Abstract
Diabetes mellitus positive for antibodies to glutamate decarboxylase is heterogeneous as far as the degree of impairment of endogenous insulin release, though antibodies to glutamate decarboxylase are the most useful marker for future insulin deficiency. To investigate what determines the prognosis of diabetes mellitus positive for antibodies to glutamate decarboxylase, we measured HLA-DRB1 alleles in three groups: 77 cases of insulin-dependent diabetes mellitus (IDDM), 44 of non-insulin-dependent diabetes mellitus (NIDDM) with secondary failure of oral hypoglycemic therapy, and 22 of NIDDM well controlled by diet and/or sulfonylurea agents. The proportion of susceptible and resistant alleles to IDDM determined the degree of insulin deficiency, and comparison of IDDM to NIDDM well controlled by diet and/or sulfonylurea agents revealed significant differences in DRB1*0405 (P < 0.05; RR = 2.82 and RR = 0.89, respectively) and DRB1*1502 (P < 0.001; RR = 0.02 and RR = 2.19, respectively). This study revealed that HLA-DRB1 alleles contribute to determining the prognosis of Japanese diabetes mellitus positive for antibodies to glutamate decarboxylase.
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REFERENCES
Castano L, Eisenbarth GS: Type-1 diabetes: A chronic autoimmune disease of human, mouse, and rat. Annu Rev Immunol 8:647–679, 1990
Atkinson MA, Maclaren NK: The pathogenesis of insulin-dependent diabetes mellitus. N Engl J Med 331:1428–1436, 1994
Nerup J, Mandrup-Poulsen T, Helqvist S, Andersen HU, Pociot F, Reimers JI, Cuartero BG, Karlsen AE, Bjerre U, Lorenzen T: On the pathogenesis of IDDM. Diabetologia 37(Suppl 2):S82–S89, 1994
Tuomilehto J, Zimmet P, Mackay IR, Koskela P, Vidgren G, Toivanen L, Tuomilehto-Wolf E, Kohtamaki K, Stengard J, Rowley MJ: Antibodies to glutamic acid decarboxylase as predictors of insulin-dependent diabetes mellitus before clinical onset of disease. Lancet 343:1383, 1994
Sabbah E, Kulmala P, Veijola R, Vahasalo P, Karjalainen J, Tuomilehto WE, Akerblom HK, Knip M: Glutamic acid decarboxylase antibodies in relation to other autoantibodies and genetic risk markers in children with newly diagnosed insulin-dependent diabetes. J Clin Endocrinol Metab 81:2455, 1996
Tuomi T, Groop LC, Zimmet PZ, Rowley MJ, Knowles W, Mackay IR: Antibodies to glutamic acid decarboxylase reveal latent autoimmune diabetes mellitus in adult with a non-insulindependent onset of disease. Diabetes 42:359–362, 1993
Zimmet PZ, Tuomi T, Mackay IR, Rowley MJ, Knowles W, Cohen M, Lang DA: Latent autoimmune diabetes mellitus in adult (LADA): The role of antibodies to glutamic acid decarboxylase in diagnosis and prediction of insulin dependency. Diabet Med 11:299–303, 1993
Fukui M, Nakano K, Shigeta H, Yoshimori K, Fujii M, Kitagawa Y, Mori H, Kajiyama S, Nakamura N, Abe N, Obayashi H, Fukui I, Ohta K, Ohta M, Kondo M: Antibodies to glutamic acid decarboxylase in Japanese diabetic patients with secondary failure of oral hypoglycaemic therapy. Diabet Med 14:148–152, 1997
National Diabetes Data Group: Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 28:1039–1057, 1979
Ohta M, Obayashi H, Takahashi K, Kitagawa Y, Nakano K, Matsuo S, Ohishi M, Itoh N, Hayashi K, Ohta K: A simple solid-phase radioimmunoassay for glutamic acid decarboxylase (GAD) antibodies in patients with diabetes mellitus. J Clin Biochem Nutr 20:139–148, 1996
Maruya E, Saji H, Yokoyama S: PCR-LIS-SSCP (low ionic strength single-stranded conformation polymorphism)—A simple method for high-resolution allele typing of HLA-DRB1,-DQB1, and-DPB1. Genome Res 6:51–57, 1996
Awata T, Kanazawa Y: Genetic markers for insulin-dependent diabetes mellitus in Japanese. Diabetes Res Clin Pract 24(Suppl):83–87, 1994
Gleichmann H, Zorcher B, Greulich B, Gries FA, Henrichs HR, Bertrams J, Kolb H: Correlation of islet cell antibodies and HLA-DR phenotypes with diabetes mellitus in adults. Diabetologia 27:90–92, 1984
Groop L, Miettinen A, Groop PH, Meri S, Koskimies S, Bottazzo GF: Organ-specific autoimmunity and HLA-DR antigens as markers of B-cell destruction in patients with type 2 diabetes. Diabetes 37:99–103, 1988
Wolf E, Spencer KM, Cudworth AG: The genetic susceptibility to Type 1 (insulin-dependent) diabetes: Analysis of the HLA-DR association. Diabetologia 24:224–230, 1983
Mario UD, Irvine WJ, Borsey DQ, Kyner JL, Weston J, Galfo C: Immune abnormalities in diabetic patients not requiring insulin at diagnosis. Diabetologia 25:392–395, 1983
Rowley MJ, Mackay IR, Chen Q, Knowles WJ, Zimmet PZ: Antibodies to glutamic acid decarboxylase discriminate major types of diabetes mellitus. Diabetes 41:548–551, 1992
Lernmark A: Immune intervention yes, but for what reason, for whom, when and how? Diabetologia 35:1096–1098, 1992
Elliott RB, Chase HP: Prevention or delay of Type 1 (insulin-dependent) diabetes mellitus in children using nicotinamide. Diabetologia 34:362–365, 1991
Keller RJ, Eisenbarth GS, Jackson RA: Insulin prophylaxis in individuals at high risk of Type 1 diabetes. Lancet 341:927–928, 1993
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Fukui, M., Nakano, K., Nakamura, N. et al. HLA-DRB1 Alleles Contribute to Determining the Prognosis of Japanese Diabetes Mellitus Positive for Antibodies to Glutamate Decarboxylase. J Clin Immunol 18, 89–92 (1998). https://doi.org/10.1023/A:1023248106674
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DOI: https://doi.org/10.1023/A:1023248106674