Skip to main content
Erschienen in: Current Diabetes Reports 11/2017

01.11.2017 | Therapies and New Technologies in the Treatment of Type 1 Diabetes (M Pietropaolo, Section Editor)

Emerging Concepts on Disease-Modifying Therapies in Type 1 Diabetes

verfasst von: Carla Greenbaum, Sandra Lord, Dana VanBuecken

Erschienen in: Current Diabetes Reports | Ausgabe 11/2017

Einloggen, um Zugang zu erhalten

Abstract

Purpose of Review

This review seeks to characterize emerging concepts related to disease-modifying therapy in type 1 diabetes.

Recent Findings

We begin by describing the new understanding that islet autoimmunity, as identified by the presence of islet autoantibodies, inevitably leads to clinical type 1 diabetes. This understanding informs the new staging paradigm for type 1 diabetes, which suggests that type 1 diabetes may be recognized and diagnosed long before symptoms develop. Although it is known that nearly all individuals with established islet autoimmunity will eventually develop symptomatic type 1 diabetes (T1D), individual characteristics such as age and biomarker profile may predict rate of disease progression and response to treatment and may therefore be used to individualize therapy.

Summary

Key research supports the use of immunotherapy in TID, although a paradigm shift is necessary before immunotherapy may transition from clinical trials to clinical practice. Recent and ongoing research as it relates to these concepts is described throughout.
Literatur
1.
Zurück zum Zitat Silverstein J, Maclaren N, Riley W, Spillar R, Radjenovic D, Johnson S. Immunosuppression with azathioprine and prednisone in recent-onset insulin-dependent diabetes mellitus. N Engl J Med. 1988;319(10):599–604.CrossRefPubMed Silverstein J, Maclaren N, Riley W, Spillar R, Radjenovic D, Johnson S. Immunosuppression with azathioprine and prednisone in recent-onset insulin-dependent diabetes mellitus. N Engl J Med. 1988;319(10):599–604.CrossRefPubMed
2.
Zurück zum Zitat Bougneres PF, Carel JC, Castano L, Boitard C, Gardin JP, Landais P, et al. Factors associated with early remission of type I diabetes in children treated with cyclosporine. N Engl J Med. 1988;318(11):663–70.CrossRefPubMed Bougneres PF, Carel JC, Castano L, Boitard C, Gardin JP, Landais P, et al. Factors associated with early remission of type I diabetes in children treated with cyclosporine. N Engl J Med. 1988;318(11):663–70.CrossRefPubMed
3.
Zurück zum Zitat Stiller CR, Laupacis A, Dupre J, Jenner MR, Keown PA, Rodger W, et al. Cyclosporine for treatment of early type I diabetes: preliminary results. N Engl J Med. 1983;308(20):1226–7.PubMed Stiller CR, Laupacis A, Dupre J, Jenner MR, Keown PA, Rodger W, et al. Cyclosporine for treatment of early type I diabetes: preliminary results. N Engl J Med. 1983;308(20):1226–7.PubMed
5.
Zurück zum Zitat •• Insel RA, Dunne JL, Atkinson MA, Chiang JL, Dabelea D, Gottlieb PA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015;38(10):1964–74. This scientific statement redefined diagnostic criteria for T1D, suggesting that individuals found to have multiple autoantibodies may be characterized as being in “Stage 1” of the disease. Almost all individuals in stage 1 of T1D will eventually progress to symptomatic diabetes. CrossRefPubMedPubMedCentral •• Insel RA, Dunne JL, Atkinson MA, Chiang JL, Dabelea D, Gottlieb PA, et al. Staging presymptomatic type 1 diabetes: a scientific statement of JDRF, the Endocrine Society, and the American Diabetes Association. Diabetes Care. 2015;38(10):1964–74. This scientific statement redefined diagnostic criteria for T1D, suggesting that individuals found to have multiple autoantibodies may be characterized as being in “Stage 1” of the disease. Almost all individuals in stage 1 of T1D will eventually progress to symptomatic diabetes. CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Ziegler AG, Rewers M, Eisenbarth G, Simell O. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. J Am Med Assoc. 2013;309(23):2473–9.CrossRef Ziegler AG, Rewers M, Eisenbarth G, Simell O. Seroconversion to multiple islet autoantibodies and risk of progression to diabetes in children. J Am Med Assoc. 2013;309(23):2473–9.CrossRef
