Lincoln A. Sargeant

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.

Fruit and vegetable intake and population glycosylated haemoglobin levels: the EPIC-Norfolk Study.

Objective: To investigate whether self-reported frequency of fruit and vegetable consumption was associated with HbA1C levels in individuals not known to have diabetes, and what dietary and lifestyle factors might explain this association.Design: Cross-sectional study.Setting: The EPIC-Norfolk Study, a population-based cohort study of diet and chronic disease.Subjects and methods: A total of 2678 men and 3318 women (45–74 y) not known to have diabetes reported weekly consumption of fruit, green leafy vegetables and other vegetables.Results: Among men, 274 (10.2%) reported seldom or never eating fruit and 127 (4.7%) seldom or never eating green leafy vegetables. Corresponding numbers in women were 157 (4.7%) and 92 (2.8%), respectively. Participants who reported never or seldom having both fruit and green leafy vegetables had higher mean (s.d.) HbA1C measurements (5.43% (0.71)) than those who reported more frequent consumption (5.34% (0.67); P=0.046). Differences by category of fruit or green leafy vegetable consumption were not substantially changed after adjustment for saturated fat, dietary fibre and plasma vitamin C.Conclusion: These findings support the hypothesis that high intake of fruit and green leafy vegetables may influence glucose metabolism independent of dietary fibre or vitamin C alone and that increased consumption may contribute to the prevention of diabetes.Sponsorship: NJW is an MRC Clinician Scientist Fellow.European Journal of Clinical Nutrition (2001) 55, 342–348

Family history of diabetes identifies a group at increased risk for the metabolic consequences of obesity and physical inactivity in EPIC-Norfolk : a population-based study

OBJECTIVE: To investigate the interaction of a family history of diabetes with obesity and physical inactivity on diabetes prevalence in middle-aged and elderly men and women.DESIGN: A cross-sectional population-based study.SUBJECTS: 2912 men and 3561 women, aged 45–74 y.MEASUREMENTS: Body mass index (BMI), HbA1C, self-administered questionnaire including questions on occupational physical activity and personal and family history of diabetes as part of the Norfolk arm of the European Prospective Investigation into Cancer (EPIC-Norfolk).RESULTS: The prevalence of diabetes increased in a dose–response relationship with increasing BMI. There was an interaction between family history and obesity on diabetes risk in subjects with a BMI of greater than 27.5 kg/m2 (P=0.049). Crude prevalence in individuals without a family history and BMI of 22.5–24.9 kg/m2 was 2.2% compared to 33.3% in those with a family history and BMI over 35 kg/m2. Thirty-eight percent of the excess risk of diabetes in people with a family history could be avoided if their BMI did not exceed 30 kg/m2. Individuals who reported sedentary occupations were at greater risk of diabetes compared to those reporting more active occupations. There was a synergistic effect of family history and self-reported occupational physical activity on diabetes risk.CONCLUSION: Individuals with a family history of diabetes are at increased risk for the metabolic consequences of obesity and form an easily identifiable group who may benefit from targeted intervention to prevent the development of obesity through increased physical activity.

Evaluation of the Framingham Risk Score in the European Prospective Investigation of Cancer-Norfolk Cohort Does Adding Glycated Hemoglobin Improve the Prediction of Coronary Heart Disease Events?

BACKGROUND There is a continuous relationship between glycated hemoglobin (HbA(1c)) and coronary heart disease (CHD) risk, even below diagnostic thresholds for diabetes mellitus. METHODS To evaluate the Framingham risk score in a UK population-based prospective cohort (European Prospective Investigation of Cancer [EPIC]-Norfolk) and to assess whether adding HbA(1c) improves the prediction of CHD. Participants aged 40 to 79 years were recruited from UK general practices, attended a health check, and were followed up for CHD events and death. The Framingham risk score was computed for 10,295 individuals with data on age, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, diabetes mellitus, and smoking status. We developed a Cox proportional hazards regression model with the original Framingham covariates and then added HbA(1c) to determine whether this improved the prediction of CHD. Model discrimination was compared by using area under the receiver operating characteristic curves (AUROCs), and the correctness of reclassification was determined by calculating the net reclassification improvement and the integrated discrimination improvement. The main outcome measures were CHD-related hospital admission and death. RESULTS A total of 430 men and 250 women developed CHD during 8.5 years of follow-up. The AUROC for the original Framingham risk score was 0.71. Using the Framingham variables with coefficients fitted from the EPIC-Norfolk data, the AUROC was 0.72 for men and 0.80 for women, compared with 0.73 and 0.80, respectively, in a score including HbA(1c). This difference was significant for men only (P = .005). The net reclassification improvement was 3.4% (P = .06) in men and -2.2% (P = .27) in women. CONCLUSIONS The Framingham risk score predicts CHD in this cohort. The addition of HbA(1c) made a small but statistically significant improvement to discrimination in men but not in women, without significant improvement in reclassification of risk category.

