المؤلفون: Battaglia M., Ahmed S., Anderson M. S., Atkinson M. A., Becker D., Bingley P. J., Bosi E., Brusko T. M., DiMeglio L. A., Evans-Molina C., Gitelman S. E., Greenbaum C. J., Gottlieb P. A., Herold K. C., Hessner M. J., Knip M., Jacobsen L., Krischer J. P., Alice Long S., Lundgren M., McKinney E. F., Morgan N. G., Oram R. A., Pastinen T., Peters M. C., Petrelli A., Qian X., Redondo M. J., Roep B. O., Schatz D., Skibinski D., Peakman M.

المساهمون: Battaglia, M., Ahmed, S., Anderson, M. S., Atkinson, M. A., Becker, D., Bingley, P. J., Bosi, E., Brusko, T. M., Dimeglio, L. A., Evans-Molina, C., Gitelman, S. E., Greenbaum, C. J., Gottlieb, P. A., Herold, K. C., Hessner, M. J., Knip, M., Jacobsen, L., Krischer, J. P., Alice Long, S., Lundgren, M., Mckinney, E. F., Morgan, N. G., Oram, R. A., Pastinen, T., Peters, M. C., Petrelli, A., Qian, X., Redondo, M. J., Roep, B. O., Schatz, D., Skibinski, D., Peakman, M.

مصطلحات موضوعية: Biological Variation, Population, Blood Glucose, Diabetes Mellitus, Type 1, Disease Progression, Humans, Insulin, Precision Medicine, Phenotype

الوصف: The clinical diagnosis of new-onset type 1 diabetes has, for many years, been considered relatively straightforward. Recently, however, there is increasing awareness that within this single clinical phenotype exists considerable heterogeneity: disease onset spans the complete age range; genetic susceptibility is complex; rates of progression differ markedly, as does insulin secretory capacity; and complication rates, glycemic control, and therapeutic intervention efficacy vary widely. Mechanistic and immunopathological studies typically show considerable patchiness across subjects, undermining conclusions regarding disease pathways. Without better understanding, type 1 diabetes heterogeneity represents a major barrier both to deciphering pathogenesis andto the translational effort of designing, conducting, and interpreting clinical trials of disease-modifying agents. This realization comes during a period of unprecedented change in clinical medicine, with increasing emphasis on greater individualization and precision. For complex disorders such as type 1 diabetes, the option of maintaining the "single disease" approach appears untenable, as does the notion of individualizing each single patient's care, obliging us to conceptualize type 1 diabetes less in terms of phenotypes (observable characteristics) and more in terms of disease endotypes (underlying biological mechanisms). Here, we provide our view on an approach to dissect heterogeneity in type 1 diabetes. Using lessons from other diseases and the data gathered to date, we aim to delineate a roadmap through which the field can incorporate the endotype concept into laboratory and clinical practice. We predict that such an effort will accelerate the implementation of precision medicine and has the potential for impact on our approach to translational research, trial design, and clinical management.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000508573600005; volume:43; issue:1; firstpage:5; lastpage:12; numberofpages:8; journal:DIABETES CARE; http://hdl.handle.net/20.500.11768/109385Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85077016324

الإتاحة: https://doi.org/20.500.11768/109385Test
https://doi.org/10.2337/dc19-0880Test
https://hdl.handle.net/20.500.11768/109385Test

