Translational Research Core 2: Type 2 Diabetes and Obesity Prevention (Core Director Assiamira Ferrara. MD PhD) H.1 Importance of Core to Translational Research and NIDDK Specific """"""""translational 2"""""""" research priorities for the NIDDK include translating the DPP *""""""""?'into diverse settings and populations and improving access to care for vulnerable populations. Several populations are at especially high risk for type 2 diabetes (T2DM), and thus appropriate for focused prevention efforts. These groups include adults with obesity, IGT/IFG or other features of the metabolic syndrome, race/ethnic minority and women with a history of gestational diabetes (GDM). As the epidemic of obesity now affects even young children (140) and evidence grows that early life experiences, including in-utero exposure to maternal obesity and hyperglycemia, influence later obesity risk, (141) interventions targeted at pregnant and/or early postpartum women and children may offer the greatestpromise for the prevention of T2DM and obesity across two generations. For this Core, we leverage our considerable joint expertise in translational obesity and T2DM prevention research among pregnant and/or postpartum women, especially those diagnosed with GDM, and children. GDM affects 7-14% of the pregnancies in the US.(142,143) GDM prevalence has increased 30 to 100% during the last decades and it is higher among race/ethnic minority.(144,145) 50% of women with a GDM history develop T2DM within 5 years after delivery.(146) A third of women diagnosed with GDM will be diagnosed with T2DM, IFG or IGT at postpartum screening.(147,148) Women with normal postpartum screening are at lower risk for T2DM in the short term, but remain at increased risk for T2DM in the long term. (149,150) Therefore, all women with GDM history should be considered for T2DM prevention programs. The success of the DPP (139) suggests that high-risk pre-diabetes status is a motivating factor for lifestyle change. The same messages delivered in the DPP are relevant to women recently diagnosed with GDM. Subgroup analyses(151) in DPP women who had a pregnancy in the prior 12 years, subjects with a history of GDM showed that intensive lifestyle intervention and metformin both decreased the risk of T2DM by approximately 50%. However, women with GDM history were less successful in adhering to physical activity and weight loss than were women without a GDM history.(151) This lower adherence may be due to their younger age and presumably, busier postpartum lives. Therefore, lifestyle interventions for pregnant/postpartum women should be focused on helping them overcome the barriers they face to increasing physical activity and achieving a healthier body weight. However, postpartum quality of care (e.g. glucose screening (147,148) and counseling on lifestyle and weight management)(93,152,153) in most GDM patients is suboptimal. Therefore women with GDM represent an underserved population for T2DM prevention efforts. Prevention of GDM is another important goal. Programs to prevent GDM may start before or during pregnancy. Excessive gestational weight gain (GWG) is emerging as an important and possibly more easily preventable risk factor for GDM.(154-156) Interventions might target women with adverse pregravid risk factors for GDM and T2DM such as overweight or obesity, (157) weight gain of more than 2 kg per year during the 5-years before pregnancy,(158) or abnormal pregravid levels of the components of the metabolic syndrome such as pre-hypertension/hypertension,(158) mild hyperglycemia (159) or dyslipidemia.(160) Preventing excessive GWG as well as weight retention or weight gain after pregnancy is also important for preventing obesity and T2DM in women without GDM. Excessive GWG is the most important determinant of postpartum weight retention, which in turn is associated with greater risk of future obesity. Therefore interventions aimed at helping women adhere to the lOM recommendations for GWG and lose weight postpartum might substantially reduce the prevalence of obesity and T2DM among young women. A recent report by the lOM (162) highlighted these gaps in research on obesity prevention among young women. Both GDM and excessive GWG are also important and independent predictors of overweight and adverse cardio-metabolic measures in offspring. Both are associated with greater birth weight for gestational age, (163-165) which in turn predicts offspring weight and risk of overweight later in life.(166) A number of studies have found that children born with intra-uterine exposure to diabetes are at higher risk for obesity and T2DM.(167-170) Higher GWG is also a strong risk factor for child overweight and its cardiometabolic sequelae.(171) Based on this evidence, the White House Task Force on Childhood Obesity(172) highlights the need to intervene on perinatal factors, such as excessive GWG and GDM in childhood obesity prevention efforts. The first years after pregnancy appear to be important times for children. During infancy, modifiable behaviors such as infant feeding, sleep duration, and rate of growth are associated with later obesity.(173-176) In the preschool years, additional contributors include consumption of sugar-sweetened beverages and television viewing.(177,178) The investigators on this Core have led extensive and influential formative work identifying many of these perinatal and early childhood risk factors that contribute to obesity and T2DM risk among women and children. In addition, we have developed innovative studies to translate these findings into real world, disseminable interventions and we have developed innovative adaptations of the DPP lifestyle intervention to be feasible for the busy life of pregnant/postpartum women as well as within the health care setting, as well as innovative interventions for young children within the health care setting and communities (see section 2).

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