Dr. Alpana Shukla on Food Order Studies: To see this interview in full, click here.
Pape: Hi. I’m Joy Pape, Medical Editor with Diabetes in Control. We’re here today at the ADA 2018 Meeting and I have the privilege of interviewing my colleague, friend, Dr. Alpana Shukla, and we work together. She is the Assistant Professor of Research in Medicine, Director of Clinical Research at the Comprehensive Weight Control Center, Division of Endocrinology, and Diabetes & Metabolism at Weill Cornell Medicine in New York. Whenever I have to sign my name, I have to put that in. It’s quite a bit, but you’re the one doing such great work. So, why don’t you tell us a little bit about you and then I’ll ask you about the study.
Shukla: Thank you, Joy. It’s such a pleasure. I’m delighted to be here today and share some of the research that we’ve been doing at our center. And as you know, one of the key areas of our research has been at looking at novel interventions for management of obesity and type 2 diabetes. And in this vein, we have been doing a series of studies which we have called the Food Order studies. We started this about three years ago and I want to share my thoughts and what we found so far about these studies.
Pape: So, this is the Food Order study. Okay. So, what do you mean by Food Order and what is its relevance to glycemic control?
Shukla: So, the term Food Order refers to the the nutrient sequence during a meal. And in particular, it refers to the order in which the carbohydrate component of the meal is actually consumed. So, we all know that the amount and the type of carbohydrate is a major determinant of the postprandial glucose response. In addition to that, the macro-nutrient composition of the meal, the amount of protein, fat, and fiber, all of these also favorably modify the post meal glucose. And accordingly, the current nutrition counseling that we offer patients with diabetes incorporates these principles and is personalized to achieve a low glycemic effect. Now, this is great and it does work provided patients can actually follow this advice. But we all know that in the real world patients have difficulty complying with reduced carbohydrate intake. And therefore, Food Order is an alternative strategy to mitigate the metabolic effects of carbohydrate. And in this vein, Dr. Louis Aronne, and I, and our entire team at the Comprehensive Weight Control Center, which includes you, Joy, we’ve been researching this field for the past three years. And we started by doing a first pilot study in 2015 where we had patients with type 2 diabetes who were well-controlled on Metformin come into our CTSC and eat the exact same meal. And the meal was like the kind of meal that people normally consumed in the real world. It had ciabatta roll and orange juice. It had vegetables as a salad and it had grilled chicken. And what we did was ask patients to consume the carbohydrate portion of the meal first, and then wait for 15 minutes, and then eat the chicken and vegetables. They came back a week later and they ate the exact same meal. And the only thing they did differently was to reverse the order in which they ate it. So, they ate the protein and vegetables first, they waited for 15 minutes, and then they had the bread and the orange juice. And I have to tell you that we had our students who were part of the research team strictly monitor all the patients, so that we insured that every patient ate everything each time. So, the whole experiment, as it were, was controlled for caloric as well as macronutrient composition, and this is what we found. So, if you look at this graph, you will see that the results are fairly remarkable. We actually use this as part of the nutrition counseling that we offer every patient–
Pape: Yes, we do.
Shukla: — who’s seen at our center.
Pape: Yes, we do.
View study slides and graphs:
Shukla: Yes, Joy. You know this. And I can tell you that this picture speaks more than a thousand words. So, when we saw these results we were actually — we were surprised, very pleasantly surprised. We expected the results to be good, but this was more dramatic than what we thought. And so, we felt like that as being responsible researchers we should validate these results. We should try and understand the mechanisms. And we did the second study, when we actually had a bigger sample size and we had patients actually consumed the exact same meal again but over 180 minutes this time. And in addition to the two interventions that I previously described which was having the carbohydrate first or the carbohydrate last, we also had a third intervention which was having patients eat all meal components together as a sandwich which is the most common way in which people eat in the real world. And what did we find? So, if you look at this graph, you will see that once again we found that the glucose response when patients had the carbohydrate last, when they ate the bread last, was much lower, almost half of what it was when they had the bread portion first. When they had all the meal components together as a sandwich, the glucose levels were better than having the carbohydrate first. But somewhat closer, not as good as what we thought it would be. So, I think all in all these results actually confirmed what was our initial finding that the best way to actually attenuate, if you like, or reduce the effect of the carbohydrate consumed in a meal is to have it at the end of the meal.
Pape: So, how is this different from giving a protein preload before a meal?
Shukla: So, as you know, Joy, there have been a lot of studies which have looked at giving protein preloads and the most common thing that they’ve used is whey protein. And in a sense the results and the methods looks similar to what our Food Order study shows. But the two key differences as I see it, one of them being that our study is a real world study. This is what people actually eat. It’s a real meal. And also, when you introduce a protein preload you’re changing the calories, you’re changing the macronutrient composition. This is not what people actually eat and it’s a difficult thing to implement in practice. The second important difference between these two interventions is that when you give a protein preload prior to a meal, it stimulates a greater insulin response. The glucose is lower but you stimulate more insulin secretion. However, when you have your protein and vegetables first and have your carbohydrates last, you have a much lower glucose response but you also require less insulin to dispose the same amount of carbohydrate when you eat it last as opposed to eating it first.
