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

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 (HbA(1c)) 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.

Applied public health research -- falling through the cracks?

BACKGROUND: There is a degree of dissonance between the types of evaluative research required by organisations providing or commissioning health care, those recommended by organisations developing evidence-based guidance, and those which research funding bodies are prepared to support. METHODS: We present a case study of efforts to establish a pragmatic but robust evaluation of local exercise referral schemes. We considered the epidemiological, ethical and practical advantages and disadvantages of a number of study designs and applied for research funding based on an uncontrolled design, outlining the difficulties of carrying out a randomised controlled trial to evaluate an existing service. RESULTS: Our proposal was praised for its relevance and clear patient outcomes, but the application was twice rejected because both funders and reviewers insisted on a randomised controlled trial design, which we had found to be impractical, unacceptable to service users and potentially unethical. CONCLUSION: The case study highlights continuing challenges for applied public health research in the current funding climate.

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.

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.

BACKGROUND: Diabetes 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. METHODS: 1139 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. RESULTS: Mortality from all causes, cardiovascular and ischaemic heart disease increased with increasing HbA1c. Participants with diagnosed diabetes or who had HbA1c > or = 7% but no self-reported diabetes had increased mortality risk from all causes and cardiovascular diseases. The respondents in the group HbA1c > or = 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%. CONCLUSION: The findings support previous reports that bio-markers of glucose metabolism are associated with long term outcomes, such as mortality and dementia.

Does depression increase the risk of developing type 2 diabetes?

BACKGROUND: Members of a scheme awarding injury pensions may allege that the onset of diabetes was precipitated or caused by depression induced by work in order to claim an injury award. AIMS: To quantify the association between depression and subsequent development of type 2 diabetes in order to determine whether an individual in a pension scheme that awards injury pensions, who develops type 2 diabetes, should be awarded an injury pension, if the development of the diabetes followed a work-related depressive episode. METHODS: Electronic and hand literature searches up to December 2006. Relative risk estimates from cohort studies of adults were pooled using fixed and random effects models. Attributable risk fraction was calculated using the Levin formula. RESULTS: The presence of depression or depressive symptoms was associated with increased risk of subsequently developing type 2 diabetes. The pooled fully adjusted relative risk estimate from the three highest quality studies was 1.25 (95% CI: 1.02-1.48) and was homogenous. However, depression was no more frequent among those with and without prevalent, but previously undiagnosed, type 2 diabetes. CONCLUSION: Depression is associated with subsequent development of type 2 diabetes. However, the relative risk estimate is small and only 20% of cases of diabetes can be attributed to depression in people with both conditions. Further research is needed to determine possible causal mechanisms for the association and to ascertain whether depression and diabetes may have a common aetiology.

The outcome of lupus nephritis in Jamaican patients.

We investigated the outcome of a cohort of black Jamaican patients with systemic lupus erythematosus (SLE) with nephritis. In 66 patients, 0 (0%), 15 (23%), 4 (6%), 32 (48%), 6 (9%), and 3 (5%) had classes 1, II, III, IV, V, and VI, respectively. Six (9%) had interstitial nephritis. The patients were placed in 2 groups for comparison. Group 1 (n = 36) consisted of classes III and IV and group 2 (n = 27), classes II and V, and interstitial nephritis. The patients in group 1 had significantly lower hemoglobin, higher mean serum creatinine, higher prevalence of hypertension, and chronicity scores. The duration of follow-up was similar between the 2 groups. The percent events free for ESRD or death at 1 year was 80.1% for group 1 and 77.4% for group 2; 2 years, 69.0% for group 1 and 77.4% group 2; 5 years, 69.0% for group 1 and 57.4% for group 2. The percent events free for death at 1 year was 93.4% in group 1 and 90.9% in group 2; at 2 years, 86.7% for group 1 and 90, 9% for group 2; and at 5 years was 86.7% for group 1 and 67.3% (29.5 to 88.0) for group 2. Sixteen patients (25.4%) developed ESRD or died. Prognosis was not different between the groups for ESRD or death (P = 0.22) or death alone (P = 0.63).

Isoprostanes, a marker of lipid peroxidation, may not be involved in the development of glucose intolerance.

