1. Committee E. 1997. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 20: 1183-1197

2. Tattersall R.B., Fajans S.S. 1975. A difference between the inheritance of classical juvenile-onset and maturity-onset type diabetes of young people. Diabetes 24: p44-53

3. Dussoix P., Vaxillaire M., Iynedjian P.B., Tiercy J.M., Ruiz J., Spinas G.A., Berger W., Zahnd G., Froguel P., Philippe J. 1997. Diagnostic heterogeneity of diabetes in lean young adults: classification based on immunological and genetic parameters. Diabetes 46: p622-631

4. Yamagata K., Furuta H., Oda N., Kaisaki P.J., Menzel S., Cox N.J., Fajans S.S., Signorini S., Stoffel M., Bell G.I. 1996. Mutations in the hepatocyte nuclear factor-4alpha gene in maturity-onset diabetes of the young (MODY1). Nature 384: p458-460

5. Froguel P., Zouali H., Vionnet N., Velho G., Vaxillaire M., Sun F., Lesage S., Stoffel M., Takeda J., Passa P., et al. 1993. Familial hyperglycemia due to mutations in glucokinase. Definition of a subtype of diabetes mellitus. N Engl J Med 328: p697-702

6. Hansen T., Eiberg H., Rouard M., Vaxillaire M., Moller A.M., Rasmussen S.K., Fridberg M., Urhammer S.A., Holst J.J., Almind K., Echwald S.M., Hansen L., Bell G.I., Pedersen O. 1997. Novel MODY3 mutations in the hepatocyte nuclear factor-1alpha gene: evidence for a hyperexcitability of pancreatic beta-cells to intravenous secretagogues in a glucose-tolerant carrier of a P447L mutation. Diabetes 46: p726-730

7. Peters A.L., Davidson M.B., Schriger D.L., Hasselblad V. 1996. A clinical approach for the diagnosis of diabetes mellitus: an analysis using glycosylated hemoglobin levels. Meta-analysis Research Group on the Diagnosis of Diabetes Using Glycated Hemoglobin Levels. Jama 276: p1246-1252

8. Stoffers D.A., Ferrer J., Clarke W.L., Habener J.F. 1997. Early-onset type-II diabetes mellitus (MODY4) linked to IPF1. Nat Genet 17: p138-139

9. Winter W.E., Maclaren N.K., Riley W.J., Clarke D.W., Kappy M.S., Spillar R.P. 1987. Maturity-onset diabetes of youth in black Americans. N Engl J Med 316: p285-291

10. Winter W.E., Obata M., Muir A., Maclaren N.K. 1991. Heritable origins of type 1 (insulin-dependent) diabetes mellitus: Immunogenetic update. Growth, Genetics and Hormones 7: 1-6

11. Johns D.R. 1995. Seminars in medicine of the Beth Israel Hospital, Boston. Mitochondrial DNA and disease. N Engl J Med 333: p638-644

12. Robbins D.C., Shoelson S.E., Rubenstein A.H., Tager H.S. 1984. Familial hyperproinsulinemia. Two cohorts secreting indistinguishable type II intermediates of proinsulin conversion. J Clin Invest 73: p714-719

13. Tager H., Given B., Baldwin D., Mako M., Markese J., Rubenstein A., Olefsky J., Kobayashi M., Kolterman O., Poucher R. 1979. A structurally abnormal insulin causing human diabetes. Nature 281: p122-125

14. Boyle P.J. 1993. Cushing's disease, glucocorticoid excess, glucocorticoid deficiency and diabetes. Diabetes Reviews 1: 301

15. Ganda O.P., Simonson D.C. 1993. Growth hormone, acromegaly and diabetes. Diabetes Review 1: 286

16. Wass J.A., Cudworth A.G., Bottazzo G.F., Woodrow J.C., Besser G.M. 1980. An assessment of glucose intolerance in acromegaly and its response to medical treatment. Clin Endocrinol (Oxf 12: p53-59

17. Cryer P.E. 1993. Catecholamines, pheochromocytomas and diabetes. Diabetes Reviews 1: 309

18. Stenstrom G., Sjostrom L., Smith U. 1984. Diabetes mellitus in phaeochromocytoma. Fasting blood glucose levels before and after surgery in 60 patients with phaeochromocytoma. Acta Endocrinol (Copenh 106: p511-515

19. Boden G., Ruiz J., Chen X. 1993. Glucagonoma syndrome, glucagon and glucose tolerance. Diabetes Reviews 1: 352

20. Reasner C.A. 1993. Autoimmune thyroid disease and type 1 diabetes. Diabetes Reviews 1: 343

21. Anderson O.O., Friis T., Ottesen B. 1977. Glucose tolerance and insulin secretion in hyperthyroidism. Acta Endocrinol 84: 576

22. Bressler P., DeFronzo R.A. 1994. Drugs and diabetes. Diabetes Reviews 2: 53

23. Houston M.C. 1988. The effects of antihypertensive drugs on glucose intolerance in hypertensive nondiabetics and diabetics. Am Heart J 115: p640-656

24. Carr A., Samaras K., Burton S., Law M., Freund J., Chisholm D.J., Cooper D.A. 1998. A syndrome of peripheral lipodystrophy, hyperlipidaemia and insulin resistance in patients receiving HIV protease inhibitors. Aids 12: pF51-58

25. Eastone J.A., Decker C.F. 1997. New-onset diabetes mellitus associated with use of protease inhibitor. Ann Intern Med 127: p948

26. Visnegarwala F., Krause K.L., Musher D.M. 1997. Severe diabetes associated with protease inhibitor therapy. Ann Intern Med 127: p947

27. Johnson C., Ahsan N., Gonwa T., Halloran P., Stegall M., Hardy M., Metzger R., Shield C., Rocher L., Scandling J., Sorensen J., Mulloy L., Light J., Corwin C., Danovitch G., Wachs M., van Veldhuisen P., Salm K., Tolzman D., Fitzsimmons W.E. 2000. Randomized trial of tacrolimus (Prograf) in combination with azathioprine or mycophenolate mofetil versus cyclosporine (Neoral) with mycophenolate mofetil after cadaveric kidney transplantation. Transplantation 69: p834-841

28. First M.R., Gerber D.A., Hariharan S., Kaufman D.B., Shapiro R. 2002. Posttransplant diabetes mellitus in kidney allograft recipients: incidence, risk factors, and management. Transplantation 73: p379-386

29. Reaven G. 1988. Role of insulin receptor in human disease. Diabetes 37: 1595

30. De Fronzo R.A., Ferrannini E. 1991. Insulin resistance. A multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. Diabetes Care 14: p173-194

31. Jarrett R.J. 1994. Why is insulin not a risk factor for coronary heart disease? Diabetologia 37: p945-947

32. Helfgott S.M. 1999. Stiff-man syndrome: from the bedside to the bench. Arthritis Rheum 42: p1312-1320

33. Taylor S.I. 1992. Lilly Lecture: molecular mechanisms of insulin resistance. Lessons from patients with mutations in the insulin-receptor gene. Diabetes 41: p1473-1490

34. Kukreja A., Maclaren N.K. 1999. The autoimmunity of immune mediated diabetes. J Clin Endocrinol Metab 84: 4371-4378

35. Ganda O.P., Srikanta S., Brink S.J., Morris M.A., Gleason R.E., Soeldner J.S., Eisenbarth G.S. 1984. Differential sensitivity to beta-cell secretagogues in "early," type I diabetes mellitus. Diabetes 33: 516-521

36. Cantor A.B., Krischer J.P., Cuthbertson D.D., Schatz D.A., Riley W.J., Malone J., Schwartz S., Quattrin T., Maclaren N.K. 1995. Age and family relationship accentuate the risk of insulin-dependent diabetes mellitus (IDDM) in relatives of patients with IDDM. J Clin Endocrinol Metab 80: 3739-3743

