RGD Reference Report - High frequency of abnormal glucose tolerance in DQA1*0102/DQB1*0602 relatives identified as part of the Diabetes Prevention Trial--Type 1 Diabetes. - Rat Genome Database

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High frequency of abnormal glucose tolerance in DQA1*0102/DQB1*0602 relatives identified as part of the Diabetes Prevention Trial--Type 1 Diabetes.

Authors: Greenbaum, CJ  Eisenbarth, G  Atkinson, M  Yu, L  Babu, S  Schatz, D  Zeidler, A  Orban, T  Wasserfall, C  Cuthbertson, D  Krischer, J  Krischer, J 
Citation: Greenbaum CJ, etal., Diabetologia. 2005 Jan;48(1):68-74. Epub 2004 Dec 16.
RGD ID: 2301815
Pubmed: PMID:15602651   (View Abstract at PubMed)
DOI: DOI:10.1007/s00125-004-1608-z   (Journal Full-text)

AIMS/HYPOTHESIS: Immunological and genetic markers can be used to assess risk of developing type 1 diabetes prior to the onset of clinical symptoms. Autoantibody-positive relatives of patients with type 1 diabetes are at increased risk for disease, while the presence of HLA DQA1*0102/DQB1*0602 is thought to confer protection. Using the unique population identified by the Diabetes Prevention Trial--Type Diabetes (DPT-1), our aim was to determine if these individuals were protected from type 1 diabetes. METHODS: We described metabolic and immunological characteristics of islet cell cytoplasmic autoantibodies-positive relatives with DQB1*0602 identified as part of DPT-1. RESULTS: We found that 32% of DQB1*0602-positive relatives identified through the DPT-1 had abnormalities of glucose tolerance despite the fact that only 19% had multiple type 1 diabetes-associated autoantibodies and only 13% had abnormal insulin secretion, markers typically associated with the disease. In addition, these markers were not associated with abnormal glucose tolerance. In contrast, the DQB1*0602-positive relatives had elevated fasting insulin (117+/-10 pmol/l) and homeostasis model assessment of insulin resistance (HOMA-R) (4.90+/-0.5) values, which are more commonly associated with type 2 diabetes. The later marker of insulin resistance was associated with glucose tolerance status. CONCLUSIONS/INTERPRETATION: Our data indicate that DQA1*0102/DQB1*0602 relatives identified through DPT-1 have a high frequency of abnormal glucose tolerance and a disease phenotype with characteristics of type 1 and type 2 diabetes. Thus, multiple pathways to abnormal glucose tolerance are present within families of these type 1 patients.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
glucose intolerance susceptibilityISOHLA-DQA1 (Homo sapiens)2301815; 2301815associated with Diabetes MellitusRGD 
glucose intolerance susceptibilityIAGP 2301815associated with Diabetes MellitusRGD 

Objects Annotated

Genes (Rattus norvegicus)
RT1-Ba  (RT1 class II, locus Ba)

Genes (Mus musculus)
H2-Aa  (histocompatibility 2, class II antigen A, alpha)

Genes (Homo sapiens)
HLA-DQA1  (major histocompatibility complex, class II, DQ alpha 1)


Additional Information