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Pre-Meal Whey Protein Alters Postprandial Insulinemia by Enhancing β-Cell Function and Reducing Insulin Clearance in T2D

Lookup NU author(s): Kieran Smith, Dr Guy TaylorORCiD, Professor Mark Walker, Dr Kelly Bowden DaviesORCiD, Professor Emma StevensonORCiD, Dr Daniel WestORCiD

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Abstract

Context: Treatments that reduce postprandial glycemia (PPG) independent of stimulating insulin secretion are appealing for the management of type 2 diabetes (T2D). Consuming pre-meal whey protein (WP) reduces PPG by delaying gastric emptying and increasing plasma insulin concentrations. However, its effects on β-cell function and insulin kinetics remains unclear.Objective: To examine the PPG-regulatory effects of pre-meal WP by modeling insulin secretion rates (ISR), insulin clearance, and β-cell function.Methods: This was a single-blind, randomized, placebo-controlled, crossover design study in 18 adults with T2D (HbA1c, 56.7 ± 8.8 mmol/mol) who underwent 2 240-minute mixed-meal tolerance tests. Participants consumed WP (15 g protein) or placebo (0 g protein) 10 minutes before a mixed-macronutrient breakfast meal. PPG, pancreatic islet, and incretin hormones were measured throughout. ISR was calculated by C-peptide deconvolution. Estimates of insulin clearance and β-cell function were modeled from glucose, insulin, and ISR. Changes in PPG incremental area under the curve (iAUC; prespecified) and insulin clearance (post hoc) were measured.Results: β-cell function was 40% greater after WP (P = .001) and was accompanied with a −22% reduction in postprandial insulin clearance vs placebo (P < .0001). Both the peak change and PPG iAUC were reduced by WP (−1.5 mmol/L and −16%, respectively; both P < .05). Pre-meal WP augmented a 5.9-fold increase in glucagon and glucagon-like peptide 1 iAUC (both P < .0001), and a 1.5-fold increase in insulin iAUC (P < .001). Although the plasma insulin response was greater following WP, ISR was unaffected (P = .133).Conclusion: In adults with T2D, pre-meal WP reduced PPG by coordinating an enhancement in β-cell function with a reduction in insulin clearance. This enabled an efficient postprandial insulinemic profile to be achieved without requiring further β-cell stimulation.Trial registry ISRCTN ID: ISRCTN17563146

Publication metadata

Author(s): Smith K, Taylor GS, Brunsgaard LH, Walker M, Bowden KA, Stevenson EJ, West DJ

Publication type: Article

Publication status: Published

Journal: The Journal of Clinical Endocrinology & Metabolism

Year: 2022

Volume: 108

Issue: 8

Pages: e603–e612

Print publication date: 01/08/2023

Online publication date: 03/02/2023

Acceptance date: 30/01/2023

Date deposited: 18/06/2025

ISSN (print): 0021-972X

ISSN (electronic): 1945-7197

Publisher: Oxford University Press

URL: https://doi.org/10.1210/clinem/dgad069

DOI: 10.1210/clinem/dgad069

Data Access Statement: The raw data supporting the conclusions of this article will be made available upon reasonable request.

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