We thank Rayner et al. (1) for their comments. The second-meal effect is defined as the effect of a meal taken several hours previously and is very different from changes brought about by immediate premeal protein loads. Provision of amino acids immediately before eating can certainly increase the β-cell insulin response, and this is demonstrated in the protocol described by Rayner and colleagues by provision of 55 g whey protein 30 min before a test meal (2). However, this stimulus to insulin secretion is not seen when the snack we describe (13.9 g protein, 7.8 g carbohydrate, 13.9 g fat; 186 kcal) is given 2 h before the test meal. The incremental area under the insulin curve was not increased, but was decreased by approximately 40% when the snack had been given (3,972 ± 413 vs. 6,540 ± 1,533 mU · h/l; P < 0.05). On the other hand, plasma free fatty acid (FFA) levels before breakfast correlated with the postprandial incremental area under the curve for plasma glucose (r = 0.5; P < 0.013). This is consistent with our previous work on the second-meal effect when the test meals were separated by 4 h. We observed a strong relationship (R = 0.69; P < 0.0005) between suppression of plasma FFA and the area under the postprandial glucose curve and similarly between prelunch plasma FFA and rise in muscle glycogen (R = −0.48; P < 0.05) (2,3). Postprandial muscle glycogen storage is profoundly suppressed after a first meal in type 2 diabetes (4). In addition to the effect on glycogen synthesis, suppression of FFA will increase rates of glucose oxidation. It appears clear that the effect of eating several hours before the test meal brings about suppression of lipolysis, improvement in insulin sensitivity and no increase in meal-related insulin secretion. Overall, several mechanisms may operate to bring about effects of variable magnitude, depending on time before the meal.
Change in rate of gastric emptying needs to be considered carefully. Pharmacological doses of glucagon-like peptide 1 analogs will decrease this, whereas physiological changes such as those induced by dipeptidyl peptidase IV inhibitors will not (5). It is unlikely that the second-meal effect relates to any change in gastric emptying or to incretin physiology.
Clarity on the interval between eating that qualifies a separate “second meal” is essential in considering all contributory mechanisms underlying the second-meal effect.
Article Information
No potential conflicts of interest relevant to this article were reported.
