Mortality and acute complications in children and young adults diagnosed with Type 1 diabetes in Yorkshire, UK: a cohort study.

AIMS: To examine all-cause and cause-specific mortality in a population-based cohort of people with early and late onset of Type 1 diabetes. METHODS: The Yorkshire Register of Diabetes in Children and Young People includes individuals with early (0-14 years) and late (15-29 years) Type 1 diabetes onset, diagnosed between 1978 and 2013. This register was linked to death certification data from the Office for National Statistics to calculate standardized mortality ratios, cumulative mortality curves using Kaplan-Meier survival estimates, and Cox regression modelling. Ethnicity was derived using Onomap. Deprivation status was classified using the Townsend index. The underlying cause of death in each case was clinically verified. RESULTS: There were 229 deaths in 5498 individuals with 100 959 person-years of follow-up. The overall standardized mortality ratio was 4.3 (95% CI 3.8 to 4.9). There were no significant differences in standardized mortality ratios according to age of onset, sex or deprivation status. The standardized mortality ratios were significantly higher for people of white ethnic origin [8.1 (95% CI 6.9 to 9.4)] than for those of South-Asian ethnic origin [3.4 (95% CI 1.7 to 6.4)]. The mortality risk was lower in those diagnosed in later years (2002 to 2013 for the early-onset and 2006 to 2013 for the late-onset group) compared with earlier years (1991 to 1997 for the early-onset and 1991 to 1997 for the late-onset group) for both onset groups [hazard ratio 0.13 (95% CI 0.05 to 0.33) vs 0.24 (95% CI 0.07 to 0.81)]. Mortality risk improved over time for chronic complications in the early-onset group only, but there was no improvement in either onset group with regard to acute complications. CONCLUSIONS: An excess of deaths in the population with Type 1 diabetes remains. Although the all-cause mortality risk has fallen over time, no improvement has been found in the mortality risk associated with acute complications.

Estimation of jaw-opening forces in adults.

OBJECTIVES: To estimate maximum jaw-opening forces in healthy participants of diverse ancestry and to estimate whether opening forces are associated with sex, age and anthropometric parameters such as height, weight and BMI. SETTING AND SAMPLE POPULATION: One hundred and forty-nine participants aged 20-60 years with overall good oral and general health. Exclusion criteria included myofascial or neck pain, symptomatic temporomandibular joint disorders (TMD), current orthodontic treatment or the absence of a natural dentition. MATERIAL AND METHODS: Jaw-opening forces were measured with an adjustable rigid extra-oral device connected to a 1000 N load cell. Seven attempts were recorded, with 10 seconds interval. Median force values were obtained after discarding the first and last attempt. The height and weight of each participant were measured and recorded, alongside age, sex and ethnicity. RESULTS: Men had greater maximum opening force median values than women (P < .001). Median (IQR) values for women were 41.16 N (30.44) and 79.00 N for men (63.86). Jaw-opening force values were poorly associated with biological and anthropometric parameters. CONCLUSION: In this study, which included a large sample of participants of broad age range and from a demographically diverse background, jaw-opening force values were greater in males than in females; however, force values were poorly associated with biological and anthropometric parameters. Future studies should explore the potential of this method as a screening tool for TMJ disorders and other conditions.

Diabetic hepatosclerosis: another diabetes microvascular complication?

BACKGROUND: Liver disease in diabetes is common and is frequently the result of hepatic steatosis. Diabetic hepatosclerosis is a relatively recent description of sinusoidal fibrosis, without steatosis, observed in liver biopsies of people with diabetes presenting with cholestasis. Its association with other microvascular complications suggests it is a form of hepatic diabetic microangiopathy. CASE REPORT: We report the case of a 50-year-old woman with longstanding Type 1 diabetes, complicated by nephropathy resulting in cadaveric renal transplant, retinopathy, gastroparesis and neuropathy with slowly healing ulceration to her right foot. She was noted to have deranged liver function tests: alanine aminotransferase, 162 IU/l; bilirubin, 44 IU/l; alkaline phosphatase, 5279 IU/l (isoenzymes; bone 1029 IU/l, liver 4250 IU/l); γ-glutamyl transferase, 662 IU/l. A non-invasive liver screen did not reveal the cause of the cholestasis. A liver biopsy demonstrated sinusoidal fibrosis without evidence of steatosis and thus a diagnosis of diabetic hepatosclerosis was made. Comparison with a biopsy performed 11 years previously at a different trust due to elevated alkaline phosphatase levels revealed slow progression of the sinusoidal fibrosis. DISCUSSION: This case describes the longest reported clinical course of diabetic hepatosclerosis, spanning 11 years, in which time the patient did not develop evidence of cirrhosis or portal hypertension. It is difficult to estimate the clinical relevance of this condition because little is known regarding its clinical course and effect on morbidity and mortality. Identified patients should undergo low-intensity, long-term follow-up to improve understanding of its clinical sequelae and relevance.

