Cancer incidence and mortality in 23 000 patients with type 1 diabetes in the UK: Long-term follow-up.

Type 2 diabetes is associated with raised risk of several cancers, but for type 1 diabetes risk data are fewer and inconsistent We assembled a cohort of 23 473 UK patients with insulin-treated diabetes diagnosed at ages <30, almost all of whom will have had type 1 diabetes, and for comparison 5058 diagnosed at ages 30 to 49, of whom we estimate two-thirds will have had type 2, and followed them for an average of 30 years for cancer incidence and mortality compared with general population rates. Patients aged <30 at diabetes diagnosis had significantly raised risks only for ovarian (standardised incidence ratio = 1.58; 95% confidence interval 1.16-2.11; P < .01) and vulval (3.55; 1.94-5.96; P < .001) cancers, with greatest risk when diabetes was diagnosed at ages 10-14. Risks of cancer overall (0.89; 0.84-0.95; P < .001) and sites including lung and larynx were significantly diminished. Patients diagnosed with diabetes at ages 30 to 49 had significantly raised risks of liver (1.76;1.08-2.72) and kidney (1.46;1.03-2.00) cancers, and reduced risk of cancer overall (0.89; 0.84-0.95). The raised ovarian and vulval cancer risks in patients with type 1 diabetes, especially with diabetes diagnosed around pubertal ages, suggest possible susceptibility of these organs at puberty to metabolic disruption at diabetes onset. Reduced risk of cancer overall, particularly smoking and alcohol-related sites, might reflect adoption of a healthy lifestyle.

Subgingival microbial diversity and respiratory decline: A cross-sectional study.

AIM: To investigate whether there is an association between subgingival microbial diversity and reduced respiratory function. MATERIALS AND METHODS: A group of dentate 58-72-year-old men in Northern Ireland had a comprehensive periodontal examination including subgingival plaque sampling. DNA was extracted from plaque samples and the V1-V3 regions of the 16S rRNA gene were analysed by high-throughput sequencing and a microbial diversity index (MDI) was derived. Spirometry measurements were made using a wedge bellows spirometer. The primary outcome variable of interest was the percentage of predicted forced expiratory volume in 1 s (% predicted FEV1 ). Analysis included multiple linear regression with adjustment for various confounders. RESULTS: Five-hundred and seven men were included in the analysis. The mean age was 63.6 years (SD = 3.1). Of these, 304 (60.0%) men had no or mild periodontitis, 105 (20.7%) had moderate periodontitis and 98 (19.3%) had severe periodontitis. Multiple linear regression analysis showed that a one unit increase in MDI was associated with a 0.71% loss (95% confidence interval: 0.06%-1.35%; p = .03) in % predicted FEV1 after adjustment for all confounders. CONCLUSIONS: In this group of dentate men from Northern Ireland, subgingival microbial diversity was associated with reduced respiratory function.

Albuminuria-Related Genetic Biomarkers: Replication and Predictive Evaluation in Individuals with and without Diabetes from the UK Biobank.

Increased albuminuria indicates underlying glomerular pathology and is associated with worse renal disease outcomes, especially in diabetic kidney disease. Many single nucleotide polymorphisms (SNPs), associated with albuminuria, could be potentially useful to construct polygenic risk scores (PRSs) for kidney disease. We investigated the diagnostic accuracy of SNPs, previously associated with albuminuria-related traits, on albuminuria and renal injury in the UK Biobank population, with a particular interest in diabetes. Multivariable logistic regression was used to evaluate the influence of 91 SNPs on urine albumin-to-creatinine ratio (UACR)-related traits and kidney damage (any pathology indicating renal injury), stratifying by diabetes. Weighted PRSs for microalbuminuria and UACR from previous studies were used to calculate the area under the receiver operating characteristic curve (AUROC). CUBN-rs1801239 and DDR1-rs116772905 were associated with all the UACR-derived phenotypes, in both the overall and non-diabetic cohorts, but not with kidney damage. Several SNPs demonstrated different effects in individuals with diabetes compared to those without. SNPs did not improve the AUROC over currently used clinical variables. Many SNPs are associated with UACR or renal injury, suggesting a role in kidney dysfunction, dependent on the presence of diabetes in some cases. However, individual SNPs or PRSs did not improve the diagnostic accuracy for albuminuria or renal injury compared to standard clinical variables.

