Justin B. Echouffo-Tcheugui

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.

Burden of Undiagnosed Hypertension in Sub-Saharan Africa A Systematic Review and Meta-Analysis

The burden of hypertension in Sub-Saharan Africa has been increasing over the past few decades. However, a large proportion of the population with hypertension remains undiagnosed, untreated, or inadequately treated, contributing to the rising burden of cardiovascular disease in the region. We conducted a systematic review and meta-analysis to assess the recent burden of hypertension in Sub-Saharan Africa, based on studies published between 2000 and 2013. We pooled data from 33 surveys involving over 110 414 participants of mean age 40 years. Hypertension prevalence varied widely across the studies (range 15%–70%), partly because of differences in participant mean ages (31–76 years). The predicted prevalence of hypertension at mean participant ages of 30, 40, 50, and 60 years were 16%, 26%, 35%, and 44%, respectively, with a pooled prevalence of 30% (95% confidence interval, 27%–34%). Of those with hypertension, only between 7% and 56% (pooled prevalence: 27%; 95% confidence interval, 23%–31%) were aware of their hypertensive status before the surveys. Overall, 18% (95% confidence interval, 14%–22%) of individuals with hypertension were receiving treatment across the studies, and only 7% (95% confidence interval, 5%–8%) had controlled blood pressure. This review found a high prevalence of hypertension, as well as low percentage of hypertension awareness, treatment, and control in Sub-Saharan Africa, highlighting the need for implementation of timely and appropriate strategies for diagnosis, control, and prevention.The burden of hypertension in Sub-Saharan Africa has been increasing over the past few decades. However, a large proportion of the population with hypertension remains undiagnosed, untreated, or inadequately treated, contributing to the rising burden of cardiovascular disease in the region. We conducted a systematic review and meta-analysis to assess the recent burden of hypertension in Sub-Saharan Africa, based on studies published between 2000 and 2013. We pooled data from 33 surveys involving over 110 414 participants of mean age 40 years. Hypertension prevalence varied widely across the studies (range 15%–70%), partly because of differences in participant mean ages (31–76 years). The predicted prevalence of hypertension at mean participant ages of 30, 40, 50, and 60 years were 16%, 26%, 35%, and 44%, respectively, with a pooled prevalence of 30% (95% confidence interval, 27%–34%). Of those with hypertension, only between 7% and 56% (pooled prevalence: 27%; 95% confidence interval, 23%–31%) were aware of their hypertensive status before the surveys. Overall, 18% (95% confidence interval, 14%–22%) of individuals with hypertension were receiving treatment across the studies, and only 7% (95% confidence interval, 5%–8%) had controlled blood pressure. This review found a high prevalence of hypertension, as well as low percentage of hypertension awareness, treatment, and control in Sub-Saharan Africa, highlighting the need for implementation of timely and appropriate strategies for diagnosis, control, and prevention. # Novelty and Significance {#article-title-55}

The ADDITION-Cambridge trial protocol: a cluster – randomised controlled trial of screening for type 2 diabetes and intensive treatment for screen-detected patients

BackgroundThe 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, the benefits of such a strategy remain uncertain.Methods and designThe ADDITION-Cambridge study aims to evaluate the effectiveness and cost-effectiveness of (i) a stepwise screening strategy for type 2 diabetes; and (ii) intensive multifactorial treatment for people with screen-detected diabetes in primary care. 63 practices in the East Anglia region participated. Three undertook the pilot study, 33 were allocated to three groups: no screening (control), screening followed by intensive treatment (IT) and screening plus routine care (RC) in an unbalanced (1:3:3) randomisation. The remaining 27 practices were randomly allocated to IT and RC. A risk score incorporating routine practice data was used to identify people aged 40–69 years at high-risk of undiagnosed diabetes. In the screening practices, high-risk individuals were invited to take part in a stepwise screening programme. In the IT group, diabetes treatment is optimised through guidelines, target-led multifactorial treatment, audit, feedback, and academic detailing for practice teams, alongside provision of educational materials for newly diagnosed participants. Primary endpoints are modelled cardiovascular risk at one year, and cardiovascular mortality and morbidity at five years after diagnosis of diabetes. Secondary endpoints include all-cause mortality, development of renal and visual impairment, peripheral neuropathy, health service costs, self-reported quality of life, functional status and health utility. Impact of the screening programme at the population level is also assessed through measures of mortality, cardiovascular morbidity, health status and health service use among high-risk individuals.DiscussionADDITION-Cambridge is conducted in a defined high-risk group accessible through primary care. It addresses the feasibility of population-based screening for diabetes, as well as the benefits and costs of screening and intensive multifactorial treatment early in the disease trajectory. The intensive treatment algorithm is based on evidence from studies including individuals with clinically diagnosed diabetes and the education materials are informed by psychological theory. ADDITION-Cambridge will provide timely evidence concerning the benefits of early intensive treatment and will inform policy decisions concerning screening for type 2 diabetes.Trial registrationCurrent Controlled trials ISRCTN86769081

Risk Models to Predict Chronic Kidney Disease and Its Progression: A Systematic Review

A systematic review of risk prediction models conducted by Justin Echouffo-Tcheugui and Andre Kengne examines the evidence base for prediction of chronic kidney disease risk and its progression, and suitability of such models for clinical use.

