Document Detail


North-American twins with IDDM. Genetic, etiological, and clinical significance of disease concordance according to age, zygosity, and the interval after diagnosis in first twin.
MedLine Citation:
PMID:  8349046     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In 224 twin pairs (132 monozygotic, 86 dizygotic, and 6 of uncertain zygosity) in whom the index twin had developed IDDM before 30 yr of age, 51 of the co-twins (38 monozygotic, 10 dizygotic, and 3 of uncertain zygosity) subsequently became diabetic. On the basis of concordance ratios, which were significantly discrepant (P < 0.01) between monozygotic and dizygotic twins, the substantial genetic role in IDDM etiology is confirmed. For the monozygotic co-twin of an IDDM case, the relative risk is significantly related to an early age at proband diagnosis (P < 0.01 for 0-4 vs. 5-9 yr of age). However, among monozygotic co-twins at any age, IDDM risk decreases as time passes after the proband diagnosis (P < 0.01 for 0-23 vs. > or = 24 mo after a proband diagnosis at 5-9 yr of age). Moreover, a structural-equation analysis suggests a profound contribution to liability (as much as 79%) from the twins' shared environment. Risk to like-sex male dizygotic co-twins is as high as that to monozygotic co-twins, significantly higher than that to like-sex female dizygotic co-twins (P < 0.005), and even higher than that to male co-twins in unlike-sex dizygotic pairs (P < 0.05). Overall, the risk to the dizygotic co-twin of a case is significantly higher (P < 0.001) than that to a non-twin sibling, as reported in the literature. The observed male excess is consistent with reported patterns of IDDM in experimental animals, and in certain circumstances in humans. Taken together, these observations suggest an important early acquired determinant of IDDM, independent of genetic determinants. On the basis of Kaplan-Meier IDDM-free survival curves, if the proband is diagnosed before 15 yr of age, the long-term risk to the co-twin is estimated at 44% (monozygotic) and 19% (dizygotic); it reaches 65% for the co-twin of a monozygotic proband diagnosed before 5 yr of age. An IDDM discordant period of no more than 3 yr was observed in 60% of the pairs destined to become concordant, offering a very brief window for intervention following the recognition of high risk.
Authors:
D Kumar; N S Gemayel; D Deapen; D Kapadia; P H Yamashita; M Lee; J H Dwyer; P Roy-Burman; G A Bray; T M Mack
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Diabetes     Volume:  42     ISSN:  0012-1797     ISO Abbreviation:  Diabetes     Publication Date:  1993 Sep 
Date Detail:
Created Date:  1993-09-16     Completed Date:  1993-09-16     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1351-63     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine, University of Southern California School of Medicine, Los Angeles 90033.
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MeSH Terms
Descriptor/Qualifier:
Age Factors
Canada / epidemiology
Diabetes Mellitus, Type 1 / diagnosis,  epidemiology,  genetics*
Diseases in Twins / diagnosis,  epidemiology,  genetics*
Female
Humans
Male
Risk Factors
Sex Factors
Time Factors
Twins, Dizygotic
Twins, Monozygotic
United States / epidemiology
Grant Support
ID/Acronym/Agency:
CA-42581/CA/NCI NIH HHS

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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