Heterogeneity of Type I diabetes: analysis of monozygotic twins in Great Britain and the United States

Aims. To determine the risk, hazard rate and factors affecting progression to diabetes in monozygotic twins of patients with Type I (insulin-dependent ) diabetes mellitus. Methods. Prospective analysis was done of two cohorts of non-diabetic monoz ygotic twins of patients with Type I diabetes from Great Britain (n = 134) and the United States (n = 53). Results. The diabetes-free survival analysis was similar between both cohor ts (p = 0.6). The combined survival analysis (n = 187, median follow-up = 1 7.7 years, range = 0.01-57) at 40 years of discordance estimated a 39 % pro bability of diabetes for the initially discordant twin. Survival analysis w ith left truncation of data estimated that probability to be 50%. For twins who became concordant (n = 47), the median discordance time was 4.2 years (range 0.4 to 39), exceeding 15 years in 23.4%. Twins of probands diagnosed at 24 years of age or younger had a 38 % probability of diabetes by 30 yea rs of discordance, com pared with 6% for twins of probands diagnosed after 24 years of age (p = 0.004). The twins of probands diagnosed before 15 year s of age had the highest diabetes hazard rate in the first discordance year , decreasing thereafter. By survival analysis, diabetes risk was higher in twins who were heterozygous for DR3-DQ2 and DR4-DQ8 than in twins with neit her DR3-DQ2 nor DR4-DQ8 (p < 0.05). Conclusion/interpretation. Monozygotic twins of patients with Type I diabet es from two different countries had similar rates of progression to diabete s. Whereas most twins did not develop diabetes, 25 % of the twins who progr essed did so after more than 14 years of discordance. An age-related hetero geneity was observed, with higher progression to diabetes for twins of pati ents diagnosed at a younger age.