Project 454785

Obesity is a growing global health concern and is a major risk factor for type 2 diabetes (T2D). Although there is large evidence demonstrating an obesity-T2D relationship, the underlying mechanism is still unclear. Recently, there has been increasing interest in a subpopulation of obese but otherwise healthy individuals, referred to as metabolically healthy obesity (MHO). The association between MHO and T2D risk have been inconsistent, likely due to the variations in defining metabolic health, inadequate in-depth participant data, and small sample size and single time-point studies. Our proposed research program aims to address these critical limitations by using detailed multiple year data from over 10,000 adults from the Nurses' Health Study and the Health Professionals Follow-up Study cohorts. These datasets provide over 30-years of rich and detailed information on important inflammatory biomarkers, lifestyle characterizations, and T2D incidence. More importantly, with the use of novel advanced technologies, this project will incorporate metabolite data to provide insight on underlying mechanisms leading to disease onset. Metabolomics, the study of metabolite profiles which are produced during metabolism, can provide robust, direct, and unbiased information on participant lifestyle and behaviour. With the data available in these large cohorts, we will be able to investigate whether MHO participants differ to other subpopulations characterized by obesity and metabolic health status, identify metabolites unique to these populations, and determine whether these metabolomic signatures indirectly connect the associations between obesity and T2D risk. Findings from this program will help disentangle the complexity of the obesity-T2D relationship, contribute to more effective and targeted health guidelines and recommendations, and help in the development of personalized preventive treatments and intervention strategies to lessen the global burden of obesity and T2D.