A Plant-Based Meal Stimulates Incretin and Insulin Secretion More Than an Energy- and Macronutrient-Matched Standard Meal in Type 2 Diabetes: A Randomized Crossover Study
Round 1
Reviewer 1 Report
Please see my comments below:
1) abstract: please provide a sentence describing the background of the study.
2) the age and BMI range were very wide. How does this influence the results? Especially the BMI range, ranging from overweight to extremely obese.
3) Please describe this in detail: a random sequence generator
4) Why tap water was used?
5) for the results, please correct for the confounders.
6) Table 2: how about the presence of micronutrients suc as zinc that might have a modulation effect on diabetes management? Please consider this as well
7) Figure 1: how long is the washout period?
8) Please decribe how the cross over was performed. This is not included in the methods section.
9) Figure 1: this is poorly done. Please modify according to the Consort statment.
10) What was the primary and secondary outcomes? Was the sample size calculated according to primary outcome? The authors poorly reported this.
Author Response
We thank Reviewer 1 for the insightful comments. We have addressed all of them one-by-one. The changes in the manuscript are highlighted in yellow. Thank you for your help in improving our paper.
Author Response File: Author Response.docx
Reviewer 2 Report
Kahleova H et al. compared the metabolic effects of standard meat (M) meal with vegan (V) meal in patients with type 2 diabetes in term of postprandial hormone levels. The study is interesting however several concerns are raised.
Major points
In addition to the different M and V meal consumption, the participants drank Café Latte with 21 g sugar in the M group however participants in the V group consumed unsweetened green tea. Since sugar is known to change glucose, insulin and other hormone levels (Chang CY et al Eur J Nutr. 2018 Feb;57(1):179-190), the reported changes in postprandial insulin, amylin and GLP-1 levels after the consumption of V meal could be in part attributed to the presence or absence of sugar found in the drink. This is a very important bias, which impacts the conclusion of the data. What was the reason for using drinks with different sugar content for the different meals?
Since there are many studies, which investigated the effect of replacing animal protein with plant protein in the diet, the authors should discuss more thoroughly their findings in the view of the current literature. Furthermore, there are several meta-analysis summarizing the current literature like Viguiliouk E et al Nutrients. 2015 Dec 1;7(12):9804-24 or Chalvon-Demersay T et al J Nutr. 2017 Mar;147(3):281-292. Many studies showed that replacing animal protein with plant protein in the diet did not affect fasting insulin level, however some studies suggest a lower fasting insulin level after the application of plant protein based diets.
In a former study, the authors investigated an isocaloric vegan meal compared to processed meat meal without macronutrient matching using patients with type 2 diabetes Belinova L et al PLoS One. 2014 Sep 15;9(9):e107561. The authors already observed the vegan meal elevated postprandial gastrointestinal hormones compared to meat meal, however this former study mainly contradicts the findings of the current study. Although the former and the current study used different vegan meals, the observed differences between the two studies should be discussed.
Furthermore, the M meal contains higher levels of saturated fatty acids and lower levels of fibers compared to V meal. The authors shortly mention these differences in the discussion but saturated fatty acids and fibers could indeed change postprandial hormone levels, therefore they needed to be discussed in more details. In order to determine whether the observed differences at the hormone levels of T2D patients are attributed to the fatty acids, one could design a study using for eg. the vegan meal and compare it with the “same” vegan meal complemented with high saturated fatty acids. Diets rich in unsaturated fatty acids (MUFA or PUFA diet) showed significantly lower level of GIP in patients with metabolic syndrome compared to saturated fatty acid rich diet (Chang CY et al Eur J Nutr. 2018 Feb;57(1):179-190). In addition to saturated fatty acids, fibers were also showed to impact glucose metabolism (Post RE et al J Am Board Fam Med. 2012;25:16–23).
Minor points
The decreased GIP level upon V meal is not discussed in the manuscript.
The time period between the two different meal interventions is not indicated.
Author Response
We thank Reviewer 2 for the insightful comments. We have addressed all of them one-by-one. The changes in the manuscript are highlighted in yellow. Thank you for your help in improving our paper.
Author Response File: Author Response.docx
Round 2
Reviewer 2 Report
Kahleova et al revised their manuscript, which is improved. However several points remain still unclear.
According to the first answer of authors, table 2 depicts the composition of the test meals in combination with the used drinks. This fact is still not well indicated, therefore it should be better pointed out in the title of table 2 and also in the methods section. As mentioned earlier, sugar consumption directly influences glucose and hormonal metabolism, therefore sugar content (in %) should be indicated for both meals in table 2. Did the authors use the same amount of sugar for both meals? If not, than different sugar content is likely another yet unconsidered factor, which probably impacts the observed findings and therefore need to be discussed. Furthermore, using Café Latte in one study group and green tea in the other was probably not a good idea, since studies showed the green tea could impact glucose metabolism, however coffee did not (for review see Kondo Y et al Nutrients. 2018 Dec 27;11(1). These possible factors need to be also discussed.
According to the observed findings and the literature, the authors now integrated the proposed references, however they did not discuss the conflicting findings. They only mention the studies, which fit to their data. The authors need to critically discuss their findings in the view of the current literature and should find possible explanation for the discrepancy between the observed findings in this manuscript and findings from other studies. For eg why other studies reported lower fasting insulin levels, which contradicts Suppl. Fig. 2B? Why does the former study of the authors Belinova et al Plos One 2014 contradict the findings of the current manuscript (like decreased GLP1 in the former and increased GLP1 in the current study)?
The decreased level of GIP upon V meal treatment is now shortly mentioned as “positive finding”, however it contradicts the “incretin effect” on postprandial insulin secretion discussed in line 211-217. If V meal increased GLP1 level, why did it decrease GIP?
Minor corrections are needed like “8,2” (in table 1 should be corrected as 8.2), “HOMA” or “HOMA-R” (correct to HOMA-IR), typos like: “stadied”, “insuloin”. In line 82, “4. Interventions” need to be moved in a new row. Affiliation is missing for the last author.
Author Response
We thank reviewer 2 for the insightful comments and all the effort to help us improve our manuscript. We highly value all the inputs and have incorporated them into our manuscript.
Author Response File: Author Response.docx