Tuesday, January 29, 2019

An Orderly Way to Better Blood Sugar Regulation

Picture this:

You’ve spent time and effort trying to lead a healthy life. In doing so, you’ve dodged the chronic diseases that many of your friends succumbed to in later life.

One day you go to your doctor because you haven’t been feeling as well as usual. After some testing, it’s clear that your blood vessels aren’t functioning as well as they used to, leading to problems with your eyes and your kidneys. Additional checks reveal that your troubles arise from poor blood sugar regulation.

This problem is all too common, for about 33% of US adults have prediabetes. Yet less than 12% of these people know they have it!

The thing is, we need cutoffs to classify diseases. But in reality, there’s an expansive continuum from vigorous health to chronic disease. So, issues don’t only arise once you cross the threshold at which you have a diagnosable disease, as studies of blood sugar dysregulation make explicit. So, in the long-term, we may all benefit from doing what we can to better regulate blood sugar.


Optimizing blood sugar regulation is a timely matter

Historically, dietary advice aimed at improving blood sugar regulation has focused on optimizing the types and quantities of foods and drinks people consume. Low-carbohydrate diets are as popular as ever among some health enthusiasts, and adhering to such diets often helps people with blood sugar dysregulation, as Dan and Stephan Guyenet discussed in this podcast.

The problem is that not everyone can stick to restrictive diets. All of us indulge from time to time. So, other than restricting dietary choices, are there things people can do to more tightly manage their blood sugar?

As I’ve pointed out in several blogs (1, 2, 3), courses (available to Pro members), a guide, and this talk, optimizing diet timing can help improve blood sugar regulation. However, when discussing this topic, I’ve mostly focused on diet timing relative to the 24-hour day.

But what about diet timing across smaller timescales?

Might timing within a single dietary event, such as a meal, be important?


Order of food consumption affects blood sugar in people who have diabetes

We’ve known for some time that in type-two diabetes, people who consume carbohydrate-rich foods after protein- and fat-rich foods experience comprehensive improvements in blood sugar control compared with others who consume carbohydrate-rich foods first at meals.

Earlier this month, Alpana Shukla and her team from Weill Cornell Medical College in New York published an interesting study exploring whether food order within a meal is important for people who have prediabetes too. Here’s what her team did:


What about prediabetes?

Shukla’s team recruited 15 overweight and obese middle-aged adults who had prediabetes*. These people visited the study center three times, with a week between visits.

At each visit, participants first gave a blood sample.

Next, they consumed a standardized meal comprising a protein-rich food (skinless chicken breast), a carbohydrate-rich food (ciabatta), and a salad (raw vegetables, olive oil, and balsamic vinegar), which predominantly contained fiber and fat. The participants had fasted for 12 hours before eating this meal.

Participants then gave blood samples 30, 60, 90, 120, 150, and 180 minutes after eating.

To test the effects of food order, each participant consumed the meal contents in a different order at each visit:

  • Carbohydrate-first: Participants first consumed the bread within 10 minutes, after which there was a 10-minute interval. They then finished the meal with the protein-rich food and salad, both consumed within 10 minutes.
  • Protein- and salad-first: As per 1), but participants switched the order and consumed the protein-rich food and salad first.
  • Salad-first: As per 1), but participants consumed the salad first, ending with the carbohydrate- and protein-rich foods.

Here’s what the scientists found:


Food order is also important in people who have prediabetes

To get an idea of the total amount of glucose in each participant’s bloodstream over time after each meal, the researchers estimated the area under the blood glucose curve in the 180-minute post-meal period. This analysis showed that the total amount of glucose in the blood was about 39% lower in the protein- and salad-first condition than in the carbohydrate-first condition. Production of insulin, a hormone that helps shuttle glucose from the blood into other tissues, did not differ between these groups.

Conversely, the total amount of insulin in the blood was 44% lower after the salad-first condition compared to the carbohydrate-first condition. But the total amount of glucose in the blood wasn’t significantly different**.

So, how shall we interpret these findings?


To improve your blood glucose regulation, eat carbohydrate-rich foods last at meals!

Surely the most important takeaway from this experiment is that people had much more stable post-meal blood sugar when they consumed carbohydrate-rich foods at the end of each meal. The findings align with the researchers’ previous work, in which they found similar results in people who have type-two diabetes (1, 2).

