The spirit of science is not merely faith in the power of reason; it is also a belief that our problems may be simpler than they appear to be.
– Colin Wilson, The Strength to Dream
This recent pilot study is an example of good science for two reasons – it suggests that a minor change in behaviour can be a shortcut to important health benefits, and it raises more questions than it answers.
Alpana P. Shukla, Radu G. Iliescu, Catherine E. Thomas, and Louis J. Aronne.
Diabetes Care 2015;38:e98–e99 | DOI: 10.2337/dc15-0429
The authors looked at the effect of food order, using a typical Western meal (628 kcal:
55 g protein, 68 g carbohydrate, and 16 g fat), incorporating vegetables, protein, and carbohydrate, on postprandial glucose and insulin excursions in overweight/obese adults with type 2 diabetes. There were only 11 subjects (5 male, 6 female), which is why it’s a pilot study; the numbers were small, so any effect, to be statistically significant, actually had to be clinically significant too. But these people could be exceptions, the effect of metformin may be necessary for the response, it might vary when different foods are eaten, the effect might not be seen with larger meals, or in free-living populations, and the long-term effect on fasting glucose and insulin wasn’t investigated; so it’s a “proof of concept” type of experiment that tells us, loud and clear, that further investigations are certainly warranted.
The study was a cross-over design, meaning that both meal orders were tested in all subjects, a week apart. The meals were made up of ciabatta bread and orange juice (the carbohydrate part) and a chicken salad with low fat vinaigrette, plus broccoli and butter (the vegetable and protein part) and these two parts were eaten, separated by 15 minutes, in 2 different orders. Insulin and glucose were measured just before the meal and at 30, 60, and 120 minutes after the start of the meal.
When the vegetable and protein part of the meal was consumed first, mean postmeal glucose levels were decreased by 28.6%, 36.7%, and 16.8% at 30, 60, and 120 min, respectively, and the incremental area under the curve (iAUC) was 73% lower. Postprandial insulin levels at 60 and 120 min and the insulin iAUC were also significantly lower when protein and vegetables were consumed first.
The authors commented that “the magnitude of the effect of food order on glucose levels is comparable to that observed with pharmacological agents that preferentially target postprandial glucose. Moreover, the reduced insulin excursions observed in this experimental setting suggest that this meal pattern may improve insulin sensitivity.”
How can this be? The same food was eaten, and 15 minutes is not a very long time; it’s a sedate meal, but not a long-drawn out one.
No mechanism is offered in the paper, but we would like to suggest one. After a meal, and especially in people with type 2 diabetes, glucose does not only appear from the food eaten. Glucose is released from glycogen (the liver’s carbohydrate stores) in the fasting state, and this appearance of glucose may continue or even increase after eating carbohydrate, likely because of the post-prandial spike in glucagon, which is released from cells in the gut, as we described in an earlier post. This rise in glucagon in people with type 2 diabetes following carbohydrate consumption has not always been seen experimentally, but it appears as a significant effect in most studies, especially when carbohydrate is fed in a meal; it can clearly be seen here, where the diet is 55% carbohydrate (designed according to AHA and USDA Dietary Guideline recommendations, and represented by the circles – the triangles represent the baseline American diet, which had almost identical effects).
(from Effect of a High-Protein, Low-Carbohydrate Diet on Blood Glucose Control in People With Type 2 Diabetes. Mary C. Gannon and Frank Q. Nuttall. Diabetes 53:2375, 2004
(This study also says “We and others also have reported that even short-term starvation (hours) results in a dramatic decrease in the blood glucose concentration in people with type 2 diabetes. This seems to be due largely to a rapid, progressive decrease in the rate of glycogenolysis.” Even when you’re fasting, glycogen release slows down once insulin drops and you start burning more fat.)
We suggest that feeding the vegetable and protein part of the meal first blunts the glucagon response to the carbohydrate portion. There could be multiple reasons for this – a delayed appearance of glucose in the gut, or the pre-emptive ability of the insulin, somatostatin 28, and incretins released in response to the protein part of the meal to suppress glucagon release, resulting in lower insulin release overall, because there is both less glucose from glycogenolysis and less glucagon, both of which require extra insulin.
This is only one possible explanation – we’d like to hear others – and verifying or refuting it will take (among other things) accurate measurement of glucagon and other peptides at many time points over the immediate post-prandial period, which is not easy.
Why might eating carbohydrate trigger the release of glucose from glycogen in some circumstances?
Imagine our early human ancestors; they didn’t eat all the time, and sources of dense and easily digestible carbohydrates were rare in some environments. It’s likely that these hominids adapted to hoard glycogen, saving it for an emergency, like sprinting from Pachycrocuta, the giant prehistoric hyena that hunted Homo erectus. And this meant that glucose, which can be used to fuel growth, and to store fat, glucose which we take for granted today, was usually restricted. In this context it made sense if, as soon as an appreciable amount of glucose was detected in the gut, some extra glucose from the glycogen store was released into the blood as well; this extra could be used wisely, and replaced later – the analogy is dipping into your savings for something special when you know there’s going to be lots of money coming in, then being a lot tighter in between paydays.
This (if it’s true) would be the adaptive system, and work when appropriate; and type 2 diabetes, by definition, means that adaptive systems of blood glucose control have become dysregulated and are poorly controlled. It’s a model that does help to explain why fasting and low carb diets can help to bring post-prandial glucose under control, but it’s a highly conjectural one, a “just-so story”.
- post-meal release of glucose from glycogen can make an important contribution to post-prandial blood glucose spikes
- post-meal glycogen release can be triggered by eating carbohydrate
- very low carb diets and fasting cause the body to conserve glycogen
- in this study, eating the carbohydrate portion 15 minutes after the protein and vegetable portion in a high-carbohydrate meal resulted in significantly lower post-prandial glucose and insulin spikes
We note that the carbohydrate timing study of Shukla et al. was “supported by the Clinical and Translational Science Center at Weill Cornell Medical College (UL1 TR000457) and the Dr.Robert C. and Veronica Atkins Curriculum in Metabolic Disease at Weill Cornell Medical College Grant” and that Dr David Ludwig, who was not an author, is thanked for helping to formulate the study hypothesis.