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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/advagg_css\/css__ce2QY63WIanKyr8eSq7eavr1XQRRmFD6ZSmwpyJi8lM__zXwFqpqmxrZOXXcd_TpBQpjuELbmIP9wBR5UuTDWAO4__YJWWMMdfCJuAFm5cUEp88OsodhO3ZA-2lzRfoBsSlk4.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EThe shifting demographics, burden, and presentation of type 1 diabetes mellitus (T1DM) suggest that the associated costs and societal burden will increase during the next 20 to 30 years, according to data. Also discussed is the nomenclature of the classification and diagnosis of diabetes, as well as data indicating that genes and antibodies can be used for the enhanced prediction of T1DM.\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPrevention \u0026amp; Screening\u003C\/li\u003E\u003C\/ul\u003E\u003Cul class=\u0022kwd-group clinical-trial\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EPrevention \u0026amp; Screening\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EEndocrinology\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes \u0026amp; Metabolic Syndrome\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EThe shifting demographics, burden, and presentation of type 1 diabetes mellitus (T1DM) suggest that the associated costs and societal burden will increase during the next 20 to 30 years, according to data presented by Dana Dabelea, MD, PhD, University of Colorado Denver, Denver, Colorado, USA.\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EAt the start of the 20th century, T1DM was rare and usually fatal. The typical patient was young, thin, and white. Since the mid-1900s, the incidence of T1DM has been increasing worldwide, with an incidence of 2% to 4% per year in 24 of 37 studies, and the average age at onset has been decreasing [Gale EA. \u003Cem\u003EDiabetes\u003C\/em\u003E 2002]. Data from the SEARCH for Diabetes in Youth Project show that between 2001 and 2009, the prevalence of T1DM increased among all racial and ethnic groups except American Indians and among all ages except children \u0026lt; 5 years of age [Dabelea D, \u003Cem\u003EJAMA\u003C\/em\u003E 2014]. In addition, the incidence of T1DM has increased significantly between 2002 and 2009 among non-Hispanic whites [Lawrence JM et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2014]. The prevalence of T1DM is projected to increase substantially by 2050, with the largest relative increase being in Hispanic youth (\u003Ca id=\u0022xref-fig-1-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F1\u0022\u003EFigure 1\u003C\/a\u003E) [Imperatore G et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2012]. Coupled with the increasing incidence of T1DM, there has been a decrease in the prevalence of high-risk human leukocyte antigen (HLA) genotypes and an increase in moderate- or low-risk HLA alleles, suggesting that environmental exposure is more able to trigger T1DM in children who were previously less genetically susceptible [Vehik K et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2008].\u003C\/p\u003E\u003Cdiv id=\u0022F1\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F1.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Projected Number of Youth With Type 1 Diabetes Among U.S. Youth \u0026amp;lt; 20 Years, by 2050\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-272831606\u0022 data-figure-caption=\u0022Projected Number of Youth With Type 1 Diabetes Among U.S. Youth \u0026amp;amp;lt; 20 Years, by 2050\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 1.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F1.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F1.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 1.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F1.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14658\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 1.\u003C\/span\u003E \n            \u003Cp id=\u0022p-4\u0022 class=\u0022first-child\u0022\u003EProjected Number of Youth With Type 1 Diabetes Among U.S. Youth \u0026lt; 20 Years, by 2050\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-1\u0022\u003EAA = African American; NHW = non-Hispanic white; T1DM = type 1 diabetes mellitus; US = United States.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-2\u0022\u003ESource: Imperatore G et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2012.