Appraisal of Triglyceride-Related Markers as Early Predictors of Metabolic Outcomes in the PREVIEW Lifestyle Intervention: A Controlled Post-hoc Trial.

Background: Individuals with pre-diabetes are commonly overweight and benefit from dietary and physical activity strategies aimed at decreasing body weight and hyperglycemia. Early insulin resistance can be estimated via the triglyceride glucose index {TyG = Ln [TG (mg/dl) × fasting plasma glucose (FPG) (mg/dl)/2]} and the hypertriglyceridemic-high waist phenotype (TyG-waist), based on TyG x waist circumference (WC) measurements. Both indices may be useful for implementing personalized metabolic management. In this secondary analysis of a randomized controlled trial (RCT), we aimed to determine whether the differences in baseline TyG values and TyG-waist phenotype predicted individual responses to type-2 diabetes (T2D) prevention programs. Methods: The present post-hoc analyses were conducted within the Prevention of Diabetes through Lifestyle intervention and population studies in Europe and around the world (PREVIEW) study completers ( n = 899), a multi-center RCT conducted in eight countries (NCT01777893). The study aimed to reduce the incidence of T2D in a population with pre-diabetes during a 3-year randomized intervention with two sequential phases. The first phase was a 2-month weight loss intervention to achieve ≥8% weight loss. The second phase was a 34-month weight loss maintenance intervention with two diets providing different amounts of protein and different glycemic indices, and two physical activity programs with different exercise intensities in a 2 x 2 factorial design. On investigation days, we assessed anthropometrics, glucose/lipid metabolism markers, and diet and exercise questionnaires under standardized procedures. Results: Diabetes-related markers improved during all four lifestyle interventions. Higher baseline TyG index ( p < 0.001) was associated with greater reductions in body weight, fasting glucose, and triglyceride (TG), while a high TyG-waist phenotype predicted better TG responses, particularly in those randomized to physical activity (PA) of moderate intensity. Conclusions: Two novel indices of insulin resistance (TyG and TyG-waist) may allow for a more personalized approach to avoiding progression to T2D. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01777893 reference, identifier: NCT01777893.
Competing Interests: TL was employed by company NetUnion Sarl. PS has received travel grants from the Cambridge Weight Plan, UK. JB-M is the President and Director of the Glycemic Index Foundation, oversees a glycemic index GI testing service at the University of Sydney and is a co-author of books about diet and diabetes. IM is a member of the UK Government Scientific Advisory Committee on Nutrition, Treasurer of the Federation of European Nutrition Societies, Treasurer of the World Obesity Federation, member of the Mars Scientific Advisory Council, member of the Mars Europe Nutrition Advisory Board, and Scientific Adviser to the Waltham Centre for Pet Nutrition. He is also a member of the Nestle Research Scientific Advisory Board and of the Novozymes Scientific Advisory Board. SP was the Fonterra Chair in Human Nutrition and Principle Investigator for NZ National Science Challenge High Value Nutrition during the PREVIEW intervention. TML is an advisor for the “Sense” diet program. AR has received honorariums from Novo Nordisk A/S, the International Sweeteners Association, Nordic Sugar and Unilever. JM is the President of IUNS. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Navas-Carretero, San-Cristobal, Siig Vestentoft, Brand-Miller, Jalo, Westerterp-Plantenga, Simpson, Handjieva-Darlenska, Stratton, Huttunen-Lenz, Lam, Muirhead, Poppitt, Pietiläinen, Adam, Taylor, Handjiev, McNarry, Hansen, Brodie, Silvestre, Macdonald, Boyadjieva, Mackintosh, Schlicht, Liu, Larsen, Fogelholm, Raben and Martinez.)