37. Rewers M., Norris J.M., Eisenbarth G.S., Erlich H.A., Beaty B., Klingensmith G., Hoffman M., Yu L., Bugawan T.L., Blair A., Hamman R.F., Groshek M., McDuffie R.S., Jr. 1996. Beta-cell autoantibodies in infants and toddlers without IDDM relatives: diabetes autoimmunity study in the young (DAISY). J Autoimmun 9: 405-410

38. Maclaren N., Lan M., Coutant R., Schatz D., Silverstein J., Muir A., Clare-Salzer M., She J.X., Malone J., Crockett S., Schwartz S., Quattrin T., De Silva M., Vander Vegt P., Notkins A., Krischer J. 1999. Only multiple autoantibodies to islet cells (ICA), insulin, GAD65, IA-2 and IA-2beta predict immune-mediated (Type 1) diabetes in relatives. J Autoimmun 12: 279-287

39. Randle P.J., Kerbey A.L., Espinal J. 1988. Mechanisms decreasing glucose oxidation in diabetes and starvation: role of lipid fuels and hormones. Diabetes Metab Rev 4: 623-638

40. Exton J.H. 1987. Mechanisms of hormonal regulation of hepatic glucose metabolism. Diabetes Metab Rev 3: 163-183

41. El-Maghrabi M.R., Claus T.H., McGrane M.M., Pilkis S.J. 1982. Influence of phosphorylation on the interaction of effectors with rat liver pyruvate kinase. J Biol Chem 257: 233-240

42. Pilkis S.J., Granner D.K. 1992. Molecular physiology of the regulation of hepatic gluconeogenesis and glycolysis. Annu Rev Physiol 54: 885-909

43. Unger R., Foster DW. 1990. Diabetes mellitus. In Williams Textbook of Endocrinology. F. D. Wilson JD, ed. Saunders, Philadelphia, p. 1255.

44. Gerich J.E., Lorenzi M., Bier D.M., Schneider V., Tsalikian E., Karam J.H., Forsham P.H. 1975. Prevention of human diabetic ketoacidosis by somatostatin. Evidence for an essential role of glucagon. N Engl J Med 292: 985-989

45. Gerich J.E., Langlois M., Noacco C., Karam J.H., Forsham P.H. 1973. Lack of glucagon response to hypoglycemia in diabetes: evidence for an intrinsic pancreatic alpha cell defect. Science 182: 171-173

46. Raskin P., Unger R.H. 1978. Hyperglucagonemia and its suppression. Importance in the metabolic control of diabetes. N Engl J Med 299: 433-436

47. Kimball S.R., Jefferson L.S. 1988. Cellular mechanisms involved in the action of insulin on protein synthesis. Diabetes Metab Rev 4: 773-787

48. Kimball S.R., Jefferson L.S. 1991. Regulation of initiation of protein synthesis by insulin in skeletal muscle. Acta Diabetol 28: 134-139

49. Cahill G.F., Jr. 1976. Starvation in man. Clin Endocrinol Metab 5: 397-415

50. Foster D.W., McGarry J.D. 1983. The metabolic derangements and treatment of diabetic ketoacidosis. N Engl J Med 309: 159-169

51. McGarry J.D. 1979. Lilly Lecture 1978. New perspectives in the regulation of ketogenesis. Diabetes 28: 517-523

52. McGarry J.D. 1992. What if Minkowski had been ageusic? An alternative angle on diabetes. Science 258: 766-770

53. Owen O.E., Morgan A.P., Kemp H.G., Sullivan J.M., Herrera M.G., Cahill G.F., Jr. 1967. Brain metabolism during fasting. J Clin Invest 46: 1589-1595

54. Owen O.E., Felig P., Morgan A.P., Wahren J., Cahill G.F., Jr. 1969. Liver and kidney metabolism during prolonged starvation. J Clin Invest 48: 574-583

55. Ashby P., Robinson D.S. 1980. Effects of insulin, glucocorticoids and adrenaline on the activity of rat adipose-tissue lipoprotein lipids. Biochem J 188: 185-192

56. Parkin S.M., Walker K., Ashby P., Robinson D.S. 1980. Effects of glucose and insulin on the activation of lipoprotin lipase and on protein-synthesis in rat adipose tissue. Biochem J 188: 193-199

57. Tavangar K., Murata Y., Pedersen M.E., Goers J.F., Hoffman A.R., Kraemer F.B. 1992. Regulation of lipoprotein lipase in the diabetic rat. J Clin Invest 90: 1672-1678

58. Todd J.A. 1997. Genetics of type 1 diabetes. Pathol Biol (Paris) 45: 219-227

59. She J.X. 1996. Susceptibility to type I diabetes: HLA-DQ and DR revisited. Immunol Today 17: 323-329

60. Noble J.A., Cavalli A.S., Erlich H.A. 1996. DPB1*5901a: a novel HLA-DPB1 allele from a Caucasian family with insulin-dependent diabetes mellitus. Tissue Antigens 47: 159-162

61. Pugliese A., Zeller M., Fernandez A., Jr., Zalcberg L.J., Bartlett R.J., Ricordi C., Pietropaolo M., Eisenbarth G.S., Bennett S.T., Patel D.D. 1997. The insulin gene is transcribed in the human thymus and transcription levels correlated with allelic variation at the INS VNTR-IDDM2 susceptibility locus for type 1 diabetes. Nat Genet 15: 293-297

62. Vafiadis P., Bennett S.T., Todd J.A., Nadeau J., Grabs R., Goodyer C.G., Wickramasinghe S., Colle E., Polychronakos C. 1997. Insulin expression in human thymus is modulated by INS VNTR alleles at the IDDM2 locus. Nat Genet 15: 289-292

63. Garchon H.J., Luan J.J., Eloy L., Bedossa P., Bach J.F. 1994. Genetic analysis of immune dysfunction in non-obese diabetic (NOD) mice: mapping of a susceptibility locus close to the Bcl-2 gene correlates with increased resistance of NOD T cells to apoptosis induction. Eur J Immunol 24: 380-384

64. Wicker L.S., Chen S.L., Nepom G.T., Elliott J.F., Freed D.C., Bansal A., Zheng S., Herman A., Lernmark A., Zaller D.M., Peterson L.B., Rothbard J.B., Cummings R., Whiteley P.J. 1996. Naturally processed T cell epitopes from human glutamic acid decarboxylase identified using mice transgenic for the type 1 diabetes-associated human MHC class II allele, DRB1*0401. J Clin Invest 98: 2597-2603

65. Bottazzo G.F., Florin-Christensen A., Doniach D. 1974. Islet-cell antibodies in diabetes mellitus with autoimmune polyendocrine deficiencies. Lancet 2: 1279-1283

66. Neufeld M., Maclaren N., Blizzard R. 1980. Autoimmune polyglandular syndromes. Pediatr Ann 9: 154-162

67. Huang W., Connor E., Rosa T.D., Muir A., Schatz D., Silverstein J., Crockett S., She J.X., Maclaren N.K. 1996. Although DR3-DQB1*0201 may be associated with multiple component diseases of the autoimmune polyglandular syndromes, the human leukocyte antigen DR4-DQB1*0302 haplotype is implicated only in beta-cell autoimmunity. J Clin Endocrinol Metab 81: 2559-2563

68. Maclaren N., Huang S., Fogh J. 1975. Antibody to cultured human insulinoma cells in insulin-dependent diabetes. Lancet 1: 997-1000

69. Neufeld M., Maclaren N.K., Riley W.J., Lezotte D., McLaughlin J.V., Silverstein J., Rosenbloom A.L. 1980. Islet cell and other organ-specific antibodies in U.S. Caucasians and Blacks with insulin-dependent diabetes mellitus. Diabetes 29: 589-592

70. Palmer J.P., Asplin C.M., Clemons P., Lyen K., Tatpati O., Raghu P.K., Paquette T.L. 1983. Insulin antibodies in insulin-dependent diabetics before insulin treatment. Science 222: 1337-1339