We investigated whether isoprostanes, as a marker of lipid peroxidation, may be involved in the development of impaired glucose tolerance (IGT) or diabetes. Using a nested case-control study, we tracked the changes in isoprostane levels, insulin sensitivity (IS) and beta-cell function (BCF) in Afro-Jamaicans who progressed to IGT and diabetes over 3.9 years. Anthropometry, glucose tolerance, insulin levels, blood pressure and urinary isoprostane concentration were measured at baseline and follow-up. IS and BCF were estimated by the method of homeostasis assessment. Fifty-two individuals who progressed to IGT or diabetes and 44 age, sex and body mass index (BMI) matched controls were studied. Progression to glucose intolerance was significantly related with baseline BCF (p< or =0.01), but not isoprostane levels or IS. Glucose concentrations (fasting and 2 h) on follow-up were significantly correlated to baseline IS, baseline BCF, follow-up IS and follow-up BCF (p-values<0.05). In multiple regression analysis, only follow-up IS and BCF (p-values< or =0.001) independently predicted fasting glucose and 2h glucose levels at follow-up. Isoprostanes were not significantly associated with IS or BCF (p-values>0.1). We concluded that isoprostanes may not be causally involved in the development of glucose intolerance, insulin resistance or deteriorating BCF.

Impaired glucose regulation in adults in Jamaica: who should have the oral glucose tolerance test?

OBJECTIVE: To compare the 1999 World Health Organization (WHO) fasting plasma glucose (FPG) criteria and the WHO 2-hour post-challenge glucose (2hPG) criteria during an oral glucose tolerance test (OGTT) in identifying adults in Jamaica with hyperglycemia. As the OGTT is not commonly used in clinical practice, factors associated with the failure of the FPG criteria to detect persons with impaired 2hPG were investigated. METHODS: A random sample of 2 096 adults, 25-74 years old, living in the town of Spanish Town, Jamaica, was evaluated for diabetes. After excluding 215 individuals for reasons such as missing data, the remaining 1 881 persons were composed of 187 who were previously known to have diabetes and 1 694 who were screened for diabetes with both FPG and 2hPG. RESULTS: The FPG criteria detected 83 cases of diabetes, compared to 72 by the 2hPG criteria. The kappa statistic comparing the two criteria was 0.31 (95% confidence interval: 0.28-0.34), indicating fair agreement. There were 261 cases of impaired glucose tolerance (IGT) and 92 cases of impaired fasting glucose (IFG). In those 92 with IFG, an OGTT would identify 34 cases of IGT and 14 cases of diabetes. Of those classified as normoglycemic by FPG criteria, 14% of them had IGT or diabetes by 2hPG criteria. The factors predicting the likelihood of non-detection of impaired glucose tolerance or diabetes by FPG were age, body mass index, central obesity, systolic blood pressure, and female sex. By receiver operating characteristic curve analysis, an FPG of 5.1 mmol/L would predict a 2hPG >/= 7.8 mmol/L. CONCLUSIONS: A few individuals classified as normal on FPG will have IGT or diabetes, and an OGTT will be needed to identify them. The yield of IGT detected by screening in Jamaica can be improved by lowering the threshold for IFG or by using clinical information to identify high-risk individuals.

Impaired glucose regulation in adults in Jamaica: who should have the oral glucose tolerance test? / Alteraciones del control de la glucemia: ¿a quiénes se les debe hacer la prueba de tolerancia a una dosis oral de glucosa?

OBJETIVO: Comparar los criterios publicados por la Organización Mundial de la Salud (OMS) en 1999 acerca del uso de la prueba de glucemia en ayunas (PGA) y de la prueba de tolerancia a una dosis oral de glucosa con valoración a las dos horas (PTG2h) para identificar a adultos hiperglucémicos en Jamaica. Como la PTG2h no se administra normalmente en un contexto clínico, se investigaron los factores asociados con la inutilidad de la PGA para detectar a personas con hiperglucemia según la PTG2h. MÉTODOS: Se examinó una muestra aleatoria de 2 096 adultos de 25 a 47 años de edad que vivían en la ciudad de Spanish Town, Jamaica, para determinar la presencia de diabetes. Una vez que se eliminó a 215 personas por diversos motivos, entre ellos la ausencia de datos, quedaron 1 881 personas entre las cuales se encontraban 187 que se sabía de antemano que tenían diabetes y otras 1 694 que fueron sometidas tanto a la PGA como a la PTG2h. RESULTADOS: La PGA permitió detectar 83 casos de diabetes, mientras que la PTG2h permitió detectar 72. El estadístico kappa de comparación entre los dos criterios de valoración fue de 0,31 (intervalo de confianza de 95%: 0,28û0,34), valor que revela una concordancia moderada. Se observaron 261 casos de intolerancia a la glucosa tras la PTG2h y 92 casos de hiperglucemia en ayunas. En estas últimas 92 personas, la PTG2h sirvió para identificar 34 casos de intolerancia a la glucosa y 14 casos de diabetes. De las personas que se mostraron normoglucémicas según la PGA, 14% tenían intolerancia a la glucosa o diabetes, según la PTG2h. Algunos factores tuvieron valor pronóstico en relación con la falta de detección de la intolerancia a la glucosa o la diabetes. Estos fueron la edad, el índice de masa corporal, la concentración de la obesidad en el tronco y el abdomen, la tensión sistólica y el sexo femenino. De acuerdo con la curva de eficacia diagnóstica, una glucemia en ayunas de 5,1 mmol/L tendría valor pronóstico con respecto a la presencia de una glucemia de 7,8 mmol/L según la PTG2h. CONCLUSIONES: Algunas personas cuya glucemia en ayunas está dentro de lo normal tienen intolerancia a la glucosa o diabetes; por lo tanto, para identificarlas es necesario hacer la PTG2h. Se puede mejorar la detección de casos de intolerancia a la glucosa en Jamaica si se reduce el umbral de normalidad para la PGA o si se toman en cuenta los datos clínicos para identificar a las personas en alto riesgo.

