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Impaired postprandial skeletal muscle vascular responses to a mixed meal challenge in normoglycaemic people with a parent with type 2 diabetes

Russell, RD ORCID: 0000-0002-1275-1472, Roberts-Thomson, KM, Hu, D, Greenaway, T, Betik, AC, Parker, L, Sharman, JE ORCID: 0000-0003-2792-0811, Richards, SM ORCID: 0000-0002-5988-0423, Rattigan, S ORCID: 0000-0001-6172-3040, Premilovac, D ORCID: 0000-0003-2770-4713, Wadley, GD and Keske, MA ORCID: 0000-0003-4214-7628 2021 , 'Impaired postprandial skeletal muscle vascular responses to a mixed meal challenge in normoglycaemic people with a parent with type 2 diabetes' , Diabetologia , doi: 10.1007/s00125-021-05572-7.

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Aims/hypothesis: Microvascular blood flow (MBF) increases in skeletal muscle postprandially to aid in glucose delivery and uptake in muscle. This vascular action is impaired in individuals who are obese or have type 2 diabetes. Whether MBF is impaired in normoglycaemic people at risk of type 2 diabetes is unknown. We aimed to determine whether apparently healthy people at risk of type 2 diabetes display impaired skeletal muscle microvascular responses to a mixed-nutrient meal.Methods: In this cross-sectional study, participants with no family history of type 2 diabetes (FH-) for two generations (n = 18), participants with a positive family history of type 2 diabetes (FH+; i.e. a parent with type 2 diabetes; n = 16) and those with type 2 diabetes (n = 12) underwent a mixed meal challenge (MMC). Metabolic responses (blood glucose, plasma insulin and indirect calorimetry) were measured before and during the MMC. Skeletal muscle large artery haemodynamics (2D and Doppler ultrasound, and Mobil-O-graph) and microvascular responses (contrast-enhanced ultrasound) were measured at baseline and 1 h post MMC.Results: Despite normal blood glucose concentrations, FH+ individuals displayed impaired metabolic flexibility (reduced ability to switch from fat to carbohydrate oxidation vs FH-; p p p p p p p p Conclusions/interpretation: Normoglycaemic FH+ participants display impaired postprandial skeletal muscle macro- and microvascular responses, suggesting that poor vascular responses to a meal may contribute to their increased risk of type 2 diabetes. We conclude that vascular insulin resistance may be an early precursor to type 2 diabetes in humans, which can be revealed using an MMC.

Item Type: Article
Authors/Creators:Russell, RD and Roberts-Thomson, KM and Hu, D and Greenaway, T and Betik, AC and Parker, L and Sharman, JE and Richards, SM and Rattigan, S and Premilovac, D and Wadley, GD and Keske, MA
Keywords: endothelium, human, imaging, insulin sensitivity, resistance
Journal or Publication Title: Diabetologia
Publisher: Springer-Verlag
ISSN: 0012-186X
DOI / ID Number: 10.1007/s00125-021-05572-7
Copyright Information:

Copyright The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021

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