7.
Zurück zum Zitat • Wherrett DK, Chiang JL, Delamater AM, DiMeglio LA, Gitelman SE, Gottlieb PA, et al. Defining pathways for development of disease-modifying therapies in children with type 1 diabetes: a consensus report. Diabetes Care. 2015;38(10):1975–85. This study shows that the risk of progression from autoantibody positivity to stage 3 (symptomatic) T1D varies based on age, with those at younger ages at greater risk of rapid progression of disease. This may justify the use of different therapies for the pediatric at-risk population versus the adult population. CrossRefPubMedPubMedCentral • Wherrett DK, Chiang JL, Delamater AM, DiMeglio LA, Gitelman SE, Gottlieb PA, et al. Defining pathways for development of disease-modifying therapies in children with type 1 diabetes: a consensus report. Diabetes Care. 2015;38(10):1975–85. This study shows that the risk of progression from autoantibody positivity to stage 3 (symptomatic) T1D varies based on age, with those at younger ages at greater risk of rapid progression of disease. This may justify the use of different therapies for the pediatric at-risk population versus the adult population. CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Mahon JL, Sosenko JM, Rafkin-Mervis L, Krause-Steinrauf H, Lachin JM, Thompson C, et al. The TrialNet natural history study of the development of type 1 diabetes: objectives, design, and initial results. Pediatr Diabetes. 2009;10(2):97–104. Mahon JL, Sosenko JM, Rafkin-Mervis L, Krause-Steinrauf H, Lachin JM, Thompson C, et al. The TrialNet natural history study of the development of type 1 diabetes: objectives, design, and initial results. Pediatr Diabetes. 2009;10(2):97–104.
9.
Zurück zum Zitat American Diabetes Association I. American Diabetes Association standards of medical Care in Diabetes 2017. Diabetes Care. 2017;40(Supplement 1):S1–S134.CrossRef American Diabetes Association I. American Diabetes Association standards of medical Care in Diabetes 2017. Diabetes Care. 2017;40(Supplement 1):S1–S134.CrossRef
10.
Zurück zum Zitat Kostraba JN, Gay EC, Cai Y, Cruickshanks KJ, Rewers MJ, Klingensmith GJ, et al. Incidence of insulin-dependent diabetes mellitus in Colorado. Epidemiology. 1992;3(3):232–8.CrossRefPubMed Kostraba JN, Gay EC, Cai Y, Cruickshanks KJ, Rewers MJ, Klingensmith GJ, et al. Incidence of insulin-dependent diabetes mellitus in Colorado. Epidemiology. 1992;3(3):232–8.CrossRefPubMed
11.
Zurück zum Zitat Group EAS, Group EASS. Familial risk of type I diabetes in European children. Diabetologia. 1998;41(10):1151–6.CrossRef Group EAS, Group EASS. Familial risk of type I diabetes in European children. Diabetologia. 1998;41(10):1151–6.CrossRef
12.
Zurück zum Zitat 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(5):1134.PubMedPubMedCentral 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(5):1134.PubMedPubMedCentral
13.
Zurück zum Zitat Concannon P, Rich SS, Nepom GT. Genetics of type 1A diabetes. N Engl J Med. 2009;360(16):1646–54.CrossRefPubMed Concannon P, Rich SS, Nepom GT. Genetics of type 1A diabetes. N Engl J Med. 2009;360(16):1646–54.CrossRefPubMed
14.
Zurück zum Zitat Hagopian S, Erlich H, Lernmark A, JinXiong S. The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. Pediatr Diabetes. 2011;12(8):133–43.CrossRef Hagopian S, Erlich H, Lernmark A, JinXiong S. The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. Pediatr Diabetes. 2011;12(8):133–43.CrossRef
15.
