PMID- 10404800
OWN - NLM
STAT- MEDLINE
DCOM- 19990726
LR  - 20061115
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 84
IP  - 7
DP  - 1999 Jul
TI  - Predictive value of human leukocyte antigen class II typing for the development 
      of islet autoantibodies and insulin-dependent diabetes postpartum in women with 
      gestational diabetes.
PG  - 2342-8
AB  - 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 
      (Pc) = 0.02], in particular in those with GADA (Pc = 0.002), or in the 24 women 
      who developed IDDM postpartum (Pc = 0.005). In women with GADA, DR4 and DQB1*0302 
      were significantly elevated (Pc = 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.
FAU - Ferber, K M
AU  - Ferber KM
AD  - Ludwig Maximilians University, Third Medical Department, Krankenhaus 
      Munchen-Schwabing, and Diabetes Research Institute, Munich, Germany.
FAU - Keller, E
AU  - Keller E
FAU - Albert, E D
AU  - Albert ED
FAU - Ziegler, A G
AU  - Ziegler AG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Autoantibodies)
RN  - 0 (HLA-DR3 Antigen)
RN  - 0 (HLA-DR4 Antigen)
SB  - IM
MH  - Alleles
MH  - Autoantibodies/*blood
MH  - Diabetes Mellitus, Type 1/*immunology
MH  - Diabetes, Gestational/*immunology
MH  - Female
MH  - *Gene Frequency
MH  - *Genes, MHC Class II
MH  - Genotype
MH  - HLA-DR3 Antigen/genetics
MH  - HLA-DR4 Antigen/genetics
MH  - Histocompatibility Testing
MH  - Humans
MH  - Islets of Langerhans/*immunology
MH  - Postpartum Period
MH  - Pregnancy
MH  - Risk Factors
EDAT- 1999/07/15 00:00
MHDA- 1999/07/15 00:01
CRDT- 1999/07/15 00:00
PHST- 1999/07/15 00:00 [pubmed]
PHST- 1999/07/15 00:01 [medline]
PHST- 1999/07/15 00:00 [entrez]
AID - 10.1210/jcem.84.7.5813 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 1999 Jul;84(7):2342-8. doi: 10.1210/jcem.84.7.5813.