Autoantibodies and associated T-cell responses to determinants within the 831-860 region of the autoantigen IA-2 in Type 1 diabetes.

B-cells influence T-cell reactivity by facilitating antigen presentation, but the role of autoantibody-secreting B-cells in regulating T-cell responses in Type 1 diabetes is poorly defined. The aims of this study were to characterise epitopes on the IA-2 autoantigen for three monoclonal antibodies from diabetic patients by amino acid substitutions of selected residues of IA-2, establish contributions of these epitopes to binding of serum antibodies in Type 1 diabetes and relate B- and T-cell responses to overlapping determinants on IA-2. The monoclonal antibodies recognised overlapping epitopes, with residues within the 831-860 region of IA-2 contributing to binding; substitution of Glu836 inhibited binding of all three antibodies. Monoclonal antibody Fab fragments and substitution of residues within the 831-836 region blocked serum antibody binding to an IA-2 643-937 construct. IL-10-secreting T-cells responding to peptides within the 831-860 region were detected by cytokine-specific ELISPOT in diabetic patients and responses to 841-860 peptide were associated with antibodies to the region of IA-2 recognised by the monoclonal antibodies. The study identifies a region of IA-2 frequently recognised by antibodies in Type 1 diabetes and demonstrates that these responses are associated with T-cells secreting IL-10 in response to a neighbouring determinant.

Children and young people with diabetes in Yorkshire: a population-based clinical audit of patient data 2005/2006.

AIMS: To provide a population-based clinical audit of children and young people with diabetes, reporting outcomes, including glycaemic control, for named individual units. METHODS: Clinical audit data on care processes and glycated haemoglobin (HbA(1c)) were collected for 1742 children and young people treated in 16 paediatric units in Yorkshire, from January 2005 to March 2006. The Yorkshire Register of Diabetes in Children and Young People provided information technology support and validation that enhanced data quality. Multi-level linear regression modelling investigated factors affecting glycaemic control. RESULTS: An HbA(1c) measure was recorded for 91.6% of patients. The National Institute for Clinical Excellence-recommended target level for HbA(1c) of < 7.5% was achieved for 14.7% of patients. HbA(1c) was positively associated with duration of diabetes and later age at diagnosis. Patients living in deprived areas had significantly poorer control compared with those from affluent areas. Significant between-unit variation in HbA(1c) was not reflected by any association with unit size. CONCLUSIONS: Our population-based clinical audit of children with diabetes is the product of an effective collaboration between those who deliver care and health services researchers. High levels of recording the key care process measuring diabetes control, compared with national figures, suggests collaboration has translated into improved services. The interesting association between poor diabetes control and higher deprivation is noteworthy and requires further investigation. Future audits require recording of clinical management and clinic structures, in addition to resources to record, assemble and analyse data.

Insulin pump therapy in childhood diabetes-cost implications for Primary Care Trusts.

AIMS: Primary Care Trusts (PCTs) are now responsible for the planning and delivery of health-care services throughout England and Wales. As the 25 PCTs throughout Yorkshire are representative of the national distribution in terms of population structure and socio-economic status, we aimed to address the paucity of information describing the burden of childhood diabetes in primary care and to evaluate the cost implications of insulin pump therapy on individual PCTs. METHODS: We extracted information from a population-based register in Yorkshire, including 1952 patients diagnosed under the age of 15 years from 1990 to 2003. Each patient's postcode was linked to an individual PCT. Incidence rates (per 100 000 patient years) were derived and assessed for evidence of heterogeneity across PCTs and within Strategic Health Authorities (SHAs). RESULTS: Incidence rates were lower in West Yorkshire (19.1, 95% CI 18.0-20.2) than North-east Yorkshire (20.3, 18.9-21.6), although this difference was not significant (P = 0.20). No significant evidence of heterogeneity in incidence rates was observed across PCTs (P = 0.46). Ninety per cent of all PCTs would expect four to seven newly diagnosed children per year, corresponding to a single general practitioner (GP) referring an individual for diagnosis once every 15 years on average. Assuming 1% of current patients under the age of 15 years with diabetes were to move onto insulin pump therapy, this would impose an additional cost of pound400-1300 per year for each PCT. The average cost was 15% lower for PCTs in West Yorkshire than North and East Yorkshire. CONCLUSIONS: The additional resources required to pay for insulin pump therapy for a small proportion of the diabetes population would be minimal given the potential benefits to these patients of improved control and anticipated reduction in long-term morbidity.

Type 2 and other forms of diabetes in 0-30 year olds: a hospital based study in Leeds, UK.