Zurück zum Zitat Greenbaum CJ, Beam CA, Boulware D, Gitelman SE, Gottlieb PA, Herold KC, et al. Fall in C-peptide during first 2 years from diagnosis: evidence of at least two distinct phases from composite type 1 diabetes TrialNet data. Diabetes. 2012;61(8):2066–73.CrossRefPubMedPubMedCentral Greenbaum CJ, Beam CA, Boulware D, Gitelman SE, Gottlieb PA, Herold KC, et al. Fall in C-peptide during first 2 years from diagnosis: evidence of at least two distinct phases from composite type 1 diabetes TrialNet data. Diabetes. 2012;61(8):2066–73.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Parikka V, Näntö-Salonen K, Saarinen M, Simell T, Ilonen J, Hyöty H, et al. Early seroconversion and rapidly increasing autoantibody concentrations predict prepubertal manifestation of type 1 diabetes in children at genetic risk. Diabetologia. 2012;55(7):1926–36. Parikka V, Näntö-Salonen K, Saarinen M, Simell T, Ilonen J, Hyöty H, et al. Early seroconversion and rapidly increasing autoantibody concentrations predict prepubertal manifestation of type 1 diabetes in children at genetic risk. Diabetologia. 2012;55(7):1926–36.
17.
Zurück zum Zitat Insel RA, Dunne JL, Ziegler AG. General population screening for type 1 diabetes: has its time come? Curr Opin Endocrinol Diabetes Obes. 2015;22(4):270–6.CrossRefPubMed Insel RA, Dunne JL, Ziegler AG. General population screening for type 1 diabetes: has its time come? Curr Opin Endocrinol Diabetes Obes. 2015;22(4):270–6.CrossRefPubMed
18.
Zurück zum Zitat TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY) study: study design. Pediatr Diabetes. 2007;8(5):286–98. TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY) study: study design. Pediatr Diabetes. 2007;8(5):286–98.
19.
Zurück zum Zitat Orban T, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, et al. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet. 2011;378(9789):412–9.CrossRefPubMedPubMedCentral Orban T, Bundy B, Becker DJ, DiMeglio LA, Gitelman SE, Goland R, et al. Co-stimulation modulation with abatacept in patients with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled trial. Lancet. 2011;378(9789):412–9.CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Orban T, Bundy B, Becker DJ, Dimeglio LA, Gitelman SE, Goland R, et al. Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes: follow-up 1 year after cessation of treatment. Diabetes Care. 2014;37(4):1069–75.CrossRefPubMedPubMedCentral Orban T, Bundy B, Becker DJ, Dimeglio LA, Gitelman SE, Goland R, et al. Costimulation modulation with abatacept in patients with recent-onset type 1 diabetes: follow-up 1 year after cessation of treatment. Diabetes Care. 2014;37(4):1069–75.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Pescovitz MD, Greenbaum CJ, Bundy B, Becker DJ, Gitelman SE, Goland R, et al. B-lymphocyte depletion with rituximab and beta-cell function: two-year results. Diabetes Care. 2014;37(2):453–9.CrossRefPubMedPubMedCentral Pescovitz MD, Greenbaum CJ, Bundy B, Becker DJ, Gitelman SE, Goland R, et al. B-lymphocyte depletion with rituximab and beta-cell function: two-year results. Diabetes Care. 2014;37(2):453–9.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Haller MJ, Gitelman SE, Gottlieb PA, Michels AW, Rosenthal SM, Shuster JJ, et al. Anti-thymocyte globulin/G-CSF treatment preserves beta cell function in patients with established type 1 diabetes. J Clin Invest. 2015;125(1):448–55.CrossRefPubMed Haller MJ, Gitelman SE, Gottlieb PA, Michels AW, Rosenthal SM, Shuster JJ, et al. Anti-thymocyte globulin/G-CSF treatment preserves beta cell function in patients with established type 1 diabetes. J Clin Invest. 2015;125(1):448–55.CrossRefPubMed
23.
Zurück zum Zitat Gitelman SG, Gottlieb PA, Rigby MR, et al. Antithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2013;1(4):306–16.CrossRefPubMed Gitelman SG, Gottlieb PA, Rigby MR, et al. Antithymocyte globulin treatment for patients with recent-onset type 1 diabetes: 12-month results of a randomised, placebo-controlled, phase 2 trial. Lancet Diabetes Endocrinol. 2013;1(4):306–16.CrossRefPubMed
24.
