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.

Carbohydrate quantity is more closely associated with glycaemic control than weight in pregnant women with type 1 diabetes: Insights from the Diabetes and Pre-eclampsia Intervention Trial (DAPIT).

BACKGROUND: The present study aimed to explore the relationships between carbohydrate intake, body mass index (BMI) and glycaemic control (HbA1c) in pregnant women with type 1 diabetes mellitus (T1DM) METHODS: Secondary analysis of data was undertaken to assess dietary intake in a cohort of women who participated in a randomised controlled trial (RCT) of antioxidant supplementation to prevent preeclampsia (DAPIT10 ). Study-specific peripheral venous blood samples were obtained for HbA1c at 26 and 34 weeks. Diet was collected using a validated semiquantitative food frequency questionnaire at 26-28 weeks of gestation which assessed dietary intake over 2 weeks. Mean daily average nutrient intakes were analysed using Q Builder nutritional software and SPSS, version 25. RESULTS: Dietary data were available for 547 pregnant women (72% of cohort) aged 29 years (95% confidence interval [CI] = 28.9-29.9) with average diabetes duration 11.8 years (95% confidence interval = 11.1-12.6). Average body mass index (BMI) (<16 weeks of gestation) was 26.7 kg/m2 (95% CI = 26.3 -27, range 18.8-45.6 kg/m2 ); 43% (n = 234) were overweight (BMI = 25.0-29.9 kg/m2 ) and 20% (n = 112) were obese (BMI ≥ 30 kg/m2 ). Differences in HbA1c and carbohydrate quantity and quality were found when adjusted for age and insulin dose. No differences between BMI group were observed for total carbohydrate and glycaemic control; however, differences were noted in fibre and glycaemic index. CONCLUSIONS: Average quantity of dietary carbohydrate influenced HbA1c when adjusted for insulin dose however, BMI had less impact. More research is required on the relationship between carbohydrate consumption and glycaemic control in pregnancy.

Clinical utility of ultrasonography-measured visceral adipose tissue depth as a tool in early pregnancy screening for gestational diabetes: a proof-of-concept study.

AIM: To examine, in a proof-of-concept study, the ability of visceral adipose tissue depth and subcutaneous fat depth measured in early pregnancy to predict subsequent gestational diabetes, and to assess the performance of these measures as screening tests for gestational diabetes compared with use of the current UK criteria. METHODS: A total of 100 women in early pregnancy were recruited from a maternity hospital in Belfast, UK. Visceral adipose tissue depth and subcutaneous fat depth were measured, and each participant underwent a 75-g oral glucose tolerance test at 28 weeks' gestation for the diagnosis of gestational diabetes using WHO 2013 criteria. RESULTS: Eighty women completed the study, of whom 15 (19%) developed gestational diabetes. Increasing visceral adipose tissue depth, but not subcutaneous fat depth, was associated with greater gestational diabetes risk after adjusting for confounding factors (odds ratio for a 1-sd rise 2.09, 95% CI 1.06-4.12; P=0.03). Visceral adipose tissue depth ≥4.27 cm had greater sensitivity compared with current National Institute of Health and Care Excellence criteria (87% vs 40%, respectively; P=0.02) and similar specificity (62% vs 74%, respectively; P=0.15) for identifying gestational diabetes. CONCLUSIONS: Ultrasonography-measured visceral adipose tissue in early pregnancy is a potential clinical tool for improving sensitivity of selective screening for gestational diabetes, which, compared with universal oral glucose tolerance testing, is likely to reduce by half the numbers requiring this test. Further larger studies are now required for confirmation, including investigation into impact on clinical outcomes.

Development of a Core Outcome Set for studies evaluating the effects of anaesthesia on perioperative morbidity and mortality following hip fracture surgery.

