Comparison of diabetes risk score estimates and cardiometabolic risk profiles in a middle-aged Irish population

Background: To compare diabetes risk assessment tools in estimating risk of developing type 2 diabetes (T2DM) and to evaluate cardiometabolic risk profiles in a middle-aged Irish population. Methods: Future risk of developing T2DM was estimated using 7 risk scores, including clinical measures with or without anthropometric, biological and lifestyle data, in the cross-sectional Mitchelstown cohort of 2,047 middle-aged men and women. Cardiometabolic phenotypes including markers of glucose metabolism, inflammatory and lipid profiles were determined. Results: Estimates of subjects at risk for developing T2DM varied considerably according to the risk assessment tool used (0.3% to 20%), with higher proportions of males at risk (0-29.2% vs. 0.1-13.4%, for men and women, respectively). Extrapolated to the Irish population of similar age, the overall number of adults at high risk of developing T2DM ranges from 3,378 to 236,632. Numbers of non-optimal metabolic features were generally greater among those at high risk of developing T2DM. However, cardiometabolic profile characterisation revealed that only those classified at high risk by the Griffin (UK Cambridge) score displayed a more pro-inflammatory, obese, hypertensive, dysglycaemic and insulin resistant metabolic phenotype. Conclusions: Most diabetes risk scores examined offer limited ability to identify subjects with metabolic abnormalities and at risk of developing T2DM. Our results highlight the need to validate diabetes risk scoring tools for each population studied and the potential for developing an Irish diabetes risk score, which may help to promote self awareness and identify high risk individuals and diabetes hot spots for targeted public health interventions

Delays in Leniency Application: Is There Really a Race to the Enforcer's Door?

This paper studies cartels’ strategic behavior in delaying leniency applications, a take-up decision that has been ignored in the previous literature. Using European Commission decisions issued over a 16-year span, we show, contrary to common beliefs and the existing literature, that conspirators often apply for leniency long after a cartel collapses. We estimate hazard and probit models to study the determinants of leniency-application delays. Statistical tests find that delays are symmetrically affected by antitrust policies and macroeconomic fluctuations. Our results shed light on the design of enforcement programs against cartels and other forms of conspiracy

Defining metabolically healthy obesity: role of dietary and lifestyle factors

Background: There is a current lack of consensus on defining metabolically healthy obesity (MHO). Limited data on dietary and lifestyle factors and MHO exist. The aim of this study is to compare the prevalence, dietary factors and lifestyle behaviours of metabolically healthy and unhealthy obese and non-obese subjects according to different metabolic health criteria. Method: Cross-sectional sample of 1,008 men and 1,039 women aged 45-74 years participated in the study. Participants were classified as obese (BMI ≥30kg/m2) and non-obese (BMI <30kg/m2). Metabolic health status was defined using five existing MH definitions based on a range of cardiometabolic abnormalities. Dietary composition and quality, food pyramid servings, physical activity, alcohol and smoking behaviours were examined. Results: The prevalence of MHO varied considerably between definitions (2.2% to 11.9%), was higher among females and generally increased with age. Agreement between MHO classifications was poor. Among the obese, prevalence of MH was 6.8% to 36.6%. Among the non-obese, prevalence of metabolically unhealthy subjects was 21.8% to 87%. Calorie intake, dietary macronutrient composition, physical activity, alcohol and smoking behaviours were similar between the metabolically healthy and unhealthy regardless of BMI. Greater compliance with food pyramid recommendations and higher dietary quality were positively associated with metabolic health in obese (OR 1.45-1.53 unadjusted model) and non-obese subjects (OR 1.37-1.39 unadjusted model), respectively. Physical activity was associated with MHO defined by insulin resistance (OR 1.87, 95% CI 1.19-2.92, p = 0.006)

Progression of Carotid Artery Intima-Media Thickness During 12 Years in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study