Trial to Encourage Adoption and Maintenance of a MEditerranean Diet (TEAM-MED): a randomised pilot trial of a peer support intervention for dietary behaviour change in adults from a Northern European population at high CVD risk.

Adhering to a Mediterranean diet (MD) is associated with reduced CVD risk. This study aimed to explore methods of increasing MD adoption in a non-Mediterranean population at high risk of CVD, including assessing the feasibility of a developed peer support intervention. The Trial to Encourage Adoption and Maintenance of a MEditerranean Diet was a 12-month pilot parallel group RCT involving individuals aged ≥ 40 year, with low MD adherence, who were overweight, and had an estimated CVD risk ≥ 20 % over ten years. It explored three interventions, a peer support group, a dietician-led support group and a minimal support group to encourage dietary behaviour change and monitored variability in Mediterranean Diet Score (MDS) over time and between the intervention groups, alongside measurement of markers of nutritional status and cardiovascular risk. 118 individuals were assessed for eligibility, and 75 (64 %) were eligible. After 12 months, there was a retention rate of 69 % (peer support group 59 %; DSG 88 %; MSG 63 %). For all participants, increases in MDS were observed over 12 months (P < 0·001), both in original MDS data and when imputed data were used. Improvements in BMI, HbA1c levels, systolic and diastolic blood pressure in the population as a whole. This pilot study has demonstrated that a non-Mediterranean adult population at high CVD risk can make dietary behaviour change over a 12-month period towards an MD. The study also highlights the feasibility of a peer support intervention to encourage MD behaviour change amongst this population group and will inform a definitive trial.

Type 1 diabetes in 2017: global estimates of incident and prevalent cases in children and adults.

AIMS/HYPOTHESIS: Data on type 1 diabetes incidence and prevalence are limited, particularly for adults. This study aims to estimate global numbers of incident and prevalent cases of type 1 diabetes in 2017 for all age groups, by country and areas defined by income and region. METHODS: Incidence rates of type 1 diabetes in children (available from 94 countries) from the IDF Atlas were used and extrapolated to countries without data. Age-specific incidence rates in adults (only known across full age range for fewer than ten countries) were obtained by applying scaling ratios for each adult age group relative to the incidence rate in children. Age-specific incidence rates were applied to population estimates to obtain incident case numbers. Duration of diabetes was estimated from available data and adjusted using differences in childhood mortality rate between countries from United Nations demographic data. Prevalent case numbers were derived by modelling the relationship between prevalence, incidence and disease duration. Sensitivity analyses were performed to quantify the impact of alternative assumptions and model inputs. RESULTS: Global numbers of incident and prevalent cases of type 1 diabetes were estimated to be 234,710 and 9,004,610, respectively, in 2017. High-income countries, with 17% of the global population, accounted for 49% of global incident cases and 52% of prevalent cases. Asia, which has the largest proportion of the world's population (60%), had the largest number of incident (32%) and prevalent (31%) cases of type 1 diabetes. Globally, 6%, 35%, 43% and 16% of prevalent cases were in the age groups 0-14, 15-39, 40-64 and 65+ years, respectively. Based on sensitivity analyses, the estimates could deviate by ±15%. CONCLUSIONS/INTERPRETATION: Globally, type 1 diabetes represents about 2% of the estimated total cases of diabetes, ranging from less than 1% in certain Pacific countries to more than 15% in Northern European populations in 2017. This study provides information for the development of healthcare and policy approaches to manage type 1 diabetes. The estimates need further validation due to limitations and assumptions related to data availability and estimation methods.

A systematic review and participant-level meta-analysis found little association of retinal microvascular caliber with reduced kidney function.

