Stemming the tide of type 2 diabetes in youth: DREAMing big, one sandbag at a time

Type 2 diabetes (T2D) is one of the fastest growing chronic diseases in Canada (Lipscombe and Hux 2007) and across the world (Danaei et al. 2011). While T2D was once considered a disease of middle age, the prevalence of T2D among children and adolescents is increasing at a rate 50% greater than youth with type 1 diabetes (Dabelea et al. 2014). In fact, cases of T2D account for 40%–80% of newly diagnosed cases of diabetes in some paediatric diabetes centers (Hannon et al. 2005). Prior to 1985, a diagnosis of T2D in the pediatric population was essentially unknown (Pinhas-Hamiel and Zeitler 2005). Over the past 30 years, rates of T2D in youth have escalated to the point where many are presenting with severe life-threatening complications related to diabetes in their young adult years (Pinhas-Hamiel and Zeitler 2007; Dart et al. 2012a, 2013; Pavkov et al. 2006; Franks et al. 2010). The current special issue is dedicated to state of the art studies related to T2D in youth and will focus on several aspects of this emerging public health concern, including early detection, prevention, stigma, gestational determinants of T2D, and cardiovascular complications of T2D. Dean and Sellers begin the issue by reflecting on decades of work in this area (Dean 1998; Dean et al. 1998; Sellers et al. 2000, 2002; Young et al. 2000). They provide a historical perspective of the emergence of the concept that T2D can affect children. They also reflect on the current trends in T2D among youth including the disproportionate rates among disadvantaged socioeconomic environments, particularly indigenous children worldwide. On a very “related” note, Cameron and O’Reilly highlight the often under-appreciated issue of the stigma that face children living with and at risk for T2D. They discuss the impact that media and social perceptions of obesity (Callahan 2013) and T2D have on youth and present novel pedagogical approaches to address these stigma from a healthcare perspective. It is becoming increasingly apparent that T2D risk is programmed in utero (Franks et al. 2006; Young et al. 2002). Periera and colleagues review the most recent pre-clinical evidence to explain how and why maternal obesity and gestational diabetes mellitus contribute to themetabolic and cardiovascular disorders that characterize T2D in youth. Importantly, they also provide an overview of interventional experimental studies aimed at preventing T2D early in life. From a prevention standpoint, insulin resistance, tissue steatosis, and mitochondrial dysfunction are all implicated in the natural history of T2D in youth. Gordon et al. summarize clinical and basic studies that shed light on how alterations in skeletal muscle mitochondrial dysfunction might contribute to whole body insulin resistance. They further discuss evidence that support highintensity exercise training as a therapy to circumvent skeletal muscle mitochondrial dysfunction for restoration of insulin sensitivity and prevention of tissue steatosis in both adults and adolescents. Brown et al. provide convincing evidence to support these claims by demonstrating the joint and independent association between visceral fat and liver fat with insulin sensitivity in obese adolescents. This work supports previous studies by this group (Lee et al. 2010; Michaliszyn et al. 2013) and members of the Diabetes Research Envishioned and Accomplished in Manitoba (DREAM) Theme (Mollard et al. 2014; Wittmeier et al. 2012; Wicklow et al. 2012) that tissue steatosis is a key determinant of T2D risk in youth. Building on the theme of prevention,McIntosh et al. describe the perceived impact of a novel community-based participatory action research program being delivered in British Columbia: The Sustainable Childhood Obesity Prevention Through Community Engagement (SCOPE), for preventing T2D in high risk youth. At amore targeted level,Wicklow and colleagues describe a novel therapeutic intervention to reduce hepatic steatosis and relieve the burden of lipotoxicity in youth. This trial builds on extensive pre-clinical studies on the role of resveratrol for improving metabolic health and will be the first translational effort in a pediatric clinical population. Finally, Cheng et al. review the anti-diabetic mechanisms of the natural product berberine and its recent use in human clinical studies for the management of T2D and its complications. In addition to insulin resistance and tissue steatosis, the rapid deterioration in -cell dysfunction is a hallmark feature of T2D in youth. The factors that lead to -cell failure in youth with T2D remain poorly understood. Jonasson et al. discuss the lessons learned from decades of scientific discoveries in the area of Maturity Onset Diabetes of the Young and how thesemay guide studies into the role of a private mutation in the HNF-1 gene (G319S) in the natural history of T2D in youth. This unique polymorphism is restricted to Oji–Cree people living in isolated northwestern regions of Ontario (Hegele et al. 1999a, 1999b) and northeastern regions of Manitoba (Sellers et al. 2002), that causes a rapid deterioration of glucose tolerance and may be sensitivity to certain environmental exposures, including gestational diabetes. One of the possible mechanisms linking gestational exposures and T2D risk in youth is epigenetic regulation, particularly adversemethylation patterns of -cells or transcripts that regulate -cell function. Dayah and Ling describe risk factors that may result in epigenetic dysregulation of -cell function, and how these risk factors may affect the epigenome at different time points throughout the lifetime of an individual. Previous studies by members of the DREAM theme revealed that youth with T2D suffer from a significant burden of cardiore-

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