We originally observed that blood glucose rise was 70% lower after the second of two identical meals 4 h apart (1). The time course of the effect is important, and it is unlikely that any incretin effect could persist for so long. Our subsequent study of muscle glycogen storage after a second meal used the same timing (2). We observed a strong relationship (R = 0.69; P < 0.0005) between suppression of plasma free fatty acid and the area under the postprandial glucose curve and similarly between prelunch plasma free fatty acid and rise in muscle glycogen (R = −0.48; P < 0.05) (2,3). The recent study (4) used a 2-h interval, which may be practically feasible in everyday life. The incretins have a very short plasma half-life consistent with acute action. It is unlikely that this small snack could be exerting incretin effects 2 h later, and the situation is very different from the study quoted, which used a 30-min interval (5). A modest rise in incretins, such as those produced by gliptins, does not affect rate of gastric emptying.
Knop (6) argues that the relative insulin secretion may be greater considering that the actual peak rise in plasma glucose is less after a second meal. Insulin response depends on the early, absorptive rise in plasma glucose. Mean plasma glucose increased similarly whether or not the prior snack had been taken (1.6 ± 0.3 vs. 1.7 ± 0.7 mmol/L at 30 min) and the insulin response was appropriate (38 ± 15 and 40 ± 8 mU). It would appear unlikely that postmeal insulin secretion is related to the effect observed.
Additionally, the second meal phenomenon can be induced by intravenous premeal infusion of arginine (2). Gut-dependent factors are therefore unlikely to be major players in the second meal phenomenon. Although we cannot exclude subtle mechanisms that may have minor contributory roles, the evidence supports a predominant role for suppression of fatty acid availability leading to greater facility in handling ingested carbohydrate. This will bring about enhanced muscle and liver glycogen synthesis as well as enhanced glucose oxidation.
Acknowledgments
No potential conflicts of interest relevant to this article were reported.