المؤلفون: Greenbaum, C., Atkinson, M., Baidal, D., Battaglia, M., Bingley, P., Bosi, E., Buckner, J., Clements, M., Colman, P., DiMeglio, L., Evans-Molina, C., Gitelman, S., Goland, R., Gottlieb, P., Herold, K., Knip, M., Krischer, J., Lernmark, A., Moore, W., Moran, A., Muir, A., Palmer, J., Peakman, M., Philipson, L., Raskin, P., Redondo, M., Rodriguez, H., Russell, W., Spain, L., Schatz, D.A., Sosenko, J., Wherrett, D., Wilson, D., Winter, W., Ziegler, A., Anderson, M., Antinozzi, P., Benoist, C., Blum, J., Bourcier, K., Chase, P., Clare-Salzler, M., Clynes, R., Cowie, C., Eisenbarth, G., Fathman, C.G., Grave, G., Harrison, L., Hering, B., Insel, R., Jordan, S., Kaufman, F., Kay, T., Kenyon, N., Klines, R., Lachin, J., Leschek, E., Mahon, J., Marks, J.B., Monzavi, R., Nanto-Salonen, K., Nepom, G., Orban, T., Parkman, R., Pescovitz, M., Peyman, J., Pugliese, A., Ridge, J., Roep, B., Roncarolo, M., Savage, P., Simell, O., Sherwin, R., Siegelman, M., Skyler, J.S., Thomas, J., Trucco, M., Wagner, J., Greenbaum, C.J., Krischer, J.P., Rafkin, L., Foulkes, M., Krause-Steinrauf, H., Lachin, J.M., Malozowski, S., Zafonte, S.J., Kenyon, N.S., Santiago, I., Bundy, B., Abbondondolo, M., Adams, T., Asif, D.A.I., Boonstra, M., Boulware, D., Burroughs, C., Cuthbertson, D., Eberhard, C., Fiske, S., Ford, J., Garmeson, J., Guillette, H., Geyer, S., Hays, B., Henderson, C., Henry, M., Heyman, K., Hsiao, B., Karges, C., Kinderman, A., Lane, L., Leinbach, A., Liu, S., Lloyd, J., Malloy, J., Maddox, K., Martin, J., Miller, J., Moore, M., Muller, S., Nguyen, T., O'Donnell, R., Parker, M., Pereyra, M.J., Reed, N., Roberts, A., Sadler, K., Stavros, T., Tamura, R., Wood, K., Xu, P., Young, K., Alies, P., Badias, F., Baker, A., Bassi, M., Beam, C., Bounmananh, L., Bream, S., Deemer, M., Freeman, D., Gough, J., Ginem, J., Granger, M., Holloway, M., Kieffer, M., Lane, P., Law, P., Linton, C., Nallamshetty, L., Oduah, V., Parrimon, Y., Paulus, K., Pilger, J., Ramiro, J., Ritzie, A.Q.L., Sharma, A., Shor, A., Song, X.H., Terry, A., Weinberger, J., Wootten, M., Harding, M.F.P., McDonough, S., Mcgee, P.F., Hess, K.O., Phoebus, D., Quinlan, S., Raiden, E., Fradkin, J., Beck, G., Blumberg, E., Gubitosi-Klug, R., Laffel, L., Veatch, R., Wallace, D., Braun, J., Brillon, D., B. lo, Mitchell, H., Naji, A., Nerup, J., Orchard, T., Steffes, M., Tsiatis, A., Zinman, B., Loechelt, B., Baden, L., Green, M., Weinberg, A., Marcovina, S., Palmer, J.P., Yu, L.P., Shultz, A., Batts, E., Fitzpatrick, K., Ramey, M., Guerra, R., Webb, C., Caffey, F., Carr, L., Ergun-Longmire, B., Fenton, C., Giebner, D., Johnson, J., Maglionico, D., Marinelli, M., Martin, K., Minnozzi, E., Riley, W., Wilson, M., Gougeon, C., Ho, J., Huang, C., Pacaud, D., Virtanen, H., Craig, C., Ghatak, A., Henderson, T., Leyland, H., Padmore, K., Paul, P., Brickman, W., Halsey-Lyda, M., Petrie, P., Rizzo, D., Steuer, R., Suchyta, K., Torchen, L., Zimmerman, D., Bode, B., Dial, M., Gazaway, K., Hosey, R., Alkanani, A., Barker, J., Barr, M., Blau, A., Burdick, P., Burke, B., Chase, H., Drye, M., Escobar, E., Fitzgerald-Miller, L., Fouts, A., Gage, V., Gall, E., Goettle, H., Harris, S., Ketchum, K., King, M., Klingensmith, G., Lehr, D., Lehr, J., Lewis, L., Logsden-Sackett, N., Lykens, J., Maahs, D., Michels, A., Pelletier, S., Rihanek, M., Rodriguez, P., Schauwecker, A., Simmons, K., Smith, J., Steck, A., Tran, B., Tran, T., Wadwa, P., Wagner, R., Wright, H., Betancourt, J., Bui, V., DeSalvo, D., Gomez, D., Jake, K., Lynds, J., McCartney, T., McDonald, A., Pena, S., Pietropaolo, M.