71. Atkinson M.A., Maclaren N.K., Riley W.J., Winter W.E., Fisk D.D., Spillar R.P. 1986. Are insulin autoantibodies markers for insulin-dependent diabetes mellitus? Diabetes 35: 894-898

72. Solimena M., Folli, F, Denis-Donini, S., Comi, G.C., Pozza, G., De Camilli, P., Vicari, A. M. 1988. Autoantibodies to glutamic acid decarboxylase in a patient with stiff-man syndrome, epilepsy, and type 1 diabetes mellitus. N Engl J Med 318: 1012-1020

73. Baekkeskov S., Aanstoot H.J., Christgau S., Reetz A., Solimena M., Cascalho M., Folli F., Richter-Olesen H., De Camilli P., Camilli P.D. 1990. Identification of the 64K autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic acid decarboxylase [published erratum appears in Nature 1990 Oct 25; 347(6295):782]. Nature 347: 151-156

74. Atkinson M.A., Kaufman D.L., Newman D., Tobin A.J., Maclaren N.K. 1993. Islet cell cytoplasmic autoantibody reactivity to glutamate decarboxylase in insulin-dependent diabetes. J Clin Invest 91: 350-356

75. Christie M.R., Genovese S., Cassidy D., Bosi E., Brown T.J., Lai M., Bonifacio E., Bottazzo G.F. 1994. Antibodies to islet 37k antigen, but not to glutamate decarboxylase, discriminate rapid progression to IDDM in endocrine autoimmunity. Diabetes 43: 1254-1259

76. Lu J., Li Q., Xie H., Chen Z.J., Borovitskaya A.E., Maclaren N.K., Notkins A.L., Lan M.S. 1996. Identification of a second transmembrane protein tyrosine phosphatase, IA-2beta, as an autoantigen in insulin-dependent diabetes mellitus: precursor of the 37-kDa tryptic fragment. Proc Natl Acad Sci U S A 93: 2307-2311

77. Solimena M., Dirkx R., Jr., Hermel J.M., Pleasic-Williams S., Shapiro J.A., Caron L., Rabin D.U. 1996. ICA 512, an autoantigen of type I diabetes, is an intrinsic membrane protein of neurosecretory granules. EMBO J 15: 2102-2114

78. Lan M.S., Wasserfall C., Maclaren N.K., Notkins A.L. 1996. IA-2, a transmembrane protein of the protein tyrosine phosphatase family, is a major autoantigen in insulin-dependent diabetes mellitus. Proc Natl Acad Sci U S A 93: 6367-6370

79. Notkins A.L., Lu J., Li Q., Vander Vegt F.P., Wasserfall C., Maclaren N.K., Lan M.S. 1996. IA-2 and IA-2 beta are major autoantigens in IDDM and the precursors of the 40 kDa and 37 kDa tryptic fragments. J Autoimmun 9: 677-682

80. Lan M.S., Maclaren N.K. 1998. Cryptic epitope and autoimmunity. Diabetes Metab Rev 14: 333-334

81. Aanstoot H.J., Kang S.M., Kim J., Lindsay L.A., Roll U., Knip M., Atkinson M., Mose-Larsen P., Fey S., Ludvigsson J., et al. 1996. Identification and characterization of glima 38, a glycosylated islet cell membrane antigen, which together with GAD65 and IA2 marks the early phases of autoimmune response in type 1 diabetes. J Clin Invest 97: 2772-2783

82. Bonifacio E., Bingley P.J., Shattock M., Dean B.M., Dunger D., Gale E.A., Bottazzo G.F. 1990. Quantification of islet-cell antibodies and prediction of insulin-dependent diabetes. Lancet 335: 147-149

83. Riley W.J., Atkinson M.A., Schatz D.A., Maclaren N.K. 1990. Comparison of islet autoantibodies in 'pre-diabetes' and recommendations for screening. J Autoimmun 1: 47-51

84. Schatz D., Maclaren N. 1995. The natural history of pre-type 1 diabetes. Current Science 2: 31-37

85. Krischer J.P., Schatz D., Riley W.J., Spillar R.P., Silverstein J.H., Schwartz S., Malone J., Shah S., Vadheim C.M., Rotter J.I., et al. 1993. Insulin and islet cell autoantibodies as time-dependent covariates in the development of insulin-dependent diabetes: a prospective study in relatives. J Clin Endocrinol Metab 77: 743-749

86. Irvine W.J., McCallum C.J., Gray R.S., Campbell C.J., Duncan L.J., Farquhar J.W., Vaughan H., Morris P.J. 1977. Pancreatic islet-cell antibodies in diabetes mellitus correlated with the duration and type of diabetes, coexistent autoimmune disease, and HLA type. Diabetes 26: 138-147

87. Riley W.J., Maclaren N.K., Krischer J., Spillar R.P., Silverstein J.H., Schatz D.A., Schwartz S., Malone J., Shah S., Vadheim C., et al. 1990. A prospective study of the development of diabetes in relatives of patients with insulin-dependent diabetes. N Engl J Med 323: 1167-1172

88. Kumar V., Sercarz E. 1998. Induction or protection from experimental autoimmune encephalomyelitis depends on the cytokine secretion profile of TCR peptide-specific regulatory CD4 T cells. J Immunol 161: 6585-6591

89. Riley W.J., Maclaren N.K., Neufeld M. 1980. Adrenal autoantibodies and Addison disease in insulin-dependent diabetes mellitus. J Pediatr 97: 191-195

90. Riley W.J., Toskes P.P., Maclaren N.K., Silverstein J.H. 1982. Predictive value of gastric parietal cell autoantibodies as a marker for gastric and hematologic abnormalities associated with insulin-dependent diabetes. Diabetes 31: 1051-1055

91. Irvine W.J., Clarke B.F., Scarth L., Cullen D.R., Duncan L.J. 1970. Thyroid and gastric autoimmunity in patients with diabetes mellitus. Lancet 2: 163-168

92. Rapoport M.J., Bistritzer T., Vardi O., Broide E., Azizi A., Vardi P. 1996. Increased prevalence of diabetes-related autoantibodies in celiac disease. J Pediatr Gastroenterol Nutr 23: 524-527

93. Song Y.H., Connor E., Li Y., Zorovich B., Balducci P., Maclaren N. 1994. The role of tyrosinase in autoimmune vitiligo. Lancet 344: 1049-1052

94. Atkinson M.A., Bowman M.A., Campbell L., Darrow B.L., Kaufman D.L., Maclaren N.K. 1994. Cellular immunity to a determinant common to glutamate decarboxylase and coxsackie virus in insulin-dependent diabetes. J Clin Invest 94: 2125-2129

95. Ellis T.M., Schatz D.A., Ottendorfer E.W., Lan M.S., Wasserfall C., Salisbury P.J., She J.X., Notkins A.L., Maclaren N.K., Atkinson M.A. 1998. The relationship between humoral and cellular immunity to IA-2 in IDDM. Diabetes 47: 566-569

96. Bach J.F., Chatenoud L. 1995. Immunosuppression in insulin-dependent diabetes mellitus: from cellular selectivity towards autoantigen specificity. Chem Immunol 60: 32-47

97. Atkinson M.A., Kaufman D.L., Campbell L., Gibbs K.A., Shah S.C., Bu D.F., Erlander M.G., Tobin A.J., Maclaren N.K. 1992. Response of peripheral-blood mononuclear cells to glutamate decarboxylase in insulin-dependent diabetes. Lancet 339: 458-459

98. Harrison L.C., Honeyman M.C., De Aizpurua H.J., Schmidli R.S., Colman P.G., Tait B.D., Cram D.S. 1993. Inverse relation between humoral and cellular immunity to glutamic acid decarboxylase in subjects at risk of insulin-dependent diabetes. Lancet 341: 1365-1369

