Some individuals with overweight/obesity may be relatively metabolically healthy (MHO) and have a lower risk of cardiovascular disease than those with metabolically unhealthy overweight/obesity (MUO). We aimed to compare changes in body weight and cardiometabolic risk factors and type 2 diabetes incidence during a lifestyle intervention between individuals with MHO vs MUO.
This post-hoc analysis included 1012 participants with MHO and 1153 participants with MUO at baseline in the randomized trial PREVIEW. Participants underwent an eight-week low-energy diet phase followed by a 148-week lifestyle-based weight-maintenance intervention. Adjusted linear mixed models and Cox proportional hazards regression models were used.
There were no statistically significant differences in weight loss (%) between participants with MHO vs MUO over 156 weeks. At the end of the study, weight loss was 2.7% (95% CI, 1.7%–3.6%) in participants with MHO and 3.0% (2.1%–4.0%) in those with MUO. After the low-energy diet phase, participants with MHO had smaller decreases in triglyceride (mean difference between MHO vs MUO 0.08 mmol·L−1 [95% CI, 0.04–0.12]; P < 0.001) but similar reductions in fasting glucose and HOMA-IR than those with MUO. However, at the end of weight maintenance, those with MHO had greater reductions in triglyceride (mean difference −0.08 mmol·L−1 [−0.12–−0.04]; P < 0.001), fasting glucose, 2-hour glucose (difference −0.28 mmol·L−1 [−0.41–−0.16]; P < 0.001), and HOMA-IR than those with MUO. Participants with MHO had smaller decreases in diastolic blood pressure and HbA1c and greater decreases in HDL cholesterol after weight loss than those with MUO, whereas the statistically significant differences disappeared at the end of weight maintenance. Participants with MHO had lower 3-year type 2 diabetes incidence than those with MUO (adjusted hazard ratio 0.37 [0.20–0.66]; P < 0.001).
Individuals with MUO had greater improvements in some cardiometabolic risk factors during the low-energy diet phase, but had smaller improvements during long-term lifestyle intervention than those with MHO.
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The study protocol and the datasets analysed during the current study are available from the corresponding author on reasonable request.
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The PREVIEW consortium would like to thank all study participants at every intervention site for their time and commitment and all scientists, advisors, and students for their dedication and contributions to the study. Specifically, we would like to thank Edith Feskens (Wageningen University), Thomas Meinert Larsen and Pia Siig Vestentoft (University of Copenhagen), Margriet S. Westerterp-Plantenga (Maastricht University), and Ian A. Macdonald (University of Nottingham).
This work was supported by EU framework programme 7 (FP7/2007–2013) grant agreement # 312057; National Health and Medical Research Council - EU Collaborative Grant, AUS 8, ID 1067711); the Glycemic Index Foundation Australia through royalties to the University of Sydney; the New Zealand Health Research Council (grant #14/191) and University of Auckland Faculty Research Development Fund; the Cambridge Weight Plan© donated all products for the low-energy diet phase; the Danish Agriculture & Food Council; the Danish Meat and Research Institute; National Institute for Health Research Biomedical Research Centre (NIHR BRC) (UK); Biotechnology and Biological Sciences Research Council (BBSRC) (UK); Engineering and Physical Sciences Research Council (EPSRC) (UK); Nutritics (Dublin) donated all dietary analyses software used by UNOTT; Juho Vainio Foundation (FIN), Academy of Finland (grant numbers: 272376, 314383, 266286, 314135), Finnish Medical Foundation, Gyllenberg Foundation, Novo Nordisk Foundation, Finnish Diabetes Research Foundation, University of Helsinki, Government Research Funds for Helsinki University Hospital (FIN), Jenny and Antti Wihuri Foundation (FIN), Emil Aaltonen Foundation (FIN); China Scholarship Council. The funding source had no role in the study design and conduct, data analysis, or manuscript preparation. Open access funding provided by Royal Library, Copenhagen University Library.
AR has received honorariums from the International Sweeteners Association and Unilever. JB-M is President and Director of the Glycemic Index Foundation, oversees of a glycemic index testing service at the University of Sydney and is a co-author of books about diet and diabetes. She is also a member of the Scientific Advisory Board of the Novo Foundation and of ZOE Global. SDP was the Fonterra Chair in Human Nutrition during the PREVIEW intervention. No relevant disclosures from other authors.
The study was approved by Research Ethics Committees of the Capital Region, Coordinating Ethical Committee of HUS (Helsinki and Uusimaa Hospital District), Medical Ethics Committee of the Maastricht University Medical Centre, UK National Research Ethics Service (NRES) and East Midlands (Leicester) Ethics Committee, Research Ethics Committee of the University of Navarra, Commission on Ethics in Scientific Research with the Medical University-Sofia (KENIMUS), The University of Sydney, Human Research Ethics Committee (HREC), and Health and Disability Ethics Committees (HDEC).
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Zhu, R., Huttunen-Lenz, M., Stratton, G. et al. Associations of obesity phenotypes with weight change, cardiometabolic benefits, and type 2 diabetes incidence during a lifestyle intervention: results from the PREVIEW study. Int J Obes 47, 833–840 (2023). https://doi.org/10.1038/s41366-023-01328-y