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

Santiago Navas-Carretero, Rodrigo San-Cristobal, Pia Siig Vestentoft, Jennie C. Brand-Miller, Elli Jalo, Margriet Westerterp-Plantenga, Elizabeth J. Simpson, Teodora Handjieva-Darlenska, Gareth Stratton, Maija Huttunen-Lenz, Tony Lam, Roslyn Muirhead, Sally Poppitt, Kirsi H. Pietiläinen, Tanja Adam, Moira A. Taylor, Svetoslav Handjiev, Melitta A. McNarry, Sylvia Hansen, Shannon BrodieMarta P. Silvestre, Ian A. Macdonald, Nadka Boyadjieva, Kelly A. Mackintosh, Wolfgang Schlicht, Amy Liu, Thomas M. Larsen, Mikael Fogelholm, Anne Raben, J. Alfredo Martinez

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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: reference, identifier: NCT01777893.

Original languageEnglish
Article number733697
JournalFrontiers in Nutrition
Publication statusPublished - 1 Nov 2021


  • carbohydrate metabolism
  • diabetes
  • hypertriglyceridemic-waist phenotype
  • lipid markers
  • obesity
  • pre-diabetes
  • precision nutrition
  • triglycerides (PubChem CID: 5460048)


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