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The insulinotropic effect of a high-protein nutrient preload is mediated by the increase of plasma amino acids in type 2 diabetes

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Abstract

Aims

Eating protein before carbohydrate reduces postprandial glucose excursions by enhancing insulin and glucagon-like peptide-1 (GLP-1) secretion in type 2 diabetes (T2D). We tested the hypothesis that this insulinotropic effect depends on the elevation of plasma amino acids (AA) after the digestion of food protein.

Methods

In 16 T2D patients, we measured plasma AA levels through the course of two 75-g oral glucose tolerance tests (OGTT) preceded by either 500-ml water or a high-protein nutrient preload (50-g Parmesan cheese, one boiled egg, and 300-ml water). Changes in beta cell function were evaluated by measuring and modelling plasma glucose, insulin, and C-peptide through the OGTT. Changes in incretin hormone secretion were assessed by measuring plasma GLP-1.

Results

Plasma AA levels were 24% higher after the nutrient preload (p < 0.0001). This increment was directly proportional to both the enhancement of beta cell function (r = 0.58, p = 0.02) and the plasma GLP-1 gradients (r = 0.57, p = 0.02) produced by the nutrient preload. Among single AA, glutamine showed the strongest correlation with changes in beta cell function (r = 0.61, p = 0.01), while leucine showed the strongest correlation with GLP-1 responses (r = 0.74, p = 0.001).

Conclusions

The elevation of circulating AA that occurs after a high-protein nutrient preload is associated with an enhancement of beta cell function and GLP-1 secretion in T2D. Manipulating the meal sequence of nutrient ingestion may reduce postprandial hyperglycaemia through a direct and GLP-1-mediated stimulation of insulin secretion by plasma AA.

Trial registration number

NCT02342834.

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Abbreviations

AA:

Amino acids

AUC:

Area under the curve

GLP-1:

Glucagon-like peptide 1

ISR:

Insulin secretion rate

ISR@FPG:

Insulin secretion rate at fasting plasma glucose

T2D:

Type 2 diabetes

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Acknowledgements

We would like to thank the volunteers enrolled in this trial and all the personnel of the Nutrition, Metabolism and Atherosclerosis Laboratory at the University of Pisa.

Funding

This work was supported by Grants from the University of Pisa (Fondi di Ateneo).

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Pisa, Via Roma 67, 56126, Pisa, Italy

    Domenico Tricò, Silvia Frascerra, Simona Baldi, Alessandro Mengozzi, Lorenzo Nesti & Andrea Natali

  2. Institute of Life Sciences, Sant’Anna School of Advanced Studies, Pisa, Italy

    Domenico Tricò

  3. Institute of Neuroscience, National Research Council, Padua, Italy

    Andrea Mari

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  1. Domenico Tricò
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  2. Silvia Frascerra
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  3. Simona Baldi
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  4. Alessandro Mengozzi
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  5. Lorenzo Nesti
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  6. Andrea Mari
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  7. Andrea Natali
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Contributions

DT conceived and designed the study, conducted the clinical studies, provided a substantial contribution to the acquisition, analysis, and interpretation of the data, and wrote the manuscript. SF and SB provided a substantial contribution to the data collection and analysis. AMe and LN provided a substantial contribution to the analysis and interpretation of the data. AMa provided a substantial contribution to the generation and interpretation of the data from the mathematical model of beta cell function and insulin sensitivity. AN conceived and designed the study, provided a substantial contribution to the analysis and interpretation of the data, and critically revised the manuscript. All authors revised the manuscript and approved the final version of the article. DT and AN are responsible for the integrity of the data and the accuracy of the data analysis.

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Correspondence to Domenico Tricò.

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Tricò, D., Frascerra, S., Baldi, S. et al. The insulinotropic effect of a high-protein nutrient preload is mediated by the increase of plasma amino acids in type 2 diabetes. Eur J Nutr 58, 2253–2261 (2019). https://doi.org/10.1007/s00394-018-1778-y

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