Zurück zum Zitat Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, Becker DJ, Gitelman SE, Goland R, et al. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N Engl J Med. 2009;361(22):2143–52.CrossRefPubMed Pescovitz MD, Greenbaum CJ, Krause-Steinrauf H, Becker DJ, Gitelman SE, Goland R, et al. Rituximab, B-lymphocyte depletion, and preservation of beta-cell function. N Engl J Med. 2009;361(22):2143–52.CrossRefPubMed
25.
Zurück zum Zitat Hagopian W, Ferry RJ, Sherry N, Carlin D, Bonvini E, Johnson S, et al. Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized placebo-controlled Protégé trial. Diabetes. 2013;62(11):3901–8.CrossRefPubMedPubMedCentral Hagopian W, Ferry RJ, Sherry N, Carlin D, Bonvini E, Johnson S, et al. Teplizumab preserves C-peptide in recent-onset type 1 diabetes: two-year results from the randomized placebo-controlled Protégé trial. Diabetes. 2013;62(11):3901–8.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Rigby MR, Harris KM, Pinckney A, DiMeglio LA, Rendell MS, Felner EI, et al. Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients. J Clin Invest. 2015;125(8):3285–96.CrossRefPubMedPubMedCentral Rigby MR, Harris KM, Pinckney A, DiMeglio LA, Rendell MS, Felner EI, et al. Alefacept provides sustained clinical and immunological effects in new-onset type 1 diabetes patients. J Clin Invest. 2015;125(8):3285–96.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Sosenko JM, Skyler JS, Palmer JP, Krische JP, Liping Y, Mahon J, et al. 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(9):2615–20. Sosenko JM, Skyler JS, Palmer JP, Krische JP, Liping Y, Mahon J, et al. 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(9):2615–20.
28.
Zurück zum Zitat Vehik K, Cuthbertson D, Ruhlig H, Schatz DA, Peakman M, Krischer JP, et al. Long-term outcome of individuals treated with oral insulin: diabetes prevention trial-type 1 (DPT-1) oral insulin trial. Diabetes Care. 2011;34(7):1585–90.CrossRefPubMedPubMedCentral Vehik K, Cuthbertson D, Ruhlig H, Schatz DA, Peakman M, Krischer JP, et al. Long-term outcome of individuals treated with oral insulin: diabetes prevention trial-type 1 (DPT-1) oral insulin trial. Diabetes Care. 2011;34(7):1585–90.CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat Bottazzo G, Lorin-Christensen A, Doniach D. Islet cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet. 1974;2:1279–83.CrossRefPubMed Bottazzo G, Lorin-Christensen A, Doniach D. Islet cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet. 1974;2:1279–83.CrossRefPubMed
32.
Zurück zum Zitat Herold KC, Gitelman S, Greenbaum C, Puck J, Hagopian W, Gottlieb P, et al. Treatment of patients with new onset type 1 diabetes with a single course of anti-CD3 mAb teplizumab preserves insulin production for up to 5 years. Clin Immunol. 2009;132(2):166–73.CrossRefPubMedPubMedCentral Herold KC, Gitelman S, Greenbaum C, Puck J, Hagopian W, Gottlieb P, et al. Treatment of patients with new onset type 1 diabetes with a single course of anti-CD3 mAb teplizumab preserves insulin production for up to 5 years. Clin Immunol. 2009;132(2):166–73.CrossRefPubMedPubMedCentral
33.
Zurück zum Zitat Herold KC, Gitelman SE, Ehlers MR, Gottlieb PA, Greenbaum CJ, Hagopian W, et al. Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders. Diabetes. 2013;62(11):3766–74.CrossRefPubMedPubMedCentral Herold KC, Gitelman SE, Ehlers MR, Gottlieb PA, Greenbaum CJ, Hagopian W, et al. Teplizumab (anti-CD3 mAb) treatment preserves C-peptide responses in patients with new-onset type 1 diabetes in a randomized controlled trial: metabolic and immunologic features at baseline identify a subgroup of responders. Diabetes. 2013;62(11):3766–74.CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Herold KC, Gitelman SE, Willi SM, Gottlieb PA, Waldron-Lynch F, Devine L, et al. Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial. Diabetologia. 2013;56(2):391–400.CrossRefPubMed Herold KC, Gitelman SE, Willi SM, Gottlieb PA, Waldron-Lynch F, Devine L, et al. Teplizumab treatment may improve C-peptide responses in participants with type 1 diabetes after the new-onset period: a randomised controlled trial. Diabetologia. 2013;56(2):391–400.CrossRefPubMed
