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Beta-cell function in juvenile diabetes and obesity

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Childhood diabetes or obesity: which comes first?

Type 2 diabetes mellitus (T2DM) is increasingly prevalent among children due to a concomitant rise in obesity. Obtaining insight into the interplay between the two conditions could lead to the development of much-needed therapeutic interventions.

Health

T2DM is a metabolic disorder where the body is unable to produce or utilise insulin effectively. Since high insulin levels favour storage rather than combustion of energy, individuals with accentuated insulin responses could be at risk of developing obesity and T2DM. To delineate if high insulin levels is an early phenomenon that dictates obesity development, the EU-funded 'Beta-cell function in juvenile diabetes and obesity' (BETA-JUDO) project is pursuing a translational approach. By bringing together researchers and clinicians across Europe, the project hopes to answer key questions regarding elevated insulin levels in young obese individuals. Additional objectives of the study include the elucidation of genetic predisposition factors alongside the development of pharmacological interventions. Scientists are performing oral glucose tolerance tests in obese and normal weight children to characterise insulin secretion. Genetic analysis aims at identifying genes potentially associated with insulin traits in obese children. When obese children with high insulin levels were followed up, a drop in insulin levels could be observed. Some of these individuals developed T2DM. A considerable part of the BETA-JUDO work is focused on the molecular mechanisms responsible for insulin hypersecretion from human pancreatic islets. An in vitro model for insulin hypersecretion, where islet cells are cultured, has been established and partners are in the process of evaluating various drugs that could normalise the aberrant phenotype. Additional characteristics associated with insulin hypersecretion are also being evaluated such as circulating levels of free fatty acids, as well as white and brown fat cells. Taken together, the BETA-JUDO study will generate important knowledge on the association between insulin hypersecretion and childhood obesity. Project activities should help reduce obesity rates in Europe through increased awareness about the dismal outcome of childhood obesity and the importance of intervention strategies.

Keywords

Type 2 diabetes mellitus, obesity, metabolism, insulin, hypersecretion, phenotype, fatty acids

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