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Hugo Pomares-Millan

Doctoral student

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Estimating the Direct Effect between Dietary Macronutrients and Cardiometabolic Disease, Accounting for Mediation by Adiposity and Physical Activity

Author

  • Hugo Pomares-Millan
  • Naeimeh Atabaki-Pasdar
  • Daniel Coral
  • Ingegerd Johansson
  • Giuseppe N. Giordano
  • Paul W. Franks

Summary, in English

Assessing the causal effects of individual dietary macronutrients and cardiometabolic disease is challenging owing to the complexity to distinguish direct effects from those mediated or confounded by other factors. To estimate these effects, intake of protein, carbohydrate, sugar, fat, and its subtypes were obtained using food frequency data derived from a Swedish population-based cohort (n~60,000). Data on clinical outcomes (i.e., type 2 diabetes (T2D) and cardiovascular disease (CVD) incidence) were obtained by linking health registry data. We assessed the magnitude of direct and mediated effects of diet, adiposity and physical activity on T2D and CVD using structural equation modelling (SEM). To strengthen causal inference, we used Mendelian randomization (MR) to model macronutrient intake exposures against clinical outcomes. We identified likely causal effects of genetically predicted carbohydrate intake (including sugar intake) and T2D, independent of adiposity and physical activity. Pairwise, serial-and parallel-mediational configurations yielded similar results. In the integrative genomic analyses, the candidate causal variant localized to the established type 2 diabetes gene TCF7L2. These findings may be informative when considering which dietary modifications included in nutritional guidelines are most likely to elicit health-promoting effects.

Department/s

  • Genetic and Molecular Epidemiology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health
  • eSSENCE: The e-Science Collaboration

Publishing year

2022-03-01

Language

English

Publication/Series

Nutrients

Volume

14

Issue

6

Document type

Journal article

Publisher

MDPI AG

Topic

  • Nutrition and Dietetics

Keywords

  • Adiposity
  • Cardiometabolic risk
  • Cardiovascular disease
  • Causal inference
  • Macronutrient intake
  • Mediation
  • Physical activity

Status

Published

Research group

  • Genetic and Molecular Epidemiology

ISBN/ISSN/Other

  • ISSN: 2072-6643