Reduced Incretin Effect in Type 2 Diabetes

We aimed to investigate whether the reduced incretin effect observed in patients with type 2 diabetes is a primary event in the pathogenesis of type 2 diabetes or a consequence of the diabetic state. Eight patients with chronic pancreatitis and secondary diabetes (A1C mean [range] of 6.9% [6.2–8.0]), eight patients with chronic pancreatitis and normal glucose tolerance (NGT; 5.3 [4.9–5.7]), eight patients with type 2 diabetes (6.9 [6.2–8.0]); and eight healthy subjects (5.5 [5.1–5.8]) were studied. Blood was sampled over 4 h on 2 separate days after a 50-g oral glucose load and an isoglycemic intravenous glucose infusion, respectively. The incretin effect (100% × [β-cell secretory response to oral glucose tolerance test − intravenous β-cell secretory response]/β-cell secretory response to oral glucose tolerance test) was significantly (P < 0.05) reduced (means ± SE) in patients with chronic pancreatitis and secondary diabetes (31 ± 4%) compared with patients with chronic pancreatitis and NGT (68 ± 3) and healthy subjects (60 ± 4), respectively. In the type 2 diabetes group, the incretin effect amounted to 36 ± 6%, significantly (P < 0.05) lower than in chronic pancreatitis patients with NGT and in healthy subjects, respectively. These results suggest that the reduced incretin effect is not a primary event in the development of type 2 diabetes, but rather a consequence of the diabetic state.