Objective. To compare the 1999 World Health Organization (WHO) fasting plasma glucose (FPG) criteria and the WHO 2-hour post-challenge glucose (2hPG) criteria during an oral glucose tolerance test (OGTT) in identifying adults in Jamaica with hyperglycemia. As the OGTT is not commonly used in clinical practice, factors associated with the failure of the FPG criteria to detect persons with impaired 2hPG were investigated. Methods. A random sample of 2 096 adults, 25­74 years old, living in the town of Spanish Town, Jamaica, was evaluated for diabetes. After excluding 215 individuals for reasons such as missing data, the remaining 1 881 persons were composed of 187 who were previously known to have diabetes and 1 694 who were screened for diabetes with both FPG and 2hPG. Results. The FPG criteria detected 83 cases of diabetes, compared to 72 by the 2hPG criteria. The kappa statistic comparing the two criteria was 0.31 (95% confidence interval: 0.28­0.34), indicating fair agreement. There were 261 cases of impaired glucose tolerance (IGT) and 92 cases of impaired fasting glucose (IFG). In those 92 with IFG, an OGTT would identify 34 cases of IGT and 14 cases of diabetes. Of those classified as normoglycemic by FPG criteria, 14% of them had IGT or diabetes by 2hPG criteria. The factors predicting the likelihood of nondetection of impaired glucose tolerance or diabetes by FPG were age, body mass index, centralobesity, systolic blood pressure, and female sex. By receiver operating characteristic curve analysis, an FPG of 5.1 mmol/L would predict a 2hPG ≥ 7.8 mmol/L. Conclusions. A few individuals classified as normal on FPG will have IGT or diabetes, and an OGTT will be needed to identify them. The yield of IGT detected by screening in Jamaica can be improved by lowering the threshold for IFG or by using clinical information to identify high-risk individuals

The clinical and epidemiologic features in 140 patients with lupus nephritis in a predominantly black population from one center in Kingston, Jamaica.

BACKGROUND: Lupus nephritis has emerged as a major factor in the overall survival of patients and may help to explain the poor prognosis associated with systemic lupus erythematosus (SLE) in black patients. METHODS: The authors reviewed the clinical and epidemiologic features of lupus nephritis in 130 women and 10 men who were mainly of African descent. RESULTS: The mean (standard deviation) age at diagnosis of SLE was 27.9 (10.3) years. The majority of patients (75%) developed renal involvement within 1 year of presentation with SLE. The most frequent extrarenal manifestations were arthritis (67%), malar rash (44%), serositis (41%), and neurologic disorders (30%). Class IV nephritis was the most common glomerular lesion, accounting for 49% of the biopsies, with class II accounting for a further 23%. Proteinuria was a common feature at presentation in all classes. Nephrotic range proteinuria was most common in classes III and IV. Prevalence of nephrotic range proteinuria was similar in classes II (23%) and V (19%). Hematuria occurred in more than one half of the patients with classes II, IV, and V disease. Fifty-nine percent of the patients had renal impairment at the time of renal biopsy. The prevalence of hypertension, the nephritic syndrome, and renal impairment was significantly higher in class IV patients compared with all the other groups. Factors that were significantly associated with classes III and IV disease compared with the other classes on univariate analysis were renal impairment, proteinuria (but not in nephrotic range), low C3 levels, and anemia. CONCLUSIONS: The clinical features of the study patients were similar to those of patients belonging to other ethnic groups, but a high proportion of the study patients had renal impairment at the time of renal biopsy.

Predicting incident diabetes in Jamaica: the role of anthropometry.

