Edith Schober

Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies

Aims/hypothesisThe aim of this study was to investigate the evidence of an increased risk of childhood-onset type 1 diabetes in children born by Caesarean section by systematically reviewing the published literature and performing a meta-analysis with adjustment for recognised confounders.MethodsAfter MEDLINE, Web of Science and EMBASE searches, crude ORs and 95% CIs for type 1 diabetes in children born by Caesarean section were calculated from the data reported in each study. Authors were contacted to facilitate adjustments for potential confounders, either by supplying raw data or calculating adjusted estimates. Meta-analysis techniques were then used to derive combined ORs and to investigate heterogeneity between studies.ResultsTwenty studies were identified. Overall, there was a significant increase in the risk of type 1 diabetes in children born by Caesarean section (OR 1.23, 95% CI 1.15–1.32, p < 0.001). There was little evidence of heterogeneity between studies (p = 0.54). Seventeen authors provided raw data or adjusted estimates to facilitate adjustments for potential confounders. In these studies, there was evidence of an increase in diabetes risk with greater birthweight, shorter gestation and greater maternal age. The increased risk of type 1 diabetes after Caesarean section was little altered after adjustment for gestational age, birth weight, maternal age, birth order, breast-feeding and maternal diabetes (adjusted OR 1.19, 95% CI 1.04–1.36, p = 0.01).Conclusions/interpretationThis analysis demonstrates a 20% increase in the risk of childhood-onset type 1 diabetes after Caesarean section delivery that cannot be explained by known confounders.

Trends in childhood type 1 diabetes incidence in Europe during 1989–2008: evidence of non-uniformity over time in rates of increase

Aims/hypothesisThe aim of the study was to describe 20-year incidence trends for childhood type 1 diabetes in 23 EURODIAB centres and compare rates of increase in the first (1989–1998) and second (1999–2008) halves of the period.MethodsAll registers operate in geographically defined regions and are based on a clinical diagnosis. Completeness of registration is assessed by capture–recapture methodology. Twenty-three centres in 19 countries registered 49,969 new cases of type 1 diabetes in individuals diagnosed before their 15th birthday during the period studied.ResultsAscertainment exceeded 90% in most registers. During the 20-year period, all but one register showed statistically significant changes in incidence, with rates universally increasing. When estimated separately for the first and second halves of the period, the median rates of increase were similar: 3.4% per annum and 3.3% per annum, respectively. However, rates of increase differed significantly between the first half and the second half for nine of the 21 registers with adequate coverage of both periods; five registers showed significantly higher rates of increase in the first half, and four significantly higher rates in the second half.Conclusions/interpretationThe incidence rate of childhood type 1 diabetes continues to rise across Europe by an average of approximately 3–4% per annum, but the increase is not necessarily uniform, showing periods of less rapid and more rapid increase in incidence in some registers. This pattern of change suggests that important risk exposures differ over time in different European countries. Further time trend analysis and comparison of the patterns in defined regions is warranted.

COXSACKIE B, MUMPS, RUBELLA, AND CYTOMEGALOVIRUS SPECIFIC IgM RESPONSES IN PATIENTS WITH JUVENILE-ONSET INSULIN-DEPENDENT DIABETES MELLITUS IN BRITAIN, AUSTRIA, AND AUSTRALIA

Patients from England, Austria, and Australia with recently diagnosed juvenile-onset insulin-dependent diabetes (type 1) mellitus (IDDM) and matched controls were tested for specific IgM responses to Coxsackie B1-5 viruses. 37 of 122 (30%) patients aged less than 15, but only 15 of 204 (6%) controls, were positive (p less than 0.005). Differences in Coxsackie B virus specific IgM responses between patients and controls were statistically significant for patients in England and Austria (p less than 0.005). Coxsackie B virus specific IgM responses were detected in only 3 of 31 patients aged greater than 16. Virus-specific IgM responses were directed against a single serotype, usually Coxsackie B4 or 5, in 23 of 37 (62.5%) children aged less than 15; 10 of 13 (77%) of children aged less than 7 had monotypic responses. Among families of Austrian patients with IDDM, 8 of 79 (10%) siblings had Coxsackie B virus specific IgM responses, 1 of whom subsequently had IDDM, but none of the 80 parents was positive. In contrast, there was no evidence of recent infection by mumps, rubella, or cytomegalovirus (CMV), since mumps-virus specific IgM was present in only 2 of 100 children with IDDM and 5 of 139 controls; no rubella or CMV specific IgM responses were detected in 60 sera from patients with IDDM.

The ‘accelerator hypothesis’: relationship between weight, height, body mass index and age at diagnosis in a large cohort of 9,248 German and Austrian children with type 1 diabetes mellitus

Aims/hypothesisThe aim of this study was to investigate whether either increased weight or BMI are associated with the earlier manifestation of type 1 diabetes mellitus in children.MethodsWe evaluated anthropometric measurements in a large cohort of 9,248 patients of European extraction who were diagnosed in the years 1990–2003 in 116 pediatric clinics throughout Germany and Austria.ResultsPatients were divided into four groups according to age (0–4.9 years, 5–9.9 years, 10–14.9 years and 15–20 years). Significantly higher standard deviation scores (SDSs) for weight and BMI at diabetes onset were found for both boys and girls in the three younger age groups (up to 14.9 years of age) compared with the reference population (p<0.00001). In addition, the BMI SDS and the weight SDS were significantly higher in the 0–4.9-years age group than in all other groups (p<0.00001), and BMI SDS at onset gradually decreased with increasing age at manifestation (p<0.0001). Over the >10-year study period, there was a continuous rise in the weight-SDS and the BMI-SDS in the cohort (p<0.0001), especially in the 5–9.9-years and the 10–14.9-years age groups. Multivariate analysis revealed a significant influence of male sex and of year of manifestation on BMI SDS (p<0.0001) and demonstrated a negative association between the patients’ BMI SDS and age at diagnosis, with a mean annual decrease in BMI SDS of −0.0248 (95% CI −0.0294 to −0.0202, p<0.0001).Conclusions/interpretationA higher BMI was associated with a younger age at diabetes onset. Increased weight gain could therefore be a risk factor for the early manifestation of type 1 diabetes.

