Rebecca K. Simmons

Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial

Summary Background Intensive treatment of multiple cardiovascular risk factors can halve mortality among people with established type 2 diabetes. We investigated the effect of early multifactorial treatment after diagnosis by screening. Methods In a pragmatic, cluster-randomised, parallel-group trial done in Denmark, the Netherlands, and the UK, 343 general practices were randomly assigned screening of registered patients aged 40–69 years without known diabetes followed by routine care of diabetes or screening followed by intensive treatment of multiple risk factors. The primary endpoint was first cardiovascular event, including cardiovascular mortality and morbidity, revascularisation, and non-traumatic amputation within 5 years. Patients and staff assessing outcomes were unaware of the practices study group assignment. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00237549. Findings Primary endpoint data were available for 3055 (99·9%) of 3057 screen-detected patients. The mean age was 60·3 (SD 6·9) years and the mean duration of follow-up was 5·3 (SD 1·6) years. Improvements in cardiovascular risk factors (HbA1c and cholesterol concentrations and blood pressure) were slightly but significantly better in the intensive treatment group. The incidence of first cardiovascular event was 7·2% (13·5 per 1000 person-years) in the intensive treatment group and 8·5% (15·9 per 1000 person-years) in the routine care group (hazard ratio 0·83, 95% CI 0·65–1·05), and of all-cause mortality 6·2% (11·6 per 1000 person-years) and 6·7% (12·5 per 1000 person-years; 0·91, 0·69–1·21), respectively. Interpretation An intervention to promote early intensive management of patients with type 2 diabetes was associated with a small, non-significant reduction in the incidence of cardiovascular events and death. Funding National Health Service Denmark, Danish Council for Strategic Research, Danish Research Foundation for General Practice, Danish Centre for Evaluation and Health Technology Assessment, Danish National Board of Health, Danish Medical Research Council, Aarhus University Research Foundation, Wellcome Trust, UK Medical Research Council, UK NIHR Health Technology Assessment Programme, UK National Health Service R&D, UK National Institute for Health Research, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Novo Nordisk, Astra, Pfizer, GlaxoSmithKline, Servier, HemoCue, Merck.

The metabolic syndrome: useful concept or clinical tool? Report of a WHO Expert Consultation

This article presents the conclusions of a WHO Expert Consultation that evaluated the utility of the ‘metabolic syndrome’ concept in relation to four key areas: pathophysiology, epidemiology, clinical work and public health. The metabolic syndrome is a concept that focuses attention on complex multifactorial health problems. While it may be considered useful as an educational concept, it has limited practical utility as a diagnostic or management tool. Further efforts to redefine it are inappropriate in the light of current knowledge and understanding, and there is limited utility in epidemiological studies in which different definitions of the metabolic syndrome are compared. Metabolic syndrome is a pre-morbid condition rather than a clinical diagnosis, and should thus exclude individuals with established diabetes or known cardiovascular disease (CVD). Future research should focus on: (1) further elucidation of common metabolic pathways underlying the development of diabetes and CVD, including those clustering within the metabolic syndrome; (2) early-life determinants of metabolic risk; (3) developing and evaluating context-specific strategies for identifying and reducing CVD and diabetes risk, based on available resources; and (4) developing and evaluating population-based prevention strategies.

Prediction of childhood obesity by infancy weight gain: an individual-level meta-analysis.

To assess the predictive ability of infant weight gain on subsequent obesity we performed a meta-analysis of individual-level data on 47,661 participants from 10 cohort studies from the UK, France, Finland, Sweden, the US and Seychelles. For each individual, weight SD scores at birth and age 1 year were calculated using the same external reference (British 1990). Childhood obesity was defined by International Obesity Task Force criteria. Each +1 unit increase in weight SD scores between 0 and 1 year conferred a twofold higher risk of childhood obesity (odds ratio = 1.97 [95% confidence interval (CI) 1.83, 2.12]), and a 23% higher risk of adult obesity (odds ratio = 1.23 [1.16, 1.30]), adjusted for sex, age and birthweight. There was little heterogeneity between studies. A risk score for childhood obesity comprising weight gain 0-1 year, mothers body mass index, birthweight and sex was generated in a random 50% selection of individuals from general population cohorts with available information (n = 8236); this score showed moderate predictive ability in the remaining 50% sample (area under receiving operating curve = 77% [95% CI 74, 80%]). A separate risk score for childhood overweight showed similar predictive ability (area under receiving operating curve = 76% [73, 79%]). In conclusion, infant weight gain showed a consistent positive association with subsequent obesity. A risk score combining birthweight and infant weight gain (or simply infant weight), together with mothers body mass index and sex may allow early stratification of infants at risk of childhood obesity.

