Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association

Richard A Insel, Jessica L Dunne, Mark A Atkinson, Jane L Chiang, Dana Dabelea, Peter A Gottlieb, Carla J Greenbaum, Kevan C Herold, Jeffrey P Krischer, Åke Lernmark, Robert E Ratner, Marian J Rewers, Desmond A Schatz, Jay S Skyler, Jay M Sosenko, Anette-G Ziegler, Richard A Insel, Jessica L Dunne, Mark A Atkinson, Jane L Chiang, Dana Dabelea, Peter A Gottlieb, Carla J Greenbaum, Kevan C Herold, Jeffrey P Krischer, Åke Lernmark, Robert E Ratner, Marian J Rewers, Desmond A Schatz, Jay S Skyler, Jay M Sosenko, Anette-G Ziegler

Abstract

Insights from prospective, longitudinal studies of individuals at risk for developing type 1 diabetes have demonstrated that the disease is a continuum that progresses sequentially at variable but predictable rates through distinct identifiable stages prior to the onset of symptoms. Stage 1 is defined as the presence of β-cell autoimmunity as evidenced by the presence of two or more islet autoantibodies with normoglycemia and is presymptomatic, stage 2 as the presence of β-cell autoimmunity with dysglycemia and is presymptomatic, and stage 3 as onset of symptomatic disease. Adoption of this staging classification provides a standardized taxonomy for type 1 diabetes and will aid the development of therapies and the design of clinical trials to prevent symptomatic disease, promote precision medicine, and provide a framework for an optimized benefit/risk ratio that will impact regulatory approval, reimbursement, and adoption of interventions in the early stages of type 1 diabetes to prevent symptomatic disease.

© 2015 by the American Diabetes Association. 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.

Figures

Figure 1
Figure 1
Early stages of type 1 diabetes.
Figure 2
Figure 2
Progression to symptomatic stage 3 type 1 diabetes from time of islet autoantibody seroconversion in stage 1 at-risk children with multiple islet autoantibodies (7).
Figure 3
Figure 3
Probability of progression to stage 3 symptomatic type 1 diabetes stratified for number of islet autoantibodies from birth (7).
Figure 4
Figure 4
Probability of progression in islet autoantibody-positive relatives of individuals with type 1 diabetes stratified for number of autoantibodies (8).
Figure 5
Figure 5
Probability of progression from dysglycemia stage 2 in DPT-1. IGT, impaired glucose tolerance (unpublished data from DPT-1 [4,32]).

References

    1. Eisenbarth GS. Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med 1986;314:1360–1368
    1. Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 2001;358:221–229
    1. Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet 2014;383:69–82
    1. Diabetes Prevention Trial–Type 1 Diabetes Study Group Effect of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med 2002;346:1685–1691
    1. Hagopian WA, Lernmark A, Rewers MJ, et al. . TEDDY—The Environmental Determinants of Diabetes in the Young: an observational clinical trial. Ann N Y Acad Sci 2006;1079:320–326
    1. Skyler JS, Greenbaum CJ, Lachin JM, et al. .; Type 1 Diabetes TrialNet Study Group . Type 1 Diabetes TrialNet—an international collaborative clinical trials network. Ann N Y Acad Sci 2008;1150:14–24
    1. Ziegler AG, Rewers M, Simell O, et al. . Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. JAMA 2013;309:2473–2479
    1. Orban T, Sosenko JM, Cuthbertson D, et al. .; Diabetes Prevention Trial–Type 1 Study Group . Pancreatic islet autoantibodies as predictors of type 1 diabetes in the Diabetes Prevention Trial–Type 1. Diabetes Care 2009;32:2269–2274