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-5\u0022\u003EDiagnosis of T1DM has become complicated. The SEARCH for Diabetes in Youth Project has recently recommended a new diabetes classification system based on 2 etiologic markers (autoimmunity and insulin sensitivity [IS]) that can distinguish 4 diabetic subtypes: autoimmune plus IS, autoimmune plus insulin resistant (IR), nonautoimmune plus IS, and nonautoimmune plus IR [Dabelea D et al. \u003Cem\u003EDiabetes Care\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003ERisk factors for poor glycemic control, which is associated with poor prognosis, include being a minority, having parents with less education, lower family income, and less private health insurance (\u003Ca id=\u0022xref-fig-2-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F2\u0022\u003EFigure 2\u003C\/a\u003E) [Petitti DB et al. \u003Cem\u003EJ Pediatr\u003C\/em\u003E 2009]. Dr. Dabelea noted that there are substantial barriers to care among families with these socioeconomic characteristics that result in higher mortality and potentially avoidable hospitalization for complications.\u003C\/p\u003E\u003Cdiv id=\u0022F2\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F2.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Risk Factors for Poor Glycemic Control\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-272831606\u0022 data-figure-caption=\u0022Risk Factors for Poor Glycemic Control\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 2.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F2.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F2.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 2.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F2.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14659\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 2.\u003C\/span\u003E \n            \u003Cp id=\u0022p-7\u0022 class=\u0022first-child\u0022\u003ERisk Factors for Poor Glycemic Control\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-3\u0022\u003EAA = African American; AI = American Indian; API = Asian Pacific Islander; Hisp = Hispanic; H.S. = high school; Grad = graduated; NHW = non-Hispanic white.\u003C\/q\u003E\u003Cq class=\u0022attrib\u0022 id=\u0022attrib-4\u0022\u003ESource: Petitti DB et al. \u003Cem\u003EJ Pediatr\u003C\/em\u003E 2009.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-8\u0022\u003EStanley Schwartz, MD, Perlman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA, believes a new approach is needed to bring the nomenclature of the classification and diagnosis of diabetes in line with therapies. He recommends a \u03b2-cell-centric approach because it has implications for not only classification but also diagnosis, prevention, therapy, and research (\u003Ca id=\u0022xref-fig-3-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F3\u0022\u003EFigure 3\u003C\/a\u003E).\u003C\/p\u003E\u003Cdiv id=\u0022F3\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F3.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Pathogenic \u0026#x3B2;-Cell-Centric Construct for Diabetes\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-272831606\u0022 data-figure-caption=\u0022Pathogenic \u0026#x3B2;-Cell-Centric Construct for Diabetes\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 3.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F3.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F3.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 3.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F3.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14660\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 3.\u003C\/span\u003E \n            \u003Cp id=\u0022p-9\u0022 class=\u0022first-child\u0022\u003EPathogenic \u03b2-Cell-Centric Construct for Diabetes\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-5\u0022\u003EAGE = advanced glycation end product; FFA = free fatty acids; HLA = human leukocyte antigen; Inflam = inflammation; MODY = maturity-onset diabetes of the young.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-10\u0022\u003EIn the \u03b2-cell-centric construct, the phenotype is dependent on the genotype (the number of genes, the number of different genes, which genes, the nature of the genes, and the severity and intensity of expression). Dr. Schwartz believes that genotyping should be the standard diagnostic marker for a diagnosis of diabetes because this will ultimately lead to selecting the right drug for the right patient. He is currently pursuing a study to identify genes that are specific to latent autoimmune diabetes of adults.