Dietary factors influencing GLP-1 secretion: a new perspective in diabetes and obesity treatment

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In a narrative review published in The American Journal of Clinical Nutrition, researchers explored the current evidence on glucagon-like peptide 1 (GLP-1) secretion in various metabolic conditions, including obesity, impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM). They examined its potential modulation through various dietary approaches.

Narrative Review: Dietary impact on fasting and stimulated GLP-1 secretion in different metabolic conditions – a narrative review. Image Credit: Inna Dodor / ShutterstockDietary impact on fasting and stimulated GLP-1 secretion in different metabolic conditions – a narrative review. Image Credit: Inna Dodor / Shutterstock

Background

T2DM poses a significant health concern globally, with obesity as a major risk factor. Nutrition could be vital in addressing this issue via energy deficits and targeted food choices that impact health. A gastrointestinal peptide hormone named GLP-1 has emerged as a key player in obesity and T2DM management, influencing pancreatic function, blood glucose, satiety, and food intake. Despite reduced GLP-1 secretion in T2DM, GLP-1 analogs have shown therapeutic success, prompting research into enhancing endogenous GLP-1 secretion through dietary adjustments. Strategies focusing on postprandial GLP-1 secretion via diet modification also offer therapeutic potential in combating obesity and T2DM.

The present review discusses fasting and postprandial GLP-1 secretion in individuals with varying metabolic conditions and degrees of glucose intolerance, further examining the impact of several diet-related factors.

Physiological functions of GLP-1 inside the gut-brain-pancreas axis

GLP-1 is primarily produced by enteroendocrine L-cells in the gastrointestinal tract and exhibits postprandial secretion influenced by nutrient sensing by activated G-protein-coupled receptors. In vitro and animal studies indicate that dietary fiber-derived nutrients and short-chain fatty acids stimulate GLP-1 secretion. GLP-1 functions as an incretin, enhancing insulin secretion, reducing glucagon release, increasing pancreatic β-cell mass, regulating gastrointestinal motility, and potentially contributing to neuroprotection, making it a promising target for nutritional interventions and further research.

GLP-1 secretion among individuals with different metabolic profiles

Studies on GLP-1 secretion in individuals with different metabolic profiles, including obesity and T2DM, have yielded conflicting results, with some indicating reduced GLP-1 levels in these conditions, while a recent meta-analysis suggested generally small and heterogeneous variations, emphasizing the need for comprehensive investigations into GLP-1 secretion across diverse metabolic states.

Glucose-stimulated GLP-1 response

The review analyzed 13 studies investigating GLP-1 response to a standard 75 g glucose oral glucose tolerance test (OGTT) in individuals with different metabolic conditions, including normal weight (NW), overweight (OW), normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM. Results indicated varying GLP-1 levels and responses across groups, with individuals with NGT achieving a peak earlier than those with IGT or T2DM. Associations were observed between GLP-1 and factors such as insulin sensitivity, age, and BMI, emphasizing the need for further research accounting for confounding factors like BMI and sex.

Food-stimulated GLP-1 response

The review additionally analyzed studies employing mixed-meal tolerance tests (MMTT) to assess GLP-1 responses in individuals with NGT, IGT, or T2DM. Results from varied meal challenges indicated both increased and decreased GLP-1 responses in T2DM compared to NGT/IGT. Heterogeneity in test meals and inconsistencies in GLP-1 responses highlight the need for further research with well-characterized cohorts to evaluate meal-stimulated GLP-1 responses better.

Role of meal composition for GLP-1 secretion

Examining the impact of whole meals or meal patterns on GLP-1 secretion is crucial for understanding human nutrition, as meal composition can significantly influence the outcomes of MMTT/challenge meal studies. The analysis of 14 intervention studies using test meals revealed inconclusive findings. Nonetheless, interventions incorporating plant-based foods, a vegan meal, or higher fiber and protein content showed increased postprandial GLP-1 secretion in individuals with different metabolic profiles. However, the impact of carbohydrate composition on GLP-1 responses appears conflicting.

GLP-1 secretion after mid- and long-term dietary interventions

Controlled intervention studies examining medium- to long-term dietary effects on GLP-1 secretion in humans are scarce. Nonetheless, evidence suggests that health-promoting diets such as paleo or Mediterranean dietary approaches to stop hypertension (MIND) may enhance fasting and postprandial GLP-1 secretion. Furthermore, increased protein content, observed in high-protein diets or protein-enriched meals, appears to contribute to sustained improvements in GLP-1 levels. However, the limited number of comparative studies calls for further research to elucidate dietary interventions' mechanisms and long-term effects on GLP-1 regulation.

The effect of probiotic, prebiotic, and synbiotic interventions on GLP-1 secretion

Human intervention studies examining the effects of prebiotic, probiotic, and synbiotic interventions on GLP-1 secretion show inconclusive results. While some studies report increased GLP-1 levels with probiotic or synbiotic supplementation, others find no significant effects, highlighting the need for further research and standardized methodologies in this area.

Diet-related factors impacting GLP-1 secretion

The various diet-related factors potentially influencing GLP-1 secretion are body mass index (BMI), weight loss, glucose tolerance, meal composition, size and processing, gender, and gut microbiota. Standardized meal tests with detailed nutrient composition and gut-related analyses in well-defined cohorts are essential for robust conclusions regarding GLP-1 responses.

Conclusion

The present review emphasizes the inconsistency in GLP-1 studies. However, it highlights the influence of factors such as metabolic profile, sex, gut microbiome, glucose tolerance, BMI, antidiabetic medication, eating behavior, and nutrient composition. Modulation of GLP-1 secretion through dietary interventions, particularly in the context of long-term diets and food patterns, holds potential for the prevention and holistic treatment of metabolic conditions, necessitating further research in this area.

Journal reference:
Dr. Sushama R. Chaphalkar

Written by

Dr. Sushama R. Chaphalkar

Dr. Sushama R. Chaphalkar is a senior researcher and academician based in Pune, India. She holds a PhD in Microbiology and comes with vast experience in research and education in Biotechnology. In her illustrious career spanning three decades and a half, she held prominent leadership positions in academia and industry. As the Founder-Director of a renowned Biotechnology institute, she worked extensively on high-end research projects of industrial significance, fostering a stronger bond between industry and academia.  

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