    1. Steck AK, Vehik K, Bonifacio E, et al. .; TEDDY Study Group . Predictors of progression from the appearance of islet autoantibodies to early childhood diabetes: The Environmental Determinants of Diabetes in the Young (TEDDY). Diabetes Care 2015;38:808–813
    1. Krischer JP; Type 1 Diabetes TrialNet Study Group . The use of intermediate endpoints in the design of type 1 diabetes prevention trials. Diabetologia 2013;56:1919–1924
    1. Noble JA, Valdes AM, Cook M, Klitz W, Thomson G, Erlich HA. The role of HLA class II genes in insulin-dependent diabetes mellitus: molecular analysis of 180 Caucasian, multiplex families. Am J Hum Genet 1996;59:1134–1148
    1. Patterson CC, Dahlquist GG, Gyürüs E, Green A, Soltész G; EURODIAB Study Group . Incidence trends for childhood type 1 diabetes in Europe during 1989-2003 and predicted new cases 2005-20: a multicentre prospective registration study. Lancet 2009;373:2027–2033
    1. Harjutsalo V, Sjöberg L, Tuomilehto J. Time trends in the incidence of type 1 diabetes in Finnish children: a cohort study. Lancet 2008;371:1777–1782
    1. Vehik K, Hamman RF, Lezotte D, et al. . Increasing incidence of type 1 diabetes in 0- to 17-year-old Colorado youth. Diabetes Care 2007;30:503–509
    1. Steck AK, Armstrong TK, Babu SR, Eisenbarth GS; Type 1 Diabetes Genetics Consortium . Stepwise or linear decrease in penetrance of type 1 diabetes with lower-risk HLA genotypes over the past 40 years. Diabetes 2011;60:1045–1049
    1. Vehik K, Hamman RF, Lezotte D, et al. . Trends in high-risk HLA susceptibility genes among Colorado youth with type 1 diabetes. Diabetes Care 2008;31:1392–1396
    1. Concannon P, Rich SS, Nepom GT. Genetics of type 1A diabetes. N Engl J Med 2009;360:1646–1654
    1. Pociot F, McDermott MF. Genetics of type 1 diabetes mellitus. Genes Immun 2002;3:235–249
    1. Santin I, Eizirik DL. Candidate genes for type 1 diabetes modulate pancreatic islet inflammation and β-cell apoptosis. Diabetes Obes Metab 2013;15(Suppl. 3):71–81
    1. Lipponen K, Gombos Z, Kiviniemi M, et al. . Effect of HLA class I and class II alleles on progression from autoantibody positivity to overt type 1 diabetes in children with risk-associated class II genotypes. Diabetes 2010;59:3253–3256
    1. Achenbach P, Hummel M, Thümer L, Boerschmann H, Höfelmann D, Ziegler AG. Characteristics of rapid vs slow progression to type 1 diabetes in multiple islet autoantibody-positive children. Diabetologia 2013;56:1615–1622
    1. Winkler C, Krumsiek J, Lempainen J, et al. . A strategy for combining minor genetic susceptibility genes to improve prediction of disease in type 1 diabetes. Genes Immun 2012;13:549–555
    1. Winkler C, Krumsiek J, Buettner F, et al. . Feature ranking of type 1 diabetes susceptibility genes improves prediction of type 1 diabetes. Diabetologia 2014;57:2521–2529
    1. Eringsmark Regnéll S, Lernmark A. The environment and the origins of islet autoimmunity and type 1 diabetes. Diabet Med 2013;30:155–160
    1. Craig ME, Nair S, Stein H, Rawlinson WD. Viruses and type 1 diabetes: a new look at an old story. Pediatr Diabetes 2013;14:149–158
    1. Stene LC, Gale EA. The prenatal environment and type 1 diabetes. Diabetologia 2013;56:1888–1897
    1. TEDDY Study Group The Environmental Determinants of Diabetes in the Young (TEDDY) study: study design. Pediatr Diabetes 2007;8:286–298
    1. Redondo MJ, Jeffrey J, Fain PR, Eisenbarth GS, Orban T. Concordance for islet autoimmunity among monozygotic twins. N Engl J Med 2008;359:2849–2850
    1. Redondo MJ, Yu L, Hawa M, et al. . Heterogeneity of type I diabetes: analysis of monozygotic twins in Great Britain and the United States. Diabetologia 2001;44:354–362
    1. Aly TA, Ide A, Jahromi MM, et al. . Extreme genetic risk for type 1A diabetes. Proc Natl Acad Sci U S A 2006;103:14074–14079
