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Articles by N. J. Wareham
Total Records ( 9 ) for N. J. Wareham
  J. B. Echouffo-Tcheugui , L. A. Sargeant , A. T. Prevost , K. M. Williams , R. S. Barling , R. Butler , T. Fanshawe , A. L. Kinmonth , N. J. Wareham and S. J. Griffin
  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.

Methods  In ADDITION-Cambridge, diabetic patients were identified among people aged 40-69 years through a stepwise screening procedure including a risk score, random and fasting capillary blood glucose, HbA1c and oral glucose tolerance test. In those without prior macrovascular disease, 10-year CVD risk was computed using UK Prospective Diabetes Study (UKPDS) and Framingham engines. The absolute risk reduction achievable and its plausible range were predicted using relative risk reductions for individual therapies from published trials and sensitivity analysis.

Results  Of the 867 individuals with undiagnosed diabetes, 19% had pre-existing CVD, 97% were overweight or obese, 86% had hypertension, 75% had dyslipidaemia, 20% had microalbuminuria and 18% were smokers. Of those with hypertension, 35% were not prescribed drugs and 42% were suboptimally treated. Of participants with dyslipidaemia, 68% were not prescribed medications and 22% were poorly controlled. Median 10-year CVD risk was 34.0%[interquartile range (IQR) 26.2-44.6] in men and 21.5% (IQR 15.7-28.7) in women using the UKPDS engine; 38.6% (IQR 27.8-53.0) in men and 24.6% (IQR 17.2-32.9) in women using Framingham equations. In the most conservative scenario (no additive effect of therapies), the absolute risk reduction achievable through multifactorial therapy ranged from 4.9 to 9.5% (UKPDS) and from 5.4 to 10.5% (Framingham). The corresponding ranges of numbers needed to treat were 11-20 and 10-19.

Conclusions  People with screen-detected diabetes have an adverse cardiovascular risk profile, which is potentially modifiable through application of existing treatment recommendations.

  R. M. Steele , F. M. Finucane , R. K. Simmons , S. J. Griffin , N. J. Wareham and U. Ekelund
  Aims  Reduced lung function is associated with an adverse metabolic risk profile, even after adjusting for body fatness. However, previous observations may have been confounded by aerobic fitness and physical activity. This study aimed to examine the association between lung function and both metabolic risk and insulin resistance in a cohort of White British adults with a family history of Type 2 diabetes, and to explore the extent to which these associations are independent of body fatness, aerobic fitness (VO2max) and objectively measured physical activity.

Methods  Adults (n = 320, mean age 40.4 ± 6.0 years) underwent measurement of physical activity energy expenditure (PAEE), spirometry [forced expiratory volume in 1 s (FEV1)] and forced vital capacity (FVC), aerobic fitness (predicted VO2max), and anthropometric and metabolic status at baseline and again after 1 year (n = 257) in the ProActive trial. Clustered metabolic risk was calculated by summing standardized values for triglycerides, fasting insulin, fasting glucose, blood pressure and the inverse of high-density lipoprotein-cholesterol. A cross-sectional analysis using linear regression with repeated measures was performed.

Results  Both FEV1 and FVC were inversely and statistically significantly associated with metabolic risk and insulin resistance after adjusting for age, sex, smoking status, height, PAEE and fitness. The associations with metabolic risk remained significant after adjusting for measures of body fatness, but those with insulin resistance did not.

Conclusions  Reduced lung function was associated with increased metabolic risk in this cohort of carefully characterized at-risk individuals. This association was independent of overall and central body fatness, objectively measured physical activity and aerobic fitness.

  L. A. Sargeant , R. K. Simmons , R. S. Barling , R. Butler , K. M. Williams , A. T. Prevost , A. L. Kinmonth , N. J. Wareham and S. J. Griffin
  Aims  One of the factors influencing the cost-effectiveness of population screening for Type 2 diabetes may be uptake. We examined attendance and practice- and individual-level factors influencing uptake at each stage of a diabetes screening programme in general practice.

