Weight loss induced increase in fasting ghrelin concentration is a predictor of weight regain: evidence from the Diabetes Remission Clinical Trial

Thom, G. et al. (2021) Weight loss induced increase in fasting ghrelin concentration is a predictor of weight regain: evidence from the Diabetes Remission Clinical Trial. Diabetes, Obesity and Metabolism, 23(3), pp. 711-719. (doi: 10.1111/dom.14274) (PMID:33369058)

Abstract

Aim: To investigate whether appetite‐related hormones were predictors of weight regain in the Diabetes Remission Clinical Trial (DiRECT). Materials and methods: DiRECT is a cluster‐randomised 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 (aged 53.6±7.5 years, BMI 34.7±4.4 kg/m2, 59% males). Intervention participants received a 24‐month weight‐management programme and controls remained on usual diabetes care. Fasting plasma concentrations of leptin, ghrelin, GLP‐1, and PYY were measured at baseline, 12 and 24‐months in all participants, and at 5‐months in a subset of interventions (n=56) and controls (n=22). Potential predictors were examined using multivariable linear regression models. Results: The intervention group lost 14.3±6.0% body‐weight at 5‐months but regained 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% 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. Conclusion: The 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 WLM.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Malkova, Dr Dalia and Brosnahan, Dr Naomi and Welsh, Professor Paul and McIntosh, Dr Alasdair and Thom, Dr George and McCombie, Ms Louise and Messow, Dr Martina and Lean, Professor Michael and Sattar, Professor Naveed and Leslie, Dr Wilma
• Authors: Thom, G., McIntosh, A., Messow, C.-M., Leslie, W. S., Barnes, A. C., Brosnahan, N., McCombie, L., Malkova, D., Al-Mrabeh, A., Zhyzhneuskaya, S., Welsh, P., Sattar, N., Taylor, R., and Lean, M. E.J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Diabetes, Obesity and Metabolism
• Publisher: Wiley
• ISSN: 1462-8902
• ISSN (Online): 1463-1326
• Published Online: 23 December 2020
• Copyright Holders: Copyright © 2020 John Wiley and Sons Ltd
• First Published: First published in Diabetes, Obesity and Metabolism 23(3):711-719
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
190677		Reversal of T2DM to normal glucose tolerance using non-surgical weight management with low-energy-liquid-diet and long-term maintenance, within routine NHS care.	Michael Lean	Diabetes UK (DIABETUK)	13/0004691	Med - Human Nutrition