    1. Gillespie KM, Aitken RJ, Wilson I, Williams AJ, Bingley PJ. Early onset of diabetes in the proband is the major determinant of risk in HLA DR3-DQ2/DR4-DQ8 siblings. Diabetes 2014;63:1041–1047
    1. Skyler JS, Krischer JP, Wolfsdorf J, et al. . Effects of oral insulin in relatives of patients with type 1 diabetes: the Diabetes Prevention Trial–Type 1. Diabetes Care 2005;28:1068–1076
    1. Mahon JL, Sosenko JM, Rafkin-Mervis L, et al. .; TrialNet Natural History Committee; Type 1 Diabetes TrialNet Study Group . The TrialNet Natural History Study of the Development of Type 1 Diabetes: objectives, design, and initial results. Pediatr Diabetes 2009;10:97–104
    1. Chiang JL, Kirkman MS, Laffel LM, Peters AL; Type 1 Diabetes Sourcebook Authors . Type 1 diabetes through the life span: a position statement of the American Diabetes Association. Diabetes Care 2014;37:2034–2054
    1. Kostraba JN, Gay EC, Cai Y, et al. . Incidence of insulin-dependent diabetes mellitus in Colorado. Epidemiology 1992;3:232–238
    1. The EURODIAB ACE Study Group and the EURODIAB ACE Substudy 2 Study Group Familial risk of type I diabetes in European children. Diabetologia 1998;41:1151–1156
    1. Hagopian WA, Erlich H, Lernmark A, et al. .; TEDDY Study Group . The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. Pediatr Diabetes 2011;12:733–743
    1. Lieberman SM, DiLorenzo TP. A comprehensive guide to antibody and T-cell responses in type 1 diabetes. Tissue Antigens 2003;62:359–377
    1. Roep BO, Peakman M. Antigen targets of type 1 diabetes autoimmunity. Cold Spring Harb Perspect Med 2012;2:a007781.
    1. Ziegler AG, Bonifacio E; BABYDIAB-BABYDIET Study Group . Age-related islet autoantibody incidence in offspring of patients with type 1 diabetes. Diabetologia 2012;55:1937–1943
    1. Parikka V, Näntö-Salonen K, Saarinen M, et al. . Early seroconversion and rapidly increasing autoantibody concentrations predict prepubertal manifestation of type 1 diabetes in children at genetic risk. Diabetologia 2012;55:1926–1936
    1. Krischer JP, Lynch KF, Schatz DA, et al. .; TEDDY Study Group . The 6 year incidence of diabetes-associated autoantibodies in genetically at-risk children: the TEDDY study. Diabetologia 2015;58:980–987
    1. Ziegler AG, Hummel M, Schenker M, Bonifacio E. Autoantibody appearance and risk for development of childhood diabetes in offspring of parents with type 1 diabetes: the 2-year analysis of the German BABYDIAB Study. Diabetes 1999;48:460–468
    1. Hummel M, Bonifacio E, Schmid S, Walter M, Knopff A, Ziegler AG. Brief communication: early appearance of islet autoantibodies predicts childhood type 1 diabetes in offspring of diabetic parents. Ann Intern Med 2004;140:882–886
    1. Chmiel R, Giannopoulou EZ, Winkler C, Achenbach P, Ziegler AG, Bonifacio E. Progression from single to multiple islet autoantibodies often occurs soon after seroconversion: implications for early screening. Diabetologia 2015;58:411–413
    1. Ziegler AG, Standl E, Albert E, Mehnert H. HLA-associated insulin autoantibody formation in newly diagnosed type I diabetic patients. Diabetes 1991;40:1146–1149
    1. Graham J, Hagopian WA, Kockum I, et al. .; Diabetes Incidence in Sweden Study Group; Swedish Childhood Diabetes Study Group . Genetic effects on age-dependent onset and islet cell autoantibody markers in type 1 diabetes. Diabetes 2002;51:1346–1355
    1. Delli AJ, Vaziri-Sani F, Lindblad B, et al. .; Better Diabetes Diagnosis Study Group . Zinc transporter 8 autoantibodies and their association with SLC30A8 and HLA-DQ genes differ between immigrant and Swedish patients with newly diagnosed type 1 diabetes in the Better Diabetes Diagnosis study. Diabetes 2012;61:2556–2564