المساهمون: Greenbaum, C., Atkinson, M., Baidal, D., Battaglia, M., Becker, D., Bingley, P., Bosi, E., Buckner, J., Clements, M., Colman, P., Dimeglio, L., Evans-Molina, C., Gitelman, S., Goland, R., Gottlieb, P., Herold, K., Knip, M., Krischer, J., Lernmark, A., Moore, W., Moran, A., Muir, A., Palmer, J., Peakman, M., Philipson, L., Raskin, P., Redondo, M., Rodriguez, H., Russell, W., Spain, L., Schatz, D. A., Sosenko, J., Wherrett, D., Wilson, D., Winter, W., Ziegler, A.

المصدر: Journal of the American Medical Association, 318(19), 1891-1902

مصطلحات موضوعية: 0301 basic medicine, Male, medicine.medical_specialty, Adolescent, medicine.medical_treatment, Administration, Oral, 030209 endocrinology & metabolism, Placebo, law.invention, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, Interquartile range, law, Internal medicine, Diabetes mellitus, medicine, Humans, Hypoglycemic Agents, Insulin, Family, Treatment Failure, Child, Original Investigation, Autoantibodies, Type 1 diabetes, Glucose tolerance test, medicine.diagnostic_test, business.industry, General Medicine, ta3121, Glucose Tolerance Test, medicine.disease, 030104 developmental biology, Diabetes Mellitus, Type 1, Child, Preschool, Cohort, Female, business, Follow-Up Studies

الوصف: Importance Type 1 diabetes requires major lifestyle changes and carries increased morbidity and mortality. Prevention or delay of diabetes would have major clinical effect. Objective To determine whether oral insulin delays onset of type 1 diabetes in autoantibody-positive relatives of patients with type 1 diabetes. Design, Setting, and Participants Between March 2, 2007, and December 21, 2015, relatives with at least 2 autoantibodies, including insulin autoantibodies and normal glucose tolerance, were enrolled in Canada, the United States, Australia, New Zealand, the United Kingdom, Italy, Sweden, Finland, and Germany. The main study group (n = 389) had first-phase insulin release on an intravenous glucose tolerance test that was higher than the threshold. The 55 patients in the secondary stratum 1 had an identical antibody profile as the main study group except they had first-phase insulin release that was lower than the threshold. Secondary strata 2 (n = 114) and strata 3 (n = 3) had different autoantibody profiles and first-phase insulin release threshold combinations. Follow-up continued through December 31, 2016. Interventions Randomization to receive 7.5 mg/d of oral insulin (n = 283) or placebo (n = 277), including participants in the main study group who received oral insulin (n = 203) or placebo (n = 186). Main Outcome and Measures The primary outcome was time to diabetes in the main study group. Significance was based on a 1-sided threshold of .05, and 1-sided 95% CIs are reported. Results Of a total of 560 randomized participants (median enrollment age, 8.2 years; interquartile range [IQR], 5.7-12.1 years; 170 boys [60%]; 90.7% white non-Hispanic; 57.6% with a sibling with type 1 diabetes), 550 completed the trial including 389 participants (median age, 8.4 years; 245 boys [63%]), 382 (96%) in the main study group. During a median follow-up of 2.7 years (IQR, 1.5-4.6 years) in the main study group, diabetes was diagnosed in 58 participants (28.5%) in the oral insulin group and 62 (33%) in the placebo group. Time to diabetes was not significantly different between the 2 groups (hazard ratio [HR], 0.87; 95% CI, 0-1.2;P = .21). In secondary stratum 1 (n = 55), diabetes was diagnosed in 13 participants (48.1%) in the oral insulin group and in 19 participants (70.3%) in the placebo group. The time to diabetes was significantly longer with oral insulin (HR, 0.45; 95% CI, 0-0.82;P = .006). The HR for time to diabetes for the between-group comparisons for the 116 participants in the other secondary stratum was 1.03 (95% CI, 0-2.11;P = .53) and for the entire cohort of 560 participants was 0.83 (95% CI, 0-1.07;P = .11), which were not significantly different. The most common adverse event was infection (n = 254), with 134 events in the oral insulin group and 120 events in the placebo group, but no significant study-related adverse events occurred. Conclusions and Relevance Among autoantibody-positive relatives of patients with type 1 diabetes, oral insulin at a dose of 7.5 mg/d, compared with placebo, did not delay or prevent the development of type 1 diabetes over 2.7 years. These findings do not support oral insulin as used in this study for diabetes prevention. Trial Registration clinicaltrials.gov Identifier:NCT00419562

