George Eisenbarth's pioneering and visionary research has provided a critical foundation that will be built on in the years ahead as we progress toward prevention of type 1 diabetes. His almost 30-year old model that type 1 diabetes was a chronic and predictable autoimmune disease with multiple identifiable progressive stages with a potential for interventions to prevent progression to symptomatic diabetes has stood the test of time. To deliver on the Eisenbarth vision and his “unfinished journey,” the field needs: (1) to improve detection of risk of type 1 diabetes, (2) to improve staging and prediction of progression, (3) to perform smaller, shorter, practical, and an increased number of prevention clinical trials, and (4) to increase awareness of the potential for risk detection, staging, and prevention of type 1 diabetes and benefit/risk of prevention.
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References
1.
EisenbarthGS. Banting Lecture 2009: an unfinished journey: molecular pathogenesis to prevention of type 1A. Diabetes, 2010; 59:759–774.
2.
BluestoneJA, HeroldK, EisenbarthG. Genetics, pathogenesis and clinical interventions in type 1 diabetes. Nature, 2010; 464:1293–1300.
3.
EisenbarthGS. Prevention of type 1A diabetes mellitus. Endocr Pract, 2012; 18:745–749.
HitmanGA. Type 1 diabetes from bench to bedside; a dedication to George Eisenbarth. Diabet Med, 2013; 30:133.
6.
PuglieseA, SkylerJS, GeorgeS. Eisenbarth: insulin and type 1 diabetes. Diabetes Care, 2013; 36:1437–1442.
7.
SrikantaS, GandaOP, SoeldnerJS, EisenbarthGS. First-degree relatives of patients with type I diabetes mellitus. Islet-cell antibodies and abnormal insulin secretion. N Engl J Med, 1985; 313:461–464.
8.
SoeldnerJS, TuttlemanM, SrikantaS, GandaOP, EisenbarthGS. Insulin-dependent diabetes mellitus and autoimmunity: islet cell autoantibodies, insulin autoantibodies, and beta-cell failure. N Engl J Med, 1985; 313:893–894.
9.
EisenbarthGS. Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med, 1986; 314:1360–1368.
10.
AtkinsonMA, EisenbarthGS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet, 2001; 358:221–229.
11.
AtkinsonMA, EisenbarthG, MichelsA. Type 1 diabetes—a season of change for concepts regarding the epidemiology, pathogenesis, treatment, prospects for disease attenuation. Lancet, 2013(accepted for publication).
12.
EisenbarthGS, SrikantaS, JacksonRA, RabinoweSL, DolinarR, HaynesBF, MorrisMA. Anti-thymocyte globulin and prednisone immunotherapy of recent onset type I diabetes mellitus. Diabetes Res, 1985; 2:271–276.
13.
Study of Thymoglobulin to Arrest Newly Diagnosed Type 1 Diabetes (START). Clinical Trials.gov Identifier NCT00515099. http://ClinicalTrials.gov/. 2013 April 16.
14.
Reversing Type 1 Diabetes After It Is Established. ClinicalTrials.gov Identifier NCT01106157. http://ClinicalTrials.gov/. 2013 April 16.
15.
ZhangZJ, DavidsonL, EisenbarthG, WeinerHL. Suppression of diabetes in NOD mice by oral administration of porcine insulin. Proc Natl Acad Sci U S A, 1991; 88:10252–10256.
16.
Oral Insulin for Prevention of Diabetes in Relatives at Risk for Type 1 Diabetes Mellitus. ClinicalTrials.gov Identifier NCT00419562. http://ClinicalTrials.gov/. 2013 April 16.
17.
AchenbachP, BarkerJ, BonifacioE. Pre-POINT Study Group. Modulating the natural history of type 1 diabetes in children at high genetic risk by mucosal insulin immunization. Curr Diab Rep, 2008; 8:87–93.
18.
IdeA, EisenbarthGS. Genetic susceptibility in type 1 diabetes and its associated autoimmune disorders. Rev Endocr Metab Disord, 2003; 4:243–253.
19.
RewersM, BugawanTL, NorrisJM, BlairA, BeatyB, HoffmanM, McDuffieRSJr, HammanRF, KlingensmithG, EisenbarthGS, ErlichHA. Newborn screening for HLA markers associated with IDDM: Diabetes Autoimmunity Study in the Young (DAISY)Diabetologia, 1996; 39:807–812.
20.
TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY) study: study design. Pediatr Diabetes, 2007; 8:286–298.
HomannD, EisenbarthGS. An immunologic homunculus for type 1 diabetes. J Clin Invest, 2006; 116:1212–1215.
23.
StadinskiBD, ZhangL, CrawfordF, MarrackP, EisenbarthGS, KapplerJW. Diabetogenic T cells recognize insulin bound to IAg7 in an unexpected, weakly binding register. Proc Natl Acad Sci U S A, 2010; 107:10978–10983.
MichelsAW, OstrovDA, ZhangL, NakayamaM, FuseM, McDanielK, RoepBO, GottliebPA, AtkinsonMA, EisenbarthGS. Structure-based selection of small molecules to alter allele-specific MHC class II antigen presentation. J Immunol, 2011; 187:5921–5930.
26.
MahonJL, SosenkoJM, Rafkin-MervisL, Krause-SteinraufH, LachinJM, ThompsonC, BingleyPJ, BonifacioE, PalmerJP, EisenbarthGS, WolfsdorfJ, SkylerJS. 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.
27.
ZieglerAG, NepomGT. Prediction and pathogenesis in type 1 diabetes. Immunity, 2010; 32:468–478.
28.
OresicM, SimellS, Sysi-AhoM, Näntö-SalonenK, Seppänen-LaaksoT, ParikkaV, KatajamaaM, HekkalaA, MattilaI, KeskinenP, YetukuriL, ReinikainenA, LähdeJ, SuorttiT, HakalaxJ, SimellT, HyötyH, VeijolaR, IlonenJ, LahesmaaR, KnipM, SimellO. 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.
29.
HarjutsaloV, SjöbergL, TuomilehtoJ. Time trends in the incidence of type 1 diabetes in Finnish children: a cohort study. Lancet, 2008; 371:1777–1782.
30.
ZieglerAG, BonifacioE. BABYDIAB-BABYDIET Study Group. Age-related islet autoantibody incidence in offspring of patients with type 1 diabetes. Diabetologia, 2012; 55:1937–1943.
31.
ParikkaV, Näntö-SalonenK, SaarinenM, SimellT, IlonenJ, HyötyH, VeijolaR, KnipM, SimellO. Early seroconversion and rapidly increasing autoantibody concentrations predict prepubertal manifestation of type 1 diabetes in children at genetic risk. Diabetologia, 2012; 55:1926–1936.
32.
InselRA, DeecherDC, BrewerJ. Perspectives in diabetes: Juvenile Diabetes Research Foundation: mission, strategy, and priorities. Diabetes, 2012; 61:30–35.
33.
StaevaTP, ChatenoudL, InselR, AtkinsonMA. Recent lessons learned from prevention and recent-onset type 1 diabetes immunotherapy trials. Diabetes, 2013; 62:9–17.
34.
InselR. Speculation on prevention of type 1 diabetes. TaylorK, HyötyH, TonioloA, ZuckermanA. Diabetes and Viruses. New York: Springer Science, 2012; 339–3480.
35.
http://jdrf.org/blog/2011/preventing-type-1-diabetes-the-leadership-role-of-jdrf/. 2013 April 16.