    1. Vehik K, Haller MJ, Beam CA, et al. .; DPT-1 Study Group . Islet autoantibody seroconversion in the DPT-1 study: justification for repeat screening throughout childhood. Diabetes Care 2011;34:358–362
    1. Vehik K, Beam CA, Mahon JL, et al. .; TrialNet Natural History Study Group . Development of autoantibodies in the TrialNet Natural History Study. Diabetes Care 2011;34:1897–1901
    1. Insel R, Dunne J, Ziegler A. General population screening for type 1 diabetes: has its time come? Curr Opin Endocrinol Diabetes Obes 2015;22:270–276
    1. Achenbach P, Warncke K, Reiter J, et al. . Stratification of type 1 diabetes risk on the basis of islet autoantibody characteristics. Diabetes 2004;53:384–392
    1. Achenbach P, Bonifacio E, Koczwara K, Ziegler AG. Natural history of type 1 diabetes. Diabetes 2005;54(Suppl. 2):S25–S31
    1. Steck AK, Johnson K, Barriga KJ, et al. . Age of islet autoantibody appearance and mean levels of insulin, but not GAD or IA-2 autoantibodies, predict age of diagnosis of type 1 diabetes: diabetes autoimmunity study in the young. Diabetes Care 2011;34:1397–1399
    1. Achenbach P, Koczwara K, Knopff A, Naserke H, Ziegler AG, Bonifacio E. Mature high-affinity immune responses to (pro)insulin anticipate the autoimmune cascade that leads to type 1 diabetes. J Clin Invest 2004;114:589–597
    1. Yu L, Dong F, Miao D, Fouts AR, Wenzlau JM, Steck AK. Proinsulin/insulin autoantibodies measured with electrochemiluminescent assay are the earliest indicator of prediabetic islet autoimmunity. Diabetes Care 2013;36:2266–2270
    1. De Grijse J, Asanghanwa M, Nouthe B, et al. .; Belgian Diabetes Registry . Predictive power of screening for antibodies against insulinoma-associated protein 2 beta (IA-2beta) and zinc transporter-8 to select first-degree relatives of type 1 diabetic patients with risk of rapid progression to clinical onset of the disease: implications for prevention trials. Diabetologia 2010;53:517–524
    1. Gorus FK, Balti EV, Vermeulen I, et al. .; Belgian Diabetes Registry . Screening for insulinoma antigen 2 and zinc transporter 8 autoantibodies: a cost-effective and age-independent strategy to identify rapid progressors to clinical onset among relatives of type 1 diabetic patients. Clin Exp Immunol 2013;171:82–90
    1. Miao D, Steck AK, Zhang L, et al. .; Type 1 Diabetes TrialNet Study Group . Electrochemiluminescence assays for insulin and glutamic acid decarboxylase autoantibodies improve prediction of type 1 diabetes risk. Diabetes Technol Ther 2015;17:119–127
    1. Bingley PJ, Williams AJ. Islet autoantibody testing: an end to the trials and tribulations? Diabetes 2013;62:4009–4011
    1. Yu L, Miao D, Scrimgeour L, Johnson K, Rewers M, Eisenbarth GS. Distinguishing persistent insulin autoantibodies with differential risk: nonradioactive bivalent proinsulin/insulin autoantibody assay. Diabetes 2012;61:179–186
    1. Miao D, Guyer KM, Dong F, et al. . GAD65 autoantibodies detected by electrochemiluminescence assay identify high risk for type 1 diabetes. Diabetes 2013;62:4174–4178
    1. Sosenko JM, Palmer JP, Rafkin-Mervis L, et al. .; Diabetes Prevention Trial–Type 1 Study Group . Incident dysglycemia and progression to type 1 diabetes among participants in the Diabetes Prevention Trial–Type 1. Diabetes Care 2009;32:1603–1607
    1. American Diabetes Association Classification and diagnosis of diabetes. Sec. 2. In Standards of Medical Care in Diabetes—2015. Diabetes Care 2015;38(Suppl. 1):S8–S16