Methods  A stepwise screening programme was undertaken among 135 825 people aged 40-69 years without known diabetes in 49 general practices in East England. The programme included a score based on routinely available data (age, sex, body mass index and prescribed medication) to identify those at high risk, who were offered random capillary blood glucose (RBG) and glycosylated haemoglobin tests. Those screening positive were offered fasting capillary blood glucose (FBG) and confirmatory oral glucose tolerance tests (OGTT).

Results  There were 33 539 high-risk individuals invited for a RBG screening test; 24 654 (74%) attended. Ninety-four per cent attended the follow-up FBG test and 82% the diagnostic OGTT. Seventy per cent of individuals completed the screening programme. Practices with higher general practitioner staff complements and those located in more deprived areas had lower uptake for RBG and FBG tests. Male sex and a higher body mass index were associated with lower attendance for RBG testing. Older age, prescription of antihypertensive medication and a higher risk score were associated with higher attendance for FBG and RBG tests.

Conclusions  High attendance rates can be achieved by targeted stepwise screening of individuals assessed as high risk by data routinely available in general practice. Different strategies may be required to increase initial attendance, ensure completion of the screening programme, and reduce the risk that screening increases health inequalities.

  M. van den Donk , A. Sandbaek , K. Borch-Johnsen , T. Lauritzen , R. K. Simmons , N. J. Wareham , S. J. Griffin , M. J. Davies , K. Khunti and G. E. H. M. Rutten
  Aims  To describe and compare attendance rates and the proportions of people identified with Type 2 diabetes mellitus in people with previously unknown diabetes who participated in screening programmes undertaken in general practice in the UK, Denmark and the Netherlands as part of the ADDITION-Europe study.

Methods  In Cambridge, routine computer data searches were conducted to identify individuals aged 40-69 years at high risk of Type 2 diabetes using the Cambridge Diabetes Risk Score. In Denmark, the Danish Diabetes Risk Score was mailed to individuals aged 40-69 years, or completed by patients visiting their general practitice. In the Netherlands, the Hoorn Symptom Risk Questionnaire was mailed to individuals aged 50-69 years. In these three centres, high-risk individuals were invited to attend subsequent steps in the screening programme, including random blood glucose, HbA1c, fasting blood glucose and/or oral glucose tolerance test. In Leicester, eligible people aged 40-69 years were invited directly for an oral glucose tolerance test. In all centres, Type 2 diabetes was defined according to World Health Organization 1999 diagnostic criteria.

Results  Attendance rates ranged from 20.2% (oral glucose tolerance test in Leicester without pre-stratification) to 95.1% (random blood glucose in opportunistic screening in Denmark in high-risk people). The percentage of people with newly detected Type 2 diabetes from the target population ranged from 0.33% (Leicester) to 1.09% (the Netherlands).

Conclusions  Screening for Type 2 diabetes was acceptable and feasible, but relatively few participants were diagnosed in all participating centres. Different strategies may be required to increase initial attendance and ensure completion of screening programmes.

  M. Rahman , R. K. Simmons , S. H. Hennings , N. J. Wareham and S. J. Griffin
  Aims  There is continuing uncertainty regarding the overall net benefits of population-based screening for Type 2 diabetes. We compared clinical measures, prescribed medication, cardiovascular morbidity and self-rated health in individuals without diabetes in a screened vs. an unscreened population.

Methods  A parallel-group, cohort study of people aged 40-65 years, free of known diabetes, identified from the population register of a general practice in Ely, Cambridgeshire (n = 4936). In 1990-1992, one third (n = 1705), selected randomly, received an invitation for screening for diabetes and cardiovascular risk factors at 5-yearly intervals (screened population). From the remainder of the sampling frame, 1705 randomly selected individuals were invited to diabetes screening 10 years later (unscreened population). Patients without known diabetes from both populations were invited for a health assessment.