OBJECTIVE This study investigated the long-term effects of intensive diabetic treatment on the progression of atherosclerosis, measured as common carotid artery intima-media thickness (IMT). RESEARCH DESIGN AND METHODS A total of 1,116 participants (52% men) in the Epidemiology of Diabetes Interventions and Complications (EDIC) trial, a long-term follow-up of the Diabetes Control and Complications Trial (DCCT), had carotid IMT measurements at EDIC years 1, 6, and 12. Mean age was 46 years, with diabetes duration of 24.5 years at EDIC year 12. Differences in IMT progression between DCCT intensive and conventional treatment groups were examined, controlling for clinical characteristics, IMT reader, and imaging device. RESULTS Common carotid IMT progression from EDIC years 1 to 6 was 0.019 mm less in intensive than in conventional (P < 0.0001), and from years 1 to 12 was 0.014 mm less (P = 0.048); but change from years 6 to 12 was similar (intensive − conventional = 0.005 mm, P = 0.379). Mean A1C levels during DCCT and DCCT/EDIC were strongly associated with progression of IMT, explaining most of the differences in IMT progression between DCCT treatment groups. Albuminuria, older age, male sex, smoking, and higher systolic blood pressure were significant predictors of IMT progression. CONCLUSIONS Intensive treatment slowed IMT progression for 6 years after the end of DCCT but did not affect IMT progression thereafter (6–12 years). A beneficial effect of prior intensive treatment was still evident 13 years after DCCT ended. These differences were attenuated but not negated after adjusting for blood pressure. These results support the early initiation and continued maintenance of intensive diabetes management in type 1 diabetes to retard atherosclerosis

Prevalence of diabetes in the Republic of Ireland: results from the National Health Survey (SLAN) 2007

Background: Current estimates of diabetes prevalence in the Republic of Ireland (RoI) are based on UK epidemiological studies. This study uses Irish data to describe the prevalence of doctor-diagnosed diabetes amongst all adults aged 18+ years and undiagnosed diabetes amongst those aged 45+ years. Methods: The survey of lifestyle attitudes and nutrition (SLAN) 2007 is based on a nationally representative sample of Irish adults aged 18+ years (n = 10,364). Self-reported doctor-diagnosed diabetes was recorded for respondents in the full sample. Diabetes medication use, measured height and weight, and non-fasting blood samples were variously recorded in sub-samples of younger (n = 967) and older (n = 1,207) respondents. Results: The prevalence of doctor-diagnosed diabetes amongst adults aged 18+ years was 3.5% (95% CI 3.1% - 3.9%). After adjustment for other explanatory variables; the risk of self-reported doctor-diagnosed diabetes was significantly related to age (p < 0.0001), employment status (p = 0.0003) and obesity (p = 0.0003). Amongst adults aged 45+ years, the prevalence of doctor-diagnosed diabetes was 8.9% (95% CI 7.3% -10.5%) and undiagnosed diabetes was 2.8% (95% CI 1.4% - 4.1%). This represented 31.2% of diabetes cases in this age group. Conclusion: Notwithstanding methodological differences, these prevalence estimates are consistent with those in the UK and France. However, the percentage of undiagnosed cases amongst adults aged 45+ years appears to be higher in the RoI. Increased efforts to improve early detection and population level interventions to address adverse diet and lifestyle factors are urgently needed

In Vitro Cell Culture Infectivity Assay for Human Noroviruses

A 3-dimensional organoid human small intestinal epithelium model was used

The cumulative effect of core lifestyle behaviours on the prevalence of hypertension and dyslipidemia

Background: Most cardiovascular disease (CVD) occurs in the presence of traditional risk factors, including hypertension and dyslipidemia, and these in turn are influenced by behavioural factors such as diet and lifestyle. Previous research has identified a group at low risk of CVD based on a cluster of inter-related factors: body mass index (BMI) < 25 Kg/m2, moderate exercise, alcohol intake, non-smoking and a favourable dietary pattern. The objective of this study was to determine whether these factors are associated with a reduced prevalence of hypertension and dyslipidemia in an Irish adult population. Methods: The study was a cross-sectional survey of 1018 men and women sampled from 17 general practices. Participants completed health, lifestyle and food frequency questionnaires and provided fasting blood samples for analysis of glucose and insulin. We defined a low risk group based on the following protective factors: BMI <25 kg/m2; waist-hip ratio (WHR) <0.85 for women and <0.90 for men; never smoking status; participants with medium to high levels of physical activity; light alcohol consumption (3.5–7 units of alcohol/week) and a "prudent" diet. Dietary patterns were assessed by cluster analysis. Results: We found strong significant inverse associations between the number of protective factors and systolic blood pressure, diastolic blood pressure and dyslipidemia. The prevalence odds ratio of hypertension in persons with 1, 2, 3, ≥ 4 protective factors relative to those with none, were 1.0, 0.76, 0.68 and 0.34 (trend p < 0.01). The prevalence odds ratio of dyslipidemia in persons with 1, 2, 3, ≥ 4 protective factors relative to those with none were 0.83, 0.98, 0.49 and 0.24 (trend p = 0.001). Conclusion: Our findings of a strong inverse association between low risk behaviours and two of the traditional risk factors for CVD highlight the importance of 'the causes of the causes' and the potential for behaviour modification in CVD prevention at a population level

Germline whole exome sequencing and large-scale replication identifies FANCM as a likely high grade serous ovarian cancer susceptibility gene.