BACKGROUND: Perioperative studies of patients following hip fracture have large heterogeneity within their reported outcomes. This study aimed to develop a core outcome set for use in perioperative studies comparing the types of anaesthesia for hip fracture surgery. METHODS: The consensus process consisted of a systematic review of the literature, three rounds of a Delphi survey, two consensus webinars, and face-to-face patient meetings. RESULTS: The Delphi participants represented nine stakeholder groups. The numbers of participants completing Rounds 1-3 were 242, 186, and 169, respectively. Seventeen outcomes that met the predefined consensus criteria were considered at two consensus meetings. A final set of 10 core outcomes was agreed: mortality, time from injury to surgery, acute coronary syndrome, hypotension, acute kidney injury, delirium, pneumonia, orthogeriatric input, being out of bed at day 1, and pain. CONCLUSIONS: We generated a consensus-based set of core outcomes recommended for use in all perioperative trials evaluating the effects of anaesthesia for hip fracture surgery. An important next step is developing consensus-based consistency on how they should be measured. CLINICAL TRIAL REGISTRATION: http://www.comet-initiative.org/studies/details/757.

Maternal vitamin D and markers of glycaemia during pregnancy in the Belfast centre of the Hyperglycaemia and Adverse Pregnancy Outcome study.

AIMS: To measure total 25-hydroxyvitamin D levels in women in mid-pregnancy who participated in the Belfast centre of the Hyperglycaemia and Adverse Pregnancy Outcome (HAPO) observational study, and to investigate the associations between levels of 25-hydroxyvitamin D and markers of gestational diabetes mellitus and lipid biomarkers. METHODS: A total of 1585 pregnant women had serum samples available for measurement. Participants were recruited from the Royal Jubilee Maternity Hospital, Belfast, Northern Ireland, at 24-32 weeks' gestation, as part of the HAPO study. 25-hydroxyvitamin D concentrations were measured using liquid chromatography tandem mass spectrometry. Glucose, C-peptide and lipid levels were previously analysed in a central laboratory. Statistical analysis was performed. RESULTS: The median (interquartile range) 25-hydroxyvitamin D concentration during pregnancy was 38.6 (24.1-60.7) nmol/l, with 65.8% of women being vitamin D-deficient (≤50 nmol/l). In regression analysis, the association between maternal 25-hydroxyvitamin D and fasting plasma glucose levels approached significance [regression coefficient -0.017 (95% CI -0.034 to 0.001); P=0.06], and a significant positive association was observed between maternal 25-hydroxyvitamin D and ß-cell function [1.013 (95% CI 1.001 to 1.024); P=0.031]. Maternal 25-hydroxyvitamin D level was positively associated with HDL [0.047 (95% CI 0.021 to 0.073) P≤ 0.001] and total cholesterol [0.085 (95% CI 0.002 to 0.167); P=0.044] in regression analysis. CONCLUSIONS: These results indicate a high prevalence of vitamin D deficiency during pregnancy, which requires identification and treatment; however, only weak associations were observed between 25-hydroxyvitamin D level and markers of glucose and insulin metabolism. This would suggest that these are of doubtful clinical significance.

Perioperative outcomes in the context of mode of anaesthesia for patients undergoing hip fracture surgery: systematic review and meta-analysis.

