Metabotyping of Overweight and Obese Children Towards Early Detection of Insulin Resistance and Low-grade Inflammation by Means of a Rectal Sampler

The impetus for this research proposal stems from the ever-increasing metabolic-related health issues impacting today's children. Particularly, the high prevalence of childhood obesity accompanied by substantial progression to 'prediabetic state' at teen age and full-blown DMT2, the most prevailing endocrine disease worldwide, at early adulthood. Several risk factors for the development of overt DMT2 and crescent atherogenic processes, including unhealthy lifestyle patterns, decreased physical activity and (subsequent) obesity, that may be considered markers of metabolic abnormalities, such as insulin resistance, are already well-established in children with impaired glucose tolerance prior to time of diagnosis around early adolescence. Moreover, even in individuals with normal glucose tolerance, insulin resistance has been pointed out a major risk factor and predictor for the development of DMT2. Conversely, the micro- and macrovascular events do not readily appear until maturity, thereby predisposing obese children to the development of several long-term complications urging the quest for diagnostic, prognostic and/or predictive biomarkers for insulin resistance and related metabolic diseases. Hence, intervening in the pre-pubertal life stage becomes of paramount importance. As a pivotal component in precision medicine, and unlike routine measurements that only include a narrow set of blood chemistry analytes, metabolomics reveals a far more comprehensive metabolic signature. Taken together that DM and related comorbidities are considered metabolic diseases with a dysregulated lipid metabolism being a central factor in the pathogenesis, metabolomics (and in particular lipidomics) is of key importance in this research proposal. Furthermore, given the collision between genes, gut microbiota and environmental changes preceding the development of DM and, in addition, the excellence of stool in reflecting the metabolic interactions and outcomes thereof, an innovative rectal sampler using a medical swab with customized surface tip for optimal gut metabolome coverage will be used. REIMS significantly reduces time (< 10 s) and workload (minimal sample preparation), enhancing research output and efficiency. The aim is the early identification of children who are destined to develop obesity-related chronic diseases.