Fig. (5).

Chronological change in functional beta cell mass in relation to beta cell workload during the development of type 2 diabetes (T2DM). Adopted from ref [18]. Recent studies have suggested that functional beta cell mass is already reduced at the onset of T2DM. Excess workload on beta cells induced by insulin resistance continues, stress-induced beta cell death (“karoshi”) may eventually occur, and beta cell mass is reduced even before the onset of diabetes. Once beta cell mass is reduced, the workload on residual beta cells is further exaggerated, reflecting the progressive nature of the disease. NGT; normal glucose tolerance, IGT; impaired glucose tolerance, DI; disposition index.