Early markers of metabolic disease in obesity - A study of postprandial triglycerides, leptin and adiponectin interactions in the view of normal and dysregulated metabolism

Abstract

Individuals in industrialized countries spend a substantial part of life in the non-fasting, postprandial state, which is also associated with increased oxidation and inflammation. Furthermore, a high body mass index (BMI) is the third cause of mortality in the world. In this PhD thesis, obese (BMI>30) individuals with and without metabolic disease (n=50) was included, in addition to a normal weight, healthy individuals(n=17). The aim of the thesis was to find sensitive, early biomarkers of metabolic dysregulations in obese individuals, and to examine postprandial triglyceride (TG) metabolism, in addition to leptin and adiponectin. The thesis finds that there are metabolic dysregulations with delayed postprandial TG clearance, insulin resistance (IR) and leptin resistance (LR) in apparently metabolically healthy obese (MHO) individuals. In addition postprandial regulation of adiponectin and leptin are altered in obese individuals. Furthermore, metabolic dysregulations can be mapped out with surrogate biomarkers, in obese individuals, such as fasting TG in the upper normal level, and IR measured by homeostasis model assessment of IR (HOMA-IR). However, the leptin:adiponectin ratio (L:A ratio) might be the most suitable biomarker, as it was found sensitive to predict delayed postprandial TG clearance, LR and IR. This thesis adds novel knowledge in the field of regulation of energy metabolism in obese individuals. It also proves that apparently MHO have early metabolic dysregulations, that is not found by classic examinations done in the clinical practice. However, more sensitive, surrogate biomarkers can help us diagnose this at an earlier stage, to further lower the risk for development of metabolic diseases, and being able to treat at an earlier stage. This is important as obesity and diabetes are increasing worldwide. Further studies are needed to find suitable cut-off values for different patient groups, especially for L:A ratio, in addition to standardized measure methods that can be used in the clinic.