    1. Handelsman Y, Bloomgarden ZT, Grunberger G, et al. . American Association of Clinical Endocrinologists and American College of Endocrinology—clinical practice guidelines for developing a diabetes mellitus comprehensive care plan—2015. Endocr Pract 2015;21(Suppl. 1):1–87
    1. Greenbaum CJ, Buckingham B, Chase HP, Krischer J; Diabetes Prevention Trial, Type 1 Diabetes (DPT-1) Study Group . Metabolic tests to determine risk for type 1 diabetes in clinical trials. Diabetes Metab Res Rev 2011;27:584–589
    1. Sosenko JM, Skyler JS, Herold KC, Palmer JP; Type 1 Diabetes TrialNet and Diabetes Prevention Trial–Type 1 Study Groups . The metabolic progression to type 1 diabetes as indicated by serial oral glucose tolerance testing in the Diabetes Prevention Trial–Type 1. Diabetes 2012;61:1331–1337
    1. Sosenko JM, Skyler JS, Beam CA, et al. .; Type 1 Diabetes TrialNet and Diabetes Prevention Trial–Type 1 Study Groups . Acceleration of the loss of the first-phase insulin response during the progression to type 1 diabetes in Diabetes Prevention Trial–Type 1 participants. Diabetes 2013;62:4179–4183
    1. Vardi P, Crisa L, Jackson RA. Predictive value of intravenous glucose tolerance test insulin secretion less than or greater than the first percentile in islet cell antibody positive relatives of type 1 (insulin-dependent) diabetic patients. Diabetologia 1991;34:93–102
    1. Sosenko JM, Palmer JP, Greenbaum CJ, et al. . Patterns of metabolic progression to type 1 diabetes in the Diabetes Prevention Trial–Type 1. Diabetes Care 2006;29:643–649
    1. Xu P, Wu Y, Zhu Y, et al. .; Diabetes Prevention Trial–Type 1 (DPT-1) Study Group . Prognostic performance of metabolic indexes in predicting onset of type 1 diabetes. Diabetes Care 2010;33:2508–2513
    1. Ferrannini E, Mari A, Nofrate V, Sosenko JM, Skyler JS; DPT-1 Study Group . Progression to diabetes in relatives of type 1 diabetic patients: mechanisms and mode of onset. Diabetes 2010;59:679–685
    1. Walker M, Mari A, Jayapaul MK, Bennett SM, Ferrannini E. Impaired beta cell glucose sensitivity and whole-body insulin sensitivity as predictors of hyperglycaemia in non-diabetic subjects. Diabetologia 2005;48:2470–2476
    1. Cnop M, Vidal J, Hull RL, et al. . Progressive loss of beta-cell function leads to worsening glucose tolerance in first-degree relatives of subjects with type 2 diabetes. Diabetes Care 2007;30:677–682
    1. Sosenko JM, Skyler JS, Krischer JP, et al. .; Diabetes Prevention Trial–Type 1 Study Group . Glucose excursions between states of glycemia with progression to type 1 diabetes in the Diabetes Prevention Trial–Type 1 (DPT-1). Diabetes 2010;59:2386–2389
    1. Sosenko JM, Palmer JP, Rafkin-Mervis L, et al. . Glucose and C-peptide changes in the perionset period of type 1 diabetes in the Diabetes Prevention Trial–Type 1. Diabetes Care 2008;31:2188–2192
    1. Fourlanos S, Narendran P, Byrnes GB, Colman PG, Harrison LC. Insulin resistance is a risk factor for progression to type 1 diabetes. Diabetologia 2004;47:1661–1667
    1. Xu P, Cuthbertson D, Greenbaum C, Palmer JP, Krischer JP; Diabetes Prevention Trial–Type 1 Study Group . Role of insulin resistance in predicting progression to type 1 diabetes. Diabetes Care 2007;30:2314–2320
    1. Bingley PJ, Mahon JL, Gale EA; European Nicotinamide Diabetes Intervention Trial Group . Insulin resistance and progression to type 1 diabetes in the European Nicotinamide Diabetes Intervention Trial (ENDIT). Diabetes Care 2008;31:146–150
    1. Vehik K, Cuthbertson D, Boulware D, et al. .; TEDDY, TRIGR, Diabetes Prevention Trial–Type 1, and Type 1 Diabetes TrialNet Natural History Study Groups . Performance of HbA1c as an early diagnostic indicator of type 1 diabetes in children and youth. Diabetes Care 2012;35:1821–1825