Work-related stress and Type 2 diabetes: systematic review and meta-analysis

BACKGROUND Work-related psychosocial stress has been hypothesized to increase the individual risk of Type 2 diabetes; however, observational epidemiological studies investigating the association between work-related psychosocial stress and Type 2 diabetes have provided an inconsistent picture. AIMS To evaluate whether work-related psychosocial stress (defined by a work-related stress model or by long work hours) is associated with the risk of Type 2 diabetes. METHODS A systematic review of the literature was conducted until March 2010. Studies eligible for inclusion were published observational epidemiological studies of adult participants in community or occupational settings if they had a measure of work-related stress on a validated scale or a measure of work hours or overtime assessed prior to, or at the same time as, assessment of Type 2 diabetes status. Where possible, meta-analysis was conducted to obtain summary odds ratios of the association. RESULTS We located nine studies (four prospective, one case-control and four cross-sectional). The meta-analyses did not show any statistically significant associations between any individual aspect of work-related psychosocial stress or job strain and risk of Type 2 diabetes. CONCLUSIONS The specific hypothesis that a working environment characterized by high psychosocial stress is directly associated with increased risk of Type 2 diabetes could not be supported from the meta-analysis.

An investigation of the population impact of variation in HbA1c levels in older people in England and Wales: From a population based multi-centre longitudinal study

BackgroundDiabetes is common in the older population and is increasing. Glycated hemoglobin (HbA1c) is an indicator of average blood glucose concentration over the past three months. The HbA1c test is currently one of clinical methods used to check diabetes control. Recent studies have suggested diabetes is a risk factor for dementia, cognitive dysfunction and physical disability. In addition, there have reported the relationship between HbA1c and mortality on all cause, cardiovascular disease and cognitive function, but few studies have investigated the relationship concentrating on the older population.The aim of this study is to investigate the association between the level of HbA1c and mortality from all causes, incident cardiovascular disease, cognitive decline and physical disability in people aged 65 and over in England and Wales.Methods1139 men and women aged 69 years and over who were participants in a ten year population based ageing multi-centre, longitudinal study who had HbA1c measurements after 5–6 years of follow up. All participants were flagged for death notification including causes at the Office of National Statistics. Information on health including vascular conditions, cognitive status, physical function and dementia were available from the study both before and after the HbA1c measurement. Survival analyses and logistic regression were conducted.ResultsMortality from all causes, cardiovascular and ischaemic heart disease increased with increasing HbA1c. Participants with diagnosed diabetes or who had HbA1c≥ 7% but no self-reported diabetes had increased mortality risk from all causes and cardiovascular diseases. The respondents in the group HbA1c ≥7% who had not been diagnosed with diabetes had a significantly higher risk (odds ratio = 4.8 95% CI: 1.1 to 21.6) of developing dementia. Individuals who had self-reported diabetes but a HbA1c level <7% had mortality and dementia incidence comparable to individuals without diabetes and HbA1c <7%.ConclusionThe findings support previous reports that bio-markers of glucose metabolism are associated with long term outcomes, such as mortality and dementia.

Who attends a UK diabetes screening programme? Findings from the ADDITION‐Cambridge study

Diabet. Med. 27, 995–1003 (2010)

Cross-sectional association between total level and type of alcohol consumption and glycosylated haemoglobin level: the EPIC-Norfolk Study.

Objective: To investigate the association between total level and type of alcohol consumed and glycaemia.Design: Cross-sectional study.Setting: The EPIC-Norfolk Study, a population-based cohort study of diet and chronic disease.Subjects and methods: Non-diabetic men (n=2842) and women (n=3572), aged 40–78 y. Alcohol intake was assessed by self-reported questionnaire, and glycaemia measured by glycosylated haemoglobin (HbA1c).Results: Ten percent of men and 18% of women reported drinking no alcohol. Among drinkers, median alcohol intake was 8 units/week for men and 3 units/week for women. In analyses stratified by sex and adjusted for age, total energy intake, education, fruit and vegetable intake, smoking, family history of diabetes, physical activity, body mass index and waist:hip ratio, alcohol intake was inversely associated with HbA1c in men and women, although the association was stronger in women. A 1 unit/week increase in alcohol intake was associated with 0.0049% (s.e.=0.00223; P-value=0.028) and 0.017% (s.e.=0.00343; P-value <0.001) reduction in HbA1c in men and women respectively. In similar multivariate analyses, wine intake was inversely associated with HbA1c in men, and wine, spirits and beer intake were inversely associated with HbA1c in women. When also adjusted for total alcohol intake, only the association between wine intake and HbA1c in men remained significant.Conclusion: Alcohol intake was associated with lower HbA1c level, an association not explained by confounding. The distinction between type of alcohol consumed was particularly important in men.Sponsorship: NJW is an MRC Clinician Scientist Fellow.

How much might cardiovascular disease risk be reduced by intensive therapy in people with screen-detected diabetes?

Aims  To assess the cardiovascular disease (CVD) risk of people with screen‐detected Type 2 diabetes and to estimate the risk reduction achievable through early intensive pharmacological intervention.

Hormone replacement therapy and glucose tolerance in EPIC‐Norfolk: a population‐based study

Hormone replacement therapy (HRT) can affect glucose homeostasis in postmenopausal women but it is unclear whether long‐term use is associated with changes in glucose tolerance. The objective was to examine the relationship of glycated haemoglobin (HbA1C) concentration with HRT use in non‐diabetic postmenopausal women.