Previously, variation in retinal vascular caliber has been reported in association with chronic kidney disease (CKD) but findings remain inconsistent. To help clarify this we conducted individual participant data meta-analysis and aggregate data meta-analysis on summary estimates to evaluate cross-sectional associations between retinal vascular caliber and CKD. A systematic review was performed using Medline and EMBASE for articles published until October 2018. The aggregate analysis used a two-stage approach combining summary estimates from eleven studies (44,803 patients) while the individual participant analysis used a one-stage approach combining raw data from nine studies (33,222 patients). CKD stages 3-5 was defined as an estimated glomerular filtration rate under 60 mL/min/1.73m2. Retinal arteriolar and venular caliber (central retinal arteriolar and venular equivalent) were assessed from retinal photographs using computer-assisted methods. Logistic regression estimated relative risk of CKD stages 3-5 associated with a 20 µm decrease (approximately one standard deviation) in central retinal arteriolar and venular equivalent. Prevalence of CKD stages 3-5 was 11.2% of 33,222 and 11.3% of 44,803 patients in the individual participant and aggregate data analysis, respectively. No significant associations were detected in adjusted analyses between central retinal arteriolar and venular equivalent and CKD stages 3-5 in the aggregate analysis for central retinal arteriolar relative risk (0.98, 95% confidence interval 0.94-1.03); venular equivalent (0.99, 0.95-1.04) or individual participant central retinal arteriolar (0.99, 0.95-1.04) or venular equivalent (1.01, 0.97-1.05). Thus, meta-analysis provided little evidence to suggest that cross sectional direct measurements of retinal vascular caliber was associated with CKD stages 3-5 in the general population. Hence, meta-analyses of longitudinal studies evaluating the association between retinal parameters and CKD stages 3-5 may be warranted.

Association between overall fruit and vegetable intake, and fruit and vegetable sub-types and blood pressure: the PRIME study (Prospective Epidemiological Study of Myocardial Infarction).

Increased fruit and vegetable (FV) intake is associated with reduced blood pressure (BP). However, it is not clear whether the effect of FV on BP depends on the type of FV consumed. Furthermore, there is limited research regarding the comparative effect of juices or whole FV on BP. Baseline data from a prospective cohort study of 10 660 men aged 50-59 years examined not only the cross-sectional association between total FV intake but also specific types of FV and BP in France and Northern Ireland. BP was measured, and dietary intake assessed using FFQ. After adjusting for confounders, both systolic BP (SBP) and diastolic BP (DBP) were significantly inversely associated with total fruit, vegetable and fruit juice intake; however, when examined according to fruit or vegetable sub-type (citrus fruit, other fruit, fruit juices, cooked vegetables and raw vegetables), only the other fruit and raw vegetable categories were consistently associated with reduced SBP and DBP. In relation to the risk of hypertension based on SBP >140 mmHg, the OR for total fruit, vegetable and fruit juice intake (per fourth) was 0·95 (95 % CI 0·91, 1·00), with the same estimates being 0·98 (95 % CI 0·94, 1·02) for citrus fruit (per fourth), 1·02 (95 % CI 0·98, 1·06) for fruit juice (per fourth), 0·93 (95 % CI 0·89, 0·98) for other fruit (per fourth), 1·05 (95 % CI 0·99, 1·10) for cooked vegetable (per fourth) and 0·86 (95 % CI 0·80, 0·91) for raw vegetable intakes (per fourth). Similar results were obtained for DBP. In conclusion, a high overall intake of fruit, vegetables and fruit juice was inversely associated with SBP, DBP and risk of hypertension, but this differed by FV sub-type, suggesting that the strength of the association between FV sub-types and BP might be related to the type consumed, or to processing or cooking-related factors.

Changes in glycated hemoglobin, diabetes knowledge, quality of life, and anxiety in children and adolescents with type 1 diabetes attending summer camps: A systematic review and meta-analysis.

Diabetes summer camps provide children and adolescents with type 1 diabetes opportunities to learn about the disease and its management in a supportive environment to help improve glycemic control, self-reliance, and quality of life. The objective of this quantitative review was to assess the advantages of attending summer camps and study any adverse psychological effects. Studies with a pre/post study design in children and adolescents attending summer camp were systematically reviewed. Five bibliographic databases were searched and relevant data extracted. Random effects meta-analyses were used to combine the individual study results to derive pooled estimates and meta-regression was used to explore between-study heterogeneity. Studies in the literature report short-term improvements in the glycemic control, diabetes knowledge (DK), quality of life (QOL) anxiety, diabetes self-management, and self-esteem. Thirty-three studies were identified, and those outcomes reported in five or more studies were included in meta-analyses. There were significant benefits with a pooled mean change for glycated hemoglobin (95% CI) of -0.59(-0.95,-0.23)% (-6.4[-10.4,-2.5]mmol/mol), and for standardized DK score of 1.99(1.28,2.70) but corresponding changes for QOL 0.17(-0.06,0.39) and for anxiety -0.32(-0.70, 0.06) were not significant. However, all outcomes showed considerable between-study heterogeneity little of which was explained by study characteristics. The findings suggest short-term benefits of camp on metabolic control, DK, QOL and anxiety in T1D children and adolescents, although the latter two were not statistically significant. Further research is warranted with more methodological rigor and longer-term follow-up to determine if there are long-term benefits associated with camp attendance.