Risk factors for first trimester miscarriage—results from a UK‐population‐based case–control study

Objective  The aim of this study was to examine the association between biological, behavioural and lifestyle risk factors and risk of miscarriage.

Risk Assessment Tools for Identifying Individuals at Risk of Developing Type 2 Diabetes

Trials have demonstrated the preventability of type 2 diabetes through lifestyle modifications or drugs in people with impaired glucose tolerance. However, alternative ways of identifying people at risk of developing diabetes are required. Multivariate risk scores have been developed for this purpose. This article examines the evidence for performance of diabetes risk scores in adults by 1) systematically reviewing the literature on available scores and 2) their validation in external populations; and 3) exploring methodological issues surrounding the development, validation, and comparison of risk scores. Risk scores show overall good discriminatory ability in populations for whom they were developed. However, discriminatory performance is more heterogeneous and generally weaker in external populations, which suggests that risk scores may need to be validated within the population in which they are intended to be used. Whether risk scores enable accurate estimation of absolute risk remains unknown; thus, care is needed when using scores to communicate absolute diabetes risk to individuals. Several risk scores predict diabetes risk based on routine noninvasive measures or on data from questionnaires. Biochemical measures, in particular fasting plasma glucose, can improve prediction of such models. On the other hand, usefulness of genetic profiling currently appears limited.

Screening for type 2 diabetes and population mortality over 10 years (ADDITION-Cambridge): a cluster-randomised controlled trial

Summary Background The increasing prevalence of type 2 diabetes poses a major public health challenge. Population-based screening and early treatment for type 2 diabetes could reduce this growing burden. However, uncertainty persists around the benefits of screening for type 2 diabetes. We assessed the effect of a population-based stepwise screening programme on mortality. Methods In a pragmatic parallel group, cluster-randomised trial, 33 general practices in eastern England were randomly assigned by the method of minimisation in an unbalanced design to: screening followed by intensive multifactorial treatment for people diagnosed with diabetes (n=15); screening plus routine care of diabetes according to national guidelines (n=13); and a no-screening control group (n=5). The study population consisted of 20 184 individuals aged 40–69 years (mean 58 years), at high risk of prevalent undiagnosed diabetes, on the basis of a previously validated risk score. In screening practices, individuals were invited to a stepwise programme including random capillary blood glucose and glycated haemoglobin (HbA1c) tests, a fasting capillary blood glucose test, and a confirmatory oral glucose tolerance test. The primary outcome was all-cause mortality. All participants were flagged for mortality surveillance by the England and Wales Office of National Statistics. Analysis was by intention-to-screen and compared all-cause mortality rates between screening and control groups. This study is registered, number ISRCTN86769081. Findings Of 16 047 high-risk individuals in screening practices, 15 089 (94%) were invited for screening during 2001–06, 11 737 (73%) attended, and 466 (3%) were diagnosed with diabetes. 4137 control individuals were followed up. During 184 057 person-years of follow up (median duration 9·6 years [IQR 8·9–9·9]), there were 1532 deaths in the screening practices and 377 in control practices (mortality hazard ratio [HR] 1·06, 95% CI 0·90–1·25). We noted no significant reduction in cardiovascular (HR 1·02, 95% CI 0·75–1·38), cancer (1·08, 0·90–1·30), or diabetes-related mortality (1·26, 0·75–2·10) associated with invitation to screening. Interpretation In this large UK sample, screening for type 2 diabetes in patients at increased risk was not associated with a reduction in all-cause, cardiovascular, or diabetes-related mortality within 10 years. The benefits of screening might be smaller than expected and restricted to individuals with detectable disease. Funding Wellcome Trust; UK Medical Research Council; National Health Service research and development support; UK National Institute for Health Research; University of Aarhus, Denmark; Bio-Rad.

Bariatric surgery for obese children and adolescents: a systematic review and meta-analysis

The number of obese young people continues to rise, with a corresponding increase in extreme obesity and paediatric‐adolescent bariatric surgery. We aimed to (i) systematically review the literature on bariatric surgery in children and adolescents; (ii) meta‐analyse change in body mass index (BMI) 1‐year post‐surgery and (iii) report complications, co‐morbidity resolution and health‐related quality of life (HRQoL).

