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.

No potential conflicts of interest relevant to this article were reported.

1.
Carey
PE
,
Halliday
J
,
Snaar
JEM
,
Morris
PG
,
Taylor
R
.
Direct assessment of muscle glycogen storage after mixed meals in normal and type 2 diabetic subjects
.
Am J Physiol Endocrinol Metab
2003
;
284
:
E688
E694
2.
Jovanovic
A
,
Gerrard
J
,
Taylor
R
.
The second-meal phenomenon in type 2 diabetes
.
Diabetes Care
2009
;
32
:
1199
1201
3.
Jovanovic
A
,
Leverton
E
,
Solanky
B
, et al
.
The second-meal phenomenon is associated with enhanced muscle glycogen storage in humans
.
Clin Sci (Lond)
2009
;
117
:
119
127
4.
Chen
MJ
,
Jovanovic
A
,
Taylor
R
.
Utilizing the second-meal effect in type 2 diabetes: practical use of a soya-yogurt snack
.
Diabetes Care
2010
;
33
:
2552
2554
5.
Ma
J
,
Stevens
JE
,
Cukier
K
, et al
.
Effects of a protein preload on gastric emptying, glycemia, and gut hormones after a carbohydrate meal in diet-controlled type 2 diabetes
.
Diabetes Care
2009
;
32
:
1600
1602
6.
Knop
FK
.
Comment on: Chen et al. Utilizing the second-meal effect in type 2 diabetes: practical use of a soya-yogurt snack. Diabetes Care 2010;33:2552–2554 (Letter)
.
Diabetes Care
2011
;
34
:
e44
.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.