Early mortality in EURODIAB population-based cohorts of type 1 diabetes diagnosed in childhood since 1989

Aims/hypothesisThe aims of this study were to provide a contemporary picture of mortality and causes of death in Europe following a diagnosis of type 1 diabetes made before the 15th birthday, and to examine excess mortality by country for possible links to incidence level or national prosperity.MethodsThirteen population-based EURODIAB registers in 12 countries followed-up 28,887 children diagnosed since 1989, either by record linkage to population registers or through contact with doctors providing care.ResultsThere were 141 deaths in the cohort during 219,061 person-years of follow-up compared with 69.1 deaths expected from national mortality rates, a standardised mortality ratio (SMR) of 2.0 (95% CI 1.7–2.4). The SMR varied from 0 to 4.7 between countries, but showed little relationship with the country’s incidence rate or gross domestic product (US

β-cell autoantibodies in children with type 2 diabetes mellitus: subgroup or misclassification?

per capita). The SMR did not change significantly with attained age, calendar period or time since diagnosis. The female SMR (2.7; 95% CI 2.0–3.5) was greater than the male SMR (1.8; 95% CI 1.4–2.2), although absolute numbers of excess deaths were similar in the two sexes. One-third of deaths were classified as directly attributable to diabetes (many with mention of ketoacidosis) and half were unrelated to diabetes. There was a non-significant excess of accidental/violent deaths (48 observed vs 40.7 expected; SMR 1.2; 95% CI 0.9–1.6) but little excess in suicides (11 observed, 10.2 expected; SMR 1.1; 95% CI 0.5–1.9).Conclusions/interpretationBefore the onset of late complications, significant excess mortality existed following the diagnosis of type 1 diabetes in childhood, even in recent years. Variation between countries in this excess could not be explained.

Comparative trial between insulin glargine and NPH insulin in children and adolescents with type 1 diabetes mellitus.

Background: In adults, a fraction of diabetic individuals with β-cell autoantibodies has initially non-insulin requiring diabetes clinically appearing as type 2 diabetes mellitus (T2DM), named latent autoimmune diabetes in adulthood (LADA). The occurrence of β-cell autoantibodies in European children and adolescents with T2DM has not been reported so far. Methods: The frequency of β-cell autoantibodies (anti-GAD, anti-IA-2, and anti-ICA) was determined in 7050 diabetic children and adolescents. The type of diabetes was classified by paediatric diabetic specialists based on the clinical presentation. Children with non-insulin dependent T2DM over a one year period were studied separately. Results: A total of 6922 children were clinically classified as having type 1 diabetes (T1DM) and 128 children as having T2DM. Thirty six per cent of the children with T2DM had at least one detectable β-cell autoantibody. These children did not differ significantly from the children with T2DM and without autoantibodies in respect of age, gender, weight status, lipids, blood pressure, C-peptide, glucose, and HbA1c at manifestation, as well as frequency of anti-thyroidal antibodies and insulin treatment during follow up. In the subgroup of the 38 children with T2DM without insulin requirement over a one year period, autoantibodies occurred in 32%. These 12 children were predominantly obese (67%), female (67%), and in the pubertal age range. Conclusion: β-cell autoantibodies were detectable in a subgroup of initially non-insulin dependent diabetic children and adolescents with the clinical appearance of T2DM. Following the terminology “latent autoimmune diabetes in adulthood (LADA)”, this subgroup might be classified as “LADY” (latent autoimmune diabetes in youth).

Phenotypical aspects of maturity-onset diabetes of the young (MODY diabetes) in comparison with Type 2 diabetes mellitus (T2DM) in children and adolescents: experience from a large multicentre database

The objective of this study was to compare the efficacy and safety of insulin glargine, a long-acting insulin analog, with NPH insulin in children and adolescents with type 1 diabetes mellitus (T1DM). In a multicenter, open-label, randomized, 6-month study, 349 patients with TIDM, aged 5-16 years, received insulin glargine once daily or NPH insulin either once or twice daily, based on their prior treatment regimen. Although there was no significant difference between the NPH insulin and insulin glargine treatment groups with respect to baseline to endpoint change in HbA1c levels, fasting blood glucose (FBG) levels decreased significantly more in the insulin glargine group (-1.29 mmol/l) than in the NPH insulin group (-0.68 mmol/L, p = 0.02). The percentage of symptomatic hypoglycemic events was similar between groups; however, fewer patients in the insulin glargine group reported severe hypoglycemia (23% vs 29%) and severe nocturnal hypoglycemia (13% vs 18%), although these differences were not statistically significant (p = 0.22 and p = 0.19, respectively). Fewer serious adverse events occurred in the insulin glargine group than in the NPH insulin group (p < 0.02). A once-daily subcutaneous dose of insulin glargine provides effective glycemic control and is well tolerated in children and adolescents with T1DM.

Glycaemic control of Type 1 diabetes in clinical practice early in the 21st century: an international comparison

Aims  To analyse and compare clinical characteristics in young patients with maturity‐onset diabetes of the young (MODY) and Type 2 diabetes mellitus (T2DM).

Quality of Life in Adolescents With Treated Coeliac Disease : Influence of Compliance and Age at Diagnosis

Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries.