This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ferber, K. M. Articles by Ziegler, A.-G. Search for Related Content PubMed PubMed Citation Articles by Ferber, K. M. Articles by Ziegler, A.-G.

Predictive Value of Human Leukocyte Antigen Class II Typing for the Development of Islet Autoantibodies and Insulin-Dependent Diabetes Postpartum in Women with Gestational Diabetes¹

Laboratory for Immunogenetics, Ludwig Maximilians University (K.M.F., E.K., E.D.A.), and the Third Medical Department, Krankenhaus München-Schwabing, and Diabetes Research Institute (K.M.F., A.-G.Z.), 80804 Munich, Germany

Address all correspondence and requests for reprints to: Priv.-Doz. Dr. Anette-G. Ziegler, Krankenhaus München-Schwabing, Diabetes Research Institute, Kölner Platz 1, 80804 Munich, Germany. E-mail: anziegler{at}lrz.uni-muenchen.de

Gestational diabetes mellitus (GDM) is a risk factor for the development of insulin-dependent diabetes mellitus (IDDM) and noninsulin-dependent diabetes mellitus postpartum. To evaluate whether there is any association of human leukocyte antigen (HLA) class II alleles (DR and DQ) with GDM and the postpartum development of IDDM, we analyzed 184 women with GDM from Germany for HLA class II alleles, islet autoantibodies [islet cell autoantibodies (ICA), glutamic acid decarboxylase autoantibodies (GADA), and protein tyrosine phosphatase IA-2 autoantibodies (IA-2A), and the postpartum development of diabetes. No elevation in the frequency of any HLA class II alleles was observed in GDM patients compared to 254 nondiabetic unrelated subjects. DR3 allele frequency was significantly increased in 43 women with islet autoantibodies [corrected P value (P_c) = 0.02], in particular in those with GADA (P_c = 0.002), or in the 24 women who developed IDDM postpartum (P_c = 0.005). In women with GADA, DR4 and DQB1_*0302 were significantly elevated (P_c = 0.009). Twenty-five (59.5%) islet antibody-positive women and 17 (74%) women who developed IDDM postpartum had a DR3- or DR4-containing genotype. The cumulative risk to develop IDDM within 2 yr postpartum in GDM women with either DR3 or DR4 was 22% compared to 7% in women without those alleles (P = 0.02) and rose to 50% in the DR3- or DR4-positive women who had required insulin during pregnancy (P = 0.006). Combining the determination of susceptible HLA alleles (DR3, DR4) with islet autoantibody measurement increased the sensitivity of identifying GDM women developing postpartum IDDM to 92%, but did not improve risk assessment above that achieved using GADA measurement alone, which was the strongest predictor of IDDM. These results indicate that women with GDM who have islet autoantibodies at delivery or develop IDDM postpartum have HLA alleles typical of late-onset type 1 diabetes, and that both HLA typing and islet antibodies can predict the development of postpartum IDDM.

This article has been cited by other articles:

				K. Lobner, A. Knopff, A. Baumgarten, U. Mollenhauer, S. Marienfeld, M. Garrido-Franco, E. Bonifacio, and A.-G. Ziegler Predictors of Postpartum Diabetes in Women With Gestational Diabetes Mellitus Diabetes, March 1, 2006; 55(3): 792 - 797. [Abstract] [Full Text] [PDF]

				P. Narendran, E. Estella, and S. Fourlanos Immunology of type 1 diabetes QJM, August 1, 2005; 98(8): 547 - 556. [Full Text] [PDF]

				L. L. Moore, M. L. Bradlee, M. R. Singer, K. J. Rothman, and A. Milunsky Chromosomal Anomalies among the Offspring of Women with Gestational Diabetes Am. J. Epidemiol., April 15, 2002; 155(8): 719 - 724. [Abstract] [Full Text] [PDF]