Enduring improvements in hepatic insulin sensitivity predict sustained remission of prediabetes during a 3-year lifestyle intervention: results from the PREVIEW multinational diabetes prevention trial
Year: 2026
Type: article
Abstract: BACKGROUND: Recent investigation advocates the use of prediabetes remission as a goal of diabetes prevention. We aimed to compare changes in metabolic markers in participants with and without sustained remission of prediabetes during a 3-year lifestyle intervention. METHODS: This post-hoc analysis used data from the PREVIEW trial, a 3-year, multinational, multicenter, randomized controlled trial aiming to examine the effects of lifestyle interventions on prevention of type 2 diabetes among high-risk adults. Adult participants with prediabetes and overweight/obesity underwent 8-weeks of rapid weight loss followed by a 148-week lifestyle intervention for weight loss maintenance. Participants who completed the full protocol and had available data (n = 846) were included in the current analysis. Participants were classified into prediabetes maintainers, relapsers, and non-responders according to blood glucose levels at 1 and 3 years. Changes in metabolic markers over 3 years were compared in those who achieved sustained remission (maintainers, n = 102) vs those who failed (non-responders, n = 618), as well as those who were successful at 1 year but then relapsed (relapsers, n = 126). RESULTS: Only 12% participants experienced sustained remission at 3 years. After adjusting for baseline covariates, compared with non-responders, maintainers achieved greater weight loss (mean difference -4.0 kg; 95% CI -5.8, -2.2 kg) and fat mass loss at 3 years. Maintainers also made further improvements in markers of hepatic insulin sensitivity, regardless of weight change. Compared with relapsers, maintainers had greater decreases in weight and fat mass, but changes in visceral adiposity index were similar. Relapsers gradually reverted to an insulin resistant state at 2 and 3 years compared with maintainers, independent of weight change. CONCLUSIONS: In a long-term lifestyle intervention, sustained remission of prediabetes was associated with enduring improvements in hepatic insulin sensitivity, regardless of weight change. In addition to weight loss, targeting hepatic insulin sensitivity per se may help prevent relapse in prediabetes.
Source: Metabolism
Authors: Ruixin Zhu, Jie Guo, Maija Huttunen-Lenz, Gareth Stratton, Nils Swindell, Ian A. Macdonald, Teodora Handjieva-Darlenska, Svetoslav Handjiev, Santiago Navas-Carretero, Sally D. Poppitt, Marta Silvestre, Wolfgang Schlicht, Mikael Fogelholm, J. Alfredo Martinez, Anne Raben, Jennie Brand-Miller
Institutions: China Agricultural University, University of Education Schwaebisch Gmuend, Swansea University, Queen's Medical Centre, Medical University of Sofia, Navarre Institute of Health Research, Centro de Investigación Biomédica en Red, Universidad de Navarra, University of Auckland, Universidade Nova de Lisboa, University of Stuttgart, University of Helsinki, Madrid Institute for Advanced Studies, Universidad de Valladolid, Spanish Biomedical Research Centre in Physiopathology of Obesity and Nutrition, University of Copenhagen, The University of Sydney
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,340
Funders: Helsingin Yliopisto, Suomen Lääketieteen Säätiö, NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research, Glycemic Index Foundation, National Institute for Health and Care Research, European Commission, University of Auckland, University of Sydney, National Natural Science Foundation of China, Academy of Finland, China Postdoctoral Science Foundation, Juho Vainion Säätiö, Novo Nordisk, Signe ja Ane Gyllenbergin Säätiö, Emil Aaltosen Säätiö, Novo Nordisk Fonden, Diabetestutkimussäätiö, Directorate for Biological Sciences, Medical Research Council, Engineering and Physical Sciences Research Council, Biotechnology and Biological Sciences Research Council, National Health and Medical Research Council, Health Research Council of New Zealand, Jenny ja Antti Wihurin Rahasto, Wageningen University and Research, H2020 Euratom
Awards: G1224646995, G1280640127, G1684829519, G2187800511, G2201528761, G2289674583, G2473961061, G2475647176, G2475892237, G250819730, G253230074, G2583954406, G3405406995, G3446761106, G3465432909, G3494606022, G3850253215, G3871240750, G4043554698, G4090551034, G4363733643, G5054526510, G5241877083, G6412048503, G6635489528, G7003971911, G7857482363, G8363947306, G8880324339, G8966511090, G96990336
OpenAlex ID: W7128086393