BACKGROUND AND AIMS: Following recent reports of increased numbers of adolescents being diagnosed with the adult or type 2 form of diabetes we aimed to describe the prevalence of both type 2 and other forms of diabetes in an urban population of children and young people in northern England. METHODS: A hospital based cross sectional study was performed in patients aged < or =30 years attending diabetic clinics in Leeds during the year 2000. RESULTS: A total of 677 subjects were identified, of whom 621 (92%) and 37 (5%) had type 1 and type 2 diabetes respectively. Four patients had confirmed maturity onset diabetes of the young, while the cause was uncertain for four. Median age of all patients was 22 years, with 396 (58%) aged 20-30; 32/37 patients with type 2 diabetes were aged 20-30. The prevalence of type 2 diabetes was 0.13 per 1000 overall, compared to 2.2 per 1000 for patients with type 1 diabetes. Of all type 2 diabetes patients, 24% were south Asian compared to 5% of the background population; 87% were categorised into the two least affluent tertiles of the Townsend score. This link with deprivation was not explained by the proportion of Asian patients across tertiles (approximately 25%). CONCLUSIONS: This study shows extremely low prevalence of type 2 diabetes in 10-19 year olds, but will provide a baseline for future comparisons. Overall, type 2 diabetes is seen more commonly in south Asians, and an association with deprivation is suggested.

Type 1 diabetes in Yorkshire, UK: time trends in 0-14 and 15-29-year-olds, age at onset and age-period-cohort modelling.

AIMS: To investigate whether the rising incidence of Type 1 diabetes in children is evident in young adults and determine whether age at onset has decreased over time. METHODS: Two geographically defined datasets from the population-based Yorkshire Diabetes Register were analysed: (i) 2718 children diagnosed under 15 years with Type 1 diabetes from 1978 to 2000 in Yorkshire; (ii) 631 young adults (15-29 years) diagnosed from 1991 to 1999 in West Yorkshire. Log-linear regression and age-period-cohort modelling evaluated changes in incidence over time and age at onset. RESULTS: Incidence rose steadily for 0-14-year-olds in Yorkshire with an average annual increase of 2.9%[95% confidence interval (CI) 2.0, 3.8]. In West Yorkshire between 1991 and 1999, the time trends for 0-14 and 15-29-year-olds were significantly different (P = 0.014). Stable rates in 15-29-year-olds contrasted with an average annual increase of 5.9% (95% CI 2.7, 9.2) for 0-14-year-olds. The mean age at onset fell from 9.2 to 8.4 years for 0-14-year-olds and from 16.0 to 14.6 years for 0-29-year-olds. Age-period-cohort modelling showed a statistically significant (P < 0.001) increased risk of developing diabetes was associated with decreasing age for those diagnosed more recently. CONCLUSIONS: A steady and continuing rise in the incidence of Type 1 diabetes over time is observed for children but not for young adults. In parallel, the age at onset is gradually decreasing and more recent birth cohorts are at increased risk. This overall pattern is consistent with the influence of an environmental agent that is gradually affecting children at younger and younger ages.

Trends in the incidence of childhood diabetes in south Asians and other children in Bradford, UK.

AIMS: To investigate incidence rates and time trends, over 21 years, of Type 1 diabetes in a migrant population of south Asian children in Bradford, UK. METHODS: Children (0-14 years) living in the city of Bradford and diagnosed with Type 1 diabetes were selected from a population-based region-wide register. Between 1978 and 1998, 289 new-onset cases were registered and classified as south Asian (Indian, Pakistani, Bangladeshi) or not, based on their full name using two different computer algorithms and visual inspection. RESULTS: Sixty-six children (22.8%) were designated as south Asian with 223 (77.2%) remaining. The overall age-sex standardized incidence for south Asian and non-south Asian children was 13.0 per 100,000 person years (95% confidence interval 9.9-16.2) and 12.9 (11.2-14.6), respectively. Rates were similar for south Asians at all ages, whereas for the mainly Caucasian children incidence differed significantly by age group (P < 0.001). An average annual increase in incidence of 4.3% (P = 0.001) was seen for all children compared with 6.5% in south Asians (P = 0.002) and 2.4% (P = 0.128) in non-south Asians. CONCLUSIONS: Children in south Asia have a low incidence of Type 1 diabetes but migrants to the UK have similar overall rates to the indigenous population. However, a more steeply rising incidence is seen in the south Asian population, and our data suggest that incidence in this group may eventually outstrip that of the non-south Asians. Genetic factors are unlikely to explain such a rapid change, implying an influence of environmental factors in disease aetiology. The similarity in rates by age group in the south Asian population is notable.