Systemic inflammation and the relationship between periodontitis, edentulism, and all-cause mortality: A 17-year prospective cohort study.

AIM: The aim was to investigate the role of systemic inflammation in the relationship between periodontitis, edentulism, and all-cause mortality in a group of men in Northern Ireland aged 58-72 years. MATERIALS AND METHODS: A representative sample of 1558 men had a detailed dental examination between 2001 and 2003. The primary end point was death from any cause. Cox's proportional hazards model was used to assess the longitudinal relationship between periodontitis, edentulism, and all-cause mortality. Accelerated failure time modelling was performed to investigate the mediating role of systemic inflammation. RESULTS: Mean age of the men at baseline was 64.3 (standard deviation 2.9) years. During a median follow-up of 17 years, 500 (32.1%) men died. After adjustment for confounding variables, compared to men with no/mild periodontitis, edentulous men had a hazard ratio for all-cause mortality of 1.52 (95% confidence interval [CI] 1.16-1.99) p < .01 and for those with severe periodontitis, it was 1.34 (95% CI 1.06-1.70) p = .01. Systemic inflammation accounted only for a minor mediating pathway effect of 10%. CONCLUSIONS: There was evidence in this group of men that those who were edentulous or had severe periodontitis had a significantly increased risk of all-cause mortality. Systemic inflammation was not a major explanatory mediator of this association.

Periodontitis and risk of prevalent and incident coronary heart disease events.

OBJECTIVE: To investigate periodontitis as a risk factor for prevalent and incident coronary heart disease (CHD) in a group of middle-aged men from Northern Ireland. METHODS: A representative sample of 1400 dentate men had a comprehensive periodontal examination between 2001 and 2003. Prevalent and incident CHD events were validated by independent cardiologists. Logistic regression was used to assess the cross-sectional relationship between periodontitis and prevalent CHD and Cox's proportional hazards analysis to assess the longitudinal relationship between periodontitis and incident CHD. RESULTS: The mean age of the men at baseline was 63.7 (SD 3.0) years. Of the 1400 men examined, 126 (9%) had prevalent CHD. After adjusting for confounding variables, men with highest mean CAL (Q4) had an odds ratio of 2.15 (95% CI 1.15-4.02), p = 0.02 for prevalent CHD in comparison to men with the lowest CAL (Q1). During a median follow-up of 12.7 years, 137 (10.8%) of the 1274 men free of CHD at baseline had an incident CHD event. After adjusting for confounding variables, the hazard ratio for incident CHD in men in Q4 versus Q1 CAL categories was 1.36 (95% CI 0.81-2.29), p = 0.24. CONCLUSIONS: In this group of dentate men, periodontitis was associated with prevalent CHD. However, there was no association with incident CHD.

Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25 year period 1989-2013: a multicentre prospective registration study.

AIMS/HYPOTHESIS: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years. METHODS: Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989-2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends. RESULTS: Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004-2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012. CONCLUSIONS/INTERPRETATION: Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.

Chronic periodontitis and reduced respiratory function.

OBJECTIVE: To investigate whether there was an association between chronic periodontitis (CP) and reduced respiratory function. METHODS: A group of dentate 58- to 72-year-old men in Northern Ireland had a comprehensive periodontal examination. Parallel to the periodontal examination, participants completed questionnaires gathering information on their medical history, social circumstances, demographic background and tobacco use. A physical examination assessed anthropometric measures. Fasting blood samples were obtained and analysed for high-sensitivity C-reactive protein (hs-CRP). Spirometry measures were performed using a wedge bellows spirometer (Vitalograph S Model). The primary outcome variable of interest was the percentage predicted forced expiratory volume in one-second (% predicted FEV1 ). Analysis included multiple linear regression with adjustment for various confounders and a regression-based mediation analysis. RESULTS: A total of 1,380 men were included in the analysis. The mean age was 63.7 years (SD 3.0). Multiple linear regression analysis showed that a doubling in mean clinical attachment loss (CAL) equated to a -3.33% (95% CI: -4.80, -1.86), p < 0.001 change in % predicted FEV1 after adjustment for all other potential confounding variables. Systemic inflammation, as measured by hs-CRP, only accounted for a minor mediating pathway effect (9%). CONCLUSIONS: In this homogenous group of dentate men, CP was significantly associated with a reduced respiratory function.

