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Multicenter Study
. 1999 Mar 13;318(7185):698-702.
doi: 10.1136/bmj.318.7185.698.

Genetic determination of islet cell autoimmunity in monozygotic twin, dizygotic twin, and non-twin siblings of patients with type 1 diabetes: prospective twin study

M J Redondo  1 , M Rewers, L Yu, S Garg, C C Pilcher, R B Elliott, G S Eisenbarth
Affiliations
Multicenter Study

Genetic determination of islet cell autoimmunity in monozygotic twin, dizygotic twin, and non-twin siblings of patients with type 1 diabetes: prospective twin study

M J Redondo et al. BMJ. .

Abstract

Objective: To test the hypothesis that non-diabetic dizygotic and monozygotic twin siblings of patients with type 1 diabetes have a similar high prevalence of islet cell autoantibodies, thus suggesting that islet cell autoimmunity is mainly environmentally determined.

Design: Prospective twin study.

Setting: Two specialist centres for diabetes in the United States.

Participants: Non-diabetic monozygotic twin (n=53), dizygotic twin (n=30), and non-twin (n=149) siblings of patients with type 1 diabetes; 101 controls.

Main outcome measures: Analysis of progression to diabetes and expression of anti-islet autoantibodies.

Results: Monozygotic twin siblings had a higher risk of progression to diabetes (12/53) than dizygotic twin siblings (0/30; P<0.005). At the last follow up 22 (41.5%) monozygotic twin siblings expressed autoantibodies compared with 6 (20%) dizygotic twin siblings (P<0.05), 16 (10.7%) non-twin siblings (P<0.0001), and 6 (5.9%) controls (P<0.0001). Monozygotic twin siblings expressed multiple (>/=2) antibodies more often than dizygotic twin siblings (10/38 v 1/23; P<0.05). By life table analysis the probability of developing positive autoantibodies was higher among the monozygotic twin siblings bearing the diabetes associated HLA DQ8/DQ2 genotype than in those without this genotype (64.2% (95% confidence interval 32.5% to 96%) v 23.5% (7% to 40%) at 10 years of discordance; P<0.05).

Conclusion: Monozygotic and dizygotic twins differ in progression to diabetes and expression of islet cell autoantibodies. Dizygotic twin siblings are similar to non-twin siblings. These two observations suggest that genetic factors play an important part in determination of islet cell autoimmunity, thus rejecting the hypothesis. In addition, there is a high penetrance of islet cell autoimmunity in DQ8/DQ2 monozygotic twin siblings.

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Figures

Figure 1
Figure 1
Life table analysis of progression to diabetes of initially discordant dizygotic and monozygotic twins. Vertical lines indicate SE. Number of participants followed at each time interval given below figure. P<0.05 for difference
Figure 2
Figure 2
Dot plot of levels of autoantibodies in non-index monozygotic and dizygotic twins according to last serum samples before end of study or before progression to diabetes (if applicable). Y axis on left plots insulin concentration on log scale and on right plots GAD65 and ICA512 (index units) on log scale. Horizontal bars represent normal upper limit at 99th centile for each autoantibody. See table 2 for number of participants for whom each antibody was measured. Closed circles=monozygotic twins; open circles=dizygotic twins
Figure 3
Figure 3
Life table analysis of progression to positive autoantibodies in non-index monozygotic twins. Subjects with and without HLA DQ8/DQ2 compared. Years of discordance indicates time from onset of diabetes in index twin. P=0.02 for difference
See this image and copyright information in PMC

Comment in

References

    1. Verge CF, Gianani R, Yu L, Pietropaolo M, Smith T, Jackson RA, et al. Late progression to diabetes and evidence for chronic β cell autoimmunity in identical twins of patients with type I diabetes. Diabetes. 1995;44:1176–1179. - PubMed
    1. Dib S, Vardi P, Connelly J, Eisenbarth GS, Soeldner JS. Immune changes associated with insulin dependent diabetes may remit without causing the disease: a study in identical twins. BMJ. 1986;292:1670. - PMC - PubMed
    1. Srikanta S, Ganda OP, Eisenbarth GS, Soeldner JS. Islet cell antibodies and β cell function in monozygotic triplets and twins initially discordant for type I diabetes mellitus. N Engl J Med. 1983;308:322–325. - PubMed
    1. Srikanta S, Ganda OP, Jackson RA, Gleason RE, Kaldany A, Gorovoy MR, et al. Type I diabetes mellitus in monozygotic twins: chronic progressive beta cell dysfunction. Ann Intern Med. 1983;99:320–326. - PubMed
    1. Kumar D, Gemayel NS, Deapen D, Kapadia D, Yamashita PH, Lee M, et al. 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. Diabetes. 1993;42:1351–1363. - PubMed

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