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Lookup NU author(s): Dr Kieran Smith, Dr Guy Taylor, Wouter PeetersORCiD, Professor Mark Walker, Dr Kelly Bowden Davies, Professor Emma Stevenson, Dr Daniel WestORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024.Aims/hypothesis: The temporal suppression of insulin clearance after glucose ingestion is a key determinant of glucose tolerance for people without type 2 diabetes. Whether similar adaptations are observed after the ingestion of a mixed-macronutrient meal is unclear. Methods: In a secondary analysis of data derived from two randomised, controlled trials, we studied the temporal responses of insulin clearance after the ingestion of a standardised breakfast meal consisting of cereal and milk in lean normoglycaemic individuals (n=12; Lean-NGT), normoglycaemic individuals with central obesity (n=11; Obese-NGT) and in people with type 2 diabetes (n=19). Pre-hepatic insulin secretion rates were determined by the deconvolution of C-peptide, and insulin clearance was calculated using a single-pool model. Insulin sensitivity was measured by an oral minimal model. Results: There were divergent time course changes in insulin clearance between groups. In the Lean-NGT group, there was an immediate post-meal increase in insulin clearance compared with pre-meal values (p<0.05), whereas insulin clearance remained stable at baseline values in Obese-NGT or declined slightly in the type 2 diabetes group (p<0.05). The mean AUC for insulin clearance during the test was ~40% lower in the Obese-NGT (1.3 ± 0.4 l min−1 m−2) and type 2 diabetes (1.4 ± 0.7 l min−1 m−2) groups compared with Lean-NGT (1.9 ± 0.5 l min−1 m−2; p<0.01), with no difference between the Obese-NGT and type 2 diabetes groups. HOMA-IR and glucagon AUC emerged as predictors of insulin clearance AUC, independent of BMI, age or insulin sensitivity (adjusted R2=0.670). Individuals with increased glucagon AUC had a 40% reduction in insulin clearance AUC (~ −0.75 l min−1 m−2; p<0.001). Conclusions/interpretation: The ingestion of a mixed-macronutrient meal augments differing temporal profiles in insulin clearance among individuals without type 2 diabetes, which is associated with HOMA-IR and the secretion of glucagon. Further research investigating the role of hepatic glucagon signalling in postprandial insulin kinetics is warranted. Trial registration: ISRCTN17563146 and ISRCTN95281775 Graphical Abstract: (Figure presented.)
Author(s): Smith K, Taylor GS, Peeters W, Walker M, Perazzolo S, Atabaki-Pasdar N, Bowden Davies KA, Karpe F, Hodson L, Stevenson EJ, West DJ
Publication type: Article
Publication status: Published
Journal: Diabetologia
Year: 2024
Pages: epub ahead of print
Online publication date: 13/08/2024
Acceptance date: 01/07/2024
Date deposited: 27/08/2024
ISSN (print): 0012-186X
ISSN (electronic): 1432-0428
Publisher: Springer Science and Business Media Deutschland GmbH
URL: https://doi.org/10.1007/s00125-024-06249-7
DOI: 10.1007/s00125-024-06249-7
Data Access Statement: The raw data supporting the conclusions of this article will be made available upon reasonable request.
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