Predicting Outcomes from Engagement With Specific Components of an Internet-Based Physical Activity Intervention With Financial Incentives: Process Analysis of a Cluster Randomized Controlled Trial.

BACKGROUND: Investigating participant engagement and nonusage attrition can help identify the likely active ingredients of electronic health interventions. Research on engagement can identify which intervention components predict health outcomes. Research on nonusage attrition is important to make recommendations for retaining participants in future studies. OBJECTIVE: This study aimed to investigate engagement and nonusage attrition in the Physical Activity Loyalty (PAL) scheme, a 6-month complex physical activity intervention in workplaces in Northern Ireland. The intervention included financial incentives with reward redemption and self-regulation techniques. Specific objectives were (1) to determine whether engagement in specific intervention components predicted physical activity at 6 months, (2) to determine whether engagement in specific intervention components predicted targeted mediators at 6 months, and (3) to investigate predictors of nonusage attrition for participants recording daily activity via the PAL scheme physical activity monitoring system and logging onto the website. METHODS: Physical activity was assessed at baseline and 6 months using pedometers (Yamax Digiwalker CW-701, Japan). Markers of engagement and website use, monitoring system use, and reward redemption were collected throughout the scheme. Random-effects generalized least-squares regressions determined whether engagement with specific intervention components predicted 6-month physical activity and mediators. Cox proportional hazards regressions were used to investigate predictors of nonusage attrition (days until first 2-week lapse). RESULTS: A multivariable generalized least-squares regression model (n=230) showed that the frequency of hits on the website's monitoring and feedback component (regression coefficient [b]=50.2; SE=24.5; P=.04) and the percentage of earned points redeemed for financial incentives (b=9.1; SE=3.3; P=.005) were positively related to 6-month pedometer steps per day. The frequency of hits on the discussion forum (b=-69.3; SE=26.6; P=.009) was negatively related to 6-month pedometer steps per day. Reward redemption was not related to levels of more internal forms of motivation. Multivariable Cox proportional hazards regression models identified several baseline predictors associated with nonusage attrition. These included identified regulation (hazard ratio [HR] 0.88, 95% CI 0.81-0.97), recovery self-efficacy (HR 0.88, 95% CI 0.80-0.98), and perceived workplace environment safety (HR 1.07, 95% CI 1.02-1.11) for using the physical activity monitoring system. The EuroQoL health index (HR 0.33, 95% CI 0.12-0.91), financial motivation (HR 0.93, 95% CI 0.87-0.99), and perceived availability of physical activity opportunities in the workplace environment (HR 0.96, 95% CI 0.93-0.99) were associated with website nonusage attrition. CONCLUSIONS: Our results provide evidence opposing one of the main hypotheses of self-determination theory by showing that financial rewards are not necessarily associated with decreases in more internal forms of motivation when offered as part of a complex multicomponent intervention. Identifying baseline predictors of nonusage attrition can help researchers to develop strategies to ensure maximum intervention adherence. TRIAL REGISTRATION: ISRCTN Registry ISRCTN17975376; http://www.isrctn.com/ISRCTN17975376 (Archived by WebCite at http://www.webcitation.org/76VGZsZug).

Mediators of Behavior Change Maintenance in Physical Activity Interventions for Young and Middle-Aged Adults: A Systematic Review.