Results  Of 3390 eligible individuals without diabetes, 1442 (43%) attended for health assessment, with no significant difference in attendance between groups. Thirteen years after the commencement of screening, self-rated functional health status and health utility were identical between the screened and unscreened populations. Clinical measures, self-reported medication and cardiovascular morbidity were similar between the two groups.

Conclusions  Screening for diabetes is not associated with long-term harms at the population level. However, screening has limited long-term impact on those testing negative; benefits may largely be restricted to those whose diabetes is detected early through screening.

  P. Chamnan , R. K. Simmons , K. T. Khaw , N. J. Wareham and S. J. Griffin
  Background  Diabetes risk assessment has been proposed as part of the National Health Service Health Checks programme, and HbA1c has recently been recommended as a diagnostic test for diabetes at a threshold of 48 mmol/mol (6.5%). We estimated the potential population impact of different stepwise screening strategies to identify individuals at high risk who might be offered preventive interventions.

Methods  Using data from 5910 participants in the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort with HbA1c measurements, we modelled different stepwise screening strategies for identifying and treating individuals at high risk of Type 2 diabetes using different HbA1c cut-off points with and without a stage of prestratification. For each strategy, we estimated the number needed to have a diagnostic test, the number needed to treat to prevent one new case of Type 2 diabetes, and the number of new cases that could be prevented in the population over 3 years. Relative risk reductions for estimated effects of intensive lifestyle intervention were derived from the US Diabetes Prevention Program.

Results  Compared with inviting all individuals in an average primary care trust for a diagnostic test, a stepwise screening approach using simple routine data such as age and anthropometric indices could prevent a slightly lower number (lower-upper estimates) of new cases of Type 2 diabetes over 3 years (224 [130-359] and 193 [109-315] cases respectively) but would only require half the population to be invited for a diagnostic blood test. A total of 162 (88-274) cases could be prevented by inviting individuals with a Cambridge risk score of ≥ 0.15, with only 40% of the total population requiring diagnostic blood tests. Using a participant completed questionnaire for risk assessment (FINDRISC) was less effective, mainly relating to the questionnaire response rate. Providing preventive interventions to those with a lower HbA1c of 37-< 48 mmol/mol (5.5-< 6.5%) could prevent more cases but with a disproportionately higher workload, compared with using the recommended HbA1c threshold of 42-< 48 mmol/mol (6.0-< 6.5%).

Conclusions  Compared with mass screening, an approach using routine data for risk stratification followed by an HbA1c test with a threshold of 42-< 48 mmol/mol (6.0-< 6.5%) for identifying individuals suitable for preventive interventions might prevent slightly fewer cases of Type 2 diabetes but with potential cost-savings.

  A. Barakat , K. M. Williams , A. T. Prevost , A.-L. Kinmonth , N. J. Wareham , S. J. Griffin and R. K. Simmons
  Aims  To describe change in physical activity over 1 year and associations with change in cardiovascular disease risk factors in a population with screen-detected Type 2 diabetes.

Methods  Eight hundred and sixty-seven individuals with screen-detected diabetes underwent measurement of self-reported physical activity, cardiovascular disease risk factors and modelled cardiovascular disease risk at baseline and 1 year (n = 736) in the ADDITION-Cambridge trial. Multiple linear regression was used to quantify the association between change in different physical activity domains and cardiovascular disease risk factors at 1 year.

Results  There was no change in self-reported physical activity over 12 months. Even relatively large changes in physical activity were associated with relatively small changes in cardiovascular disease risk factors after allowing for changes in self-reported medication and diet. For every 30 metabolic equivalent-h increase in recreational activity (equivalent to 10 h/brisk walking/week), there was an average reduction of 0.1% in HbA1c in men (95% CI −0.15 to −0.01, P = 0.021) and an average reduction of 2 mmHg in systolic blood pressure in women (95% CI −4.0 to −0.05, P = 0.045).

