Based on the diabetes incidence, sub-analysis of early and late onset mice showed that in early onset mice spermidine substantially increased the percentage of FoxP3+ T-cells, total Tregs and activated CTLA4+ Tregs in pLN while in late onset mice spermidine substantially reduced the percentage of total Tregs and activated CTLA4+ Tregs in pLN. Here, CTLA4 is linked to diabetes mellitus.