Background: Regular physical activity is important for maintaining physical and mental health. Benefits are optimized when physical activity is maintained. Understanding causal mechanisms is important to inform future interventions. Purpose: To investigate mediators of physical activity maintenance. Methods: Six databases were searched (Medline, EMBASE, PsycINFO, CINAHL, Cochrane Database of Systematic Reviews, and Web of Science). Eligibility criteria included adult nonclinical populations, validated measure of physical activity behavior at baseline and at least 6 months postbaseline, control/comparison group(s), and reported mediators of physical activity behavior change. Mediators were examined according to (i) formal mediation tests, (ii) mediator association with physical activity outcome, and (iii) intervention effects on mediators. Results: There were few formal mediation tests conducted (n = 12/39 included studies), and various other methodological limitations were identified. There was some evidence that effective mediators in formal mediation tests at 6 months and later included the "behavioral processes of change" (n = 5/6). Many of the included interventions were not effective for changing targeted mediators (only 34% of 413 tests of mediator changes were significant). Conclusions: There were a number of methodological and statistical limitations in the evidence base. In future, prespecified formal mediation tests should be carried out and could be aided by a formal framework. Social and environmental variables should be considered in addition to intrapersonal variables. Improving knowledge of how to change hypothesized mediators, based on theory and evidence, will reveal how physical activity behavior change maintenance can be achieved. Maintenance research would be enhanced by establishing a formal definition of behavior change "maintenance." PROSPERO registration: PROSPERO 2015:CRD- 42015025462.

Effectiveness and cost-effectiveness of a loyalty scheme for physical activity behaviour change maintenance: results from a cluster randomised controlled trial.

BACKGROUND: We evaluated the effectiveness and cost-effectiveness of a loyalty scheme based intervention involving rewards for increasing physical activity in public sector employees. METHODS: A cluster randomised wait-list controlled trial in public sector organisations in Northern Ireland. We randomly assigned clusters (1:1) using a computer generated random sequence. Researchers were masked to allocation, but participants were not. Employees aged 18-65 years with no self-reported medical contraindications to physical activity were included. The Physical Activity Loyalty Scheme (PAL) intervention was based on high-street loyalty cards where participants earned points for minutes of activity that could be redeemed for rewards, complemented by evidence-based behaviour change techniques. The primary outcome was objectively measured mean steps/day at 6 months using a validated pedometer (Yamax Digi-Walker CW-701) over 7 days, assessed with intention to treat analysis. Secondary outcomes included health, mental wellbeing, quality of life, work absenteeism and presenteeism, and use of healthcare resources. Cost-effectiveness, cost-benefit and mediation analyses were conducted. Trial registered with Current Controlled Trials, number ISRCTN17975376. RESULTS: Between September 2014 and October 2015, we recruited and randomly assigned 37 clusters (from nine organisations; mean clusters per organisation = four) and 853 participants to the intervention (n = 19 with 457 participants) or control group (n = 18 with 396 participants). Primary outcome data were available for 249 (54·4%) intervention and 236 (59·6%) control participants. Mean steps/day were significantly lower in the intervention vs control group (adjusted mean difference = - 336, 95% CI: -612 to - 60, p = 0·02) at 6 months. Participants redeemed only 39% (SD 43%) of their earned points. Using the Quality Adjusted Life Year outcome, the intervention was not cost effective from an NHS/PSS perspective. A net cost analysis from an employer perspective demonstrated the intervention group was associated with a mean of 2·97 h less absenteeism over a 4 week period (p = 0·62), which could result in net savings ranging from £66 to £735 depending on the wage rate employed. At 4-weeks post-baseline there were significant increases in identified regulation, integrated regulation, intrinsic motivation, social norms and intentions in intervention compared to control participants. CONCLUSIONS: Our mixed results pose challenges that are too infrequently exposed in public heath intervention trials. Although the intervention successfully altered several hypothesised mediating constructs it did not translate into long-term behaviour change. Our incentive level may have been too low to incentivise change, despite being designed a priori by a Contingent Valuation Survey. There were also major re-structuring of several organisations which presented significant implementation challenges, and technical limitations. TRIAL REGISTRATION: ISRCTN17975376 (Registered 19/09/2014).

Mortality in type 1 diabetes diagnosed in childhood in Northern Ireland during 1989-2012: A population-based cohort study.

