Early environmental events as a cause of IDDM. Evidence and implications

Leslie, R. D. G.; Rb, Elliott

doi:10.2337/diabetes.43.7.843

Cited by 88 publications

(82 citation statements)

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“…Previous studies [23] suggest that childhood onset Type I diabetes could be caused by environmental factors operating over a limited but critical period in early childhood. If the expression of these hypothetical environmental factors have a seasonal pattern but the time ªwindowº for any effect is narrow, there might be seasonality of birth in subjects diagnosed at a particular age which is hidden in the total population of children with Type I diabetes.…”

Section: Discussionmentioning

confidence: 99%

Seasonality of birth in patients with childhood Type I diabetes in 19 European regions

McKinney

2001

Diabetologia

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Season of birth appears to be associated with the development of many diseases, including conditions not generally thought to be season-dependent [1].The experiences of the growing fetus and neonate are thought to affect future susceptibility to diseases [2]. Systematic cyclical variations in the patterns of births could reflect environmental factors which also have cyclical variations.The cause of childhood Type I (insulin-dependent) diabetes mellitus is still not clear. Genetic susceptibility accounts for only a small proportion of the possible determinants [3] and non-genetic factors therefore play an important role. After analysing sets of data from different countries, several studies have identified a number of environmental risk factors for the development of Type I diabetes, particularly Diabetologia (2001) Abstract Aims/hypothesis. Differences in seasonality of birth patterns between the general population and the group who develop Type I (insulin-dependent) diabetes mellitus indicate that environmental factors operating around the antenatal and perinatal period could be important. We investigated whether the same unsual patterns in seasonality of birth observed in children with Type I diabetes in Great Britain could also be found in other European populations. Methods. Population-based incidence cohorts of children diagnosed with Type I diabetes under 15 years of age from 1989 onwards were analysed. Previously reported data sets from Great Britain were also included together with data on children diagnosed over an additional 5 year period (1988±1992). To assess the role of seasonality in diabetes, we used the method of Walter and Elwood to examine monthly birth figures for each country or region. Results. Outside of Great Britain, no seasonality of birth was seen for any single or combination of European countries. Significant sinusoidal patterns were observed in Scotland, Yorkshire and Leicester, although the peak for Leicester appeared around autumn rather than spring. There was little evidence that sex or age at diagnosis played a part in differences in seasonal patterns, either overall or for any individual country. Conclusions/interpretation. We found no uniform seasonal pattern of birth in childhood diabetes patients across European populations, either overall or according to sex and age. This study provides no consistent evidence that environmental factors, which vary from season to season, have any influence on the fetal or neonatal life to determine the onset of Type I diabetes. However, a study of seasonality that takes into account possible changes both over time and over geographical areas could provide more insights. [Diabetologia (2001)

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Section: Discussionmentioning

confidence: 99%

Seasonality of birth in patients with childhood Type I diabetes in 19 European regions

McKinney

2001

Diabetologia

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“…Such a decline in disease risk in young, but not adult onset twins, suggests that the non-genetic events leading to Type I diabetes in the young twins occur within a finite period. This loss of effect of non-genetic factors with age and time from diagnosis of the index twin could be due to lack of exposure or loss of susceptibility [33]. Given the similarity between British and the twins from the United States, in their pattern of disease progression it is likely that these non-genetic factors are ubiquitous.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2001

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Twin studies have helped to define the importance of genetic and environmental factors in the aetiology of disease [1±9]. By measuring concordance rates (both twins affected) in identical (monozygotic) and nonidentical (dizygotic) twins, estimates of genetic influence can be obtained. In primarily genetic disorders, concordance rates should be higher in monozygotic than in dizygotic twins. Differences between monozygotic twins must be due to factors not coded in the germ line, i. e. non-germ-line genetic (e. g. somatic) or environmental factors. Monozygotic twins also show differences in genes that undergo random rearrangement such as immunoglobulin and T-cell receptor genes.Comprehensive population-based studies of twins have only recently been initiated, so most of the information available on diabetic twins is from clinic- AbstractAims. 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 monozygotic 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 cohorts (p = 0.6). The combined survival analysis (n = 187, median follow-up = 17.7 years, range = 0.01±57) at 40 years of discordance estimated a 39 % probability of diabetes for the initially discordant twin. Survival analysis with 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 years of discordance, compared with 6 % for twins of probands diagnosed after 24 years of age (p = 0.004). The twins of probands diagnosed before 15 years 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 neither DR3-DQ2 nor DR4-DQ8 (p < 0.05). Conclusion/interpretation. Monozygotic twins of patients with Type I diabetes from two different countries had similar rates of progression to diabetes. Whereas most twins did not develop diabetes, 25 % of the twins who progressed did so after more than 14 years of discordance. An age-related heterogeneity was observed, with higher progression to diabetes for twins of patients diagnosed at a younger age. [Diabetologia (2001) 44: 354±362]

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“…Although the aetiology of the disease is largely unknown, these increases within genetically stable populations suggest the role of environmental influences. It has been proposed that events occurring early in life could be of particular importance [4].…”

Section: Introductionmentioning

confidence: 99%

Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data

et al. 2010

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Early environmental events as a cause of IDDM. Evidence and implications

Cited by 88 publications

References 0 publications

Seasonality of birth in patients with childhood Type I diabetes in 19 European regions

Seasonality of birth in patients with childhood Type I diabetes in 19 European regions

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

Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data

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