    1. Stene LC, Barriga K, Hoffman M, et al. . Normal but increasing hemoglobin A1c levels predict progression from islet autoimmunity to overt type 1 diabetes: Diabetes Autoimmunity Study in the Young (DAISY). Pediatr Diabetes 2006;7:247–253
    1. Helminen O, Aspholm S, Pokka T, et al. . HbA1c predicts time to diagnosis of type 1 diabetes in children at risk. Diabetes 2015;64:1719–1727
    1. Barker JM, Goehrig SH, Barriga K, et al. .; DAISY Study . Clinical characteristics of children diagnosed with type 1 diabetes through intensive screening and follow-up. Diabetes Care 2004;27:1399–1404
    1. Elding Larsson H, Vehik K, Bell R, et al. .; TEDDY Study Group; SEARCH Study Group; Swediabkids Study Group; DPV Study Group; Finnish Diabetes Registry Study Group . Reduced prevalence of diabetic ketoacidosis at diagnosis of type 1 diabetes in young children participating in longitudinal follow-up. Diabetes Care 2011;34:2347–2352
    1. Winkler C, Schober E, Ziegler AG, Holl RW. Markedly reduced rate of diabetic ketoacidosis at onset of type 1 diabetes in relatives screened for islet autoantibodies. Pediatr Diabetes 2012;13:308–313
    1. Triolo TM, Chase HP, Barker JM; DPT-1 Study Group . Diabetic subjects diagnosed through the Diabetes Prevention Trial–Type 1 (DPT-1) are often asymptomatic with normal A1C at diabetes onset. Diabetes Care 2009;32:769–773
    1. Dabelea D, Rewers A, Stafford JM, et al. .; SEARCH for Diabetes in Youth Study Group . Trends in the prevalence of ketoacidosis at diabetes diagnosis: the SEARCH for Diabetes in Youth study. Pediatrics 2014;133:e938–e945
    1. Rewers A, Dong F, Slover RH, Klingensmith GJ, Rewers M. Incidence of diabetic ketoacidosis at diagnosis of type 1 diabetes in Colorado youth, 1998-2012. JAMA 2015;313:1570–1572
    1. Fernandez Castañer M, Montaña E, Camps I, et al. . Ketoacidosis at diagnosis is predictive of lower residual beta-cell function and poor metabolic control in type 1 diabetes. Diabetes Metab 1996;22:349–355
    1. Bowden SA, Duck MM, Hoffman RP. Young children (<5 yr) and adolescents (>12 yr) with type 1 diabetes mellitus have low rate of partial remission: diabetic ketoacidosis is an important risk factor. Pediatr Diabetes 2008;9:197–201
    1. Cameron FJ, Scratch SE, Nadebaum C, et al. .; DKA Brain Injury Study Group . Neurological consequences of diabetic ketoacidosis at initial presentation of type 1 diabetes in a prospective cohort study of children. Diabetes Care 2014;37:1554–1562
    1. The Diabetes Control and Complications Trial Research Group Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. Ann Intern Med 1998;128:517–523
    1. Steffes MW, Sibley S, Jackson M, Thomas W. Beta-cell function and the development of diabetes-related complications in the diabetes control and complications trial. Diabetes Care 2003;26:832–836
    1. Ludvigsson J, Heding LG, Larsson Y, Leander E. C-peptide in juvenile diabetics beyond the postinitial remission period. Relation to clinical manifestations at onset of diabetes, remission and diabetic control. Acta Paediatr Scand 1977;66:177–184
    1. Orchard TJ, Nathan DM, Zinman B, et al. .; Writing Group for the DCCT/EDIC Research Group . Association between 7 years of intensive treatment of type 1 diabetes and long-term mortality. JAMA 2015;313:45–53
    1. Lundgren M, Sahlin A, Svensson C, et al. .; DiPiS Study Group . Reduced mortality at diagnosis and improved glycemic control in children previously enrolled in DiPiS follow-up. Pediatr Diabetes 2014;15:494–501