We analyzed whole exome sequencing data in germline DNA from 412 high grade serous ovarian cancer (HGSOC) cases from The Cancer Genome Atlas Project and identified 5,517 genes harboring a predicted deleterious germline coding mutation in at least one HGSOC case. Gene-set enrichment analysis showed enrichment for genes involved in DNA repair (p = 1.8×10-3). Twelve DNA repair genes - APEX1, APLF, ATX, EME1, FANCL, FANCM, MAD2L2, PARP2, PARP3, POLN, RAD54L and SMUG1 - were prioritized for targeted sequencing in up to 3,107 HGSOC cases, 1,491 cases of other epithelial ovarian cancer (EOC) subtypes and 3,368 unaffected controls of European origin. We estimated mutation prevalence for each gene and tested for associations with disease risk. Mutations were identified in both cases and controls in all genes except MAD2L2, where we found no evidence of mutations in controls. In FANCM we observed a higher mutation frequency in HGSOC cases compared to controls (29/3,107 cases, 0.96 percent; 13/3,368 controls, 0.38 percent; P=0.008) with little evidence for association with other subtypes (6/1,491, 0.40 percent; P=0.82). The relative risk of HGSOC associated with deleterious FANCM mutations was estimated to be 2.5 (95% CI 1.3 - 5.0; P=0.006). In summary, whole exome sequencing of EOC cases with large-scale replication in case-control studies has identified FANCM as a likely novel susceptibility gene for HGSOC, with mutations associated with a moderate increase in risk. These data may have clinical implications for risk prediction and prevention approaches for high-grade serous ovarian cancer in the future and a significant impact on reducing disease mortality

Clinical features and outcomes of patients with type 2 myocardial infarction: Insights from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial

This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This author accepted manuscript is made available following 12 month embargo from date of publication (Oct 2017) in accordance with the publisher’s archiving policyBackground: Type 2 myocardial infarction (MI) is characterized by an imbalance between myocardial blood supply and demand, leading to myocardial ischemia without coronary plaque rupture, but its diagnosis is challenging. Methods: In the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial, patients with non-ST-segment elevation acute coronary syndromes were included. We aimed to describe provoking factors, cardiac biomarker profiles, treatment patterns, and clinical outcomes of patients with type 2 MIs. MI events during trial follow-up were adjudicated by an independent clinical events classification committee (CEC) and were classified according to the Third Universal Definition of MI. Using available source documents retrieved as part of the CEC process, we performed a retrospective chart abstraction to collect details on the type 2 MIs. Cox regression models were used to explore the association between MI type (type 1 or type 2) and all-cause death. Results: Overall, 10.3% (n=1327) of TRACER participants had a total of 1579 adjudicated MIs during a median follow-up of 502 days (interquartile range [IQR] 349–667). Of all MIs, 5.2% (n=82) were CECadjudicated type 2 MIs, occurring in 76 patients. The incidence of type 2 MI was higher in the first month following randomization, after which the distribution became more scattered. The most frequent potential provoking factors for type 2 MIs were tachyarrhythmias (38.2%), anemia/bleeding (21.1%), hypotension/shock (14.5%), and hypertensive emergencies (11.8%). Overall, 36.3% had a troponin increase >10× the upper limit of normal. Coronary angiography was performed in 22.4% (n=17) of patients during hospitalizations due to type 2 MIs. The hazard of death was numerically higher following type 2 MI (vs. no MI, adj. HR 8.25, 95% CI 4.57–14.92; p<.0001) than that of type 1 MI (vs. no MI, adj. HR 5.71, 95% CI 4.62–7.06; p<.0001). Conclusions: Type 2 MIs were more prevalent in the first month after ACS were characterized by the presence of triggers and infrequent use of an invasive strategy, and were associated with a high risk of death. Further efforts are needed to better define the role and implications of type 2 MI in both clinical practice and research