Diabetes/Overweight Epidemiology; the importance of effect modification.
01 / 2009 - unknown
Website Groningen Institute for Healthy Aging
More than half of the elderly population in the Netherlands (and in the western world) has long-lasting overweight or obesity. A large amount of body fat is related to an increased occurrence of age-related chronic diseases, notably type 2 diabetes mellitus and cardiovascular disease. Previous research by Prof. dr. R.P. Stolk and others has indicated that the explanations are beyond the amount of body fat (obesity), but that the distribution of excess fat (intra-abdominal versus subcutaneous) is more important. Moreover, intra-abdominal fat and the related insulin resistance are strong risk factors for measures of biologic aging, like diabetes and other chronic diseases, cognitive function, activities of daily living (ADL), and perceived health. Therefore, UMCG research projects in this field mainly focus on the role of fat distribution in the prediction and occurrence of chronic diseases. Fat distribution: An important hypothesis is that fat distribution is not a (strong) causal risk factor but increases disease occurrence by modifying the effects of known risk factors. The occurrence of disease in an obese individual depends on the combined effect of fat distribution and these other factors, as illustrated in the figure on this page. For example, diabetes genes (like TCF7L2) as well as physical activity influence insulin sensitivity, which has more effect in persons with central obesity bearing insulin resistance. This may be the reason why some sedentary persons develop diabetes and others get a myocardial infarction. This difference is not explained by current studies on physical inactivity. Modification might also explain the absence of substantial disease prevention by current weight loss programs, since these do not take additional known risk factors into account. Liver fat: In gene-environment interaction studies (as well as environmental-environmental interaction studies) it is critical to obtain maximal precision in the assessment of all factors involved (determinants, modifier, outcome). This has resulted in recognizing the role of liver fat as important ectopic fat depot within the intra-abdominal fat. Future studies will investigate the role of muscle fat and myocardial fat as potential risk factors. To obtain more precise measurements of fat distribution in (large scale) epidemiological studies the UMCG has developed and validated ultrasound techniques to quantitatively assess subcutaneous, intra-abdominal and liver fat. LifeLines: Research into effect modification is preferably conducted in large observational follow-up studies, to enable the analysis of effects in subgroups defined by the potential modifying factor. The recently started LifeLines cohort study is very well suited to perform these studies. More information on LifeLines can be found through the link to the projects site at the bottom of the page (partially in Dutch). In addition, the UMCG is involved in several (international) clinical studies on the diagnosis of fat distribution and physical activity, as well on the risk of increased intra-abdominal fat, insulin resistance and type 2 diabetes mellitus. Questions about obesity in combination with known risk factors are particularly suited to be answered in epidemiological research. Knowledge on the modification of risk factors will enable individually tailored prevention programs. For some individuals this might mean other actions than weight loss for optimal prevention.