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      Reduced Prevalence of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Young Children Participating in Longitudinal Follow-Up

      research-article
      Author(s): , MD, PHD 1 , , PHD 2 , , PHD 3 , , MD, PHD 4 , , MD 5 , , MD 6 , , MD, PHD 7 , 8 , 9 , , MD, PHD 10 , , MD, PHD 11 , , MD, PHD 12 , , MD 13 , , MD 14 , on behalf of the TEDDY Study Group, SEARCH Study Group, Swediabkids Study Group, DPV Study Group, Finnish Diabetes Registry Study Group *
      Publication date (Electronic):
      Journal: Diabetes Care
      Publisher: American Diabetes Association

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          Abstract

          OBJECTIVE

          Young children have an unacceptably high prevalence of diabetic ketoacidosis (DKA) at the clinical diagnosis of type 1 diabetes. The aim of this study was to determine whether knowledge of genetic risk and close follow-up for development of islet autoantibodies through participation in The Environmental Determinants of Diabetes in the Young (TEDDY) study results in lower prevalence of DKA at diabetes onset in children aged <2 and <5 years compared with population-based incidence studies and registries.

          RESEARCH DESIGN AND METHODS

          Symptoms and laboratory data collected on TEDDY participants diagnosed with type 1 diabetes between 2004 and 2010 were compared with data collected during the similar periods from studies and registries in all TEDDY-participating countries (U.S., SEARCH for Diabetes in Youth Study; Sweden, Swediabkids; Finland, Finnish Pediatric Diabetes Register; and Germany, Diabetes Patienten Verlaufsdokumenation [DPV] Register).

          RESULTS

          A total of 40 children younger than age 2 years and 79 children younger than age 5 years were diagnosed with type 1 diabetes in TEDDY as of December 2010. In children <2 years of age at onset, DKA prevalence in TEDDY participants was significantly lower than in all comparative registries (German DPV Register, P < 0.0001; Swediabkids, P = 0.02; SEARCH, P < 0.0001; Finnish Register, P < 0.0001). The prevalence of DKA in TEDDY children diagnosed at <5 years of age (13.1%) was significantly lower compared with SEARCH (36.4%) ( P < 0.0001) and the German DPV Register (32.2%) ( P < 0.0001) but not compared with Swediabkids or the Finnish Register.

          CONCLUSIONS

          Participation in the TEDDY study is associated with reduced risk of DKA at diagnosis of type 1 diabetes in young children.

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          Most cited references18

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          The rise of childhood type 1 diabetes in the 20th century.

          E. Gale (2002)
          The incidence of childhood type 1 diabetes increased worldwide in the closing decades of the 20th century, but the origins of this increase are poorly documented. A search through the early literature revealed a number of useful but neglected sources, particularly in Scandinavia. While these do not meet the exacting standards of more recent surveys, tentative conclusions can be drawn concerning long-term changes in the demography of the disease. Childhood type 1 diabetes was rare but well recognized before the introduction of insulin. Low incidence and prevalence rates were recorded in several countries over the period 1920-1950, and one carefully performed study showed no change in childhood incidence over the period 1925-1955. An almost simultaneous upturn was documented in several countries around the mid-century. The overall pattern since then is one of linear increase, with evidence of a plateau in some high-incidence populations and of a catch-up phenomenon in some low-incidence areas. Steep rises in the age-group under 5 years have been recorded recently. The disease process underlying type 1 diabetes has changed over time and continues to evolve. Understanding why and how this produced the pandemic of childhood diabetes would be an important step toward reversing it.
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            Newborn screening for HLA markers associated with IDDM: diabetes autoimmunity study in the young (DAISY).

            M. Rewers, T Bugawan, J Norris … (1996)
            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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              The Environmental Determinants of Diabetes in the Young (TEDDY) Study.

              (2008)
              The etiology of type 1 diabetes (T1D) remains unknown, but a growing body of evidence points to infectious agents and/or components of early childhood diet. The National Institutes of Health has established the TEDDY Study consortium of six clinical centers in the United States and Europe and a data coordinating center to identify environmental factors predisposing to, or protective against, islet autoimmunity and T1D. From 2004-2009, TEDDY will screen more than 360,000 newborns from both the general population and families already affected by T1D to identify an estimated 17,804 children with high-risk HLA-DR,DQ genotypes. Of those, 7,801 (788 first-degree relatives and 7,013 newborns with no family history of T1D) will be enrolled in prospective follow-up beginning before the age of 4.5 months. As of May 2008, TEDDY has screened more than 250,000 newborns and enrolled nearly 5,000 infants--approximately 70% of the final cohort. Participants are seen every 3 months up to 4 years of age, with subsequent visits every 6 months until the subject is 15 years of age. Blood samples are collected at each visit for detection of candidate infectious agents and nutritional biomarkers; monthly stool samples are collected for infectious agents. These samples are saved in a central repository. Primary endpoints include (1) appearance of one or more islet autoantibodies (to insulin, GAD65 or IA-2) confirmed at two consecutive visits; (2) development of T1D. By age 15, an estimated 800 children will develop islet autoimmunity and 400 will progress to T1D; 67 and 27 children have already reached these endpoints.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Diabetes Care
                Journal ID (hwp): diacare
                Journal ID (pmc): dcare
                Journal ID (publisher-id): Diabetes Care
                Title: Diabetes Care
                Publisher: American Diabetes Association
                ISSN (Print): 0149-5992
                ISSN (Electronic): 1935-5548
                Publication date (Print): November 2011
                Publication date (Electronic): 15 October 2011
                Volume: 34
                Issue: 11
                Pages: 2347-2352
                Affiliations
                [1] 1Department of Pediatrics, Skåne University Hospital, Lund University, Malmö, Sweden
                [2] 2Pediatric Epidemiology Center, University of South Florida, Tampa, Florida
                [3] 3Department of Epidemiology, Wake Forrest University, Winston-Salem, North Carolina
                [4] 4Department of Epidemiology, Colorado School of Public Health, Aurora, Colorado
                [5] 5Department of Pediatrics, University of Cincinnati, Cincinnati, Ohio
                [6] 6Department of Pediatrics, University of Washington, Seattle, Washington
                [7] 7Children’s Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland
                [8] 8Folkhälsan Research Center, Helsinki, Finland
                [9] 9Department of Pediatrics, Tampere University Hospital, Tampere, Finland
                [10] 10Department of Pediatrics, University of Oulu, Oulu, Finland
                [11] 11Department of Pediatrics, The Sahlgrenska Academy at University of Gothenburg, Göteborg, Sweden
                [12] 12Department of Health and Environment, Linköping University, Linköping, Sweden
                [13] 13Institute of Epidemiology, University of Ulm, Ulm, Germany
                [14] 14Department of Pediatrics, University of Florida, Gainesville, Florida
                Author notes
                Corresponding author: Helena Elding Larsson, helena.larsson@ 123456med.lu.se .

                H.E.L. and M.J.H. contributed equally to this work.

                Article
                Publisher ID: 1026
                DOI: 10.2337/dc11-1026
                PMC ID: 3198296
                PubMed ID: 21972409
                SO-VID: 8179b2f4-0893-4b28-bdef-063a2847814a
                Copyright © © 2011 by the American Diabetes Association.
                License:

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.

                History
                Date received : 31 May 2011
                Date accepted : 17 August 2011
                Categories
                Subject: Original Research
                Subject: Clinical Care/Education/Nutrition/Psychosocial Research

                ScienceOpen disciplines: Endocrinology & Diabetes
                Data availability:
                ScienceOpen disciplines: Endocrinology & Diabetes

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