35.
Zurück zum Zitat Keymeulen B, Vandemeulebroucke E, Ziegler AG, Mathieu C, Kaufman L, Hale G, et al. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med. 2005;352(25):2598–608.CrossRefPubMed Keymeulen B, Vandemeulebroucke E, Ziegler AG, Mathieu C, Kaufman L, Hale G, et al. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med. 2005;352(25):2598–608.CrossRefPubMed
36.
Zurück zum Zitat Keymeulen B, Walter M, Mathieu C, Kaufman L, Gorus F, Hilbrands R, et al. Four-year metabolic outcome of a randomised controlled CD3-antibody trial in recent-onset type 1 diabetic patients depends on their age and baseline residual beta cell mass. Diabetologia. 2010;53(4):614–23.CrossRefPubMed Keymeulen B, Walter M, Mathieu C, Kaufman L, Gorus F, Hilbrands R, et al. Four-year metabolic outcome of a randomised controlled CD3-antibody trial in recent-onset type 1 diabetic patients depends on their age and baseline residual beta cell mass. Diabetologia. 2010;53(4):614–23.CrossRefPubMed
37.
Zurück zum Zitat Rigby MR, DiMeglio LA, Rendell MS, Felner EI, Dostou JM, Gitelman SE, et al. Targeting of memory T cells with alefacept in new-onset type 1 diabetes (T1DAL study): 12 month results of a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Diabetes Endocrinol. 2013;1(4):284–94.CrossRefPubMedPubMedCentral Rigby MR, DiMeglio LA, Rendell MS, Felner EI, Dostou JM, Gitelman SE, et al. Targeting of memory T cells with alefacept in new-onset type 1 diabetes (T1DAL study): 12 month results of a randomised, double-blind, placebo-controlled phase 2 trial. Lancet Diabetes Endocrinol. 2013;1(4):284–94.CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Group DPTS. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med. 2002;346(22):1685–91.CrossRef Group DPTS. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med. 2002;346(22):1685–91.CrossRef
39.
Zurück zum Zitat Sosenko JMPJ, Rafkin-Mervis L, Krischer JP, Cuthbertson D, Matheson D, Skyler JS. Glucose and C-peptide changes in the perionset period of type 1 diabetes in the diabetes prevention trial-type 1. Diabetes Care. 2008;31(11):2188–92.CrossRefPubMedPubMedCentral Sosenko JMPJ, Rafkin-Mervis L, Krischer JP, Cuthbertson D, Matheson D, Skyler JS. Glucose and C-peptide changes in the perionset period of type 1 diabetes in the diabetes prevention trial-type 1. Diabetes Care. 2008;31(11):2188–92.CrossRefPubMedPubMedCentral
40.
Zurück zum Zitat (NIDDK) NIoDaDaKD. Teplizumab for prevention of type 1 diabetes in relatives “at-risk”. In: ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US) 2000- [cited 2017 Mar 31].Available from: http://clinicaltrials.gov/show/ NCT01030861 NLM Identifier: NCT01030861. (NIDDK) NIoDaDaKD. Teplizumab for prevention of type 1 diabetes in relatives “at-risk”. In: ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US) 2000- [cited 2017 Mar 31].Available from: http://​clinicaltrials.​gov/​show/​ NCT01030861 NLM Identifier: NCT01030861.
41.
Zurück zum Zitat (NIDDK) NIoDaDaKD. ATG-GCSF in new onset type 1 diabetes. In: ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US) 2000- [cited 2017 March 31].Available from: http://clinicaltrials.gov/show/ NCT02215200 NLM Identifier:NCT02215200. (NIDDK) NIoDaDaKD. ATG-GCSF in new onset type 1 diabetes. In: ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US) 2000- [cited 2017 March 31].Available from: http://​clinicaltrials.​gov/​show/​ NCT02215200 NLM Identifier:NCT02215200.
42.
Zurück zum Zitat Du Toit G, Roberts G, Sayre PH, Bahnson HT, Radulovic S, Santos AF, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372(9):803–13.CrossRefPubMedPubMedCentral Du Toit G, Roberts G, Sayre PH, Bahnson HT, Radulovic S, Santos AF, et al. Randomized trial of peanut consumption in infants at risk for peanut allergy. N Engl J Med. 2015;372(9):803–13.CrossRefPubMedPubMedCentral
43.