BACKGROUND: Previous meta-analyses on the anaesthetic management of patients undergoing surgery for hip fracture have focused on randomized trials. Furthermore, heterogeneity in outcome reporting across the studies has made it difficult to inform best practice guidelines for patient care. METHODS: This systematic review examined how perioperative outcomes were reported and defined in the context of comparing modes of anaesthesia for hip fracture surgery. Outcomes were included from randomised and non-randomised studies published between January 2000 and July 2017. Meta-analyses were performed for regional versus general anaesthesia, with sensitivity analyses performed for spinal versus general anaesthesia. RESULTS: By including data from 15 large observational studies in this meta-analysis, we have increased the number of patients for whom outcomes were assessed from approximately 3000 to 202 000. There was no significant difference in 30-day mortality (OR 1.02; 95% CI 0.96, 1.07, I2 31%; n=200 616), prevalence of pneumonia (OR 1.07; 95% CI 0.94, 1.23, I2 34%; n=65 011), acute myocardial infarction (OR 0.96; 95% CI 0.88, 1.04, I2 0%, n=64 904), delirium (OR 1.07; 95% CI 0.72, 1.58, I2 93%, n=19 923), or renal failure (OR 0.94; 95% CI 0.54, 1.64, I2 0%, n=27 873) for regional compared with general anaesthesia [corrected]. There was a small statistically significant difference for length of stay (standardized mean difference -0.03; 95% CI -0.05, -0.02; I2 0%; n=78 711) favouring regional anaesthesia, which is unlikely to be clinically significant. Sensitivity analyses for the same outcomes examining spinal only vs general anaesthesia showed minor statistical significance for length of stay favouring spinal. We also present data highlighting the scale of the inconsistencies in reported outcomes across 32 studies, making evaluation in a standardized manner very difficult. As an example, mortality was reported in nine different ways throughout the studies. CONCLUSIONS: We highlight the need for agreement on outcome definitions and for a minimum core outcome set to be measured and reported in hip fracture studies. This would strengthen the evidence-based approach to delivering optimal care.

Barriers to adopting a Mediterranean diet in Northern European adults at high risk of developing cardiovascular disease.

BACKGROUND: Strong evidence links the consumption of a Mediterranean diet (MD) with a reduced cardiovascular disease (CVD) risk; however, there is uncertainty as to whether non-Mediterranean regions will adopt this diet. The present qualitative research aimed to investigate attitudes towards a MD in individuals at high CVD risk in a Northern European population. This information is needed to inform development of MD interventions in non-Mediterranean high-risk populations. METHODS: Focus groups (n = 12) were held with individuals at high CVD risk from Northern Europe (≥2 CVD risk factors, aged ≥50 years, no established CVD/type 2 diabetes). Attitudes to dietary change towards a MD were explored. Data were analysed using inductive thematic analysis. RESULTS: Sixty-seven adults participated (60% female, mean age 64 years). There was some awareness of the term MD but limited knowledge of its composition. Barriers to general dietary change were evident, including perception of expense, concern over availability, expectation of time commitment, limited knowledge, lack of cooking skills, amount and conflicting nature of media information on diets, changing established eating habits and resistance to dietary change. Barriers specific to MD adoption were also identified, including perceived difficulty living in a colder climate, perceived impact on body weight, acceptability of a MD and cultural differences. CONCLUSIONS: Knowledge of a MD was limited in this Northern European sample at high CVD risk. In addition to general barriers to dietary change, barriers specific to a MD were identified. These findings have implications for the development of interventions aiming to promote MD adoption in non-Mediterranean populations.

Effect of pregnancy planning on maternal and neonatal outcomes in women with Type 1 diabetes.

AIMS: To assess the effect of pregnancy planning on maternal and neonatal outcomes in women with Type 1 diabetes. METHODS: Pregnancy planning was assessed retrospectively in a cohort of women who participated in the Diabetes and Pre-eclampsia Intervention Trial (DAPIT). Pregnancy planning was determined based on self-report as to whether pregnancy was planned or unplanned. The effect of pregnancy planning on maternal and neonatal outcomes was examined, controlling for confounding variables. RESULTS: A total of 747 women were included in the study, of whom 39% considered their pregnancy unplanned. Characteristics associated with unplanned pregnancy included being younger (P<0.001), being a current smoker (P<0.001), being from a lower social class (P<0.001) and having higher HbA1c values prior to and throughout pregnancy (P≤0.005). Significantly fewer women with unplanned vs planned pregnancies received pre-pregnancy counselling (24% vs 64%; P<0.001). Infants of women with unplanned pregnancies were more likely to be small for gestational age (<5th centile; P=0.004), to be admitted to the neonatal care unit (P=0.001) and to have a longer stay in hospital (P=0.01). Outcomes did not differ between the groups in relation to pre-eclampsia, congenital malformations or a composite adverse outcome. CONCLUSIONS: Risks associated with diabetes in pregnancy need to be highlighted to all women, their partners and families, and healthcare professionals. Further research is required to determine if these groups are fully aware of the risks associated with diabetes in pregnancy.