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::efc5f4c6586f8e69acbc23f847f51bc8Test
https://hdl.handle.net/1887/116074Test

المؤلفون: Greenbaum C., Atkinson M., Baidal D., Battaglia M., Becker D., Bingley P., Bosi E., Buckner J., Clements M., Colman P., DiMeglio L., Evans-Molina C., Gitelman S., Goland R., Gottlieb P., Herold K., Knip M., Krischer J., Lernmark A., Moore W., Moran A., Muir A., Palmer J., Peakman M., Philipson L., Raskin P., Redondo M., Rodriguez H., Russell W., Spain L., Schatz D. A., Sosenko J., Wherrett D., Wilson D., Winter W., Ziegler A.

المساهمون: Greenbaum, C., Atkinson, M., Baidal, D., Battaglia, M., Becker, D., Bingley, P., Bosi, E., Buckner, J., Clements, M., Colman, P., Dimeglio, L., Evans-Molina, C., Gitelman, S., Goland, R., Gottlieb, P., Herold, K., Knip, M., Krischer, J., Lernmark, A., Moore, W., Moran, A., Muir, A., Palmer, J., Peakman, M., Philipson, L., Raskin, P., Redondo, M., Rodriguez, H., Russell, W., Spain, L., Schatz, D. A., Sosenko, J., Wherrett, D., Wilson, D., Winter, W., Ziegler, A.

مصطلحات موضوعية: Administration, Oral, Adolescent, Autoantibodies, Child, Preschool, Diabetes Mellitus, Type 1, Family, Female, Follow-Up Studies, Glucose Tolerance Test, Humans, Hypoglycemic Agents, Insulin, Male, Treatment Failure

الوصف: IMPORTANCE: Type 1 diabetes requires major lifestyle changes and carries increased morbidity and mortality. Prevention or delay of diabetes would have major clinical effect. OBJECTIVE: To determine whether oral insulin delays onset of type 1 diabetes in autoantibody-positive relatives of patients with type 1 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Between March 2, 2007, and December 21, 2015, relatives with at least 2 autoantibodies, including insulin autoantibodies and normal glucose tolerance, were enrolled in Canada, the United States, Australia, New Zealand, the United Kingdom, Italy, Sweden, Finland, and Germany. The main study group (n = 389) had first-phase insulin release on an intravenous glucose tolerance test that was higher than the threshold. The 55 patients in the secondary stratum 1 had an identical antibody profile as the main study group except they had first-phase insulin release that was lower than the threshold. Secondary strata 2 (n = 114) and strata 3 (n = 3) had different autoantibody profiles and first-phase insulin release threshold combinations. Follow-up continued through December 31, 2016. INTERVENTIONS: Randomization to receive 7.5 mg/d of oral insulin (n = 283) or placebo (n = 277), including participants in the main study group who received oral insulin (n = 203) or placebo (n = 186). MAIN OUTCOME AND MEASURES: The primary outcome was time to diabetes in the main study group. Significance was based on a 1-sided threshold of .05, and 1-sided 95% CIs are reported. RESULTS: Of a total of 560 randomized participants (median enrollment age, 8.2 years; interquartile range [IQR], 5.7-12.1 years; 170 boys [60%]; 90.7% white non-Hispanic; 57.6% with a sibling with type 1 diabetes), 550 completed the trial including 389 participants (median age, 8.4 years; 245 boys [63%]), 382 (96%) in the main study group. During a median follow-up of 2.7 years (IQR, 1.5-4.6 years) in the main study group, diabetes was diagnosed in 58 participants (28.5%) in the oral insulin group and 62 (33%) in the ...

