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      A novel approach for the analysis of longitudinal profiles reveals delayed progression to type 1 diabetes in a subgroup of multiple-islet-autoantibody-positive children

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          Abstract

          Progression to type 1 diabetes in children and adolescents is not uniform. Based on individual genetic background and environment, islet autoimmunity may develop at variable age, exhibit different autoantibody profiles and progress to clinical diabetes at variable rates. Here, we aimed to quantify the qualitative dynamics of sequential islet autoantibody profiles in order to identify longitudinal patterns that stratify progression rates to type 1 diabetes in multiple-autoantibody-positive children.

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          Most cited references39

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          Error Detecting and Error Correcting Codes

          R. Hamming (1950)
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            Newborn screening for HLA markers associated with IDDM: diabetes autoimmunity study in the young (DAISY).

            Autoimmunity causing insulin-dependent diabetes mellitus (IDDM) begins in early childhood due to interactions between genes and unknown environmental factors that may be identified through follow-up of a large cohort of genetically susceptible children. Such a cohort has been established using a simple and rapid cord blood screening for HLA alleles. The DRB1 and DQB1 second exon sequences were co-amplified using the polymerase chain reaction and hybridized with single and pooled sequence-specific oligonucleotide probes. Four individual probes were used to detect the susceptibility alleles DRB1*03, DRB1*04, and DQB1*0302 as well as the usually protective DRB1*15/16 (DR2) alleles. In addition, pooled probes allow the distinction of DR3/3 from the DR3/x genotype (where x is neither DR2, 3, nor 4) and DR4/4 from DR4/x. Among 5000 newborns from the general Denver population, we have found the high-risk genotype (DRB1*03/ DRB1*04, DQB1*0302) to be present in 2.4% of non-Hispanic whites, 2.8% of Hispanics, and 1.6% of African Americans. The moderate-risk genotypes (DRB1*04, DQB1*0302/DRB1*04, DQB1*0302, DRB1*04, DQB1*0302/x, or DRB1*03/DRB1*03) are present in 17% of American non-Hispanic whites, 24% of Hispanics and in 10% of African Americans. These results demonstrate the feasibility of a large-scale newborn screening for genes associated with IDDM. The ultimate role for such a screening in future routine prediction and prevention of IDDM will depend on the availability of an effective and acceptable form of clinical intervention.
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              Clinical applications of diabetes antibody testing.

              P Bingley (2009)
              Autoantibodies to glutamate decarboxylase, islet antigen-2, insulin, and zinc transporter-8 are characteristic of type 1 diabetes. They are detectable before clinical onset and define the subgroup of patients with latent autoimmune diabetes in adults. Autoantibody assays are increasingly available to clinicians. This article reviews the prognostic significance of autoantibodies and considers the utility of diabetes antibody testing in routine clinical practice. The medical literature to May 2009 was reviewed for key articles and consensus statements covering use of islet autoantibody testing for prediction and classification of diabetes and implications for therapy. Sensitive and specific glutamate decarboxylase and islet antigen-2 antibody assays are widely available, although to insulin autoantibody assays remain variable. Islet autoantibodies appear early in life, and testing for multiple antibodies identifies unaffected individuals at very high risk of type 1 diabetes with high sensitivity. This is important for research, but currently no intervention prevents or delays diabetes, and evidence of benefit from awareness of risk is weak. In non-insulin-treated diabetes, patients with autoantibodies progress to insulin requirement more rapidly, but evidence that testing benefits the individual patient is limited. Antibody testing is useful in classifying diabetes of other types. Islet autoantibody testing allows prediction of type 1 diabetes and definition of the latent autoimmune diabetes in adults subgroup of non-insulin-treated patients. Although useful for research, until therapies modulating the disease process become available, the benefit to individual patients is generally questionable. With a few exceptions, diabetes antibody testing does not yet have a role in routine clinical care.
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                Author and article information

                Journal
                Diabetologia
                Diabetologia
                Springer Science and Business Media LLC
                0012-186X
                1432-0428
                October 2016
                July 11 2016
                October 2016
                : 59
                : 10
                : 2172-2180
                Article
                10.1007/s00125-016-4050-0
                27400691
                a910d938-9684-487d-b83d-1e48c1ab8fa5
                © 2016

                http://www.springer.com/tdm

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