Effect of implementation of a preconception counselling resource for women with diabetes: A population based study.

AIM: To evaluate the effect of regional implementation of a preconception counselling resource into routine diabetes care on pregnancy planning indicators. METHODS: A preconception counselling DVD was distributed to women by diabetes care teams and general practices. Subsequently, in a prospective population-based study, pregnancy planning indicators were evaluated. The post-DVD cohort (n=135), including a viewed-DVD subgroup (n=58), were compared with an historical cohort (pre-DVD, n=114). Primary outcome was HbA1c at first diabetes-antenatal visit. Secondary outcomes included preconception folic acid consumption, planned pregnancy and HbA1c recorded in the 6 months preconception. RESULTS: Mean first visit HbA1c was lower post-DVD vs. pre-DVD: 7.5% vs. 7.8% [58.4 vs. 61.8mmol/mol]; p=0.12), although not statistically significant. 53% and 20% of women with type 1 and 2 diabetes, respectively, viewed the DVD. The viewed-DVD subgroup were significantly more likely to have lower first visit HbA1c: 6.9% vs. 7.8% [52.1 vs. 61.8mmol/mol], P<0.001; planned pregnancy (88% vs. 59%, P<0.001); taken folic acid preconception (81% vs. 43%, P=0.001); and had HbA1c recorded preconception (88% vs. 53%, P<0.001) than the pre-DVD cohort. CONCLUSIONS: Implementation of a preconception counselling resource was associated with improved pregnancy planning indicators. Women with type 2 diabetes are difficult to reach. Greater awareness within primary care of the importance of preconception counselling among this population is needed.

Serum 25-hydroxyvitamin D and insulin resistance in people at high risk of cardiovascular disease: a euglycaemic hyperinsulinaemic clamp study.

CONTEXT: In observational studies, low serum 25-hydroxyvitamin D (25-OHD) concentration is associated with an increased risk of type 2 diabetes mellitus (DM). Increasing serum 25-OHD may have beneficial effects on insulin resistance or beta-cell function. Cross-sectional studies utilizing suboptimal methods for assessment of insulin sensitivity and serum 25-OHD concentration provide conflicting results. OBJECTIVE: This study examined the relationship between serum 25-OHD concentration and insulin resistance in healthy overweight individuals at increased risk of cardiovascular disease, using optimal assessment techniques. METHODS: A total of 92 subjects (mean age 56·0, SD 6·0 years), who were healthy but overweight (mean body mass index 30·9, SD 2·3 kg/m(2) ), underwent assessments of insulin sensitivity (two-step euglycaemic hyperinsulinaemic clamp, HOMA2-IR), beta-cell function (HOMA2%B), serum 25-OHD concentration and body composition (DEXA). RESULTS: Mean total 25-OHD concentration was 32·2, range 21·8-46·6 nmol/l. No association was demonstrated between serum 25-OHD concentration and insulin resistance. CONCLUSIONS: In this study using optimal assessment techniques to measure 25-OHD concentration, insulin sensitivity and body composition, there was no association between serum 25-OHD concentration and insulin resistance in healthy, overweight individuals at high risk of developing cardiovascular disease. This study suggests the documented inverse association between serum 25-OHD concentration and risk of type 2 DM is not mediated by a relationship between serum 25-OHD concentration and insulin resistance.

Increasing fruit and vegetable intake has no effect on retinal vessel caliber in adults at high risk of developing cardiovascular disease.