Incidence rate trends in childhood type 1 diabetes in Yorkshire, UK 1978-2007: effects of deprivation and age at diagnosis in the South Asian and non-South Asian populations.

AIMS: Incidence of Type 1 diabetes in children is increasing worldwide. Earlier studies suggest that UK south Asian immigrants develop similar rates to the overall UK population, although incidence is lower in their country of origin. This study examines incidence rate trends of childhood Type 1 diabetes in Yorkshire 1978-2007, focusing on differences between south Asians and non-south Asians. METHODS: Data from the population-based Yorkshire Register of Diabetes in Children and Young People were used to estimate incidence (per 100,000 childhood population < 15 years per year) of Type 1 diabetes, stratified by sex, age and ethnicity validated using two name-recognition programs. Age-sex standardized rates were calculated for 1978-2007 and assessed by ethnic-group and deprivation for 1990-2007. We used Poisson regression to assess incidence trends and predict rates until 2020. RESULTS: From 1978-2007, 3912 children were diagnosed. Overall incidence was 18.1 per 100,000 childhood population (< 15 years) per year (95% CI17.6-18.7) and increased significantly over time: 13.2 (1978-1987) to 17.3 (1988-1997) to 24.2 (1998-2007). Average annual percentage change was 2.8% (2.5-3.2). Incidence for non-south Asians (21.5; 20.7-22.4) was significantly higher than for south Asians (14.7; 12.4-17.1). Average annual percentage change increased significantly over 18 years (1990-2007) in non-south Asians (3.4%; 2.7-4.2) compared with a non-significant rise of 1.5% (-1.5 to 4.6) in south Asians. Deprivation score did not affect overall incidence. CONCLUSIONS: Type 1 diabetes incidence rose almost uniformly for non-south Asians, but not for south Asians, contrary to previous studies. Overall rates are predicted to rise by 52% from 2007 to 2020 to 39.0 per 100,000 per year.

Paediatric intensive care admissions for acute diabetes complications.

AIM: To describe the admission characteristics and outcomes of children admitted to paediatric intensive care because of acute diabetes complications in England and Wales. METHODS: Retrospective review of children admitted to paediatric intensive care in England and Wales between April 2003 and March 2007 with acute diabetes complications using data from the Paediatric Intensive Care Audit Network (PICANet). RESULTS: There were 341 admissions in 330 patients for acute diabetes complications, comprising 0.6% of all 56 322 intensive care admissions. There was a steady annual increase during this period from 0.54% to 0.67%. The majority of admissions were for ketoacidosis (87%), with more female admissions than males (56% vs. 44%). Forty per cent of the diabetes admissions were aged 11-15 years. There were five deaths (1.5%), all female. CONCLUSIONS: Acute diabetes complications are an increasing cause of admission to paediatric intensive care, particularly for teenage girls. The overall mortality rate was low for intensive care admissions for diabetes. Earlier diagnosis of new cases, heightened awareness of this condition and better management of existing diabetic patients may obviate the need for costly intensive care treatment.

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.

Can the theory of planned behaviour predict maintenance of a frequently repeated behaviour?

The present study used the theory of planned behaviour to predict self-monitoring of blood glucose in patients with type 1 diabetes. Sixty-four adult patients with type 1 diabetes completed a questionnaire assessing the variables of the TPB in addition to demographic variables and a measure of conscientiousness. Self-report measures of daily self-monitoring behaviour were obtained for a two-week period. The extended model predicted 46% of the variance in behavioural intention and 57% of variance in self-monitoring behaviour, suggesting that the TPB is able to predict useful levels of variance, comparable to initiation, even in familiar and frequently repeated maintenance behaviours. Implications of these results are discussed.