OBJECTIVE: To investigate long-term mortality rates and causes of death in individuals diagnosed with type 1 diabetes before the age of 15 years during the period 1989-2012 or known to paediatric diabetes teams in 1989, in Northern Ireland. METHODS: A cohort of 3129 patients from the Northern Ireland Childhood Diabetes Register was linked to death registrations and underlying causes, coded according to ICD-9 or ICD-10. Standardized mortality ratios (SMRs) were calculated as the ratio of observed to expected deaths by sex, attained age, time since diagnosis, calendar period, and cause of death. RESULTS: Subjects were followed to December 31, 2012 giving 39 764 person-years of follow-up (median 12.1 years). In total, 59 subjects had died (1.5 per 1000 person-years) compared with 19.9 deaths expected, an SMR of 296 (95% confidence interval (CI) 229-382). Women had a significantly higher excess risk of mortality than men with SMRs of 535 (95% CI 361-764) and 203 (95% CI 136-291), respectively. Over half of the deaths (56%) were judged to be related or possibly related to diabetes with most of these due to acute (n = 24) or late (n = 6) complications. CONCLUSIONS: Subjects with type 1 diabetes diagnosed less than 15 years of age had 3 times the mortality risk of the general population. Over half of the deaths were related to acute or chronic complications of diabetes.

Circulating adipokines are associated with pre-eclampsia in women with type 1 diabetes.

AIMS/HYPOTHESIS: The incidence of pre-eclampsia, a multisystem disorder of pregnancy, is fourfold higher in type 1 diabetic than non-diabetic women; it is also increased in women with features of the metabolic syndrome and insulin resistance. In a prospective study of pregnant women with type 1 diabetes, we measured plasma levels of adipokines known to be associated with insulin resistance: leptin, fatty acid binding protein 4 (FABP4), adiponectin (total and high molecular weight [HMW]; also known as high molecular mass), retinol binding protein 4 (RBP4) and resistin and evaluated associations with the subsequent development of pre-eclampsia. METHODS: From an established prospective cohort of pregnant type 1 diabetic women, we studied 23 who developed pre-eclampsia and 24 who remained normotensive; for reference values we included 19 healthy non-diabetic normotensive pregnant women. Plasma adipokines were measured (by ELISA) in stored samples from three study visits (Visit 1- Visit 3) at different gestational ages (mean ± SD): Visit 1, 12.4 ± 1.8 weeks; Visit 2, 21.7 ± 1.4 weeks; and Visit 3, 31.4 ± 1.5 weeks. All the women were free of microalbuminuria and hypertension at enrolment. All study visits preceded the clinical onset of pre-eclampsia. RESULTS: In all groups, leptin, the ratio of leptin to total or HMW adiponectin, FABP4 concentration, ratio of FABP4 to total or HMW adiponectin and resistin level increased, while total and HMW adiponectin decreased, with gestational age. At Visit 1: (1) in diabetic women with vs without subsequent pre-eclampsia, leptin, ratio of leptin to total or HMW adiponectin, and ratio of FABP4 to total or HMW adiponectin, were increased (p < 0.05), while total adiponectin was decreased (p < 0.05); and (2) in normotensive diabetic vs non-diabetic women, total adiponectin was elevated (p < 0.05). At Visits 2 and 3: (1) the primary findings in the two diabetic groups persisted, and FABP4 also increased in women with subsequent pre-eclampsia (p < 0.05); and (2) there were no differences between the two normotensive groups. By logistic regression analyses after covariate adjustment (HbA1c, insulin kg-1 day-1 and gestational age), the best predictive models for pre-eclampsia were as follows: Visit 1, doubling of leptin, OR 9.0 (p < 0.01); Visit 2, doubling of the leptin:total adiponectin ratio, OR 3.7 (p < 0.05); and Visit 3, doubling of FABP4 concentration, OR 25.1 (p < 0.01). The associations were independent of BMI. CONCLUSIONS/INTERPRETATION: As early as the first trimester in type 1 diabetic women, adipokine profiles that suggest insulin resistance are associated with subsequent pre-eclampsia, possibly reflecting maternal characteristics that precede pregnancy. These associations persist in the second and third trimesters, and are independent of BMI. Insulin resistance may predispose women with type 1 diabetes to pre-eclampsia.

Periodontitis and incident type 2 diabetes: a prospective cohort study.

OBJECTIVES: The aim of this study was to investigate periodontitis as a risk factor for incident type 2 diabetes mellitus (T2DM) in a group of men aged 58-72 years. METHODS: One thousand three hundred and thirty-one dentate, diabetes-free men in Northern Ireland underwent a detailed periodontal examination during 2001-2003. Follow-up was by bi-annual questionnaire and for those reporting diabetes their general medical practitioner was contacted to validate diabetes type, treatment and diagnosis date. Cox's proportional hazard models were used to estimate the effect of periodontitis on incident diabetes. Multivariable analysis included adjustment for various known confounders. RESULTS: The mean age of the men was 63.7 (SD 3.0) years. There were 80 cases (6.0%) of incident T2DM. Follow-up was for a median period of 7.8 years (IQR 6.7-8.3). After adjusting for confounding variables, the hazard ratio (HR) for incident T2DM in men with moderate/severe periodontitis versus those with no/mild periodontitis was 1.69 (95% CI 1.06-2.69), p = 0.03. CONCLUSION: There was evidence in this homogenous group of dentate men, that those with moderate to severe periodontitis had a significantly increased risk of incident T2DM.

