Nearly 65% of adults in the United States actively try to increase their protein intake by consuming naturally protein-rich foods and foods and drinks fortified with protein isolates to improve their health. However, data from recent population studies have shown high protein consumption is associated with an increased risk of developing type 2 diabetes (T2D). This adverse effect might be specific to the type of protein consumed because several studies have found high animal protein, but not high plant protein, consumption was associated with increased T2D risk. There is experimental evidence from studies conducted in people and in mice to support a causal relationship between dietary protein intake and metabolic dysfunction. However, the effect of chronic high protein intake on glucose homeostasis and the mechanisms that cause protein-mediated metabolic dysfunction are not known. The reason(s) for the differences in the metabolic effects observed between high animal protein and high plant protein consumption are also not known, but could be due to differences in the amino acid composition and structure of animal and plant proteins per se and/or their biological matrix, which includes complex cell walls, lectins, and protease inhibitors in protein-rich plant foods, that can impair gut microbial access to proteins and/or induce the microbial production of beneficial metabolites, such as short-chain fatty acids. The goal of this proposal is to determine the effect of a high- protein diet in which the increase in protein intake is derived from different sources (animal vs plant and protein-rich whole foods vs protein isolates) on: i) liver and muscle insulin sensitivity; ii) the metabolic response to a meal, and iii) 24-h plasma concentration profiles of glucose, glucoregulatory hormones, and protein-derived metabolites purported to cause metabolic dysfunction. Our overarching hypothesis is that diets enriched with either animal or plant protein isolates, or animal protein-rich whole foods, but not plant protein-rich whole foods, cause alterations in the plasma hormones and protein metabolites that can cause insulin resistance and stimulate hepatic glucose production, thereby raising 24-h plasma glucose concentration.

Public Health Relevance

Diet is a critical modifiable determinant of human health and disease. High protein consumption (including naturally protein-rich foods and protein enriched food products) has become popular to prevent obesity. However this trend could potentially be harmful, because recent population studies have demonstrated an association between high protein consumption and the risk of developing type 2 diabetes (high blood sugar). The risk was found to be attributable primarily to animal proteins. However, it is not clear if the adverse effects of high animal protein intake is directly attributable to animal proteins per se or the effect of dietary components and bioactive substances that accompany high animal protein consumption. The studies we propose will determine the effect of high protein intake from different sources (animal or plant) either as protein supplements or as protein-rich foods (e.g., meat, legumes) on blood sugar concentration throughout the day.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Clinical and Integrative Diabetes and Obesity Study Section (CIDO)
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Lee, Christine G
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Washington University
Internal Medicine/Medicine
Schools of Medicine
Saint Louis
United States
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