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Weight loss-induced increase in fasting ghrelin concentration is a predictor of weight regain: Evidence from the Diabetes Remission Clinical Trial (DiRECT)

Lookup NU author(s): Dr Ahmad Al-Mrabeh, Dr Sviatlana Zhyzhneuskaya, Dr Patrick Welsh, Professor Roy Taylor



This is the authors' accepted manuscript of an article that has been published in its final definitive form by John Wiley & Sons Ltd, 2020.

For re-use rights please refer to the publisher's terms and conditions.


AimTo investigate whether appetite‐related hormones were predictors of weight regain in the Diabetes Remission Clinical Trial (DiRECT).Materials and MethodsDiRECT is a cluster‐randomized clinical trial, designed to assess the effect of weight loss on type 2 diabetes remission. For this post hoc analysis, data were available for 253 (147 interventions, 106 controls) individuals with type 2 diabetes (age 53.6 ± 7.5 years, body mass index 34.7 ± 4.4 kg/m2, 59% men). Intervention participants received a 24‐month weight management programme, and controls remained on usual diabetes care. Fasting plasma concentrations of leptin, ghrelin, glucagon‐like peptide‐1 and peptide YY were measured at baseline, 12 months and 24 months in all participants, and at 5 months in a subset of participants in the intervention (n = 56) and control groups (n = 22). Potential predictors were examined using multivariable linear regression models.ResultsThe intervention group lost 14.3 ± 6.0% body weight at 5 months but regained weight over time, with weight losses of 10.0 ± 7.5% at 12 months and 7.6 ± 6.3% at 24 months. Weight loss in controls was 1.1 ± 3.7% and 2.1 ± 5.0% at 12 and 24 months, respectively. Body weight increased by 2.3% (95% confidence interval [CI] 0.4, 4.1; P = 0.019) between 12 and 24 months for every 1‐ng/mL increase in ghrelin between baseline and 12 months, and weight regain between 12 and 24 months was increased by 1.1% (95% CI 0.2, 2.0; P = 0.023) body weight for every 1‐ng/mL increase in ghrelin at 12 months.ConclusionThe rise in ghrelin (but not any other measured hormone) during diet‐induced weight loss was a predictor of weight regain during follow‐up, and concentrations remained elevated over time, suggesting a small but significant compensatory drive to regain weight. Attenuating the effects of ghrelin may improve weight‐loss maintenance.

Publication metadata

Author(s): Thom G, McIntosh A, Messow C-M, Leslie WL, Barnes A, Brosnahan N, McCombie L, Malkova D, Al-Mrabeh A, Zhyzhneuskaya S, Welsh P, Sattar N, Taylor R, Lean MEJ

Publication type: Article

Publication status: Published

Journal: Diabetes, Obesity and Metabolism

Year: 2020

Volume: 23

Issue: 3

Pages: 711-719

Print publication date: 08/09/2020

Online publication date: 22/11/2020

Acceptance date: 26/11/2020

Date deposited: 26/02/2021

ISSN (print): 1462-8902

ISSN (electronic): 1463-1326

Publisher: John Wiley & Sons Ltd



PubMed id: 33369058


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Funder referenceFunder name
13/0004691Diabetes UK