    1. Wood JR, Miller KM, Maahs DM, et al. .; T1D Exchange Clinic Network . Most youth with type 1 diabetes in the T1D Exchange clinic registry do not meet American Diabetes Association or International Society for Pediatric and Adolescent Diabetes clinical guidelines. Diabetes Care 2013;36:2035–2037
    1. Naughton MJ, Yi-Frazier JP, Morgan TM, et al. .; SEARCH for Diabetes in Youth Study Group . Longitudinal associations between sex, diabetes self-care, and health-related quality of life among youth with type 1 or type 2 diabetes mellitus. J Pediatr 2014;164:1376–1383.e1
    1. Livingstone SJ, Levin D, Looker HC, et al. .; Scottish Diabetes Research Network Epidemiology Group; Scottish Renal Registry . Estimated life expectancy in a Scottish cohort with type 1 diabetes, 2008-2010. JAMA 2015;313:37–44
    1. Lind M, Svensson AM, Kosiborod M, et al. . Glycemic control and excess mortality in type 1 diabetes. N Engl J Med 2014;371:1972–1982
    1. Oresic M, Simell S, Sysi-Aho M, et al. . Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes. J Exp Med 2008;205:2975–2984
    1. Oresic M, Gopalacharyulu P, Mykkänen J, et al. . Cord serum lipidome in prediction of islet autoimmunity and type 1 diabetes. Diabetes 2013;62:3268–3274
    1. La Torre D, Seppänen-Laakso T, Larsson HE, et al. .; DiPiS Study Group . Decreased cord-blood phospholipids in young age-at-onset type 1 diabetes. Diabetes 2013;62:3951–3956
    1. Oresic M. Metabolomics in the studies of islet autoimmunity and type 1 diabetes. Rev Diabet Stud 2012;9:236–247
    1. Lee HS, Burkhardt BR, McLeod W, et al. .; TEDDY Study Group . Biomarker discovery study design for type 1 diabetes in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Diabetes Metab Res Rev 2014;30:424–434
    1. Dunne JL, Triplett EW, Gevers D, et al. . The intestinal microbiome in type 1 diabetes. Clin Exp Immunol 2014;177:30–37
    1. Giongo A, Gano KA, Crabb DB, et al. . Toward defining the autoimmune microbiome for type 1 diabetes. ISME J 2011;5:82–91
    1. de Goffau MC, Fuentes S, van den Bogert B, et al. . Aberrant gut microbiota composition at the onset of type 1 diabetes in young children. Diabetologia 2014;57:1569–1577
    1. Endesfelder D, zu Castell W, Ardissone A, et al. . Compromised gut microbiota networks in children with anti-islet cell autoimmunity. Diabetes 2014;63:2006–2014
    1. Kostic AD, Gevers D, Siljander H, et al. .; DIABIMMUNE Study Group . The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe 2015;17:260–273
    1. Levy H, Wang X, Kaldunski M, et al. . Transcriptional signatures as a disease-specific and predictive inflammatory biomarker for type 1 diabetes. Genes Immun 2012;13:593–604
    1. Chen YG, Cabrera SM, Jia S, et al. . Molecular signatures differentiate immune states in type 1 diabetic families. Diabetes 2014;63:3960–3973
    1. Ferreira RC, Guo H, Coulson RM, et al. . A type I interferon transcriptional signature precedes autoimmunity in children genetically at risk for type 1 diabetes. Diabetes 2014;63:2538–2550
    1. Kallionpää H, Elo LL, Laajala E, et al. . Innate immune activity is detected prior to seroconversion in children with HLA-conferred type 1 diabetes susceptibility. Diabetes 2014;63:2402–2414
    1. Gaglia JL, Harisinghani M, Aganj I, et al. . Noninvasive mapping of pancreatic inflammation in recent-onset type-1 diabetes patients. Proc Natl Acad Sci U S A 2015;112:2139–2144
    1. Akirav EM, Lebastchi J, Galvan EM, et al. . Detection of β cell death in diabetes using differentially methylated circulating DNA. Proc Natl Acad Sci U S A 2011;108:19018–19023
    1. Husseiny MI, Kuroda A, Kaye AN, Nair I, Kandeel F, Ferreri K. Development of a quantitative methylation-specific polymerase chain reaction method for monitoring beta cell death in type 1 diabetes. PLoS One 2012;7:e47942.