\u003C\/p\u003E\u003Cp id=\u0022p-11\u0022\u003EAlthough glycemic criteria and C-peptides will remain of use with the \u03b2-cell-centric construct, the monogenetic causes of diabetes should be determined to develop new or use existing therapies to improve \u03b2-cell function and to pay more attention to inflammation as a contributor to the loss of functional \u03b2-cells. IR is clearly a target for therapy because it impairs \u03b2-cell function through lipo-and glucotoxicity, inflammation, and its adipocytokine effect. Potential therapies include weight reduction, anti-inflammatory drugs, quick-release bromocriptine, thiazolidinediones, and soon pro- and prebiotics.\u003C\/p\u003E\u003Cp id=\u0022p-12\u0022\u003EThere are environmental risk factors for diabetes that require a new focus within primary prevention [Atkinson MA, Eisenbarth GS. \u003Cem\u003ELancet\u003C\/em\u003E 2001]. These include genetic antibody screening, the potential use of immune modulators, environmental modulation, and the definition of risk factors. Diagnostic markers (genes, \u03b2-cell issues, inflammation, and IR) can be used to identify types of diabetes and potential therapies.\u003C\/p\u003E\u003Cp id=\u0022p-13\u0022\u003EThere are 11 targets for treatment of T1DM that decrease glucose and produce lipotoxicity (\u003Ca id=\u0022xref-fig-4-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F4\u0022\u003EFigure 4\u003C\/a\u003E). Four have a direct effect on \u03b2-cells (\u03b2-cell, \u03b1-cell glucagon defect, decreased incretin effect, and inflammation) that can be treated with incretin drugs, and 7 have an indirect effect on \u03b2-cells (liver, muscle, fat, kidney, brain, stomach and intestine, and colon-biome). The best approach is to treat as many of the 11 targets as needed to obtain the lowest possible levels of blood glucose and HbA1C without undue weight gain or hypoglycemia. Dr. Schwartz called for a new committee to reclassify diabetes based on the \u03b2-cell-centric construct for better prevention, diagnosis, and treatment of diabetes.\u003C\/p\u003E\u003Cdiv id=\u0022F4\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F4.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Eleven Targets for Diabetes Treatment\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-272831606\u0022 data-figure-caption=\u0022Eleven Targets for Diabetes Treatment\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 4.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F4.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F4.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 4.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F4.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14606\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 4.\u003C\/span\u003E \n            \u003Cp id=\u0022p-14\u0022 class=\u0022first-child\u0022\u003EEleven Targets for Diabetes Treatment\u003C\/p\u003E\n         \u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-15\u0022\u003EAnette-Gabriele Ziegler, MD, Institute of Diabetes Research, Technische Universit\u00e4t M\u00fcnchen, Munich, Germany, presented data indicating that genes and antibodies can be used for the enhanced prediction of the course of T1DM.\u003C\/p\u003E\u003Cp id=\u0022p-16\u0022\u003ECheckpoints that define the natural history of T1DM can be used to determine the risk and rate of T1DM progression in children. The first checkpoint is the incidence of islet autoimmunity, which occurs between the ages of \u223c 9 months and 2 years (when it peaks). Early initiation of autoimmunity and rapid increases in autoantibody titers are associated with a progression to overt diabetes before puberty, emphasizing the importance of early life events in the development of T1DM [Ziegler AG et al. \u003Cem\u003EDiabetologia\u003C\/em\u003E 2012].\u003C\/p\u003E\u003Cp id=\u0022p-17\u0022\u003EThe second checkpoint is the occurrence of multiple islet autoantibodies (ABs), which is highest 1 year after seroconversion. Progression to T1DM in children with multiple islet ABs was faster in those with islet AB seroconversion at \u0026lt; 3 years, the majority of whom progressed to diabetes during the next 15 years in a linear fashion [Ziegler AG et al. \u003Cem\u003EJAMA\u003C\/em\u003E 2013]. Risk is persistently \u223c 11% per year.\u003C\/p\u003E\u003Cp id=\u0022p-18\u0022\u003EThe probability of developing islet autoimmunity is strongly linked to the HLA complex. HLA Class II genotypes and minor susceptibility genes can be used to predict T1DM and screen families. Other risk factors such as T-cells, type I interferon transcriptional signature [Ferreira RC et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2014], and respiratory infection prior to seroconversion can indicate states of increased T1DM susceptibility.