BACKGROUND AND AIM: Retinal vessel abnormalities are associated with cardiovascular disease (CVD) risk. To date, there are no trials investigating the effect of dietary factors on the retinal microvasculature. This study examined the dose response effect of fruit and vegetable (FV) intake on retinal vessel caliber in overweight adults at high CVD risk. METHODS AND RESULTS: Following a 4 week washout period, participants were randomized to consume either 2 or 4 or 7 portions of FV daily for 12 weeks. Retinal vessel caliber was measured at baseline and post-intervention. A total of 62 participants completed the study. Self-reported FV intake indicated good compliance with the intervention, with serum concentrations of zeaxanthin and lutein increasing significantly across the groups in a dose-dependent manner (P for trend < 0.05). There were no significant changes in body composition, 24-h ambulatory blood pressure or fasting blood lipid profiles in response to the FV intervention. Increasing age was a significant determinant of wider retinal venules (P = 0.004) whereas baseline systolic blood pressure was a significant determinant of narrower retinal arterioles (P = 0.03). Overall, there was no evidence of any short-term dose-response effect of FV intake on retinal vessel caliber (CRAE (P = 0.92) or CRVE (P = 0.42)). CONCLUSIONS: This study demonstrated no effect of increasing FV intake on retinal vessel caliber in overweight adults at high risk of developing primary CVD. CLINICAL TRIAL REGISTRATION: NCT00874341.

A Role for Behavior in the Relationships Between Depression and Hostility and Cardiovascular Disease Incidence, Mortality, and All-Cause Mortality: the Prime Study.

BACKGROUND: Behavioral factors are important in disease incidence and mortality and may explain associations between mortality and various psychological traits. PURPOSE: These analyses investigated the impact of behavioral factors on the associations between depression, hostility and cardiovascular disease(CVD) incidence, CVD mortality, and all-cause mortality. METHODS: Data from the PRIME Study (N = 6953 men) were analyzed using Cox proportional hazards models, following adjustment for demographic and biological CVD risk factors, and other psychological traits, including social support. RESULTS: Following initial adjustment, both depression and hostility were significantly associated with both mortality outcomes (smallest SHR = 1.24, p < 0.001). Following adjustment for behavioral factors, all relationships were attenuated both when accounting for and not accounting for other psychological variables. Associations with all-cause mortality remained significant (smallest SHR = 1.14, p = 0.04). Of the behaviors included, the most significant contribution to outcomes was found for smoking, but a role was also found for fruit and vegetable intakes and high alcohol consumption. CONCLUSIONS: These findings demonstrate well-known associations between depression, hostility, and mortality and suggest the potential importance of behaviors in explaining these relationships.

Seasonal variation in month of diagnosis in children with type 1 diabetes registered in 23 European centers during 1989-2008: little short-term influence of sunshine hours or average temperature.

BACKGROUND: The month of diagnosis in childhood type 1 diabetes shows seasonal variation. OBJECTIVE: We describe the pattern and investigate if year-to-year irregularities are associated with meteorological factors using data from 50 000 children diagnosed under the age of 15 yr in 23 population-based European registries during 1989-2008. METHODS: Tests for seasonal variation in monthly counts aggregated over the 20 yr period were performed. Time series regression was used to investigate if sunshine hour and average temperature data were predictive of the 240 monthly diagnosis counts after taking account of seasonality and long term trends. RESULTS: Significant sinusoidal pattern was evident in all but two small centers with peaks in November to February and relative amplitudes ranging from ± 11 to ± 38% (median ± 17%). However, most centers showed significant departures from a sinusoidal pattern. Pooling results over centers, there was significant seasonal variation in each age-group at diagnosis, with least seasonal variation in those under 5 yr. Boys showed greater seasonal variation than girls, particularly those aged 10-14 yr. There were no differences in seasonal pattern between four 5-yr sub-periods. Departures from the sinusoidal trend in monthly diagnoses in the period were significantly associated with deviations from the norm in average temperature (0.8% reduction in diagnoses per 1 °C excess) but not with sunshine hours. CONCLUSIONS: Seasonality was consistently apparent throughout the period in all age-groups and both sexes, but girls and the under 5 s showed less marked variation. Neither sunshine hour nor average temperature data contributed in any substantial way to explaining departures from the sinusoidal pattern.

The chromosome 3q25 locus associated with fetal adiposity is not associated with childhood adiposity.