Zurück zum Zitat Health M. Trial of intranasal insulin in children and young adults at risk of type 1 diabetes (INITII). ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US) 2000- [cited 2017 March 31] Available from: http://clinicaltrials.gov/show/ NCT00336674 NLM Identifier:NCT00336674. Health M. Trial of intranasal insulin in children and young adults at risk of type 1 diabetes (INITII). ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US) 2000- [cited 2017 March 31] Available from: http://​clinicaltrials.​gov/​show/​ NCT00336674 NLM Identifier:NCT00336674.
44.
Zurück zum Zitat University L. Diabetes Prevention - Immune Tolerance (DIAPREV-IT). ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US) 2000- [cited 2017 April 13] Available from: http://clinicaltrials.gov/show/ NCT01122446 NLM Identifier: NCT01122446. University L. Diabetes Prevention - Immune Tolerance (DIAPREV-IT). ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US) 2000- [cited 2017 April 13] Available from: http://​clinicaltrials.​gov/​show/​ NCT01122446 NLM Identifier: NCT01122446.
45.
Zurück zum Zitat University L. Prevention Trial: Immune-tolerance With Alum-GAD (Diamyd) and vitamin D3 to Children With Multiple Islet Autoantibodies (DiAPREV-IT2). ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US) 2000- [cited 2017 April 13] Available from: http://clinicaltrials.gov/show/ NCT02387164 NLM Identifier: NCT02387164. University L. Prevention Trial: Immune-tolerance With Alum-GAD (Diamyd) and vitamin D3 to Children With Multiple Islet Autoantibodies (DiAPREV-IT2). ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US) 2000- [cited 2017 April 13] Available from: http://​clinicaltrials.​gov/​show/​ NCT02387164 NLM Identifier: NCT02387164.
46.
Zurück zum Zitat (NIDDK) NIoDaDaKD. CTLA4-Ig (abatacept) for prevention of abnormal glucose tolerance and diabetes in relatives at-risk for type 1. In: ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US) 2000- [cited 2017 March 31].Available from: http://clinicaltrials.gov/show/ NCT01773707 NLM Identifier:NCT01773707. (NIDDK) NIoDaDaKD. CTLA4-Ig (abatacept) for prevention of abnormal glucose tolerance and diabetes in relatives at-risk for type 1. In: ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US) 2000- [cited 2017 March 31].Available from: http://​clinicaltrials.​gov/​show/​ NCT01773707 NLM Identifier:NCT01773707.
47.
Zurück zum Zitat Bluestone J. T1DM Immunotherapy Using Polyclonal Tregs + IL-2 (TILT). In: ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US) 2000- [cited 2017 April 13] Available from: http://clinicaltrials.gov/show/ NCT02772679 NLM Identifier: NCT02772679. Bluestone J. T1DM Immunotherapy Using Polyclonal Tregs + IL-2 (TILT). In: ClinicalTrialsgov [Internet] Bethesda (MD): National Library of Medicine (US) 2000- [cited 2017 April 13] Available from: http://​clinicaltrials.​gov/​show/​ NCT02772679 NLM Identifier: NCT02772679.
48.
Zurück zum Zitat Tao B, Pietropaolo M, Atkinson M, Schatz D, Taylor D. Estimating the cost of type 1 diabetes in the U.S.: a propensity score matching method. PLos One. 2010;5(7):e11501.CrossRefPubMedPubMedCentral Tao B, Pietropaolo M, Atkinson M, Schatz D, Taylor D. Estimating the cost of type 1 diabetes in the U.S.: a propensity score matching method. PLos One. 2010;5(7):e11501.CrossRefPubMedPubMedCentral
49.
Zurück zum Zitat Miller RG, Secrest A, Sharma RK, Songer TJ, Orchard TJ. Improvements in the life expectancy of type 1 diabetes: the Pittsburge Epidemiology of Diabetes Complications study cohort. Diabetes. 2012;61(11):2987–92. Miller RG, Secrest A, Sharma RK, Songer TJ, Orchard TJ. Improvements in the life expectancy of type 1 diabetes: the Pittsburge Epidemiology of Diabetes Complications study cohort. Diabetes. 2012;61(11):2987–92.
Metadaten
Titel
Emerging Concepts on Disease-Modifying Therapies in Type 1 Diabetes
verfasst von
Carla Greenbaum
Sandra Lord
Dana VanBuecken
Publikationsdatum
01.11.2017
Verlag
Springer US
Erschienen in
Current Diabetes Reports / Ausgabe 11/2017
Print ISSN: 1534-4827
Elektronische ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-017-0932-x

