Age-period-cohort modelling of type 1 diabetes incidence rates among children included in the EURODIAB 25-year follow-up study.

AIMS: Specific patterns in incidence may reveal environmental explanations for type 1 diabetes incidence. We aimed to study type 1 diabetes incidence in European childhood populations to assess whether an increase could be attributed to either period or cohort effects. METHODS: Nineteen EURODIAB centres provided single year incidence data for ages 0-14 in the 25-year period 1989-2013. Case counts and person years were classified by age, period and cohort (APC) in 1-year classes. APC Poisson regression models of rates were fitted using restricted cubic splines for age, period and cohort per centre and sex. Joint models were fitted for all centres and sexes, to find a parsimonious model. RESULTS: A total of 57,487 cases were included. In ten and seven of the 19 centres the APC models showed evidence of nonlinear cohort effects or period effects, respectively, in one or both sexes and indications of sex-specific age effects. Models showed a positive linear increase ranging from approximately 0.6 to 6.6%/year. Centres with low incidence rates showed the highest overall increase. A final joint model showed incidence peak at age 11.6 and 12.6 for girls and boys, respectively, and the rate-ratio was according to sex below 1 in ages 5-12. CONCLUSION: There was reasonable evidence for similar age-specific type 1 diabetes incidence rates across the EURODIAB population and peaks at a younger age for girls than boys. Cohort effects showed nonlinearity but varied between centres and the model did not contribute convincingly to identification of environmental causes of the increase.

Microvascular autoregulation in children and adolescents with type 1 diabetes mellitus.

AIMS/HYPOTHESIS: Deterioration of microvascular function may have an early onset in individuals with type 1 diabetes mellitus. We hypothesised that microvascular autoregulation is impaired in children with type 1 diabetes and can be detected non-invasively by postocclusive reactive hyperaemia (PORH). METHODS: Microvascular autoregulation was assessed in 58 children with type 1 diabetes and 58 age- and sex-matched healthy controls by PORH using laser Doppler fluxmetry. Baseline perfusion, biological zero (defined as a 'no flow' laser Doppler signal during suprasystolic occlusion), peak perfusion following occlusion, time to peak and recovery time (time until baseline perfusion is resumed) were recorded and compared between the groups. RESULTS: Peak perfusion was higher in children with type 1 diabetes than in healthy controls (1.7 ± 0.93 AU [arbitrary units] vs 1.29 ± 0.46 AU; p = 0.004), and biological zero was lower in children with type 1 diabetes vs controls (0.14 ± 0.04 AU vs 0.19 ± 0.04 AU; p < 0.0001). No differences were seen between the groups in baseline perfusion, time to peak during PORH and recovery time following PORH. CONCLUSIONS/INTERPRETATION: PORH reveals impaired microvascular autoregulation in children with type 1 diabetes. The higher peak perfusion might reflect a decline in the vasoconstrictive ability of arteriolar smooth muscle cells upstream of capillary beds in children with type 1 diabetes.