Preventing diabetes in obese Latino youth with prediabetes: a study protocol for a randomized controlled trial.

BACKGROUND: Obese Latino adolescents are disproportionately impacted by insulin resistance and type 2 diabetes. Prediabetes is an intermediate stage in the pathogenesis of type 2 diabetes and represents a critical opportunity for intervention. However, to date, no diabetes prevention studies have been conducted in obese Latino youth with prediabetes, a highly vulnerable and underserved group. Therefore, we propose a randomized-controlled trial to test the short-term (6-month) and long-term (12-month) efficacy of a culturally-grounded, lifestyle intervention, as compared to usual care, for improving glucose tolerance and reducing diabetes risk in 120 obese Latino adolescents with prediabetes. METHODS: Participants will be randomized to a lifestyle intervention or usual care group. Participants in the intervention group will attend weekly nutrition and wellness sessions and physical activity sessions twice a week for six months, followed by three months of booster sessions. The overall approach of the intervention is framed within a multilevel Ecodevelopmental model that leverages community, family, peer, and individual factors during the critical transition period of adolescence. The intervention is also guided by Social Cognitive Theory and employs key behavioral modification strategies to enhance self-efficacy and foster social support for making and sustaining healthy behavior changes. We will test intervention effects on quality of life, explore the potential mediating effects of changes in body composition, total, regional, and organ fat on improving glucose tolerance and increasing insulin sensitivity, and estimate the initial incremental cost effectiveness of the intervention as compared with usual care for improving glucose tolerance. DISCUSSION: The proposed trial builds upon extant collaborations of a transdisciplinary team of investigators working in concert with local community agencies to address critical gaps in how diabetes prevention interventions for obese Latino youth are developed, implemented and evaluated. This innovative approach is an essential step in the development of scalable, cost-effective, solution oriented programs to prevent type 2 diabetes in this and other populations of high-risk youth. TRIAL REGISTRATION: NCT02615353, registered on June 8, 2016.

Contrastsing synaptic roles of MDGA1 and MDGA2.

Neurodevelopmental disorders are frequently linked to mutations in synaptic organizing molecules. MAM domain containing glycosylphosphatidylinositol anchor 1 and 2 (MDGA1 and MDGA2) are a family of synaptic organizers suggested to play an unusual role as synaptic repressors, but studies offer conflicting evidence for their localization. Using epitope-tagged MDGA1 and MDGA2 knock-in mice, we found that native MDGAs are expressed throughout the brain, peaking early in postnatal development. Surprisingly, endogenous MDGA1 was enriched at excitatory, but not inhibitory, synapses. Both shRNA knockdown and CRISPR/Cas9 knockout of MDGA1 resulted in cell-autonomous, specific impairment of AMPA receptor-mediated synaptic transmission, without affecting GABAergic transmission. Conversely, MDGA2 knockdown/knockout selectively depressed NMDA receptor-mediated transmission but enhanced inhibitory transmission. Our results establish that MDGA2 acts as a synaptic repressor, but only at inhibitory synapses, whereas both MDGAs are required for excitatory transmission. This nonoverlapping division of labor between two highly conserved synaptic proteins is unprecedented.

Low serum sodium levels at hospital admission: Outcomes among 2.3 million hospitalized patients.

BACKGROUND: Hyponatremia is the most common electrolyte disorder among hospitalized patients. Controversies still exist over the relationship between hyponatremia and outcomes of hospitalized patients. METHODS: To analyze the association of low serum sodium levels at hospital admission with in-hospital mortality and patient disposition and to compare the distribution of the risk of death associated with hyponatremia across the lifespan of hospitalized patients, we conducted an observational study of 2.3 million patients using data extracted from the Cerner Health Facts database between 2000 and 2014. Logistic regression models were used in the analyses. RESULTS: At hospital admission 14.4% of hospitalized patients had serum sodium levels [Na] <135 mEq/L. In adjusted multinomial logistic regression analysis, we found that the risk of in-hospital mortality significantly increases for [Na] levels < 135 or ≥143 to ≤145 mEq/L compared to the reference interval of 140 to <143 mEq/L (p<0.001). We observed similar trends for the relationship between [Na] levels and discharge to hospice or to a nursing facility. We demonstrated that younger age groups (18 to <45, 45 to <65) had a higher risk of in-hospital mortality compared to older age groups (65 to <75, ≥75) for [Na] levels <130 mEq/L or 143 to ≤145 mEq/L (p<0.001). CONCLUSIONS: Hyponatremia is common among hospitalized patients and is significantly associated with in-hospital mortality, discharge to hospice or to a nursing facility. The risk of death and other outcomes was more evident for [Na] <135 mEq/L. The mortality associated with low [Na] was significantly higher in younger versus older patients.