99. Gelber C., Paborsky L., Singer S., McAteer D., Tisch R., Jolicoeur C., Buelow R., McDevitt H., Fathman C.G. 1994. Isolation of nonobese diabetic mouse T-cells that recognize novel autoantigens involved in the early events of diabetes. Diabetes 43: 33-39

100. Kaufman D.L., Clare-Salzler M., Tian J., Forsthuber T., Ting G.S., Robinson P., Atkinson M.A., Sercarz E.E., Tobin A.J., Lehmann P.V. 1993. Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes. Nature 366: 69-72

101. Tisch R., Yang X.D., Singer S.M., Liblau R.S., Fugger L., McDevitt H.O. 1993. Immune response to glutamic acid decarboxylase correlates with insulitis in non-obese diabetic mice. Nature 366: 72-75

102. Semana G., Gausling R., Jackson R.A., and , Hafler D.A. 1999. T cell autoreactivity to proinsulin epitopes in diabetic patients and healthy subjects. J Autoimmun 12: 259-267

103. Alleva D.G., Crowe P.D., Jin L., Kwok W.W., Ling N., Gottschalk M., Conlon P.J., Gottlieb P.A., Putnam A.L., and, Gaur A. 2001. A disease-associated cellular immune response in type 1 diabetes to an immunodominant epitope of insulin. J Clin Invest 107: 173-180

104. Roep B.O., Atkinson M.A., van Endert P.M., Gottlieb P.A., Wilson S.B., Sachs J.A. 1999. Autoreactive T cell responses in insulin-dependent (Type 1) diabetes mellitus. Report of the first international workshop for standardization of T cell assays. J Autoimmun 13: 267-282

105. Endl J., Otto H., Jung G., Dreisbusch B., Donie F., Stahl P., Elbracht R., Schmitz G., Meinl E., Hummel M., Ziegler A.G., Wank R., Schendel D.J. 1997. Identification of naturally processed T cell epitopes from glutamic acid decarboxylase presented in the context of HLA-DR alleles by T lymphocytes of recent onset IDDM patients. J Clin Invest 99: 2405-2415

106. Honeyman M.C., Stone N., de Aizpurua H., Rowley M.J., Harrison L.C. 1997. High T cell responses to the glutamic acid decarboxylase (GAD) isoform 67 reflect a hyperimmune state that precedes the onset of insulin-dependent diabetes. J Autoimmun 10: 165-173

107. Lohmann T., Leslie R.D., Hawa M., Geysen M., Rodda S., Londei M. 1994. Immunodominant epitopes of glutamic acid decarboxylase 65 and 67 in insulin-dependent diabetes mellitus. Lancet 343: 1607-1608

108. Lohmann T., Leslie R.D., Londei M. 1996. T cell clones to epitopes of glutamic acid decarboxylase 65 raised from normal subjects and patients with insulin-dependent diabetes. J Autoimmun 9: 385-389

109. Panina-Bordignon P., Lang R., van Endert P.M., Benazzi E., Felix A.M., Pastore R.M., Spinas G.A., Sinigaglia F. 1995. Cytotoxic T cells specific for glutamic acid decarboxylase in autoimmune diabetes. J Exp Med 181: 1923-1927

110. Weiss U., Manfras B.J., Terjung D., Eiermann T., Wolpl A., Loliger C., Kuhnl P., Boehm B.O. 1995. In vitro stimulation with glutamic acid decarboxylase (GAD65) leads to an oligoclonal response of peripheral T-cells in an IDDM patient. Scand J Immunol 42: 673-678

111. Karvonen M., Tuomilehto J., Libman I., La Porte R. 1993. A review of the recent epidemiological data on the worldwide incidence of type 1 (insulin-dependent) diabetes mellitus. World Health Organization DIAMOND Project Group [published erratum appears in Diabetologia 1994 Jun; 38(6):642]. Diabetologia 36: 883-892

112. Maclaren N.K., Atkinson M.A. 1997. Insulin-dependent diabetes mellitus: the hypothesis of molecular mimicry between islet cell antigens and microorganisms. Mol Med Today 3: 76-83

113. See D.M., Tilles J.G. 1998. The pathogenesis of viral-induced diabetes. Clin Diagn Virol 9: p85-88

114. Vreugdenhil G.R., Geluk A., Ottenhoff T.H., Melchers W.J., Roep B.O., Galama J.M. 1998. Molecular mimicry in diabetes mellitus: the homologous domain in coxsackie B virus protein 2C and islet autoantigen GAD65 is highly conserved in the coxsackie B-like enteroviruses and binds to the diabetes associated HLA-DR3 molecule. Diabetologia 41: 40-46

115. Srinivasappa J., Saegusa J., Prabhakar B.S., Gentry M.K., Buchmeier M.J., Wiktor T.J., Koprowski H., Oldstone M.B., Notkins A.L. 1986. Molecular mimicry: frequency of reactivity of monoclonal antiviral antibodies with normal tissues. J Virol 57: 397-401

116. Yoon J.W., Ray U.R. 1985. Perspectives on the role of viruses in insulin-dependent diabetes. Diabetes Care 1: 39-44

117. Jenson A.B., Rosenberg H.S., Notkins A.L. 1980. Pancreatic islet-cell damage in children with fatal viral infections. Lancet 2: 354-358

118. Yoon J.W., Austin M., Onodera T., Notkins A.L. 1979. Isolation of a virus from the pancreas of a child with diabetic ketoacidosis. N Engl J Med 300: 1173-1179

119. Prince G.A., Jenson A.B., Billups L.C., Notkins A.L. 1978. Infection of human pancreatic beta cell cultures with mumps virus. Nature 271: 158-161

120. Yoon J.W., Selvaggio S., Onodera T., Wheeler J., Jenson A.B. 1981. Infection of cultured human pancreatic B cells with reovirus type 3. Diabetologia 20: 462-467

121. Parkkonen P., Hyoty H., Koskinen L., Leinikki P. 1992. Mumps virus infects beta cells in human fetal islet cell cultures upregulating the expression of HLA class I molecules. Diabetologia 35: p63-69

122. Yoon J.W., Onodera T., Jenson A.B., Notkins A.L. 1978. Virus-induced diabetes mellitus. XI. Replication of coxsackie B3 virus in human pancreatic beta cell cultures. Diabetes 27: 778-781

123. Yoon J.W., Onodera T., Notkins A.L. 1978. Virus-induced diabetes mellitus. XV. Beta cell damage and insulin-dependent hyperglycemia in mice infected with coxsackie virus B4. J Exp Med 148: 1068-1080

124. Campbell I.L., Harrison L.C., Ashcroft R.G., Jack I. 1988. Reovirus infection enhances expression of class I MHC proteins on human beta-cell and rat RINm5F cell. Diabetes 37: p362-365

125. Pak C.Y., Eun H.M., McArthur R.G., Yoon J.W. 1988. Association of cytomegalovirus infection with autoimmune type 1 diabetes. Lancet 2: 1-4

126. Kaufman D.L., Erlander M.G., Clare-Salzler M., Atkinson M.A., Maclaren N.K., Tobin A.J. 1992. Autoimmunity to two forms of glutamate decarboxylase in insulin-dependent diabetes mellitus. J Clin Invest 89: 283-292

127. Ellis T.M., Atkinson M.A. 1996. The clinical significance of an autoimmune response against glutamic acid decarboxylase. Nat Med 2: p148-153

128. Tian J., Lehmann P.V., Kaufman D.L. 1994. T cell cross-reactivity between coxsackievirus and glutamate decarboxylase is associated with a murine diabetes susceptibility allele. J Exp Med 180: p1979-1984

129. Szopa T.M., Titchener P.A., Portwood N.D., Taylor K.W. 1993. Diabetes mellitus due to viruses--some recent developments. Diabetologia 36: p687-695

130. Schloot N.C., Roep B.O., Wegmann D.R., Yu L., Wang T.B., Eisenbarth G.S. 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: p332-338

131. Honeyman M.C., Stone N.L., Harrison L.C. 1998. T-cell epitopes in type 1 diabetes autoantigen tyrosine phosphatase IA-2: potential for mimicry with rotavirus and other environmental agents. Mol Med 4: 231-239

132. Sutkowski N., Palkama T., Ciurli C., Sekaly R.P., Thorley-Lawson D.A., Huber B.T. 1996. An Epstein-Barr virus-associated superantigen. J Exp Med 184: 971-980

133. White J., Herman A., Pullen A.M., Kubo R., Kappler J.W., Marrack P. 1989. The V beta-specific superantigen staphylococcal enterotoxin B: stimulation of mature T cells and clonal deletion in neonatal mice. Cell 56: p27-35

134. Serreze D.V., Leiter E.H., Kuff E.L., Jardieu P., Ishizaka K. 1988. Molecular mimicry between insulin and retroviral antigen p73. Development of cross-reactive autoantibodies in sera of NOD and C57BL/KsJ db/db mice. Diabetes 37: p351-358

135. Hao W., Serreze D.V., McCulloch D.K., Neifing J.L., Palmer J.P. 1993. Insulin (auto)antibodies from human IDDM cross-react with retroviral antigen p73. J Autoimmun 6: p787-798

136. Conrad B., Weissmahr R.N., Boni J., Arcari R., Schupbach J., Mach B. 1997. A human endogenous retroviral superantigen as candidate autoimmune gene in type I diabetes. Cell 90: 303-313

137. Conrad B., Weidmann E., Trucco G., Rudert W.A., Behboo R., Ricordi C., Rodriquez-Rilo H., Finegold D., Trucco M. 1994. Evidence for superantigen involvement in insulin-dependent diabetes mellitus aetiology. Nature 371: 351-355

138. Lan M.S., Mason A., Coutant R., Chen Q.Y., Vargas A., Rao J., Gomez R., Chalew S., Garry R., Maclaren N.K. 1998. HERV-K10s and immune-mediated (type 1) diabetes. Cell 95: 14-16; discussion 16

139. Lehmann P.V., Sercarz E.E., Forsthuber T., Dayan C.M., Gammon G. 1993. Determinant spreading and the dynamics of the autoimmune T-cell repertoire. Immunol Today 14: p203-208

140. Kaufman D.L., Clare-Salzler M., Tian J., Forsthuber T., Ting G.S., Robinson P., Atkinson M.A., Sercarz E.E., Tobin A.J., Lehmann P.V. 1993. Spontaneous loss of T-cell tolerance to glutamic acid decarboxylase in murine insulin-dependent diabetes. Nature 366: 69-72

141. Naserke H.E., Ziegler A.G., Lampasona V., Bonifacio E. 1998. Early development and spreading of autoantibodies to epitopes of IA-2 and their association with progression to type 1 diabetes. J Immunol 161: p6963-6969

142. Wilbanks G.A., Streilein J.W. 1990. Characterization of suppressor cells in anterior chamber-associated immune deviation (ACAID) induced by soluble antigen. Evidence of two functionally and phenotypically distinct T-suppressor cell populations. Immunology 71: p383-389

143. Ke Y., Kapp J.A. 1996. Oral antigen inhibits priming of CD8+ CTL, CD4+ T cells, and antibody responses while activating CD8+ suppressor T cells. J Immunol 156: p916-921

144. Zhang Z.X., Yang L., Young K.J., Du Temple B., Zhang L. 2000. Identification of a previously unknown antigen-specific regulatory T cell and its mechanism of suppression. Nat Med 6: p782-789

145. Wilson S.B., Kent S.C., Patton K.T., Orban T., Jackson R.A., Exley M., Porcelli S., Schatz D.A., Atkinson M.A., Balk S.P., Strominger J.L., Hafler D.A. 1998. Correction: Extreme Th1 bias of invariant Valpha24JalphaQ T cells in type 1 diabetes. Nature 391: 177-181

146. Kukreja A., Costi G., Marker J., Zhang C., Sun Z., Lin-Su K., Ten S., Sanz M., Exley M., Wilson B., Porcelli S., Maclaren N. 2002. Multiple immuno-regulatory defects in type-1 diabetes. J Clin Invest 109: 131-140

147. Baxter A.G., Kinder S.J., Hammond K.J., Scollay R., Godfrey D.I. 1997. Association between alphabetaTCR+CD4-CD8- T-cell deficiency and IDDM in NOD/Lt mice. Diabetes 46: 572-582

148. Hammond K, Poulton L., Palmisano L., Silveira P., Godfrey D., Baxter G. 1998. [alpha]/[beta]-T Cell Receptor (TCR)+CD4CD8 (NKT) Thymocytes Prevent Insulin-dependent Diabetes Mellitus in Nonobese Diabetic (NOD)/Lt

Mice by the Influence of Interleukin (IL)-4 and/or IL-10. J Exp Med 187: 1047-1056

149. Salomon B., Lenschow D.J., Rhee L., Ashourian N., Singh B., Sharpe A., Bluestone J.A. 2000. B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 12: 431-440

150. Bodansky H.J., Staines A., Stephenson C., Haigh D.a., Cartwright R. 1992. Evidence for an environmental effect in the aetiology of insulin dependent diabetes in a transmigratory population. Br Med J 304: 1020-1022

151. Bach J.F. 1994. Insulin-dependent diabetes mellitus as an autoimmune disease. Endocr Rev 15: 516-542

152. Wilberz S., Partke H.J., Dagnaes-Hansen F.a., Herberg L. 1991. Persistent MHV (mouse hepatitis virus) infection reduces the incidence of diabetes mellitus in non-obese diabetic mice. Diabetologia 34: 2-5

153. Takei I., Asaba Y., Kasatani T., Maruyama T., Watanabe K., Yanagawa T., Saruta T.a., Ishii T. 1992. Suppression of development of diabetes in NOD mice by lactate dehydrogenase virus infection. J Autoimmun 5: 665-673

154. Martins T.C.a., Aguas A.P. 1999. Mechanisms of Mycobacterium avium-induced resistance against insulin-dependent diabetes mellitus (IDDM) in non-obese diabetic (NOD) mice: role of Fas and Th1 cells. Clin Exp Immunol 115: 248-254

155. Oldstone M.B. 1990. Viruses as therapeutic agents. I. Treatment of nonobese insulin-dependent diabetes mice with virus prevents insulin-dependent diabetes mellitus while maintaining general immune competence. J Exp Med 171: 2077-2089

156. Cooke A., Tonks P., Jones F., O'Shea H., Hutchings P., Fulford A., Dunne D. 1999. Infection with Schistosoma mansoni prevents insulin dependent diabetes mellitus in mpm-obese diabetic mice. parasite Immunol 21: 169-176

157. Akerblom H.K., Knip M. 1998. Putative environmental factors in Type 1 diabetes. Diabetes Metab Rev 14: p31-67

158. Atkinson M.A.a., Eisenbarth G.S. 2001. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet 358: 221-229

159. Dahl-Jorgensen K., Joner G., Hanssen K.F. 1991. Relationship between cows' milk consumption and incidence of IDDM in childhood. Diabetes Care 14: p1081-1083

160. Scott F.W. 1990. Cow milk and insulin-dependent diabetes mellitus: is there a relationship? Am J Clin Nutr 51: p489-491

161. Patterson C.C., Dahlquist G., Soltesz G., Green A. 2001. Is childhood-onset type I diabetes a wealth-related disease? An ecological analysis of European incidence rates. Diabetologia 44: B9-16

162. Fava D., Leslie R.D., Pozzilli P. 1994. Relationship between dairy product consumption and incidence of IDDM in childhood in Italy. Diabetes Care 17: p1488-1490

163. Norris J.M., Beaty B., Klingensmith G., Yu L., Hoffman M., Chase H.P., Erlich H.A., Hamman R.F., Eisenbarth G.S., Rewers M. 1996. Lack of association between early exposure to cow's milk protein and beta-cell autoimmunity. Diabetes Autoimmunity Study in the Young (DAISY). Jama 276: p609-614

164. Organization W.H. 1978. Nitrates, nitrites and N-nitroso compounds. In Environmental Health Criteria 5. WHO, Geneva.