\u003C\/p\u003E\u003Cp id=\u0022p-19\u0022\u003EEarly peri- and postnatal environmental exposures such as maternal diabetes (decreases risk), early exposure to solid food (increases risk), and early infection load (increases risk) are associated with islet autoimmunity. Progression to multiple islet AB and T1DM are strongly associated with high-affinity insulin AB [Achenbach P et al. \u003Cem\u003EJ Clin Invest\u003C\/em\u003E 2004], pro-insulin reactive insulin autoantibodies (IAA), A8\u201313 reactive IAA, high-affinity glutamic acid decarboxylase autoantibodies (GADA) and middle- or c-terminal reactive GADA [Mayr A et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2007].\u003C\/p\u003E\u003Cp id=\u0022p-20\u0022\u003EThe rate of progression to symptomatic T1DM seems to be affected by age at initiation of islet autoimmunity, sex, and non-HLA susceptibility genes. Environmental exposures may also \u2018pre-condition\u2019 the rate of progression. Interestingly, children delivered by cesarean section have a \u0026gt; 2-times higher risk for T1DM than children born by vaginal delivery and have a faster progression to T1DM after seroconversion. Cesarean section does not increase the risk for islet AB (\u003Ca id=\u0022xref-fig-5-1\u0022 class=\u0022xref-fig\u0022 href=\u0022#F5\u0022\u003EFigure 5\u003C\/a\u003E) [Bonifacio E et al. \u003Cem\u003EDiabetes\u003C\/em\u003E 2011].\u003C\/p\u003E\u003Cdiv id=\u0022F5\u0022 class=\u0022fig pos-float  odd\u0022\u003E\u003Cdiv class=\u0022highwire-figure\u0022\u003E\u003Cdiv class=\u0022fig-inline-img-wrapper\u0022\u003E\u003Cdiv class=\u0022fig-inline-img\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F5.large.jpg?width=800\u0026amp;height=600\u0026amp;carousel=1\u0022 title=\u0022Progression to Type 1 Diabetes in Children Born by Cesarean Versus Vaginal Delivery\u0022 class=\u0022fragment-images colorbox-load\u0022 rel=\u0022gallery-fragment-images-272831606\u0022 data-figure-caption=\u0022Progression to Type 1 Diabetes in Children Born by Cesarean Versus Vaginal Delivery\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003E\u003Cimg class=\u0022fragment-image\u0022 alt=\u0022Figure 5.\u0022 src=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F5.medium.gif\u0022\/\u003E\u003C\/a\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cul class=\u0022highwire-figure-links inline\u0022\u003E\u003Cli class=\u00220 first\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F5.large.jpg?download=true\u0022 class=\u0022highwire-figure-link highwire-figure-link-download\u0022 title=\u0022Download Figure 5.\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload figure\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00221\u0022\u003E\u003Ca href=\u0022http:\/\/d282kpwvnogo5m.cloudfront.net\/content\/spmdc\/14\/19\/25\/F5.large.jpg\u0022 class=\u0022highwire-figure-link highwire-figure-link-newtab\u0022 target=\u0022_blank\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EOpen in new tab\u003C\/a\u003E\u003C\/li\u003E\u003Cli class=\u00222 last\u0022\u003E\u003Ca href=\u0022\/highwire\/powerpoint\/14608\u0022 class=\u0022highwire-figure-link highwire-figure-link-ppt\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EDownload powerpoint\u003C\/a\u003E\u003C\/li\u003E\u003C\/ul\u003E\u003C\/div\u003E\u003Cdiv class=\u0022fig-caption attrib\u0022\u003E\u003Cspan class=\u0022fig-label\u0022\u003EFigure 5.\u003C\/span\u003E \n            \u003Cp id=\u0022p-21\u0022 class=\u0022first-child\u0022\u003EProgression to Type 1 Diabetes in Children Born by Cesarean Versus Vaginal Delivery\u003C\/p\u003E\n         \u003Cq class=\u0022attrib\u0022 id=\u0022attrib-6\u0022\u003EReproduced from Bonifacio et al. Cesarean Section and Interferon-Induced Helicase Gene Polymorphisms Combine to Increase Childhood Type 1 Diabetes Risk. \u003Cem\u003EDiabetes\u003C\/em\u003E 20;60:3300\u20133306. With permission from the American Diabetes Association.\u003C\/q\u003E\u003Cdiv class=\u0022sb-div caption-clear\u0022\u003E\u003C\/div\u003E\u003C\/div\u003E\u003C\/div\u003E\u003Cp id=\u0022p-22\u0022\u003EPopulation-based screening at birth for multiple islet AB and the combination of HLA and AB screening are useful approaches for detecting T1DM and preventing the progression to symptomatic T1DM.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2014 MD Conference Express\u00ae\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/14\/19\/25.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_figures.js?nzp35p\u0022\u003E\u003C\/script\u003E\n\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzp35p\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}