Troponin I and cardiovascular risk prediction in the general population: the BiomarCaRE consortium.

AIMS: Our aims were to evaluate the distribution of troponin I concentrations in population cohorts across Europe, to characterize the association with cardiovascular outcomes, to determine the predictive value beyond the variables used in the ESC SCORE, to test a potentially clinically relevant cut-off value, and to evaluate the improved eligibility for statin therapy based on elevated troponin I concentrations retrospectively. METHODS AND RESULTS: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, we analysed individual level data from 10 prospective population-based studies including 74 738 participants. We investigated the value of adding troponin I levels to conventional risk factors for prediction of cardiovascular disease by calculating measures of discrimination (C-index) and net reclassification improvement (NRI). We further tested the clinical implication of statin therapy based on troponin concentration in 12 956 individuals free of cardiovascular disease in the JUPITER study. Troponin I remained an independent predictor with a hazard ratio of 1.37 for cardiovascular mortality, 1.23 for cardiovascular disease, and 1.24 for total mortality. The addition of troponin I information to a prognostic model for cardiovascular death constructed of ESC SCORE variables increased the C-index discrimination measure by 0.007 and yielded an NRI of 0.048, whereas the addition to prognostic models for cardiovascular disease and total mortality led to lesser C-index discrimination and NRI increment. In individuals above 6 ng/L of troponin I, a concentration near the upper quintile in BiomarCaRE (5.9 ng/L) and JUPITER (5.8 ng/L), rosuvastatin therapy resulted in higher absolute risk reduction compared with individuals <6 ng/L of troponin I, whereas the relative risk reduction was similar. CONCLUSION: In individuals free of cardiovascular disease, the addition of troponin I to variables of established risk score improves prediction of cardiovascular death and cardiovascular disease.

The Predictive Value of Depressive Symptoms for All-Cause Mortality: Findings From the PRIME Belfast Study Examining the Role of Inflammation and Cardiovascular Risk Markers.

OBJECTIVES: To improve understanding about the potential underlying biological mechanisms in the link between depression and all-cause mortality and to investigate the role that inflammatory and other cardiovascular risk factors may play in the relationship between depressive symptoms and mortality. METHODS: Depression and blood-based biological markers were assessed in the Belfast PRIME prospective cohort study (N = 2389 men, aged 50-59 years) in which participants were followed up for 18 years. Depression was measured using the 10-item Welsh Pure Depression Inventory. Inflammation markers (C-reactive protein [CRP], neopterin, interleukin [IL]-1 receptor antagonist [IL-1Ra], and IL-18) and cardiovascular-specific risk factors (N-terminal pro-b-type natriuretic peptide, midregion pro-atrial natriuretic peptide, midregion pro-adrenomedullin, C-terminal pro-endothelin-1 [CT-proET]) were obtained at baseline. We used Cox proportional hazards modeling to examine the association between depression and biological measures in relation to all-cause mortality and explore the mediating effects. RESULTS: During follow-up, 418 participants died. Higher levels of depressive symptoms were associated with higher levels of CRP, IL-1Ra, and CT-proET. After adjustment for socioeconomic and life-style risk factors, depressive symptoms were significantly associated with all-cause mortality (hazard ratio = 1.10 per scale unit, 95% confidence interval = 1.04-1.16). This association was partly explained by CRP (7.3%) suggesting a minimal mediation effect. IL-1Ra, N-terminal pro-b-type natriuretic peptide, midregion pro-atrial natriuretic peptide, midregion pro-adrenomedullin, and CT-proET contributed marginally to the association between depression and subsequent mortality. CONCLUSIONS: Inflammatory and cardiovascular risk markers are associated with depression and with increased mortality. However, depression and biological measures show additive effects rather than a pattern of meditation of biological factors in the association between depression and mortality.