OBJECTIVE: To evaluate the performance of the body mass index (BMI), waist circumference, waist-to-hip ratio (WHR), and waist-to-height ratio (WHTR) in predicting incident diabetes in Jamaica. RESEARCH METHODS AND PROCEDURES: A cohort of 728 nondiabetic adults (290 men and 438 women), ages 25 to 74 years and residents of Spanish Town, Jamaica, were followed for a mean of 4 years. Participants had fasting and 2-hour postchallenge glucose concentrations measured at baseline and follow-up. RESULTS: There were 51 cases of incident diabetes (17 men and 34 women). All indices were independent predictors of diabetes, and none was clearly superior. The area under the receiver operating characteristics curves (95% confidence interval) for BMI was 0.74 (0.59 to 0.88) for men and 0.62 (0.51 to 0.72) for women. For waist circumference, these values were 0.78 (0.65 to 0.91) in men and 0.61 (0.50 to 0.71) in women. Similar results were obtained for WHR and WHTR. "Optimal" cut-off points for BMI were 24.8 kg/m(2) (men) and 29.3 kg/m(2) (women). For waist circumference, these were 88 cm and 84.5 cm for men and women, respectively. Corresponding values for WHR were 0.87 and 0.80 and for WHTR were 0.51 and 0.54, respectively. DISCUSSION: Cut-off points for waist circumference and WHR were similar to those proposed in developed countries for women but lower in men. Waist circumference could be useful in health promotion as an alternative to BMI.

Management of diabetes mellitus in three settings in Jamaica

Objetivos. Evaluar la calidad de la atención a los pacientes diabéticos en tres consultorios (uno privado y dos públicos) de Jamaica, un país con ingresos medios y una alta prevalencia de diabetes (13 por ciento). Métodos. Durante un censo de 6 semanas realizado en 1995 se recogieron retrospectivamente datos sobre 437 pacientes diabéticos en estos tres consultorios: un ambulatorio de especialidades de un hospital público (AEP), una clinica privada (CP) y una policlínica pública (PP). Resultados. La mediana de edad de los pacientes osciló entre 56 años en el AEP y la CP y 63 años en la PP. La duración mediana del período de observación fue de 6,0 años en el AEP, 9,2 en la CP y 6,3 en la PP. menos de 10 por ciento de los pacientes fueron controlados únicamente con dieta. El tratamiento prescrito con más frecuencia en el AEP fue la insulina (46 por ciento, frente a 7 por ciento en cada uno de los otros dos consultorios). Las sulfonilureas, solas o combinadas con metformina, fueron los agentes más utilizados en la CP y la PP. en total 40 por ciento de los pacientes tuvieron un control satisfactorio de la glucemia (8 mmol/L en ayunas o 10 mmol/L tras las comidas) y no hubo diferencias significativas entre los consultorios con respecto al porcentaje de pacientes con control satisfactorio de la glucemia (P=0,26). La glucemia había sido registrada en el año anterior en 84 por ciento de los pacientes del AEP, 79 por ciento de la CP y 67 por ciento de la PP. Las determinaciones de la hemoglobina glucosilada fueron raras: 16 por ciento en el AEP, 10 por ciento en la CP y 0 por ciento en la PP. En total, en 96 por ciento de los pacientes se había vigilado la hipertensión y en 81 por ciento la proteinuria. La vigilancia de las complicaciones retinianas y podiátricas fue generalmente infrecuente y había sido registrada en las historias clínicas principalmente en los pacientes atendidos en el AEP (14 por ciento para las complicaciones podiátricas y 13 por ciento para las retinarias). Según las histórias clínicas, el personal de los tres consultorios raramente aconsejó a los pacientes sobre la dieta, el ejercicio y otras medidas no farmacológicas. La conducta clínica ante la diabetes en Jamaica no cumple las directrices internacionales y es necesario sensibilizar mejor a los profesionales sanitarios acerca de estas normas con el fin de reducir las consecuencias de la enfermedad

A sonographic study of kidney dimensions in a sample of healthy Jamaicans

A sonographic study of 49 randomly selected healthy Jamaicans was conducted to establish a guide for renal dimensions in the population. The mean length of the right kidney was 9.7 ñ 0.7 cm and the left 10 ñ 0.7 cm. The left kidney was longer than the right in the overall group and in males. There was no difference in width between right or left kidneys in the groups as a whole or within either gender. There was a significant association between the weight of males and the width of their kidneys; however, this association was not seen in females. The lone association between weight of the participants and renal length occurred in females and only with respect to the left kidney. Lengths and widths of kidneys were not associated with height in either gender. Renal surface area (RSA) was similar between the genders and also between right and left kidneys. Similarly, there was no significant association between renal length and body surface area (BSA) overall or within the genders. Renal index (RI) which is more reliable at assessing renal parenchymal mass than renal length alone was 20.92 and 22.86 for the right and left kidneys, respectively in males. Similarly, RI for the right and left kidneys in females was 23.76 and 25.54, respectively.