High Doses of Oral Calcitriol (up to 6μg/day) and Paricalcitol (up to 72 μg/day) Have Successfully Intercepted Progression to Clinical Type 1 Diabetes for over 3 Years in a 10-Year-Old Boy

Presentation Number: SUN 615
Date of Presentation: April 2nd, 2017

Dimitrios T Papadimitriou*
Athens Medical School, Athens, Greece

Abstract

Background

The role of Vitamin-D in innate and adaptive immunity is critical. It has been shown that redirection of human autoreactive T-cells upon interaction with dendritic cells can be modulated by an analog of 1,25-dihydroxyvitamin D3 (1). In the plenary session entitled “Cell therapy in Type 1 Diabetes” that closed the ESPE 2016 meeting in Paris, Bart Roep (Leiden, The Netherlands) announced the initiation of phase 1 clinical trials in humans: dendritic cells will be isolated from the patient’s peripheral blood, will be cultured with calcitriol and then re-injected to an abdominal intradermal position to “teach” the rest of the immune cells not to attack the β-cell anymore. Moreover, T1D autoantibodies can be “negativated” with oral calcitriol (2).

 

Clinical Case

In October 2013, a 10.5-year-old boy was referred for fasting hyperglycemia. OGGT showed IGT with 161 mg/dl at 2hrs. C-peptide was 0.8 ng/ml. All 4 commercially available diabetes associated autoantibodies were positive, HbA1c 5.8% and HLA DR3/4 positive. Based on our previous research, he was started on calcitriol initially 0.5 mcg x 3/day, gradually increased within 1.5 years at 2 mcg x 3/day. Clinical and biological follow-up was every 3 months. All but anti-GAD autoantibodies were turned negative with c-peptide fluctuating between 1-1.5 ng/ml and OGGT being stable with values between 200-250 mg/dl at 120΄and HbA1c < 6.5% until 7 months ago, when anti-GAD rose from 26 to 300 IU/L and IAA became positive again at 13 IU/L (<1.1). At that point (July 2016) insulin endogenous production was up to 73 IU/L with a blood sugar at 223 mg/dl in 120΄ at the OGTT and HbA1c 6.2%. Due to an elevated calcium at the upper tolerable level of 12 mmol/l, we switched to paricalcitol 12 mcg x 3/day. There was an immediate within 1 week improvement in daily capillary measurements until October 2016, when the new work-up showed a considerable decrease of IAA at 1.2 but a further increase of anti-GAD to 320 IU/L. At that point we doubled the paricalcitol dose at 24 mcg x 3/day. 72 mcg of paricalcitol were better tolerated than 6 mcg of calcitriol with Ca at 11.5 mmol/l and a Ca/Cr ratio at a 2-hr morning sample moderately elevated at 0.56. Unfortunately, at the regular follow-up performed on 19/1/17, HbA1c had risen at 7.8% with a fasting blood glucose of 120 rising to 325 at 120΄ with a good c-peptide at 1.5 ng/ml. Anti-GAD were practically identical at 300 IU/L, and despite a fall in IAA at 1.2 IU/L, initiation of an intensified insulin scheme with insulin aspart and degludec was decided.

Conclusion

This is the first case of pre-diabetes type 1 and subclinical Type 1 Diabetes with 4 positive autoantibodies that interception to clinical disease has been made possible with well tolerated high doses of oral calcitriol and paricalcitol for over 3 years. New perspectives on immunomodulation with powerful vit-D agonists selective for the immune system may be driven from this clinical battle.


 

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