These inferences are derived from the IL-1β/IL-1Ra hysteresis and are consistent with some long-standing findings [11], [12], as well as recent progresses in the field, such as multistage development of the disease [3], [5], long-term effect of temporary IL-1Ra in overt-diabetes [20] and the efficiency of glucose control in pre-diabetes but not overt-diabetes [31], [36]. The gene discussed is IL1B; the disease is diabetes mellitus.