While we can’t compare the sizes of the effects of food order on blood sugar between studies because of small differences in the studies’ methods, food order seems to have remarkably potent consequences. The size of the difference in blood sugar responses between the carbohydrate-first and protein- and salad-first conditions is comparable to that of antidiabetic drugs used to rein in blood sugar responses to meals.

Simply saving carbohydrate-rich foods for the end of a meal may dramatically improve blood sugar regulation
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We don’t know exactly why food order at meals has these effects. It’s probably partly because protein-rich foods typically increase production of a hormone named GLP-1 by the gut, as shown by one of Shukla’s earlier studies in which the protein-first conditions led to the highest blood GLP-1 concentrations. As GLP-1 enhances insulin secretion by the pancreas, many protein-rich foods substantially raise insulin production. This isn’t a bad thing though, for the result is better blood sugar regulation, as shown by numerous studies reporting that whey protein improves blood sugar responses to meals, for example.

I expect this GLP-1-boosting effect of consuming protein-rich foods first has additional benefits too. In this experiment, all participants had to finish their food. But outside of the lab, people stop eating when they feel like it. GLP-1 isn’t only directly involved in blood sugar regulation, it tends to reduce food intake too. So, it’s plausible to me that by raising GLP-1, having protein items first might also reduce ensuing calorie intake at meals, which would probably further improve blood sugar regulation!

Finally, GLP-1 tends to slow the emptying of the stomach’s contents and hence the rate of carbohydrate absorption from the gut, which should contribute to better blood sugar regulation. Fat and fiber also reduce the speed of this process, which would help explain the superiority of the salad-first condition over the carbohydrate-first one.


Food for thought

Hats off to the scientists, this study was very well thought out.

Nevertheless, we should keep a few things in mind.

First, the participants weren’t in great shape – their BMI was 34.2 kg/m2, on average, making most of them quite obese. Would we see similar effects of food order in lean people?

Next, prediabetes was identified based on participants’ HbA1c levels, which usually reflect average blood sugar over the last 90 days or so. But what about people with impaired fasting glucose? And people with healthy blood sugar regulation?

Consider also that the researchers only measured blood sugar responses to a single combination of foods. Perhaps the size of the effect of food order would be smaller if the carbohydrate-rich food tested didn’t spike blood sugar so much, for instance?

The scientists also analysed responses to a single meal at each visit. But wouldn’t it be interesting to use continuous glucose monitoring to understand the effects of food order over longer timespans? Especially since blood sugar responses to meals often affect responses to subsequent meals. It follows that the beneficial effects of consuming carbohydrates last might potentiate positive responses to later meals.

Then we should remember that while this research rightly focused on blood glucose responses to meals, blood lipid and blood amino acid responses to meals are also key determinants of metabolic health. I’m still amazed by how many smart people overlook just how important lipid regulation is in the development of diabetes, for example.

Please also remember that the way people ate in these conditions is atypical – after all, they had a 10-minute break between the two parts of each meal. This is representative of situations such as eating multiple courses at a mealtime, but many people don’t eat this way most of the time. Still, it’s interesting to think about this in light of the common practice of beginning meals with salads in many parts of the world.

Finally, in reality, loads of factors influence blood sugar responses to meals, from obvious ones, such as meal composition, to esoteric ones, including chewing and even perceptions of time.



If you remember one thing from this blog, I hope it’s that it’s probably best to save carbohydrate-rich foods for later in your meals. I see no reason to think why this wouldn’t hold true for people with healthy blood sugar regulation too.

It’s likely especially useful start meals with protein-rich foods and vegetables at occasions when you’re prone to indulging on lots of tasty foods, like buffets. Start these events with a protein-rich salad. And interject a pause between platefuls.

Finally, while not the focus of this blog, having a high-protein snack (such as a whey protein drink) before such occasions is an easy way to curb your tendency to overeat and improve your metabolic responses to the subsequent meal.



* HbA1c 5.7 to 6.4% (mean 6.0%).

**While the area under the blood glucose curve did not differ between the groups, the incremental glucose peak – an alternative measure of blood sugar regulation – was superior in the salad-first condition.



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