Increased newborn adiposity is associated with later adverse metabolic outcomes. Previous genome-wide association studies (GWAS) demonstrated strong association of a locus on chromosome 3 (3q25.31) with newborn sum of skinfolds, a measure of overall adiposity. Whether this locus is associated with childhood adiposity is unknown. Genotype and sum of skinfolds data were available for 293 children at birth and age 2, and for 350 children at birth and age 6 from a European cohort (Belfast, UK) who participated in the Hyperglycemia and Adverse Pregnancy Outcome GWAS. We examined single nucleotide polymorphisms (SNPs) at the 3q25.31 locus associated with newborn adiposity. Linear regression analyses under an additive genetic model adjusting for maternal body mass index were performed. In both cohorts, a positive association was observed between all SNPs and sum of skinfolds at birth (P=2.3 × 10(-4), ß=0.026 and P=4.8 × 10(-4), ß=0.025). At the age of 2 years, a non-significant negative association was observed with sum of skinfolds (P=0.06; ß =-0.015). At the age of 6 years, there was no evidence of association (P=0.86; ß=0.002). The 3q25.31 locus strongly associated with newborn adiposity had no significant association with childhood adiposity suggesting that its impact may largely be limited to fetal fat accretion.

General practice-recorded depression and antidepressant use in young people with newly diagnosed Type 1 diabetes: a cohort study using the Clinical Practice Research Datalink.

AIMS: To investigate whether young people with Type 1 diabetes have an increased rate of depression and antidepressant use and whether their risk varies by age group, time from diabetes diagnosis, calendar period of diagnosis or complications status. METHODS: A cohort of incident cases of patients with Type 1 diabetes diagnosed before 35 years of age (n = 5548) was identified within the Clinical Practice Research Datalink and individually age and sex matched with up to two control subjects without diabetes (n = 10 657). Patients with depression were identified through general practice-recorded depression codes and antidepressant prescriptions. Cox regression models gave hazard ratios for depression in people with Type 1 diabetes compared with control subjects. RESULTS: People with Type 1 diabetes were twice as likely to have a record of antidepressant use and general practice-diagnosed depression as their matched control subjects (hazard ratio 2.08, 95% CI 1.73-2.50, P < 0.001). These associations varied by time from diagnosis, with marked increases observed within the first 5 years of diagnosis (hazard ratio 2.14, 95% CI 1.51-3.03, P < 0.001), and by age at diabetes diagnosis, with excesses noted even in the 10- to 19-year age group (hazard ratio 1.45, 95% CI 1.06-1.98, P = 0.02). CONCLUSIONS: This population-based study shows that people with Type 1 diabetes have higher rates of general practice-recorded depression and antidepressant use. The excess is present within 5 years of diabetes diagnosis, suggesting psychological input for patients is warranted in the early years of their condition.

Chronic kidney disease and diabetes in the national health service: a cross-sectional survey of the U.K. national diabetes audit.

AIMS: We investigated the prevalence of chronic kidney disease and attainment of therapeutic targets for HbA1c and blood pressure in a large U.K.-based diabetes population. METHODS: The U.K. National Diabetes Audit provided data from 1 January 2007 to 31 March 2008. Inclusion criteria were a documented urinary albumin:creatinine ratio and serum creatinine. Patients were stratified according to chronic kidney disease stage and albuminuria status. Chronic kidney disease was defined as an estimated glomerular filtration rate < 60 ml min(-1) 1.73 m(-2) , albuminuria or both. The proportions of patients achieving nationally defined glycaemic and systolic blood pressure targets were determined. RESULTS: The cohort comprised 1,423,669 patients, of whom 868,616 (61%) met inclusion criteria. Of the patients analysed, 92.2% had Type 2 diabetes. A higher proportion of people with Type 2 diabetes (42.3%) had renal dysfunction compared with those with Type 1 diabetes (32.4%). Achievement of systolic blood pressure and HbA1c targets was poor. Among people with Type 1 diabetes, 67.8% failed to achieve an HbA1c < 58 mmol/mol (7.5%). Of all people with diabetes, 37.8% failed to achieve a systolic blood pressure < 140 mmHg. Blood pressure control was poor in advanced chronic kidney disease. For example, mean (standard deviation) systolic blood pressure rose from 128.6 (15.4) mmHg among people with Type 1 diabetes and normal renal function to 141.0 (23.6) mmHg in those with chronic kidney disease stage 5 and macroalbuminuria. CONCLUSIONS: The high prevalence of chronic kidney disease and poor attainment of treatment targets highlights a large subset of the diabetes population at increased risk of cardiovascular mortality or progressive kidney disease.

