Adult weight change and cardiometabolic disease: studies into underlying pathways

Verkouter, I. (2022)

Doctoral Thesis

The aim of this thesis was to study the cardiometabolic consequences of obesity and weight gain during the life course. We investigated the association between body mass index (BMI) and cardiometabolic disease using Mendelian randomization. We observed that all BMI-associated gene sets, grouped based on tissue expression, were similarly associated with increased risks of cardiometabolic disease. We observed that abdominal adiposity in adolescence was associated with early changes in metabolomic measures indicative of an atherogenic profile already present in young men. Weight gain during adulthood was specifically related to an atherogenic metabolic profile, in addition to increased adipocyte size. Adult weight gain between age 20 years and middle age was associated with increased visceral and liver fat at middle age. Additionally, the association between adult weight gain and insulin resistance at middle age was partly mediated by increased levels of visceral and liver fat at middle age. Lastly, we observed that a favourable body fat distribution as well as metabolic profile are associated with a decreased risk of incident cardiometabolic disease in a population with obesity. Overall, the results of this thesis emphasize the importance of maintaining a stable body weight during young adulthood throughout middle age.  

• Weight Gain
• Body Weight Changes
• Obesity
• Body Mass Index
• Type 2 Diabetes Mellitus
• Cardiovascular Diseases
• Intra-Abdominal Fat
• Fatty Liver
• Metabolomics
• Mendelian Randomization Analysis

• All authors: Verkouter, I.
• Supervisor: Rosendaal, F.R.
• Co-supervisor: Mutsert, R. de; Noordam, R.
• Committee: Willems van Dijk, J.A.P.; Slagboom, P.; Timpson, N.J.; Beulens, J.W.
• Qualification: Doctor (dr.)
• Awarding Institution: Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
• Date: 2022-05-17
• ISBN (print): 9789464582307
• Sponsorship: The work described in this thesis was funded by the Netherlands Cardiovascular Research Initiative: an initiative with support of the Dutch Heart Foundation (grant No. CVON2014-02 ENERGISE). Financial support from the Netherlands Association for the Study of Obesity (NASO) is greatly acknowledged. Financial support by the Dutch Heart Foundation for the publication of this thesis is gratefully acknowledged.