Space-time clustering analyses of type 1 diabetes among 0- to 29-year-olds in Yorkshire, UK.

AIMS/HYPOTHESIS: Infections have been suggested to play a role in the aetiology of type 1 diabetes. The presence of space-time clustering is consistent with the notion of an environmental component in disease aetiology, possibly linked to infections. We tested for evidence of space-time clustering among children and young adults under 30 years of age using data from a population-based register in Yorkshire, UK. SUBJECTS AND METHODS: Two data sets of children and young people diagnosed with type 1 diabetes were analysed: (1) children aged 0-14 years and resident in Yorkshire during 1978-2002; (2) those aged 15-29 years and resident in West Yorkshire during 1991-2002. Tests for space-time interactions between cases were applied. Addresses at diagnosis were geo-coded and used as the basis for the analyses. RESULTS: The study analysed 3,019 type 1 diabetic patients in the 0-14 years age group and 989 patients in the 15-29 years group. Statistically significant space-time clustering based on place and time of diagnosis was detected both for the 10-14-year-olds (p=0.04) and for the 15-19-year-olds (p=0.01). CONCLUSIONS/INTERPRETATION: Previous studies of clustering of type 1 diabetes have generally been restricted to childhood. Our results from a data set that includes teenagers and young adults show that space-time clustering was limited to young people aged 10-19 years. This finding is consistent with an aetiology involving late exposure to infection. However, the question of whether this is directly diabetogenic or unmasks latent diabetes cannot be addressed by this methodology.

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.

International parallels in leukaemia and diabetes epidemiology.

Acute lymphoblastic leukaemia (ALL) and type 1 diabetes have an environmental aetiology and common epidemiological features. Incidence rates and national characteristics of both conditions were investigated in 40 countries worldwide. There was a significant positive correlation between diseases. Markers of wealth and affluence were significantly associated with high incidence.

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.

Retinopathy screening in children and adolescents with diabetes.

Diabetic retinopathy is a complication of diabetes that affects the blood vessels of the retina. The majority of patients with diabetic retinopathy exhibit background retinopathy. In approximately 10% of patients, background retinopathy will progress to sight-threatening retinopathy. The aims of our study were to measure the prevalence of retinopathy among our population and to assess the optimal time of screening children and adolescents with type 1 diabetes.

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.

Population mixing and childhood diabetes.

BACKGROUND: Exposure to infections, particularly in early life, may modify the risk of developing childhood diabetes. Population mixing, based on the number and diversity of incoming migrants to an area can be used as a proxy measure for exposure to infections. We tested the hypothesis that incidence of childhood Type 1 diabetes is higher in areas of low population mixing. METHODS: Children (<15 years) diagnosed with diabetes between 1986--1994 in Yorkshire, UK (n = 994) were analysed with demographic data and denominator populations from the 1991 UK Census. Population mixing was estimated separately for 'any age' (>1 year) and children (1--15 years) for each area, using the proportion of migrants and an index of diversity based on numbers and origins of migrants. Regression models calculated the effect of 'any age' and childhood population mixing on the incidence of diabetes, controlling for population density, ethnicity and proportion of migrants. RESULTS: Areas with low levels of population mixing of children (bottom decile), were significantly associated with higher incidence of childhood diabetes for 0-14 years (incidence rate ratio [IRR] = 1.46, 95% CI : 1.01--2.11). When stratified by age different effects were observed for childhood population mixing with raised IRR for ages 5-9 (2.23, 95% CI : 1.20--4.11) and 10-14 (1.47, 95% CI : 0.89--2.42), and decreased IRR for 0--4-year-olds (0.56, 95% CI : 0.17--1.82). CONCLUSION: The incidence of childhood diabetes is highest in areas where limited childhood population mixing occurs and the diversity of origins of incoming children is low; those over 4 years are at greatest risk. This is consistent with an infectious hypothesis where absence of stimulation to the developing immune system increases vulnerability to late infectious exposure, which may precipitate diabetes.