Air pollution and risk of type 2 diabetes mellitus: A systematic review and meta-analysis

AIM Whether exposure to relatively high levels of air pollution is associated with diabetes occurrence remains unclear. We sought to assess and quantify the association between exposure to major air pollutants and risk of type 2 diabetes. METHODS PubMed and EMBASE databases (through September 2013) were searched using a combination of terms related to exposure to gaseous (NO2 and NOx) or particulate matter pollutants (PM2.5, PM10 and PM10-2.5) and type 2 diabetes. Descriptive and quantitative information were extracted from selected studies. We used random-effects models meta-analysis to derive overall risk estimates per type of pollutant. RESULTS We included ten studies (five cross-sectional and five prospective), assessing the effects of air pollutants on the occurrence of diabetes. In prospective investigations, the overall effect on diabetes occurrence was significant for both NO2 (adjusted hazard ratio [HR], 1.13; 95% confidence interval [95%CI], 1.01-1.22; p < 0.001; I(2) = 36.4%, pheterogeneity = 0.208) and PM2.5 (HR, 1.11; 95%CI, 1.03-1.20; p < 0.001; I(2) = 0.0%, pheterogeneity = 0.827). Odds ratios were reported by two cross-sectional studies which revealed similar associations between both NO2 and PM2.5 with type 2 diabetes. Across studies, risk estimates were generally adjusted for age, gender, body mass index and cigarette smoking. CONCLUSIONS Available evidence supports a prospective association of main air pollutants with an increased risk for type 2 diabetes. This finding may have implications for population-based strategies to reduce diabetes risk.

Screening for Type 2 Diabetes and Dysglycemia

Type 2 diabetes mellitus (T2DM) and dysglycemia (impaired glucose tolerance and/or impaired fasting glucose) are increasingly contributing to the global burden of diseases. The authors reviewed the published literature to critically evaluate the evidence on screening for both conditions and to identify the gaps in current understanding. Acceptable, relatively simple, and accurate tools can be used to screen for both T2DM and dysglycemia. Lifestyle modification and/or medication (e.g., metformin) are cost-effective in reducing the incidence of T2DM. However, their application is not yet routine practice. It is unclear whether diabetes-prevention strategies, which influence cardiovascular risk favorably, will also prevent diabetic vascular complications. Cardioprotective therapies, which are cost-effective in preventing complications in conventionally diagnosed T2DM, can be used in screen-detected diabetes, but the magnitude of their effects is unknown. Economic modeling suggests that screening for both T2DM and dysglycemia may be cost-effective, although empirical data on tangible benefits in preventing complications or death are lacking. Screening for T2DM is psychologically unharmful, but the specific impact of attributing the label of dysglycemia remains uncertain. Addressing these gaps will inform the development of a screening policy for T2DM and dysglycemia within a holistic diabetes prevention and control framework combining secondary and high-risk primary prevention strategies.

Evidence of reduced β-cell function in Asian Indians with mild dysglycemia.

OBJECTIVE To examine β-cell function across a spectrum of glycemia among Asian Indians, a population experiencing type 2 diabetes development at young ages despite low BMI. RESEARCH DESIGN AND METHODS One-thousand two-hundred sixty-four individuals without known diabetes in the Diabetes Community Lifestyle Improvement Program in Chennai, India, had a 75-g oral glucose tolerance test, with glucose and insulin measured at 0, 30, and 120 min. Type 2 diabetes, isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT), combined impaired fasting glucose and impaired glucose tolerance, and normal glucose tolerance (NGT) were defined by American Diabetes Association guidelines. Measures included insulin resistance and sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR], modified Matsuda Index, 1/fasting insulin) and β-cell function (oral disposition index = [Δinsulin0–30/Δglucose0–30] × [1/fasting insulin]). RESULTS Mean age was 44.2 years (SD, 9.3) and BMI 27.4 kg/m2 (SD, 3.8); 341 individuals had NGT, 672 had iIFG, IGT, or IFG plus IGT, and 251 had diabetes. Patterns of insulin resistance or sensitivity were similar across glycemic categories. With mild dysglycemia, the absolute differences in age- and sex-adjusted oral disposition index (NGT vs. iIFG, 38%; NGT vs. iIGT, 32%) were greater than the differences in HOMA-IR (NGT vs. iIFG, 25%; NGT vs. iIGT, 23%; each P < 0.0001). Compared with NGT and adjusted for age, sex, BMI, waist circumference, and family history, the odds of mild dysglycemia were more significant per SD of oral disposition index (iIFG: odds ratio [OR], 0.36; 95% CI, 0.23–0.55; iIGT: OR, 0.37; 95% CI, 0.24–0.56) than per SD of HOMA-IR (iIFG: OR, 1.69; 95% CI, 1.23–2.33; iIGT: OR, 1.53; 95% CI, 1.11–2.11). CONCLUSIONS Asian Indians with mild dysglycemia have reduced β-cell function, regardless of age, adiposity, insulin sensitivity, or family history. Strategies in diabetes prevention should minimize loss of β-cell function.