Performance of the UK Prospective Diabetes Study Risk Engine and the Framingham Risk Equations in Estimating Cardiovascular Disease in the EPIC- Norfolk Cohort

OBJECTIVE The purpose of this study was to examine the performance of the UK Prospective Diabetes Study (UKPDS) Risk Engine (version 3) and the Framingham risk equations (2008) in estimating cardiovascular disease (CVD) incidence in three populations: 1) individuals with known diabetes; 2) individuals with nondiabetic hyperglycemia, defined as A1C ≥6.0%; and 3) individuals with normoglycemia defined as A1C <6.0%. RESEARCH DESIGN AND METHODS This was a population-based prospective cohort (European Prospective Investigation of Cancer-Norfolk). Participants aged 40–79 years recruited from U.K. general practices attended a health examination (1993–1998) and were followed for CVD events/death until April 2007. CVD risk estimates were calculated for 10,137 individuals. RESULTS Over 10.1 years, there were 69 CVD events in the diabetes group (25.4%), 160 in the hyperglycemia group (17.7%), and 732 in the normoglycemia group (8.2%). Estimated CVD 10-year risk in the diabetes group was 33 and 37% using the UKPDS and Framingham equations, respectively. In the hyperglycemia group, estimated CVD risks were 31 and 22%, respectively, and for the normoglycemia group risks were 20 and 14%, respectively. There were no significant differences in the ability of the risk equations to discriminate between individuals at different risk of CVD events in each subgroup; both equations overestimated CVD risk. The Framingham equations performed better in the hyperglycemia and normoglycemia groups as they did not overestimate risk as much as the UKPDS Risk Engine, and they classified more participants correctly. CONCLUSIONS Both the UKPDS Risk Engine and Framingham risk equations were moderately effective at ranking individuals and are therefore suitable for resource prioritization. However, both overestimated true risk, which is important when one is using scores to communicate prognostic information to individuals.

Cardiovascular risk assessment scores for people with diabetes: a systematic review

People with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Multivariate cardiovascular risk scores have been used in many countries to identify individuals who are at high risk of CVD. These risk scores include those originally developed in individuals with diabetes and those developed in a general population. This article reviews the published evidence for the performance of CVD risk scores in diabetic patients by: (1) examining the overall rationale for using risk scores; (2) systematically reviewing the literature on available scores; and (3) exploring methodological issues surrounding the development, validation and comparison of risk scores. The predictive performance of cardiovascular risk scores varies substantially between different populations. There is little evidence to suggest that risk scores developed in individuals with diabetes estimate cardiovascular risk more accurately than those developed in the general population. The inconsistency in the methods used in evaluation studies makes it difficult to compare and summarise the predictive ability of risk scores. Overall, CVD risk scores rank individuals reasonably accurately and are therefore useful in the management of diabetes with regard to targeting therapy to patients at highest risk. However, due to the uncertainty in estimation of true risk, care is needed when using scores to communicate absolute CVD risk to individuals.

A simple risk score identifies individuals at high risk of developing Type 2 diabetes: a prospective cohort study

BACKGROUND Randomized trials have demonstrated that Type 2 diabetes is preventable among high-risk individuals. To date, such individuals have been identified through population screening using the oral glucose tolerance test. OBJECTIVE To assess whether a risk score comprising only routinely collected non-biochemical parameters was effective in identifying those at risk of developing Type 2 diabetes. METHODS Population-based prospective cohort (European Prospective Investigation of Cancer-Norfolk). Participants aged 40-79 recruited from UK general practices attended a health check between 1993 and 1998 (n = 25 639) and were followed for a mean of 5 years for diabetes incidence. The Cambridge Diabetes Risk Score was computed for 24 495 individuals with baseline data on age, sex, prescription of steroids and anti-hypertensive medication, family history of diabetes, body mass index and smoking status. We examined the incidence of diabetes across quintiles of the risk score and plotted a receiver operating characteristic (ROC) curve to assess discrimination. RESULTS There were 323 new cases of diabetes, a cumulative incidence of 2.76/1000 person-years. Those in the top quintile of risk were 22 times more likely to develop diabetes than those in the bottom quintile (odds ratio 22.3; 95% CI: 11.0-45.4). In all, 54% of all clinically incident cases occurred in individuals in the top quintile of risk (risk score > 0.37). The area under the ROC was 74.5%. CONCLUSION The risk score is a simple, effective tool for the identification of those at risk of developing Type 2 diabetes. Such methods may be more feasible than mass population screening with biochemical tests in defining target populations for prevention programmes.