Heterologous Adipose–Derived Mesenchymal Stem Cells and Vitamin D Supplementation in Patients with Recent–Onset Type 1 Diabetes Mellitus–Six Months Follow-Up

Objective: To evaluate the safety and efficacy of 6 months followup of infusion of heterologous adipose tissue derived mesenchymal stem cells (ADMSCs) of healthy donors + daily cholecalciferol (VD) in patients with recentonset T1D.

Methods: In this prospective open trial, patients with recentonset T1D between 1635 y/o received a single infusion of heterologous ADMSCs (kg x 10⁶) + daily oral VD (2.000UI). Glycated hemoglobin (HbA1c), basal and stimulated Cpeptide (CP) after a mixed meal, insulin dose, adverse events, and glycemic variability (GV) through continuous glucose monitoring (CGM) were assessed at baseline (T0), after 3 (T3) and 6 (T6) months. Patients were compared to controls with recentonset T1D included in previous study that received 1) standard insulin treatment (INS); 2) insulin and VD. Chisquare and Wilcoxon tests were used for statistical analysis.

Results: Six patients (3 males) with mean age of 27 ± 7.1 y/o underwent ADMSC + VD intervention. There were no differences in insulin dose/kg (p=0.6), peak CP (p=0.75) and area under the curve of stimulated CP (p=0,25). All patients had increase in basal CP (p=0.03). HbA1c improved at T3 (0.03), with no difference at T6 (p=0.07). GV did not change after intervention. Increase in Basal CP and stimulated CP were similar between groups, ADMSCs+VD, VD and INS (Basal CP=100% vs. 58.8% vs. 45%, respectively, p=0.057, and stimulated CP=66.7% vs. 58.8% vs. 25% p= 0.058). One patient developed central retinal vein occlusion at T3, with resolution at T6 and another had recurrence of a benign ovarian tumor at T6.

Discussion: In patients with T1D, heterologous ADMSCs + VD supplementation is feasible and appears to be safe after 6 months of followup and resulted in improvement of basal CP. Although GV did not change after the infusion, all patients had an excellent glycemic control, preserved βcell function and low insulin requirements after the intervention with little complications.