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000415870300019; volume:318; issue:19; firstpage:1891; lastpage:1902; numberofpages:12; journal:JAMA; http://hdl.handle.net/20.500.11768/109390Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85036515544

الإتاحة: https://doi.org/20.500.11768/109390Test
https://doi.org/10.1001/jama.2017.17070Test
https://hdl.handle.net/20.500.11768/109390Test

المؤلفون: Redondo, M. J., Grant, S. F. A., Davis, A., Greenbaum, C.

المصدر: Diabetic Medicine; Feb2017, Vol. 34 Issue 2, p286-290, 5p

مصطلحات موضوعية: ALLELES, AUTOANTIBODIES, BLACK people, C-peptide, ENZYMES, GENES, GENETIC counseling, GENETIC polymorphisms, GENETICS, GLYCOSYLATED hemoglobin, HISPANIC Americans, IMMUNITY, INSULIN, ISLANDS of Langerhans, TYPE 1 diabetes, MEDICAL needs assessment, NUCLEOTIDES, PEDIATRICS, RESEARCH funding, WHITE people, ZINC, HLA-B27 antigen, GENETIC testing, BODY mass index, HUMAN research subjects, PATIENT selection, DATA analysis software, MEMBRANE transport proteins, GENOTYPES

مستخلص: Aims To test the hypothesis that non-obese individuals with childhood-onset Type 1 diabetes and the rs7903146 TT genotype would be less likely to have high-risk human leukocyte antigen ( HLA) genotypes and alleles. Methods We studied a cohort of 105 non-obese participants in the T1D Exchange Biobank Residual Insulin Study who had childhood-onset Type 1 diabetes [mean ( sd) age at onset and recruitment, respectively, 9.9 (4.15) and 14.4 (4.13) years; 84.8% non-Hispanic white]. We analysed islet autoantibodies (glutamic acid decarboxylase 65, islet cell autoantigen 512/islet antigen-2 and zinc transporter 8), non-fasting random C-peptide levels, HLA type and TCF7L2 single nucleotide polymorphism rs7903146 in this cohort. Results None of the 13 individuals with the rs7903146 TT genotype carried the highest Type 1 diabetes risk HLA genotype, i.e. DRB1*03:01/ DR4 ( DRB1*0401, *04:05 or *04:02), compared with 29.4% (27/92) of those without it ( P=0.023). The DRB1*03:01 allele was present in 15.4% (2/13) of individuals with the single nucleotide polymorphism, compared with 59.8% (55/92) of those without it ( P=0.003). Analyses restricted to autoantibody-positive individuals ( n=80) yielded similar results. The HLA DRB1*15:01 allele, which affords dominant protection against Type 1 diabetes, was found in one participant, who had multiple islet autoantibodies and carried the rs7903146 TT genotype. Conclusions These findings further support the hypothesis that TCF7L2 gene variation contributes to diabetogenesis in a subset of young people with Type 1 diabetes, opening possible new pathways for therapy and prevention. [ABSTRACT FROM AUTHOR]

: Copyright of Diabetic Medicine is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Alleva, D. G., Maki, R. A., Putnam, A. L., Robinson, J. M., Kipnes, M. S., Dandona, P., Marks, J. B., Simmons, D. L., Greenbaum, C. J., Jimenez, R. G., Conlon, P. J., Gottlieb, P. A.

المصدر: Scandinavian Journal of Immunology; Jan2006, Vol. 63 Issue 1, p59-69, 11p, 3 Charts, 4 Graphs

مصطلحات موضوعية: IMMUNOREGULATION, DIABETES, LIGANDS (Biochemistry), AMINO acids, INSULIN, PEOPLE with diabetes, LYMPHOCYTES, CLINICAL trials

مستخلص: NBI-6024 is an altered peptide ligand (APL) corresponding to the 9–23 amino acid region of the insulin B chain (B(9−23)), an epitope recognized by inflammatory interferon-γ-producing T helper (Th)1 lymphocytes in type 1 diabetic patients. Immunomodulatory effects of NBI-6024 administration in recent-onset diabetic patients in a phase I clinical trial (NBI-6024-0003) were measured in peripheral blood mononuclear cells using the enzyme-linked immunosorbent spot assay. Analysis of the mean magnitude of cytokine responses to B(9−23) and NBI-6024 for each cohort showed significant increases in interleukin-5 responses (a Th2 regulatory phenotype) in cohorts that received APL relative to those receiving placebo. A responder analysis showed that Th1 responses to B(9−23) and NBI-6024 were observed almost exclusively in the placebo-treated diabetic population but not in nondiabetic control subjects and that APL administration (five biweekly subcutaneous injections) significantly and dose-dependently reduced the percentage of patients with these Th1 responses. The results of this phase I clinical study strongly suggest that NBI-6024 treatment shifted the Th1 pathogenic responses in recent-onset type 1 diabetic patients to a protective Th2 regulatory phenotype. The significance of these findings on the clinical outcome of disease is currently under investigation in a phase II multidose study. [ABSTRACT FROM AUTHOR]