Depression and mortality: artifact of measurement and analysis?

BACKGROUND: Previous research demonstrates various associations between depression, cardiovascular disease (CVD) incidence and mortality, possibly as a result of the different methodologies used to measure depression and analyse relationships. This analysis investigated the association between depression, CVD incidence (CVDI) and mortality from CVD (MCVD), smoking related conditions (MSRC), and all causes (MALL), in a sample data set, where depression was measured using items from a validated questionnaire and using items derived from the factor analysis of a larger questionnaire, and analyses were conducted based on continuous data and grouped data. METHODS: Data from the PRIME Study (N=9798 men) on depression and 10-year CVD incidence and mortality were analysed using Cox proportional hazards models. RESULTS: Using continuous data, both measures of depression resulted in the emergence of positive associations between depression and mortality (MCVD, MSRC, MALL). Using grouped data, however, associations between a validated measure of depression and MCVD, and between a measure of depression derived from factor analysis and all measures of mortality were lost. LIMITATIONS: Low levels of depression, low numbers of individuals with high depression and low numbers of outcome events may limit these analyses, but levels are usual for the population studied. CONCLUSIONS: These data demonstrate a possible association between depression and mortality but detecting this association is dependent on the measurement used and method of analysis. Different findings based on methodology present clear problems for the elucidation and determination of relationships. The differences here argue for the use of validated scales where possible and suggest against over-reduction via factor analysis and grouping.

Haptoglobin phenotype, pre-eclampsia, and response to supplementation with vitamins C and E in pregnant women with type-1 diabetes.

OBJECTIVE: The phenotype of the antioxidant and pro-angiogenic protein haptoglobin (Hp) predicts cardiovascular disease risk and treatment response to antioxidant vitamins in individuals with diabetes. Our objective was to determine whether Hp phenotype influences pre-eclampsia risk, or the efficacy of vitamins C and E in preventing pre-eclampsia, in women with type-1 diabetes. DESIGN: This is a secondary analysis of a randomised controlled trial in which women with diabetes received daily vitamins C and E, or placebo, from 8 to 22 weeks of gestation until delivery. SETTING: Twenty-five antenatal metabolic clinics across the UK (in north-west England, Scotland, and Northern Ireland). POPULATION: Pregnant women with type-1 diabetes. METHODS: Hp phenotype was determined in white women who completed the study and had plasma samples available (n = 685). MAIN OUTCOME MEASURE: Pre-eclampsia. RESULTS: Compared with Hp 2-1, Hp 1-1 (OR 0.59, 95% CI 0.30-1.16) and Hp 2-2 (OR 0.93, 95% CI 0.60-1.45) were not associated with significantly decreased pre-eclampsia risk after adjusting for treatment group and HbA1c at randomisation. Our study was not powered to detect an interaction between Hp phenotype and treatment response; however, our preliminary analysis suggests that vitamins C and E did not prevent pre-eclampsia in women of any Hp phenotype (Hp 1-1, OR 0.77, 95% CI 0.22-2.71; Hp 2-1, OR 0.81, 95% CI 0.46-1.43; Hp 2-2, 0.67, 95% CI 0.34-1.33), after adjusting for HbA1c at randomisation. CONCLUSIONS: The Hp phenotype did not significantly affect pre-eclampsia risk in women with type-1 diabetes.

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

AIMS/HYPOTHESIS: The 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. METHODS: All 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. RESULTS: Ascertainment 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/INTERPRETATION: The 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.