165. Kostraba J.N., Gay E.C., Rewers M., Hamman R.F. 1992. Nitrate levels in community drinking waters and risk of IDDM. An ecological analysis. Diabetes Care 15: p1505-1508

166. Virtanen S.M., Jaakkola L., Rasanen L., Ylonen K., Aro A., Lounamaa R., Akerblom H.K., Tuomilehto J. 1994. Nitrate and nitrite intake and the risk for type 1 diabetes in Finnish children. Childhood Diabetes in Finland Study Group. Diabet Med 11: p656-662

167. Like A.A., Rossini A.A. 1976. Streptozotocin-induced pancreatic insulitis: new model of diabetes mellitus. Science 193: p415-417

168. Myers M.A. 1999.Environmental factors and type 1 diabetes-is the secretory granule the target? Elsevier Science B.V., Amsterdam.

169. Group T.D.C.a.C.T.R. 1993. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 329: 977-986

170. Group D.C.a.C.T.D.E.o.D.I.a.C.E.R. 2001. Beneficial effects of intensive therapy of diabetes during adolescence: Outcomes after the conclusion of the Diabetes Control and Complication Trail (DCCT). J Pediatr 139: 804-812

171. 1988. Cyclosporin-induced remission of IDDM after early intervention. Association of 1 yr of cyclosporin treatment with enhanced insulin secretion. The Canadian-European Randomized Control Trial Group. Diabetes 37: 1574-1582

172. Stiller C.R., Dupre J., Gent M., Jenner M.R., Keown P.A., Laupacis A., Martell R., Rodger N.W., von Graffenried B., Wolfe B.M. 1984. Effects of cyclosporine immunosuppression in insulin-dependent diabetes mellitus of recent onset. Science 223: 1362-1367

173. Feutren G., Papoz L., Assan R., Vialettes B., Karsenty G., Vexiau P., Du Rostu H., Rodier M., Sirmai J., Lallemand A., et al. 1986. Cyclosporin increases the rate and length of remissions in insulin-dependent diabetes of recent onset. Results of a multicentre double-blind trial. Lancet 2: 119-124

174. Silverstein J., Maclaren N., Riley W., Spillar R., Radjenovic D., Johnson S. 1988. Immunosuppression with azathioprine and prednisone in recent-onset insulin-dependent diabetes mellitus. N Engl J Med 319: 599-604

175. De Filippo G., Carel J.C., Boitard C., Bougneres P.F. 1996. Long-term results of early cyclosporin therapy in juvenile IDDM. Diabetes 45: 101-104

176. Carel J.C., Boitard C., Eisenbarth G., Bach J.F., Bougneres P.F. 1996. Cyclosporine delays but does not prevent clinical onset in glucose intolerant pre-type 1 diabetic children. J Autoimmun 9: 739-745

177. Lampeter E.F., Klinghammer A., Scherbaum W.A., Heinze E., Haastert B., Giani G., Kolb H. 1998. The Deutsche Nicotinamide Intervention Study: an attempt to prevent type 1 diabetes. DENIS Group. Diabetes 47: 980-984

178. Atkinson M.A., Maclaren N.K. 1990. What causes diabetes? Sci Am 263: 62-63, 66-71

179. Shah S.C., Malone J.I., Simpson N.E. 1989. A randomized trial of intensive insulin therapy in newly diagnosed insulin-dependent diabetes mellitus. N Engl J Med 320: 550-554

180. Keller R.J., Eisenbarth G.S., Jackson R.A. 1993. Insulin prophylaxis in individuals at high risk of type I diabetes. Lancet 341: 927-928

181. Diabetes Prevetion Trial-Type 1 Diabetes Study Group. 2002. Effects of Insulin in Relatives of Patients with Type 1 Diabetes Mellitus. Diabetes Prevention Trial-Type 1 Diabetes Study Group. New Engl J Med. 346:1685-1691.

182. Zhang Z.J., Davidson L., Eisenbarth G., Weiner H.L. 1991. Suppression of diabetes in nonobese diabetic mice by oral administration of porcine insulin. Proc Natl Acad Sci U S A 88: 10252-10256

183. Ramiya V.K., Shang X.Z., Wasserfall C.H., Maclaren N.K. 1997. Effect of oral and intravenous insulin and glutamic acid decarboxylase in NOD mice. Autoimmunity 26: 139-151

184. Coutant R., Zeidler A., Rappaport R., Schatz D., Schwartz S., Malone J., Raskin P., Rogers D., Bode B., Crockett S., Marks J., Deeb L., ,, Chalew S., Maclaren N. 1998. Oral insulin therapy in newly diagnosed immune mediated (type 1) diabetes. Preliminary Analysis of a randomized double blind placebo controlled study. In ADA, New Oleans, LA.

185. Muir A., Peck A., Clare-Salzler M., Song Y.H., Cornelius J., Luchetta R., Krischer J., Maclaren N. 1995. Insulin immunization of nonobese diabetic mice induces a protective insulitis characterized by diminished intraislet interferon-gamma transcription. J Clin Invest 95: 628-634

186. Ramiya V.K., Shang X.Z., Pharis P.G., Wasserfall C.H., Stabler T.V., Muir A.B., Schatz D.A., Maclaren N.K. 1996. Antigen based therapies to prevent diabetes in NOD mice. J Autoimmun 9: 349-356

187. Lin-Su K., Kukreja A., Maclaren N.K. 2001. Diabetes Vaccines: A Future to Be Realized. Diabetes Technology & Therapeutics 3: 451-431

188. Daniel D., Wegmann D.R. 1996. Protection of nonobese diabetic mice from diabetes by intranasal or subcutaneous administration of insulin peptide B-(9-23). Proc Natl Acad Sci U S A 93: 956-960

189. Wong F.S., Karttunen J., Dumont C., Wen L., Visintin I., Pilip I.M., Shastri N., Pamer E.G., Janeway C.A., Jr. 1999. Identification of an MHC class I-restricted autoantigen in type 1 diabetes by screening an organ-specific cDNA library. Nat Med 5: 1026-1031

190. Ramiya V.K., Lan M.S., Wasserfall C.H., Notkins A.L., Maclaren N.K. 1997. Immunization therapies in the prevention of diabetes. J Autoimmun 10: 287-292

191. Herold K.C., Hagopian W., Auger J.A., Poumian-Ruiz E., Taylor L., Donaldson D., Gitelman S.E., Harlan D.M., Xu D., Zivin R.A., Bluestone J.A. 2002. Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus. N Engl J Med 346: p1692-1698

192. Sutherland D.E., Gruessner R.W., Gruessner A.C. 2001. Pancreas transplantation for treatment of diabetes mellitus. World J Surg 25: p487-496

193. Website of the Clinical Islet Transplant Program, Alberta U.o. www.med.ualberta.ca/islet/hist.html.

194. Shapiro A.M., Lakey J.R. 2000. Future trends in islet cell transplantation. Diabetes Technol Ther 2: p449-452

195. Ryan E.A., Lakey J.R., Rajotte R.V., Korbutt G.S., Kin T., Imes S., Rabinovitch A., Elliott J.F., Bigam D., Kneteman N.M., Warnock G.L., Larsen I., Shapiro A.M. 2001. Clinical outcomes and insulin secretion after islet transplantation with the Edmonton protocol. Diabetes 50: p710-719

