Not only is type 2 diabetes in youth a paediatric disease now, but it is increasing in families and communities. And as studies such as the SEARCH for Diabetes in Youth, RISE, or TODAY have shown, it seems to be a more aggressive disease than either type 2 diabetes in adults or youth-onset type 1 diabetes. But there are several questions that we don't know the answer to. Hello, I am Dana Dabelea from the University of Colorado Anschutz Medical Campus. I'm Professor of Epidemiology and Paediatrics and a clinical chronic disease epidemiologist. I'd like to talk to you about type 2 diabetes with onset at a young age. Type 2 diabetes used to be called adult-onset diabetes, but now we are seeing it occurs in children and adolescents and very young adults in many populations around the world. Not only is type 2 diabetes in youth a paediatric disease now, but it is increasing in families and communities. And as studies such as the SEARCH for Diabetes in Youth, RISE, or TODAY have shown, it seems to be a more aggressive disease than either type 2 diabetes in adults or youth-onset type 1 diabetes. But there are several questions that we don't know the answer to, and we need more research to understand type 2 diabetes in youth. Number one, we know, that at least in the western world, type 2 diabetes in youth occurs almost exclusively in children who are overweight or obese. However, not all children who are overweight or obese develop type 2 diabetes. So what makes a fraction of these overweight obese children develop type 2 diabetes, whereas the others do not? Is it genetic susceptibility? If so, are the genes responsible the same ones that we've identified in adults, or are there other genes? Is it exposure to overnutrition in early life, even in utero? Is it a combination of the above? We don't know the answer to these questions, and more research is needed, such as that conducted in observational natural history studies that we're part of. Number two, what is the pathophysiology of youth-onset type 2 diabetes? We know from studies such as RISE, which compared head-to-head youths with new-onset type 2 diabetes and impaired glucose tolerance and adults with the same conditions, that children for the same degree of BMI had more insulin resistance than adults. In addition, children also had hyperreactive beta cells, and the reasons for these differences between type 2 diabetes in children and in adults have not been elucidated in the RISE study. So we need more longitudinal cohorts, natural history cohorts, to understand the pathophysiology of youth-onset type 2 diabetes. Number 3, we have learned from well-designed epidemiological studies that exposure to overnutrition in utero, resulting from exposure to maternal diabetes in utero or maternal obesity in utero, are strong risk factors for type 2 diabetes in youth. We have also learned that the intrauterine exposures explain almost 50 % of youth-onset type 2 diabetes in diverse populations. What we don't know is what are the specific intrauterine mechanisms, the specific intrauterine programming effects responsible for these long-term outcomes? What are the fuels that result in overnutrition? Is it glucose? Is it lipids? Triglycerides? Free fatty acids? A combination of all of the above? So we need mechanistic studies, perhaps nested in longitudinal cohort studies such as we conduct in the Healthy Start cohort in Colorado, where we are starting to understand the epigenetic mechanisms, the signalling proteins responsible for these long-term effects. And we're using different types of tissues in which we're exploring this question, such as mesenchymal stem cells, to elucidate the mechanisms responsible for in utero programming. Number four, we also need better therapies to control hypoglycaemia, to prevent beta cell decline, and control comorbidities of youth-onset type 2 diabetes. The RISE study clearly showed that metformin and insulin are not enough to prevent beta cell decline in youth with recent-onset type 2 diabetes, as opposed to what happens in adults. Moreover, only half of those treated with metformin in the TODAY trial showed durable glycaemic control. So we need more studies with newer agents, such as the GLP-1 receptor agonists and even bariatric surgery when indicated, to understand medications that can control hyperglycaemia and beta cell decline. Since these are expensive drugs, at least in the United States, we also need research to better understand how to provide access to care and make these therapies affordable for those who need them most. Number five: Finally, a word about prevention. First, as we learn from well-conducted observational natural history studies about the pathophysiology and triggers of youth-onset type 2 diabetes, we do need studies targeting high-risk youth with personalised prevention approaches tailored to individual biology and pathophysiology. We have strong evidence from well-conducted studies in adults, such as the US and the Finnish diabetes prevention programmes on how to prevent type 2 diabetes in high-risk adults. But such studies do not exist in high-risk children, and we do not have individualised therapies for obesity in either children or adults. In addition, we also need studies focusing on primordial prevention, preventing risk factors for diabetes before they even occur. Such studies might need to start during pregnancy or even pre-conceptually, and they need to continue throughout the life-course to really break the intergenerational cycle of obesity and diabetes.