Weitere Artikel der Ausgabe 11/2017

Current Diabetes Reports 11/2017 Zur Ausgabe

Therapies and New Technologies in the Treatment of Type 1 Diabetes (M Pietropaolo, Section Editor)

Modulation of Type 1 Diabetes Risk by the Intestinal Microbiome

Therapies and New Technologies in the Treatment of Type 1 Diabetes (M Pietropaolo, Section Editor)

Targeting Innate Immunity for Type 1 Diabetes Prevention

Microvascular Complications—Retinopathy (JK Sun and PS Silva, Section Editors)

Metabolomics of Diabetic Retinopathy

Lifestyle Management to Reduce Diabetes/Cardiovascular Risk (B Conway and H Keenan, Section Editors)

A Review of Technology-Assisted Interventions for Diabetes Prevention

Microvascular Complications—Neuropathy (R Pop-Busui, Section Editor)

Psychological and Biomechanical Aspects of Patient Adaptation to Diabetic Neuropathy and Foot Ulceration

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

CAR-M-Zellen: Warten auf das große Fressen

22.05.2024 Onkologische Immuntherapie Nachrichten

Auch myeloide Immunzellen lassen sich mit chimären Antigenrezeptoren gegen Tumoren ausstatten. Solche CAR-Fresszell-Therapien werden jetzt für solide Tumoren entwickelt. Künftig soll dieser Prozess nicht mehr ex vivo, sondern per mRNA im Körper der Betroffenen erfolgen.

Chronische Verstopfung: „Versuchen Sie es mit grünen Kiwis!“

22.05.2024 Obstipation Nachrichten

Bei chronischer Verstopfung wirken Kiwis offenbar besser als Flohsamenschalen. Das zeigen die Daten aus einer randomisierten Studie, die der Gastroenterologe Oliver Pech beim Praxis-Update vorstellte.

So häufig greift rheumatoide Arthritis auf Organe über

21.05.2024 Rheumatoide Arthritis Nachrichten

Im Verlauf von rheumatoider Arthritis entwickeln viele Patienten extraartikuläre Manifestationen. Schwedische Forscher haben sich mit der Inzidenz und den Risikofaktoren befasst.

Blutdrucksenkung könnte Uterusmyome verhindern

Frauen mit unbehandelter oder neu auftretender Hypertonie haben ein deutlich erhöhtes Risiko für Uterusmyome. Eine Therapie mit Antihypertensiva geht hingegen mit einer verringerten Inzidenz der gutartigen Tumoren einher.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.