.

Purpose of the Study:

  • To investigate the efficacy and safety of calcitriol and paricalcitol in the secondary prevention of Type 1 Diabetes (T1D) in high-risk children.
  • To assess the impact of these vitamin D analogs on T1D autoantibody status, glucose metabolism, and disease progression.
  • To evaluate the potential for achieving remission in new-onset T1D patients.

Main Methods:

  • A prospective, interventional, non-randomized clinical trial (PRECAL study) enrolled 50 high-risk children (T1Ab+, HLA-predisposed).
  • Participants received oral calcitriol or paricalcitol alongside cholecalciferol repletion.
  • Autoantibodies (T1Ab), glucose metabolism, and calcium metabolism were monitored regularly.

Main Results:

  • In children without pre-T1D/T1D, T1Ab negativized within 0.57 years, or they did not develop T1D.
  • Among pre-T1D cases, one achieved T1Ab negativity, one did not progress, and two developed T1D.
  • New-onset T1D patients experienced remission (6/9) or immediate progression (3/9); relapsed patients re-negativized T1Ab upon therapy resumption.

Conclusions:

  • Secondary prevention of T1D appears feasible with calcitriol and paricalcitol, particularly when initiated early after seroconversion.
  • The treatment demonstrated reasonable safety, with manageable side effects like transient hypercalciuria/hypercalcemia.
  • Vitamin D analogs show promise in preventing T1D development, inducing remission, and re-normalizing autoantibody status in at-risk children.
Keywords:
HLAautoimmunitycalcitriolcalcitriol analogsparicalcitolprediabetespreventiontype 1 diabetestype 1 diabetes autoantibodiesvitamin Dβ-cell

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