: Copyright of Scandinavian Journal of Immunology is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Maria J. Redondo, Kevan C. Herold, Mark A. Atkinson, Simi Ahmed, David A. G. Skibinski, Polly J. Bingley, Peter A. Gottlieb, Mark Peakman, S. Alice Long, Linda A. DiMeglio, Alessandra Petrelli, Richard A. Oram, Carla J. Greenbaum, Markus Lundgren, Mark S. Anderson, Desmond A. Schatz, Noel G. Morgan, Carmella Evans-Molina, Manuela Battaglia, Xiaoning Qian, Tomi Pastinen, Dorothy J. Becker, Eoin F. McKinney, Todd M. Brusko, Emanuele Bosi, Bart O. Roep, Jeffrey P. Krischer, Martin J. Hessner, Stephen E. Gitelman, Mikael Knip, Laura M. Jacobsen, Michael C. Peters

المساهمون: Battaglia, M., Ahmed, S., Anderson, M. S., Atkinson, M. A., Becker, D., Bingley, P. J., Bosi, E., Brusko, T. M., Dimeglio, L. A., Evans-Molina, C., Gitelman, S. E., Greenbaum, C. J., Gottlieb, P. A., Herold, K. C., Hessner, M. J., Knip, M., Jacobsen, L., Krischer, J. P., Alice Long, S., Lundgren, M., Mckinney, E. F., Morgan, N. G., Oram, R. A., Pastinen, T., Peters, M. C., Petrelli, A., Qian, X., Redondo, M. J., Roep, B. O., Schatz, D., Skibinski, D., Peakman, M.

المصدر: Diabetes Care

مصطلحات موضوعية: Blood Glucose, Endotype, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Translational research, Disease, Perspectives in Care, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, Internal Medicine, medicine, Genetic predisposition, Humans, Insulin, 030212 general & internal medicine, Precision Medicine, Intensive care medicine, Advanced and Specialized Nursing, Type 1 diabetes, business.industry, Precision medicine, medicine.disease, 3. Good health, Clinical trial, Diabetes Mellitus, Type 1, Phenotype, Biological Variation, Population, Disease Progression, business

الوصف: The clinical diagnosis of new-onset type 1 diabetes has, for many years, been considered relatively straightforward. Recently, however, there is increasing awareness that within this single clinical phenotype exists considerable heterogeneity: disease onset spans the complete age range; genetic susceptibility is complex; rates of progression differ markedly, as does insulin secretory capacity; and complication rates, glycemic control, and therapeutic intervention efficacy vary widely. Mechanistic and immunopathological studies typically show considerable patchiness across subjects, undermining conclusions regarding disease pathways. Without better understanding, type 1 diabetes heterogeneity represents a major barrier both to deciphering pathogenesis and to the translational effort of designing, conducting, and interpreting clinical trials of disease-modifying agents. This realization comes during a period of unprecedented change in clinical medicine, with increasing emphasis on greater individualization and precision. For complex disorders such as type 1 diabetes, the option of maintaining the “single disease” approach appears untenable, as does the notion of individualizing each single patient’s care, obliging us to conceptualize type 1 diabetes less in terms of phenotypes (observable characteristics) and more in terms of disease endotypes (underlying biological mechanisms). Here, we provide our view on an approach to dissect heterogeneity in type 1 diabetes. Using lessons from other diseases and the data gathered to date, we aim to delineate a roadmap through which the field can incorporate the endotype concept into laboratory and clinical practice. We predict that such an effort will accelerate the implementation of precision medicine and has the potential for impact on our approach to translational research, trial design, and clinical management.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::28537cfa6851fd3118b18969e39f2fadTest