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Lookup NU author(s): Emeritus Professor Roy Taylor, Alison Barnes, Dr Kieren Hollingsworth, Keaton Irvine, Dr Alexandra Solovyova, Tara Kelly, Dr Carmen Martin-RuizORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2023 The Author(s). Weight loss in overweight or obese individuals with Type 2 diabetes (T2D) can normalize hepatic fat metabolism, decrease fatty acid oversupply to β cells and restore normoglycaemia. One in six people has BMI <27 kg/m2 at diagnosis, and their T2D is assumed to have different aetiology. The Personal Fat Threshold hypothesis postulated differing individual thresholds for lipid overspill and adverse effects on β-cell function. To test this hypothesis, people with Type 2 diabetes and body mass index <27kg/m2 (n = 20) underwent repeated 5% weight loss cycles. Metabolic assessments were carried out at stable weight after each cycle and after 12 months. To determine how closely metabolic features returned to normal, 20 matched normoglycemic controls were studied once. Between baseline and 12 months: BMI fell (mean ± SD), 24.8 ± 0.4 to 22.5 ± 0.4 kg/m2 (P<0.0001) (controls: 21.5 ± 0.5); total body fat, 32.1 ± 1.5 to 27.6 ± 1.8% (P<0.0001) (24.6 ± 1.5). Liver fat content and fat export fell to normal as did fasting plasma insulin. Post-meal insulin secretion increased but remained subnormal. Sustained diabetes remission (HbA1c < 48 mmol/mol off all glucose-lowering agents) was achieved by 70% (14/20) by initial weight loss of 6.5 (5.5-10.2)%. Correction of concealed excess intra-hepatic fat reduced hepatic fat export, with recovery of β-cell function, glycaemic improvement in all and return to a non-diabetic metabolic state in the majority of this group with BMI <27 kg/m2 as previously demonstrated for overweight or obese groups. The data confirm the Personal Fat Threshold hypothesis: aetiology of Type 2 diabetes does not depend on BMI. This pathophysiological insight has major implications for management.
Author(s): Taylor R, Barnes AC, Hollingsworth KG, Irvine KM, Solovyova AS, Clark L, Kelly T, Martin-Ruiz C, Romeres D, Koulman A, Meek CM, Jenkins B, Cobelli C, Holman RR
Publication type: Article
Publication status: Published
Journal: Clinical Science
Year: 2023
Volume: 137
Issue: 16
Pages: 1333-1346
Print publication date: 31/08/2023
Online publication date: 18/08/2023
Acceptance date: 17/08/2023
Date deposited: 12/09/2023
ISSN (print): 0143-5221
ISSN (electronic): 1470-8736
Publisher: Portland Press Ltd
URL: https://doi.org/10.1042/CS20230586
DOI: 10.1042/CS20230586
PubMed id: 37593846
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