Pape: So, is this relevant to patients with type 1 diabetes and patients with type 2 diabetes on insulin?
Shukla: So, I think it is — I think — we believe it is relevant. We haven’t actually studied this in that population, but our results show that when you eat in this manner you require less insulin. So, we think that it’s likely that patients will have better control and they may require less insulin for the same amount of carbohydrate consumed. It’s definitely an area that we wish to pursue further and we are actively looking to do a study in this field.
Pape: Right. So, I know the study hasn’t been done yet, but I can speak to my experience with having taught patients this and I’ve seen it also. But again, it hasn’t been studied yet. Now, have you studied this intervention in patients who don’t have diabetes?
Shukla: So, we just finished the study in patients who had prediabetes. And in fact, I have just submitted the results for publication at this point. It’s under review. But I’m very happy to share some of the data which we actually showed at the Obesity Week Conference last year. And in fact, the results in the prediabetic population were also similar to what we found in patients with type 2 diabetes. And that having the carbohydrate last was significantly lower to post meal glucose response. In this study we actually did a third intervention which is interesting because one of the things that people have raised after the first two studies were done was, “We can’t always eat the protein and vegetables first because it’s just not natural to the way we eat and we prefer to have the protein and carbohydrate together.” And that is actually natural to a way that a lot of people — a lot of cultural meal patterns worldwide. And so, keeping that in mind what we did in this experiment was to introduce the third intervention which was having a big vegetable portion first which had a salad dressing, so some amount of fat. And then we had them consume the protein and carbohydrate together. And this is a much simpler thing to do for a lot of people. And in fact, what we found was even with this intervention the glucose levels were much lower. In fact, the glucose peaks were similarly reduced by eating either the salad first or the protein and vegetables first.
Pape: Does this intervention have any implications for satiety or weight management?
Shukla: So, that’s a very good question, Joy. And as you know at our center, weight management is at the very heart of what we do. And we’re constantly looking for innovative ways to change behavior or make it easier for patients to actually manage energy intake. And I think that in that range, the result of the study are very interesting because in addition to what I’ve already shown, the glucose and insulin responses, we also measured GLP-1 and we also measured ghrelin. And what we found was that when the carbohydrate is eaten at the end of the meal, you stimulate a greater GLP-1 response. And a very interesting finding was that the ghrelin levels remain suppressed for much longer when the carbohydrates is consumed last. When patients consume the carbohydrate first, ghrelin levels were suppressed as you would expect. But by the end of three hours, it had rebounded back to preprandial levels. So, we think taken together with the glucose, the lower insulin response, the increased GLP response and creating a suppression of ghrelin. I think all of these findings suggest that this intervention would have implications with satiety and possibly for weight management. We are certainly planning to investigate this further and we do use this as part of our clinical practice. And I think we believe it works, but we want to show the evidence that it does. In fact, in a randomized control design.
Pape: Yeah. I’m thinking about my patients who come in before they learn this technique —
Pape: –and they’re telling us they’re hungry all the time or they’re hungry in two or three hours. And we work with them on this, which really isn’t that difficult.
Pape: And I’m not hearing as much that, “I’m hungry all the time,” or, “I’m hungry right away,” so it makes sense from what you’re saying.
Pape: So, how do you plan to take this research forward?
Shukla: So, I’m very happy to say that we have actually received funding to actually carry our research forward. And as a team, we have been thinking that we’ve done these three experiments in the acute setting, but the real test is to assess whether people can actually do this in the real world. And if they do this is it going to make a difference to their overall glycemic control. And so, we’re actually in the process of starting our first study, prospective study, and this one is going to be in patients who have gestational diabetes. A group where we feel is a good group to assess adherence because we think that they are likely to comply with the recommendations, any recommendations, that’s going to improve fetal outcome. And so, we’re about to enroll our first patient next week.
Shukla: Yes, it’s very exciting. And the second study that we are going to start possibly in the next two months is looking at the Food Order intervention in patients with obesity and prediabetes because I think that is actually a group in which this could prove to be what we hope a diabetes prevention tool.
Pape: Yes. Yes, we are both really excited to look at that. You talked about your study and it was published. It will make that available. It was published where and when?
Shukla: So, the very first study was published in Diabetes Care, then the second study was published in BMJ Open. And then the third, the Ghrelin sub-study, was published in Diabetes Care last year.
Pape: So, I have a question for you for all that you and what you’ve learned. So, you have a saying and what is that? If you were to give someone some advice, some simple advice to use in life, what would that be?
Shukla: “Eat bread last,” that is my mandatory slide and I — that we have in our office and we show this to all our patients.