Age at Diagnosis of Type 1 Diabetes and the Effect of Immunomodulatory Therapies on Residual Beta Cell Function

Introduction

Age and season at diagnosis of type 1 diabetes (T1D) influence the amount of residual beta cell function, which is higher in subjects with the onset of the disease in adult age as compared to those diagnosed in childhood or in adolescence [1] [2]. Furthermore, the lack of correlation between HbA1c and C-peptide values (with the lowest C-peptide levels found in subjects <9 years of age at diagnosis) indicates that the process of beta cell damage is very destructive and unique in this young age group, probably reflecting a different pathogenic disease process [3].

Among the immunomodulatory agents, which have been tested in recent onset of T1D, nicotinamide (NA) and 1,25-dihydroxyvitamin D3 (calcitriol) have shown some beneficial effects on beta cells. In in vitro actions NA is capable of interfering with the pathogenic process leading to T1D and, above all, can preserve and improve stimulated beta-cell function in subjects diagnosed after puberty [4]. Similarly, a number of recent studies underline the importance of vitamin D in the pathogenesis of T1D [5] [6] [7]. Thus, epidemiological data showed that supplementation of vitamin D has protective effects on T1D and, if administered at birth, reduces the incidence of T1D later in life [6] [7]. More recently, data from our own group showed a reduction of 1,25-dydroxyvitamin D3 in subjects with recent onset of T1D [8]. In the most recent trial of the IMDIAB group (IMDIAB XI trial), we have demonstrated that calcitriol at a dose of 0.25 μg/day on separate days reduces temporarily the insulin requirement [9]. In the present study, we have performed a post hoc analysis of the IMDIAB XI data taking into account the age and the serum C-peptide at diagnosis of T1D as parameters that might have influenced the outcome of calcitriol and NA therapies.

References

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