Birthweight and risk of type 1 diabetes in children and young adults: a population-based register study

Abstract

Aims/hypothesis: We investigated the association between type 1 diabetes and birthweight by age at disease onset. Methods: This population-based case-referent study used data from two nationwide case registers that are linked to the Swedish Medical Birth Registry and cover incident cases of type 1 diabetes in the 0-to 14-year (since 1 July 1977) and 15-to 34-year age groups (since 1 January 1983). Of the cases linked to the Medical Birth Registry, a total of 9,283 cases with onset before 15 years of age was recorded before 1 January 2003, and 1,610 cases were recorded with onset before 30 years of age and born after 1973 (together 95% of eligible cases). Multiple births and babies of diabetic mothers were excluded. Sexspecific birthweight by gestational week is expressed as multiples of the standard deviation (SDS) and adjusted for year of birth, maternal age and parity. Results: Cases with onset before 10 years of age (n=5,792) showed a significant linear trend in odds ratio (OR) by SDS of adjusted birthweight (OR by SDS: 0.062; 95% CI: 0.037-0.086; p<0.0001), while cases with onset at the age of 10-29 years showed no significant trend (OR by SDS: 0.004; 95% CI: −0.007 to 0.0014; p=0.22). Conclusions/interpretation: The association between type 1 diabetes risk and birthweight seems to be limited to cases with disease onset in younger years.

Children developing type 1 diabetes before 6 years of age have increased linear growth independent of HLA genotypes

“…MPH = SDS birth length or height−SDS MPH Diff., difference from study, care was taken to obtain the birth length and birthweight data from the growth curves maintained for each child by the Child Health Services. Several epidemiological studies have reported that type 1 diabetic children have a higher birthweight [10][11][12][13]. This was not observed in the present group of children developing diabetes before 6 years of age.…”

“…High birthweight has been reported as a risk factor for type 1 diabetes [10][11][12][13]. We have demonstrated that children born with type 1 diabetes high-risk HLA genotypes had an increased risk of high birthweight corrected for gestational age (i.e.…”

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

“…However, the observed association between childhood-onset type 1 diabetes and birthweight may not hold for adult-onset type 1 diabetes, as two large studies [58,59] investigating type 1 diabetes diagnosed in young adults have shown little evidence of association with birthweight.…”

The relation between size at birth and risk of type 1 diabetes is not influenced by adjustment for the insulin gene (-23HphI) polymorphism or HLA-DQ genotype

“…Several HLA-DQ and -DR alleles and genotypes are associated with risk and protection to different degrees [3], and the INS variable number of tandem repeats (VNTR) class I or its surrogate marker, the -23HphI A allele, has consistently been found to confer increased risk of type 1 diabetes [4,5]. Accumulating evidence suggests that environmental factors may play a role early in life [6] and that there is an effect of size at birth and other perinatal factors on the risk of type 1 diabetes, generally of relatively small magnitude [7][8][9][10][11]. Several large-scale studies have found a high birthweight to be associated with a modest but statistically significant increase in the risk of childhood-onset type 1 diabetes [8,9,11], although other, predominately smaller studies have not found a significant association [e.g.…”

“…Accumulating evidence suggests that environmental factors may play a role early in life [6] and that there is an effect of size at birth and other perinatal factors on the risk of type 1 diabetes, generally of relatively small magnitude [7][8][9][10][11]. Several large-scale studies have found a high birthweight to be associated with a modest but statistically significant increase in the risk of childhood-onset type 1 diabetes [8,9,11], although other, predominately smaller studies have not found a significant association [e.g. 7,12].…”