The number of individuals with obesity and type 2 diabetes mellitus (T2DM) is increasing. An alarming aspect is decline in age of onset of T2DM, which is coupled to rise in childhood obesity. Accentuated insulin secretion is observed early in young obese individuals. In many subjects insulin hypersecretion is evident when insulin sensitivity is essentially normal. Based on these observations we propose insulin hypersecretion as an etiological factor promoting lipid deposition, insulin resistance, cellular dysfunction and death in insulin-producing beta-cells and insulin-target brown adipocytes. Pharmacology-based treatment strategies are limited for this growing patient group and the aim of the proposal is to identify novel strategies reducing insulin hypersecretion, which has not been considered a target for intervention in young obese individuals. To address the issue, pediatric obesity clinics and academic centres with focus on beta-cell biology, brown adipocyte imaging, transcript and protein profiling, genetics, epidemiology and bioinfomatics have formed a consortium with two SMEs specialized on biomarker discovery and clinical trials and one large drug company. In the project well-characterized European patient cohorts of more than 3000 obese children will be further characterized with regard to insulin secretion and brown adipocyte mass. Currently used drugs and new principles of intervention based on novel genes, idenitifed in the project and linked with insulin hypersecretion, will be examined for effects on insulin hypersecretion in translational work including the young obese subjects and isolated human islets. Following comprehensive analysis candidate compounds/principles attenuating insulin hypersecretion will be selected, from which novel therapeutic strategies are expected to emerge. Such therapeutic strategies will be of importance for afflicted individuals and European health economy and lead to new opportunities for European industry.
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Funding SchemeCP-FP - Small or medium-scale focused research project