Conclusions  Few associations were observed between change in different physical activity domains and cardiovascular disease risk factors in this trial cohort. Cardiovascular disease risk reduction appeared to be driven largely by factors other than changes in self-reported physical activity in the first year following diagnosis.

  L. A. Savory , S. J. Griffin , K. M. Williams , A. T. Prevost , A.-L. Kinmonth , N. J. Wareham and R. K. Simmons


To describe change in self-reported diet and plasma vitamin C, and to examine associations between change in diet and cardiovascular disease risk factors and modelled 10-year cardiovascular disease risk in the year following diagnosis of Type 2 diabetes.


Eight hundred and sixty-seven individuals with screen-detected diabetes underwent assessment of self-reported diet, plasma vitamin C, cardiovascular disease risk factors and modelled cardiovascular disease risk at baseline and 1 year (n = 736) in the ADDITION-Cambridge trial. Multivariable linear regression was used to quantify the association between change in diet and cardiovascular disease risk at 1 year, adjusting for change in physical activity and cardio-protective medication.


Participants reported significant reductions in energy, fat and sodium intake, and increases in fruit, vegetable and fibre intake over 1 year. The reduction in energy was equivalent to an average-sized chocolate bar; the increase in fruit was equal to one plum per day. There was a small increase in plasma vitamin C levels. Increases in fruit intake and plasma vitamin C were associated with small reductions in anthropometric and metabolic risk factors. Increased vegetable intake was associated with an increase in BMI and waist circumference. Reductions in fat, energy and sodium intake were associated with reduction in HbA1c, waist circumference and total cholesterol/modelled cardiovascular disease risk, respectively.


Improvements in dietary behaviour in this screen-detected population were associated with small reductions in cardiovascular disease risk, independently of change in cardio-protective medication and physical activity. Dietary change may have a role to play in the reduction of cardiovascular disease risk following diagnosis of diabetes.

  J. A. Black , S. J. Sharp , N. J. Wareham , A. Sandbaek , G. E. H. M. Rutten , T. Lauritzen , K. Khunti , M. J. Davies , K. Borch-Johnsen , S. J. Griffin and R. K. Simmons


Little is known about the long-term effects of intensive multifactorial treatment early in the diabetes disease trajectory. In the absence of long-term data on hard outcomes, we described change in 10-year modelled cardiovascular risk in the 5 years following diagnosis, and quantified the impact of intensive treatment on 10-year modelled cardiovascular risk at 5 years.


In a pragmatic, cluster-randomized, parallel-group trial in Denmark, the Netherlands and the UK, 3057 people with screen-detected Type 2 diabetes were randomized by general practice to receive (1) routine care of diabetes according to national guidelines (1379 patients) or (2) intensive multifactorial target-driven management (1678 patients). Ten-year modelled cardiovascular disease risk was calculated at baseline and 5 years using the UK Prospective Diabetes Study Risk Engine (version 3β).


Among 2101 individuals with complete data at follow up (73.4%), 10-year modelled cardiovascular disease risk was 27.3% (sd 13.9) at baseline and 21.3% (sd 13.8) at 5-year follow-up (intensive treatment group difference -6.9, sd 9.0; routine care group difference -5.0, sd 12.2). Modelled 10-year cardiovascular disease risk was lower in the intensive treatment group compared with the routine care group at 5 years, after adjustment for baseline cardiovascular disease risk and clustering (-2.0; 95% CI -3.1 to -0.9).


Despite increasing age and diabetes duration, there was a decline in modelled cardiovascular disease risk in the 5 years following diagnosis. Compared with routine care, 10-year modelled cardiovascular disease risk was lower in the intensive treatment group at 5 years. Our results suggest that patients benefit from intensive treatment early in the diabetes disease trajectory, where the rate of cardiovascular disease risk progression may be slowed.

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