Risk models to predict hypertension: a systematic review.

Background As well as being a risk factor for cardiovascular disease, hypertension is also a health condition in its own right. Risk prediction models may be of value in identifying those individuals at risk of developing hypertension who are likely to benefit most from interventions. Methods and Findings To synthesize existing evidence on the performance of these models, we searched MEDLINE and EMBASE; examined bibliographies of retrieved articles; contacted experts in the field; and searched our own files. Dual review of identified studies was conducted. Included studies had to report on the development, validation, or impact analysis of a hypertension risk prediction model. For each publication, information was extracted on study design and characteristics, predictors, model discrimination, calibration and reclassification ability, validation and impact analysis. Eleven studies reporting on 15 different hypertension prediction risk models were identified. Age, sex, body mass index, diabetes status, and blood pressure variables were the most common predictor variables included in models. Most risk models had acceptable-to-good discriminatory ability (C-statistic>0.70) in the derivation sample. Calibration was less commonly assessed, but overall acceptable. Two hypertension risk models, the Framingham and Hopkins, have been externally validated, displaying acceptable-to-good discrimination, and C-statistic ranging from 0.71 to 0.81. Lack of individual-level data precluded analyses of the risk models in subgroups. Conclusions The discrimination ability of existing hypertension risk prediction tools is acceptable, but the impact of using these tools on prescriptions and outcomes of hypertension prevention is unclear.

Chronic non-communicable diseases in Cameroon - burden, determinants and current policies

Cameroon is experiencing an increase in the burden of chronic non-communicable diseases (NCDs), which accounted for 43% of all deaths in 2002. This article reviews the published literature to critically evaluate the evidence on the frequency, determinants and consequences of NCDs in Cameroon, and to identify research, intervention and policy gaps. The rising trends in NCDs have been documented for hypertension and diabetes, with a 2-5 and a 10-fold increase in their respective prevalence between 1994 and 2003. Magnitudes are much higher in urban settings, where increasing prevalence of overweight/obesity (by 54-82%) was observed over the same period. These changes largely result from the adoption of unfavorable eating habits, physical inactivity, and a probable increasing tobacco use. These behavioral changes are driven by the economic development and social mobility, which are part of the epidemiologic transition. There is still a dearth of information on chronic respiratory diseases and cancers, as well as on all NDCs and related risk factors in children and adolescents. More nationally representative data is needed to tract risk factors and consequences of NCDs. These conditions are increasingly been recognized as a priority, mainly through locally generated evidence. Thus, national-level prevention and control programs for chronic diseases (mainly diabetes and hypertension) have been established. However, the monitoring and evaluation of these programs is necessary. Budgetary allocations data by the ministry of health would be helpful, to evaluate the investment in NCDs prevention and control. Establishing more effective national-level tobacco control measures and food policies, as well as campaigns to promote healthy diets, physical activity and tobacco cessation would probably contribute to reducing the burden of NCDs.

Screening for type 2 diabetes: an update of the evidence

A growing body of evidence on diabetes screening has been published during the last 10 years. Type 2 diabetes meets many but not all of the criteria for screening. Concerns about potential harms of screening have largely been resolved. Screening identifies a high‐risk population with the potential to gain from widely available interventions. However, in spite of the findings of modelling studies, the size of the benefit of earlier initiation of treatment and the overall cost‐effectiveness remains uncertain, in contrast to other screening programmes (such as for abdominal aortic aneurysms) that are yet to be fully implemented. There is also uncertainty about optimal specifications and implementation of a screening programme, and further work to complete concerning development and delivery of individual‐ and population‐level preventive strategies. While there is growing evidence of the net benefit of earlier detection of individuals with prevalent but undiagnosed diabetes, there remains limited justification for a policy of universal population‐based screening for type 2 diabetes at the present time. Data from ongoing studies should inform the key assumptions in existing modelling studies and further reduce uncertainty.