196. Berney T., Ricordi C. 2000. Islet cell transplantation: the future? Langenbecks Arch Surg 385: p373-378

197. Groth C.G., Tibell A., Wennberg L., Korsgren O. 1999. Xenoislet transplantation: experimental and clinical aspects. J Mol Med 77: p153-154

198. Ramiya V.K., Maraist M., Arfors K.E., Schatz D.A., Peck A.B., Cornelius J.G. 2000. Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells. Nat Med 6: p278-282

199. Bonner-Weir S., Taneja M., Weir G.C., Tatarkiewicz K., Song K.H., Sharma A., O'Neil J.J. 2000. In vitro cultivation of human islets from expanded ductal tissue. Proc Natl Acad Sci U S A 97: p7999-8004

200. Apelqvist A., Li H., Sommer L., Beatus P., Anderson D.J., Honjo T., Hrabe de Angelis M., Lendahl U., Edlund H. 1999. Notch signalling controls pancreatic cell differentiation. Nature 400: p877-881

201. Soria B., Roche E., Berna G., Leon-Quinto T., Reig J.A., Martin F. 2000. Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice. Diabetes 49: p157-162

202. Newgard C.B. 2001. Lessons learned from bioengineered beta-cell. J Diabetes Complications 15: 11

203. Papas K.K., Long R.C., Sambanis A., Constantinidis I. 1999. Development of a bioartificial pancreas: II. Effects of oxygen on long-term entrapped betaTC3 cell cultures. Biotechnol Bioeng 66: p231-237

204. Lee H.C., Kim S.J., Kim K.S., Shin H.C., Yoon J.W. 2000. Remission in models of type 1 diabetes by gene therapy using a single-chain insulin analogue. Nature 408: p483-488

205. Cheung A.T., Dayanandan B., Lewis J.T., Korbutt G.S., Rajotte R.V., Bryer-Ash M., Boylan M.O., Wolfe M.M., Kieffer T.J. 2000. Glucose-dependent insulin release from genetically engineered K cells. Science 290: p1959-1962

206. Reaven G.M. 1993. Role of insulin resistance in human disease (syndrome X): an expanded definition. Annu Rev Med 44: 121-131

207. Kahn C.R., Flier J.S., Bar R.S., Archer J.A., Gorden P., Martin M.M., Roth J. 1976. The syndromes of insulin resistance and acanthosis nigricans. Insulin-receptor disorders in man. N Engl J Med 294: p739-745

208. Oral E.A., Simha V., Ruiz E., Andewelt A., Premkumar A., Snell P., Wagner A.J., De Paoli A.M., Reitman M.L., Taylor S.I., Gorden P., Garg A. 2002. Leptin-replacement therapy for lipodystrophy. N Engl J Med 346: p570-578

209. Galloway P.J., Donaldson M.D., Wallace A.M. 2001. Sex hormone binding globulin concentration as a prepubertal marker for hyperinsulinaemia in obesity. Arch Dis Child 85: p489-491

210. Karnieli E., Cohen P., Barzilai N., Ish-Shalom Z., Armoni M., Rafaelov R., Barzilai D. 1985. Insulin resistance in Cushing's syndrome. Horm Metab Res 17: p518-521

211. Rogers D.L. 1991. Acanthosis nigricans. Semin Dermatol 10: p160-163

212. Nerup J., Platz, P, Anderson OO, et al. 1974. HLA -anitgens and diabetes mellitus. Lancet II: 864-866

213. Pociot F. 1996. Insulin-dependent diabetes mellitus--a polygenic disorder? Dan Med Bull 43: 216-248

214. Bell G.I., Horita S., Karam J.H. 1984. A polymorphic locus near the human insulin gene is associated with insulin-dependent diabetes mellitus. Diabetes 33: 176-183

215. Julier C., Hyer R.N., Davies J., Merlin F., Soularue P., Briant L., Cathelineau G., Deschamps I., Rotter J.I., Froguel P., et al. 1991. Insulin-IGF2 region on chromosome 11p encodes a gene implicated in HLA-DR4-dependent diabetes susceptibility. Nature 354: 155-159

216. Field L.L., Tobias R., Magnus T. 1994. A locus on chromosome 15q26 (IDDM3) produces susceptibility to insulin-dependent diabetes mellitus. Nat Genet 8: 189-194

217. Davies J.L., Kawaguchi Y., Bennett S.T., Copeman J.B., Cordell H.J., Pritchard L.E., Reed P.W., Gough S.C., Jenkins S.C., Palmer S.M., et al. 1994. A genome-wide search for human type 1 diabetes susceptibility genes. Nature 371: 130-136

218. Hashimoto L., Habita C., Beressi J.P., Delepine M., Besse C., Cambon-Thomsen A., Deschamps I., Rotter J.I., Djoulah S., James M.R., et al. 1994. Genetic mapping of a susceptibility locus for insulin-dependent diabetes mellitus on chromosome 11q. Nature 371: p161-164

219. Delepine M., Pociot F., Habita C., Hashimoto L., Froguel P., Rotter J., Cambon-Thomsen A., Deschamps I., Djoulah S., Weissenbach J., Nerup J., Lathrop M., Julier C. 1997. Evidence of a non-MHC susceptibility locus in type I diabetes linked to HLA on chromosome 6. Am J Hum Genet 60: 174-187

220. Merriman T., Twells R., Merriman M., Eaves I., Cox R., Cucca F., McKinney P., Shield J., Baum D., Bosi E., Pozzilli P., Nistico L., Buzzetti R., Joner G., Ronningen K., Thorsby E., Undlien D., Pociot F., Nerup J., Bain S., Barnett A., Todd J. 1997. Evidence by allelic association-dependent methods for a type 1 diabetes polygene (IDDM6) on chromosome 18q21. Hum Mol Genet 6: 1003-1010

221. Owerbach D., Gabbay K.H. 1995. The HOXD8 locus (2q31) is linked to type I diabetes. Interaction with chromosome 6 and 11 disease susceptibility genes. Diabetes 44: p132-136

222. Mein C.A., Esposito L., Dunn M.G., Johnson G.C., Timms A.E., Goy J.V., Smith A.N., Sebag-Montefiore L., Merriman M.E., Wilson A.J., Pritchard L.E., Cucca F., Barnett A.H., Bain S.C., Todd J.A. 1998. A search for type 1 diabetes susceptibility genes in families from the United Kingdom. Nat Genet 19: 297-300

223. Reed P., Cucca F., Jenkins S., Merriman M., Wilson A., McKinney P., Bosi E., Joner G., Ronningen K., Thorsby E., Undlien D., Merriman T., Barnett A., Bain S., Todd J. 1997. Evidence for a type l diabetes susceptibility locus (IDDM10) on human chromosome 10p11-q11. Hum Mol Genet 6: 1011-1016

224. Field L.L., Tobias R., Thomson G., Plon S. 1996. Susceptibility to insulin-dependent diabetes mellitus maps to a locus (IDDM11) on human chromosome 14q24.3-q31. Genomics 33: 1-8

225. Copeman J.B., Cucca F., Hearne C.M., Cornall R.J., Reed P.W., Ronningen K.S., Undlien D.E., Nistico L., Buzzetti R., Tosi R., et al. 1995. Linkage disequilibrium mapping of a type 1 diabetes susceptibility gene (IDDM7) to chromosome 2q31-q33. Nat Genet 9: 80-85

226. Morahan G., Huang D., Tait B.D., Colman P.G., Harrison L.C. 1996. Markers on Distal Chromosome 2q Linked to Insulin-Dependent Diabetes Mellitus. Science 272: 1808-1810

227. Verge C.F., Vardi P., Babu S., Bao F., Erlich H.A., Bugawan T., Tiosano D., Yu L., Eisenbarth G.S., Fain P.R. 1998. Evidence for oligogenic inheritance of type 1 diabetes in a large Bedouin Arab family. J Clin Invest 102: 1569-1575

228. Delepine M., Nicolino M., Barrett T., Golamaully M., Lathrop G.M., Julier C. 2000. EIF2AK3, encoding translation initiation factor 2-alpha kinase 3, is mutated in patients with Wolcott-Rallison syndrome. Nat Genet 25: 406-409

229. Studies E.C.F.I.G. 2001. A genomewide scan for type 1-diabetes susceptibility in Scandinavian families:Identification of new loci with evidence of interactions. Am J Hum Genet 69: 1301-1313

230. Concannon P., Gogolin-Ewens K.J., Hinds D.A., Wapehorst B., Morrison V.A., Stirling B., Mitra M., Farmer J., Williams S.R., Cox N.J., Bell G.I., Risch N., Spielman R.S. 1998. A second-generation screen of the human genome for susceptibility to insulin-dependent diabetes mellitus. Nat Genet 19: 292-296

231. Cucca F., Goy J.V., Kawaguchi Y., Esposito L., Merriman M.E., Wilson A.J., Cordell H.J., Bain S.C., Todd J.A. 1998. A male-female bias in type 1 diabetes and linkage to chromosome Xp in MHC HLA-DR3-positive patients. Nat Genet 19: 301-302

232. Pontoglio M., Prie D., Cheret C., Doyen A., Leroy C., Froguel P., Velho., Yaniv M., Friedlander G. 2000. HNF-1a control renal glucose reabsorption in mouse and man. EMBO Rep 1:359-365.

233. Horikawa Y., Iwasaki N., Hara M., Furuta H., Hinokio Y., Cockburn BN., Lindner T., Yamagata K., Ogata M., Tomonaga O., Kuroki H., Kasahara T., Iwamoto Y., Bell GI. 1997. Mutation in hepatocyte nuclear factor-1b gene (TCF2) associated with MODY. Nature Genet 17:384-385.

234. Roll U, Christie MR, Fuchtenbusch M, Payton MA, Hawkes CJ, Ziegler AG. 1996. Perinatal autoimmunity in offspring of diabetic parents: The German multicenter BABY-DIAB study: detection of humarol immune responses to islet antigens in early childhood. Diabetes 45:967-973.

235. Hamalainen AM, Ronkainen MS, Akerblom HK, Knip M. 2000. Postnatal elimination of transplacentally acquired disease-associated antibodies in infants born to families with type 1 diabetes: The Finnish TRIGR Study Group: Trial to Reduce IDDM in the Genetically at Risk. J Clin Endocrinol Metab. 85:4249-4253.

236. Greeley SA, Katsumata M, Yu L, Eisenbarth GS, Moore DJ, Goodarzi H, Barker CF, Naji A, Noorchashm H. 2002. Elimination of maternally transmitted autoantibodies prevents diabetes in nonobese diabetic mice. Nat Me. 8:399-402.

237. Koczwara K, Bonifacio E, Ziegler AG. 2004. Transmission of Maternal Islet Antibodies and Risk of Autoimmune Diabetes in Offspring of Mothers with Type 1 Diabetes. Diabetes 53:1-4.

238. ENDIT Group. 2003. Intervening before the onset of type 1 diabetes: baseline data from the European Nicotinamide Diabetes Intervention Trial (ENDIT). Diabetologio. 46:339-346.

239. Chaillous L, Lefevre H, Thivolet C, Boitard C, Lahlou N, Atlan-Gepner C, Bouhanick B, Mogenet A, Nicolino M, Carel JC, Lecomte P, Marechaud R, Bougneres P, Charbonnel B, Sai P. 2000. Oral insulin administration and residual beta-cell function in recent onset type 1 diabetes: a multicenter randomized controlled trial. Diabete Insuline Orale Group. Lancet. 356:545-549.

240. Pozzilli P, Pitocco D, Visalli N, Cavallo MG, Buzzetti R, Crino A, Spera S, Suraci C, Multari G, Cervoni M, Manca Bitti ML, Matteoli MC, Marietti G, Ferrazzoli F, Cassone Faldetta MR, Giordano C, Sbriglia M, Sarugeri E, Ghirlanda G. 2000. No effect of oral insulin on residual beta-cell function in recent onset type 1 diabetes(the IMDIAB VII). Diabetologio. 43:1000-1004.

241. Ergun-Longmire B, Marker J, Zeidler A, Rapaport R, Raskin P, Bode B, Schatz D, Vargas A, Rogers D, Schwartz S, Malone J, Krischer J, Maclaren NK. 2004. Oral insulin therapy to prevent progression of immune-mediated (type 1) diabetes. Ann N Y Acad Sci. 1029:260-77.

242. Neu A., Willasch A., ehehalt S., Kehrer M., Hub R., ranke M.B. 2001. Diabetes incidence in children of different nationalities: an epidemiological approach to the pathogenesis of diabetes. Diabetologia. 44(suppl 3):B21-B26.

243. Hummel M, Bonifacio E, Schmid S, Walter M, Knopff A, Ziegler AG. 2004. Brief Communication: Early Appearance of Islet Autoantibodies Predict Childhood Type 1 Diabetes in Offspring of Diabetic Parents. Ann Intern Med 140:882-886.

244. Onkamo P, Väänänen M, Karvonen M, Tuomilehto J. 1999. Worrldwide increase in incidence of type 1 diabetes-the analysis of the data on published incidence trends. Diabetologia 42:1395-1403.

245. Maclaren NK, Lan MS, Schatz D, Malone J, Notkins AL, Krischer J. 2003. Multiple autoantibodies as predictors of Type 1 diabetes in a general population. Diabetologia. 46:873-4.

246. Samuelsson U, Sundkvist G, Borg H, Fernlund P, Ludvigsson J. 2001. Islet autoantibodies in the prediction of diabetes in school children. Diabetes Res Clin Pract. 51:51-7.

247. LaGasse JM, Brantley MS, Leech NJ, Rowe RE, Monks S, Palmer JP, Nepom GT, McCulloch DK, Hagopian WA; Washington State Diabetes Prediction Study. 2002. Successful prospective prediction of type 1 diabetes in schoolchildren through multiple defined autoantibodies: an 8-year follow-up of the Washington State Diabetes Prediction Study. Diabetes Care. 25:505-11.

248. Kimpimaki T, Kulmala P, Savola K, Kupila A, Korhonen S, Simell T, Ilonen J, Simell O, Knip M. 2002. Natural history of beta-cell autoimmunity in young children with increased genetic susceptibility to type 1 diabetes recruited from the general population. J Clin Endocrinol Metab. 87:4572-4579.

249. Tazawa Y, Noguchi H, Nishinomiya F, Takada G. 1997. Serum alanine aminotransferase activity in obese children. Acta Paediatr. 86:238-241.

250. Marchesini G, Brizi M, Bianchi G, Tomasetti S, Zoli M, Melchionda N. 2001. Metformin in non-alcoholic steatohepatitis. Lancet. 358:893-894.

251. Tominaga K, Kurata JH, Chen YK, Fujimoto E, Miyagawa S, Abe I, Kusano Y. 1995. Prevalence of fatty liver in Japanese children and relationship to obesity. An epidemiological ultrasonographic survey. Dig Dis Sci. 40:2002-2009.

252. Kawasaki T, Hashimoto N, Kikuchi T, Takahashi H, Uchiyama M. 1997. The relationship between fatty liver and hyperinsulinemia in obese Japanese children. J Pediatr Gastroenterol Nutr. 24:317-321.

253.Ten S and Maclaren N. 2004. Insulin Resistance Syndrome in Children. J Clin Endocrinol Metab 89:2526-2539.

254. Naya FJ, Huang HP, Qiu Y, Mutoh H, DeMayo FJ, Leiter AB, Tsai MJ. 1997. Diabetes, defective pancreatic morphogenesis, and abnormal enteroendocrinedifferentiation in BETA2/neuroD-deficient mice. Genes De. 11:2323-2334.