Our study showed different postprandial incretin and insulin secretion following the ingestion of a V-meal when compared with a standard M-meal, matched for energy and macronutrient composition. Overall postprandial plasma glucose responses did not differ between meals, and we detected significantly higher stimulated insulin and C-peptide responses, higher concentrations of GLP-1, and lower levels of GIP, after the plant-based meal compared with the standard M-meal. Several parameters of beta-cell function were improved after the plant-based meal, namely total insulin secretion, insulin secretion at a fixed glucose value 5 mmol/L, rate sensitivity, and the potentiation factor. No difference was observed in HOMA-IR or PREDIM as measures of insulin resistance.
We observed an increase in postprandial GLP-1 concentrations and a decrease in GIP levels after the V-meal. In addition, there was a strong positive relationship between the changes of GLP-1 and changes in C-peptide secretion. The incretin release accounts for 50% to 70% of total postprandial insulin secretion. GLP-1 has been primarily associated, together with GIP, with the incretin effect, the postprandial augmentation of insulin secretion by gut hormones [25
]. It is well understood that in patients with diabetes, the incretin effect is diminished [26
] due to impaired beta-cell sensitivity [28
]. Several hypotheses have been formulated to explain loss of beta-cell sensitivity. Widely accepted concepts include hyperglycemia- and hyperlipidemia-associated receptor desensitization [29
We have demonstrated previously that a processed M-meal leads to postprandial hyperlipidemia, increased lipoperoxidation, persistent postprandial hyperinsulinemia, and lower secretion of gastrointestinal hormones, including GLP-1, compared with an energy-matched V-meal in people with T2D [8
]. Interestingly, in the previous study, V-meal resulted in higher GLP-1 and GIP secretion. It has been shown that GIP secretion may also reflect the quality of carbohydrates [30
], which may have influenced the findings. The current study used cooked meat in the standard M-meal and we matched both meals in macronutrient content in order to provide further insights into the pathophysiology of incretin and insulin secretion in T2D. It is also important to note that some dietary interventions, such as a whole grain diet, have been shown to improve beta-cell function independent of incretin secretion. In this particular study, GLP-1 secretion was lower and GIP remained unchanged after 8 weeks of a whole-grain diet compared with a refined-grain diet in people with prediabetes [31
Several studies have suggested that a high intake of saturated fat naturally present in meat contributes to the risk of glucose intolerance [1
] due to impaired beta-cell sensitivity and function. Fat quantity and quality have been shown to affect the gastrointestinal peptide release in people with metabolic syndrome [32
In addition to fat quality, carbohydrate quality needs to be taken into account. The V-meal contained naturally more fiber and less sugar than the M-meal and these differences may have influenced the findings [32
Another important mechanism is replacing animal protein with plant protein, which has been shown to reduce blood lipids and blood pressure [33
], to lower fasting plasma glucose and fasting insulin levels, and to improve glycemic control in diabetes [34
]. It is important to note that in order to see changes in fasting plasma glucose and insulin levels, a longer-term intervention is needed. As our study was an acute feeding trial, we were only able to track the differences in postprandial changes.
Additionally, plant-foods are naturally rich in fiber, which may have influenced postprandial insulin levels [35
]. Furthermore, micronutrients, such as zinc [37
], polyphenols [38
], and other phytochemicals may also have played their positive role in postprandial incretin and insulin secretion. Our results are in line with these hypotheses and further demonstrate that a plant-based meal may improve the secretion of incretins and insulin in people with T2D where secretion has already been compromised.
The decreased postprandial plasma concentrations of GIP detected following ingestion of the V-meal compared with the M-meal are a further positive finding, as increased levels of the anabolic hormone GIP have been shown to directly promote fat storage and energy deposition [39
]. While GLP-1 levels are usually diminished in T2D, GIP levels may be increased due to lowered beta-cell GIP-receptor expression, resulting in GIP resistance in T2D [40
]. Interestingly, not only dietary interventions, but also metabolic surgery affects the secretion of incretins. For example, duodenal-jejunal bypass liner, and endoscopic method that mimics small intestine mechanisms of a Roux-en-Y gastric bypass, has also been shown to increase GLP-1 and decrease GIP concentrations [41
]. Therefore, decreased GIP concentrations in our study may reflect lower GIP resistance after the plant-based meal.
A consensus report by the American Diabetes Association and the European Association for the Study of Diabetes recommends an incretin-based therapy (GLP-1 analogue or DPP-4 inhibitor) following the failure of metformin monotherapy [42
]. Improvement in beta-cell function is considered one of the main benefits of incretin-based therapy [43
]. Our data suggest that plant-based meals may also improve beta-cell function, which may have important clinical implications for dietary treatment of T2D.
4.4. Strengths and Limitations
The main strength of this study is our comprehensive measurement of the postprandial state in a physiological setting, after ingestion of two sandwiches. We identified the mechanisms behind the improvements in glucose metabolism associated with plant-based diets. We recorded markers of both signal and response to better consider the interplay of digestion and metabolism. Finally, our meals were commonly consumed meals served in amounts corresponding to those ingested during a typical meal, making the study results highly applicable and practical.
We also recognize several limitations. The diabetes duration was fairly short in our study participants, increasing the likelihood to observe an increase in postprandial incretin and insulin secretion. This observation may not be generalizable for people with T2D with a long duration of the disease. Furthermore, our study included two test meals, and did not reflect habitual dietary patterns. The differences in postprandial incretin and insulin secretion identified in this study suggest that longer-term studies would be beneficial to show if a vegan diet may prevent the development of diabetes or slow down diabetes progression. The meals differed in saturated fat, dietary fiber, sugar content, amino acid composition, micronutrient content, polyphenols, and other phytochemicals, all of which may have influenced our results. Additionally, although we used two hot caffeinated drinks with both meals, coffee and green tea may have influenced glucose and insulin secretion slightly differently [46
]. Furthermore, we have not matched the meals in micronutrient content and have not tested the bioavailability of these micronutrients after digestion of both meals. However, these components are characteristic for plant-based meals compared with standard meals containing meat and other animal products, so while this difference is not controlled for in this study, it does increase the generalizability of our results.