Comment on: Greenbaum et al. Through the Fog: Recent Clinical Trials to Preserve b-Cell Function in Type 1 Diabetes. Diabetes 2012;61:1323–1330

The interesting article by Greenbaum et al. (1)attempts to trace future pathways toward cura-tive treatments of type 1 diabetes by analyzingthe lessons from the previously published trials, particularly those performed in recently diagnosed di-abetic patients. The authors emphasize the constant finding observed in the trials with some efficacy on pres-ervation of b-cell function (anti-CD3, anti–B cells, and CTLA-4 Ig), i.e., a biphasic evolution of C-peptide secre-tion. There was an early significant improvement of C-peptide secretion noted at 6 months in comparison with that in control subjects, but thereafter the C-peptide se-cretion decline paralleled that observed in the placebo groups. The authors interpreted this biphasic evolution by the coexistence of two pathogenic mechanisms involved in the b-cell loss. In addition to the chronic T-cell–mediated aggression of b-cells, which is targeted by the immune modulation, there is likely an acute inflammation not in