    1. Usmani-Brown S, Lebastchi J, Steck AK, Beam C, Herold KC, Ledizet M. Analysis of β-cell death in type 1 diabetes by droplet digital PCR. Endocrinology 2014;155:3694–3698
    1. Fisher MM, Perez Chumbiauca CN, Mather KJ, Mirmira RG, Tersey SA. Detection of islet β-cell death in vivo by multiplex PCR analysis of differentially methylated DNA. Endocrinology 2013;154:3476–3481
    1. Herold KC, Usmani-Brown S, Ghazi T, et al. .; Type 1 Diabetes TrialNet Study Group . β Cell death and dysfunction during type 1 diabetes development in at-risk individuals. J Clin Invest 2015;125:1163–1173
    1. Sosenko JM, Krischer JP, Palmer JP, et al. .; Diabetes Prevention Trial–Type 1 Study Group . A risk score for type 1 diabetes derived from autoantibody-positive participants in the Diabetes Prevention Trial–Type 1. Diabetes Care 2008;31:528–533
    1. Sosenko JM, Skyler JS, Palmer JP, et al. .; Type 1 Diabetes TrialNet Study Group; Diabetes Prevention Trial–Type 1 Study Group . The prediction of type 1 diabetes by multiple autoantibody levels and their incorporation into an autoantibody risk score in relatives of type 1 diabetic patients. Diabetes Care 2013;36:2615–2620
    1. Sosenko JM, Skyler JS, DiMeglio LA, et al. .; Type 1 Diabetes TrialNet Study Group; Diabetes Prevention Trial–Type 1 Study Group . A new approach for diagnosing type 1 diabetes in autoantibody-positive individuals based on prediction and natural history. Diabetes Care 2015;38:271–276
    1. Walter M, Albert E, Conrad M, et al. . IDDM2/insulin VNTR modifies risk conferred by IDDM1/HLA for development of type 1 diabetes and associated autoimmunity. Diabetologia 2003;46:712–720
    1. Schenker M, Hummel M, Ferber K, et al. . Early expression and high prevalence of islet autoantibodies for DR3/4 heterozygous and DR4/4 homozygous offspring of parents with type I diabetes: the German BABYDIAB study. Diabetologia 1999;42:671–677
    1. Bonifacio E, Hummel M, Walter M, Schmid S, Ziegler AG. IDDM1 and multiple family history of type 1 diabetes combine to identify neonates at high risk for type 1 diabetes. Diabetes Care 2004;27:2695–2700
    1. Lampeter EF, Klinghammer A, Scherbaum WA, et al. .; DENIS Group . The Deutsche Nicotinamide Intervention Study: an attempt to prevent type 1 diabetes. Diabetes 1998;47:980–984
    1. Gale EA, Bingley PJ, Emmett CL, Collier T; European Nicotinamide Diabetes Intervention Trial (ENDIT) Group . European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes. Lancet 2004;363:925–931
    1. Näntö-Salonen K, Kuplia A, Simell S, et al. . Nasal insulin to prevent type 1 diabetes in children with HLA genotypes and autoantibodies conferring increased risk of disease: a double-blind, randomised controlled trial. Lancet 2008;372:1746–1755
    1. Vandemeulebroucke E, Gorus FK, Decochez K, et al. .; Belgian Diabetes Registry . Insulin treatment in IA-2A-positive relatives of type 1 diabetic patients. Diabetes Metab 2009;35:319–327
    1. Andersson C, Carlsson A, Cilio C, et al. .; DiAPREV-IT Study Group . Glucose tolerance and beta-cell function in islet autoantibody-positive children recruited to a secondary prevention study. Pediatr Diabetes 2013;14:341–349

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren