Zusammenfassung
Der Diabetes mellitus Typ 1 (insulinpflichtiger Diabetes) wird durch eine immunvermittelte Zerstörung der β-Zellen in den Pankreasinseln verursacht. Bei klinischer Manifestation der Hyperglykämie sind bereits 80% der β-Zellen zerstört.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
Literatur
Alvarez-Marfany M, Roman SH, Drexler AJ, Robertson C, Stagnaro-Green A (1994) Long-term prospective study of postpartum thyroid dysfunction in women with insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 79: 10–16
Atkinson MA, Kaufman DL, Newman D, Tobin AJ, Maclaren NK (1993) Islet cell cytoplasmic autoantibody reactivity to glutamate acid decarboxylase in insulin-dependent diabetes. J Clin Invest 91: 350–356
Atkinson MA, Bowman MA, Campbell L, Darrow BL, Kaufman DL, Maclaren NK (1994) Cellular immunity to a determinant common to glutamate acid decarboxylase and coxsackie virus in insulin-dependent diabetes. J Clin Invest 94: 2125–2129
Baekkeskov S, Nielsen JH, Marner B, Bilde T, Ludvigsson J, Lernmark A (1982) Autoantibodies in newly diagnosed diabetic children immunoprecipitate human pancreatic islet cell proteins. Nature 298: 167–169
Baekkeskov S, Aanstoot HJ, Christgau S, Reetz A, Solimena M, Cascalho M, Folli F, Richter-Olesen H, DeCamilli P (1990) Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature 347: 151–156
Bingley PJ, Bonifacio E, Gale EA (1993) Can we really predict IDDM? Diabetes 42: 213–220
Boehm BO, Manfras B, Seissler J, Schoffling K, Gluck M, Holzberger G, Seidl S, Kuehnl P, Trucco M, Scherbaum WA (1991) Epidemiology and immunogenetic background of islet cell antibody-positive nondiabetic schoolchildren. Diabetes 40: 1435–1439
Borch-Johnsen K, Joner G, Mandrup-Poulsen T, et al., (1984) Relation between breast-feeding and incidence rates of insulin-dependent diabetes mellitus. A hypothesis. Lancet 2: 1083–1086
Bottazzo GF, Lendrum R (1976) Separate autoantibodies to human pancreatic glucagon and somatostatin cells. Lancet 2: 873–876
Bottazzo GF, Florin-Christensen A, Doniach D (1974) Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet 2: 1279–1283
Bottazzo GF, Dean BM, McNally JM, MacKay EH, Swift PG, Gamble DR (1985) In situ characterization of autoimmune phenomena and expression of HLA molecules in the pancreas in diabetic insulitis. N Engl J Med 313: 353–360
Castano L, Russo E, Zhou L, Lipes MA, Eisenbarth GS (1991) Identification and cloning of a granule autoantigen (carboxypeptidase-H) associated with type I diabetes. J Clin Endocrinol Metab 73: 1197–1201
Child DF, Williams CP, Jones RP, Hudson PR, Jones M, Smith CJ (1995) Heat shock protein studies in type i and type 2 diabetes and human islet cell culture. Diabet Med 12: 595–599
Colle E, Siemiatycki J, West R, Belmonte MM, Crepeau MP, Poirier R, Wilkins J (1981) Incidence of juvenile onset diabetes in Montreal–demonstration of ethnic differences and socio-economic class differences. J Chronic Dis 34: 611–616
Dahlquist GG, Blom LG, Persson LA, Sandstrom AI, Wall SG (1990) Dietary factors and the risk of developing insulin dependent diabetes in childhood. BMJ 300: 1302–1306
Dahlquist G, Savilahti E, Landin-Olsson M (1992) An increased level of antibodies to beta-lactoglobulin is a risk determinant for early-onset type 1 (insulin-dependent) diabetes mellitus independent of islet cell antibodies and early introduction of cow’s milk. Diabetologia 35: 980–984
Dahlquist GG, Ivarsson S, Lindberg B, Forsgren M (1995) Maternal enteroviral infection during pregnancy as a risk factor for childhood IDDM. A population-based case-control study. Diabetes 44: 408–413
Davies JL, Kawaguchi Y, Bennett ST, et al., (1994) A genomewide search for human type diabetes susceptibility genes. Nature 371: 130–136
Drell DW, Notkins AL (1987) Multiple immunological abnormalities in patients with type 1 insulin-dependent) diabetes mellitus. Diabetologia 30: 132–143
Foulis AK, McGill M, Farquharson MA (1991) Insulitis in type 1 insulin-dependent) diabetes mellitus in man–macrophages, lymphocytes, and interferon-gamma containing cells. J Pathol 165: 97–103
Genovese S, Bingley PJ, Bonifacio E, Christie MR, Shattock M, Bonfanti R, Foxon R, Gale EA, Bottazzo, GF (1994) Combined analysis of IDDM-related autoantibodies in healthy schoolchildren [letter]. Lancet 344: 756
Gepts W (1984) The pathology of the pancreas in human diabetes. In: Andreani D, Di Mario U, Federlin KF, Heding LG (eds) Immunology in diabetes. Kimpton Medical, London, pp 21–34
Hagopian WA, Michelsen B, Karlsen AE, Larsen F, Moody A, Grubin CE, Rowe R, Petersen J, McEvoy R, Lernmark A (1993) Autoantibodies in IDDM primarily recognize the 65,000-M(r) rather than the 67,000-M(r) isoform of glutamic acid decarboxylase. Diabetes 42: 631–636
Hallberg A, Juhlin C, Berne C, Kampe O, Karlsson FA (1995) Islet cell antibodies: variable immunostaining of pancreatic islet cells and carcinoid tissue. J Intern Med 238: 207–213
Hanninen A, Jalkanen S, Salmi M, Toikkanen S, Nikolakaros G, Simell O (1992) Macrophages, T cell receptor usage, and endothelial cell activation in the pancreas at the onset of insulin-dependent diabetes mellitus. J Clin Invest 90: 1901–1910
Harrison LC, De-Aizpurua H, Loudovaris T, Campbell IL, Cebon JS, Tait BD, Colman PG (1991) Reactivity to human islets and fetal pig proislets by peripheral blood mononuclear cells from subjects with preclinical and clinical insulin-dependent diabetes. Diabetes 4o: 1128–1133
Harrison LC, Chu SX, DeAizpurua HJ, Graham M, Honeyman MC, Colman PG (1992) Islet-reactive T cells are a marker of preclinical insulin-dependent diabetes. J Clin Invest 89: 1161–1165
Honeyman MC, Cram DS, Harrison LC (1993) Transcription factor jun-B is target of autoreactive T-cells in IDDM. Diabetes 42: 626–630
Hou J, Said C, Franchi D, Dockstader P, Chatterjee NK (1994) Antibodies to glutamic acid decarboxylase and P2-C peptides in sera from coxsackie virus B4-infected mice and IDDM patients. Diabetes 43: 1260–1266
Hussain MJ, Peakman M, Gallati H, Lo SS, Hawa M, Viberti GC, Watkins PJ, Leslie RD, Vergani D (1996) Elevated serum levels of macrophage-derived cytokines precede and accompany the onset of IDDM. Diabetologia 39: 60–69
Hyoty H, Hiltunen M, Knip M, et al., (1995) A prospective study of the role of coxsackie B and other enterovirus infections in the pathogenesis of IDDM. Childhood Diabetes in Finland ( DiMe) Study Group. Diabetes 44: 652–657
Itoh N, Hanafusa T, Miyazaki A, et al., (1993) Mononuclear cell infiltration and its relation to the expression of major histocompatibility complex antigens and adhesion molecules in pancreas biopsy specimens from newly diagnosed insulin-dependent diabetes mellitus patients. J Clin Invest 92: 2313–2322
Johnson JH, Crider BP, McCorkle K, Alford M, Unger RH (1990) Inhibition of glucose transport into rat islet cells by immunoglobulins from patients with new-onset insulin-dependent diabetes mellitus. N Engl J Med 322: 653–659
Karjalainen J (1990) Islet cell antibodies as predictive markers for IDDM in children with high background incidence of disease. Diabetes 39: M44–50
Karjalainen J, Martin JM, Knip M, Ilonen J, Robinson BH, Savilahti E, Akerblom HK, Dosch HM (1992) A bovine albumin peptide as a possible trigger of insulin-dependent diabetes mellitus. N Engl J Med 327: 302–307
Karvonen M, Tuomilehto J, Libman I, LaPorte R (1993) A review of the recent epidemiological data on the worldwide incidence of type 1 (insulin-dependent) diabetes mellitus. Diabetologia 36: 883–892
Keilacker H, Rjasanowski I, Besch W, Kohnert KD (1995) Auto-antibodies to insulin and to proinsulin in types diabetic patients and in at-risk probands differentiate only little between both antigens. Horm Metab Res 27: 90–94
Kuglin B, Rjasanowski I, Bertrams J, Gries FA, Kolb H, Michaelis D (1990) Antibodies to proinsulin and insulin as predictive markers of type I diabetes. Diabet Med 7: 310–314
Kulmala P, Savola K, Petersen JS, Vahasalo P, Karjalainen J, Lopponen T, Dyrberg T, Akerblom HK, Knip M (1998) Prediction of insulin-dependent diabetes mellitus in siblings of children with diabetes–a population-based study. J Clin Invest l01: 327–336
Kumar D, Gemayel NS, Deapen D, Kapadia D, Yamashita PH, Lee M, Dwyer JH, Roy-Burman P, Bray GA, Mack TM (1993) North-American twins with IDDM. Genetic, etiological, and clinical significance of disease concordance according to age, zygosity, and the interval after diagnosis in first twin. Diabetes 42: 1351–1363
Lan MS, Lu J, Goto Y, Notkins AL (1994) Molecular cloning and identification of a receptor-type protein tyrosine phosphatase, IA-2; from human insulinoma. DNA Cell Biol 13: 505–514
Mandrup-Poulsen T, Helqvist S, Wogensen LD, et al., (1990) Cytokine and free radicals as effector molecules in the destruction of pancreatic beta cells. Curr Top Microbiol Immunol 164: 169–193
Menser MA, Forrest JM, Bransby RD (1978) Rubella infection and diabetes mellitus. Lancet 1: 57–60
Moelbak AG, Christau B, Marner B, Borch-Johnsen K, Nerup J (1998) Incidence of insulin-dependent diabetes mellitus in age groups over 3o years in Denmark. Diabet Med II: 650–655
Nepom GT (1990) A unified hypothesis for the complex genetics of HLA associations with IDDM. Diabetes 39: 1153–1157
Ohashi PS, Oehen S, Buerki K, Pircher H, Ohashi CT, Odermatt B, Malissen B, Zinkernagel RM, Hengartner H (1991) Ablation of „tolerance“ and induction of diabetes by virus infection in viral antigen transgenic mice. Cell 65: 305–317
Oldstone MB, Nerenberg M, Southern P, Price J, Lewicki H (1991) Virus infection triggers insulin-dependent diabetes mellitus in a transgenic model: role of anti-self (virus) immune response. Cell 65: 319–331
Olmos P, A’Hern R, Heaton DA, Millward BA, Risley D, Pyke DA, Leslie RD (1988) The significance of the concordance rate for type 1 (insulin-dependent) diabetes in identical twins. Diabetologia 31: 747–750
Ongagna JC, Levy-Marchal C (1995) Anti-37kDa antibodies are associated with the development of IDDM in individuals with islet cell antibodies. Diabetologia 38: 370–375
Palmer JP (1987) Insulin autoantibodies: their role in the pathogenesis of IDDM. Diabetes Metab Rev 3: 1005–1015
Palmer JP, Asplin CM, Clemons P, Lyen K, Tatpati O, Raghu PK, Paquette TL (1983) Insulin antibodies in insulin-dependent diabetics before insulin treatment. Science 222: 1337–1339
Panina-Bordignon P, Lang R, van-Endert PM, et al., (1995) Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes. J Exp Med 181: 1923–1927
Pastore MR, Bazzigaluppi E, Bonfanti R, Dozio N, Sergi A, Balini A, Belloni C, Meschi F, Bonifacio E, Bosi E (1998) Two-step islet autoantibody screening for risk assessment of type 1 diabetes in relatives. Diabetes Care 21: 1445–1450
Pietropaolo M, Castano L, Babu S, et al., (1993) Islet cell auto-antigen 69 kD (ICA69). Molecular cloning and characterization of a novel diabetes-associated autoantigen. J Clin Invest 92: 359–371
Pociot F, Molvig J, Wogensen L, Worsaae H, Nerup J (1992) A TaqI polymorphism in the human interleukin-i beta (IL-1 beta) gene correlates with IL-1 beta secretion in vitro. Eur J Clin Invest 22: 396–402
Pociot F, Ronningen KS, Bergholdt R, Lorenzen T, Johannesen J, Ye K, Dinarello CA, Nerup J (1994) Genetic susceptibility markers in Danish patients with type]. (insulin-dependent) diabetes - evidence for polygenicity in man. Danish Study Group of Diabetes in Childhood. Autoimmunity 19: 169–178
Rabin DU, Pleasic SM, Shapiro JA, Yoo-Warren H, Oles J, Hicks JM, Goldstein DE, Rae PM (1994) Islet cell antigen 512 is a diabetes-specific islet autoantigen related to protein tyrosine phosphatases. J Immunol 152: 3183–3188
Richter W, Eiermann TH, Endl J, Seissler J, Wolfahrt S, Brandt M, Jungfer H, Scherbaum WA (1993) Human monoclonal islet specific autoantibodies share features of islet cell and 64kDa antibodies. Diabetologia 36: 785–790
Roep BO, Arden SD, de-Vries RR, Hutton JC (1990) T-cell clones from a type-i-diabetes patient respond to insulin secretory granule proteins. Nature 345: 632–634
Saukkonen T, Savilahti E, Vaarala O, Virtala ET, Tuomilehto J, Akerblom HK (1994) Children with newly diagnosed IDDM have increased levels of antibodies to bovine serum albumin but not to ovalbumin. Childhood Diabetes in Finland Study Group. Diabetes Care 17: 970–976
Schloot NC, Roep BO, Wegmann DR, Yu L, Wang TB, Eisenbarth GS (1997) T-cell reactivity to GAD65 peptide sequences shared with coxsackie virus protein in recent-onset IDDM, post-onset IDDM patients and control subjects. Diabetologia 40: 332–338
Segall M (1988) HLA and genetics of IDDM. Holism vs. reductionism? Diabetes 37: 1005–1008
Sibley RK, Sutherland DE, Goetz F, Michael AF (1985) Recurrent diabetes mellitus in the pancreas iso-and allograft. A light and electron microscopic and immunohistochemical analysis of four cases. Lab Invest 53: 132–144
Song YH, Li Y, Maclaren NK (1996) The nature of autoantigens targeted in autoimmune endocrine diseases. Immunol. Today 17: 232–238
Szopa T, Titchener P, Portwood N, Tayler K (1998) Diabetes mellitus due to viruses: Some recent developments. Diabetologia 36: 687–695
The Diabetes Control and Complications Trial Research Group (1998) Effect of intensive therapy on residual β-cell function in patients with type 1 diabetes in the diabetes control and complications trial. Ann Intern Med 128: 517–523
Tian J, Lehmann PV, Kaufman DL (1994) T cell cross-reactivity between coxsackie virus and glutamate decarboxylase is associated with a murine diabetes susceptibility allele. J Exp Med 180: 1979–1984
Tiberti C, Dotta F, Anastasi E, Torresi P, Multari G, Vecci E, Andreani D, Di-Mario U (1995) Anti-ganglioside antibodies in new onset types diabetic patients and high risk subjects. Autoimmunity 22: 43–48
Tun RY, Peakman M, Alviggi L, Hussain MJ, Lo SS, Shattock M, Pyke DA, Bottazzo GF, Vergani D, Leslie RD (1994) Importance of persistent cellular and humoral immune changes before diabetes develops: prospective study of identical twins. BMJ 308: 1063–1068
Turner R, Stratton I, Horton V, Manley S, Zimmet P, Mackay IR, Shattock M, Bottazzo GF, Holman R (1997) UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid de-carboxylase for prediction of insulin requirement in type 2 diabetes. Lancet 350: 1288–1293
Vardi P, Ziegler AG, Mathews JH, et al., (1988) Concentration of insulin autoantibodies at onset of type I diabetes. Inverse log-linear correlation with age. Diabetes Care 11: 736–739
Velloso LA, Kampe O, Hallberg A, Christmanson L, Betsholtz C, Karlsson FA (1993) Demonstration of GAD-65 as the main immunogenic isoform of glutamate decarboxylase in type 1 diabetes and determination of autoantibodies using a radioligand produced by eukaryotic expression. J Clin Invest 91: 2084–2090
Verge CF, Howard NJ, Irwig L, Simpson JM, Mackerras D, Silink M (1994) Environmental factors in childhood IDDM. A population-based, case-control study. Diabetes Care 17: 1381–1389
Virtanen SM, Saukkonen T, Savilahti E, Ylonen K, Rasanen L, Aro A, Knip M, Tuomilehto J, Akerblom HK (1994) Diet, cow’s milk protein antibodies and the risk of IDDM in Finnish children. Childhood Diabetes in Finland Study Group. Diabetologia 37: 381–387
Vreugdenhil GR, Geluk A, Ottenhoff THM, Melchers WJG, Roep BO, Galama JMD (1998) Molecular mimicry in diabetes mellitus: the homologous domain in coxsackie B virus protein 2C and islet autoantigen GAD(65) is highly conserved in the coxsackie B-like enteroviruses and binds to the diabetes associated HLA-DR3 molecule. Diabetologia 41: 40–46
Yoon JW (1995) A new look at viruses in types diabetes. Diabetes Metab Rev 11: 83–107
Yoon JW, Austin M, Onodera T, Notkins AL (1979) Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N Engl J Med 300: 1173–1179
Yu L, Gianani R, Eisenbarth GS (1994) Quantitation of glutamic acid decarboxylase autoantibody levels in prospectively evaluated relatives of patients with type I diabetes. Diabetes 43: 1229–1233
Zimmet PZ, Elliott RB, Mackay IR, Tuomi T, Rowley MJ, Pilcher CC, Knowles WI (1994) Autoantibodies to glutamic acid decarboxylase and insulin in islet cell antibody positive presymptomatic type I diabetes mellitus: frequency and segregation by age and gender. Diabet Med 11: 866–871
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer-Verlag Berlin Heidelberg
About this chapter
Cite this chapter
Spinas, G.A. (2001). Pathogenese des Diabetes mellitus Typ1. In: Böhm, B.O., Palitzsch, KD., Rosak, C., Spinas, G.A. (eds) Klinische Diabetologie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59539-4_2
Download citation
DOI: https://doi.org/10.1007/978-3-642-59539-4_2
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-64016-2
Online ISBN: 978-3-642-59539-4
eBook Packages: Springer Book Archive