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      Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002–2012

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          The cation efflux transporter ZnT8 (Slc30A8) is a major autoantigen in human type 1 diabetes.

          Type 1 diabetes (T1D) results from progressive loss of pancreatic islet mass through autoimmunity targeted at a diverse, yet limited, series of molecules that are expressed in the pancreatic beta cell. Identification of these molecular targets provides insight into the pathogenic process, diagnostic assays, and potential therapeutic agents. Autoantigen candidates were identified from microarray expression profiling of human and rodent pancreas and islet cells and screened with radioimmunoprecipitation assays using new-onset T1D and prediabetic sera. A high-ranking candidate, the zinc transporter ZnT8 (Slc30A8), was targeted by autoantibodies in 60-80% of new-onset T1D compared with <2% of controls and <3% type 2 diabetic and in up to 30% of patients with other autoimmune disorders with a T1D association. ZnT8 antibodies (ZnTA) were found in 26% of T1D subjects classified as autoantibody-negative on the basis of existing markers [glutamate decarboxylase (GADA), protein tyrosine phosphatase IA2 (IA2A), antibodies to insulin (IAA), and islet cytoplasmic autoantibodies (ICA)]. Individuals followed from birth to T1D showed ZnT8A as early as 2 years of age and increasing levels and prevalence persisting to disease onset. ZnT8A generally emerged later than GADA and IAA in prediabetes, although not in a strict order. The combined measurement of ZnT8A, GADA, IA2A, and IAA raised autoimmunity detection rates to 98% at disease onset, a level that approaches that needed to detect prediabetes in a general pediatric population. The combination of bioinformatics and molecular engineering used here will potentially generate other diabetes autoimmunity markers and is also broadly applicable to other autoimmune disorders.
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            Prevalence and trends in obesity and severe obesity among children in the United States, 1999-2012.

            Childhood obesity is the focus of public health efforts and accurate estimates of the prevalence and severity of obesity are needed for policy decisions and directions for future research. To examine the prevalence of obesity and severe obesity over time for 14 years of the continuous National Health and Nutrition Examination Survey, 1999 to 2012, and to examine differences in the trends by age, race/ethnicity, and sex. Representative sample (N = 26 690) of children in the United States, ages 2 to 19 years, in repeated cross-sections of the National Health and Nutrition Examination Survey, 1999 to 2012. Prevalence of overweight (body mass index [BMI] ≥ 85th percentile), obesity (BMI ≥ 95th percentile for age and sex), class 2 obesity (BMI ≥ 120% of the 95th percentile or BMI ≥ 35), and class 3 obesity (BMI ≥ 140% of the 95th percentile or BMI ≥ 40). From 2011 to 2012, 17.3% (95% CI, 15.3-19.3) of children in the United States aged 2 to 19 years were obese. Additionally, 5.9% (95% CI, 4.4-7.4) of children met criteria for class 2 obesity and 2.1% (95% CI, 1.6-2.7) met criteria for class 3 obesity. Although these rates were not significantly different from 2009 to 2010, all classes of obesity have increased over the last 14 years. Nationally representative data do not show any significant changes in obesity prevalence in the most recently available years, although the prevalence of obesity may be stabilizing. Continuing research is needed to determine which, if any, public health interventions can be credited with this stability. Unfortunately, there is an upward trend of more severe forms of obesity and further investigations into the causes of and solutions to this problem are needed.
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              Approximate Is Better than "Exact" for Interval Estimation of Binomial Proportions

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                Author and article information

                Journal
                New England Journal of Medicine
                N Engl J Med
                New England Journal of Medicine (NEJM/MMS)
                0028-4793
                1533-4406
                April 13 2017
                April 13 2017
                : 376
                : 15
                : 1419-1429
                Article
                10.1056/NEJMoa1610187
                5592722
                28402773
                3e66c07c-87d0-4fbc-89fd-ec947e9d54ee
                © 2017
                History

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