The aim of this analysis is to compare screening strategies with haemoglobin A(1c) (HbA(1c)), fasting plasma glucose (FPG) or combined measures in the identification of individuals at high risk for diabetes. Applying American Diabetes Association thresholds for FPG and HbA(1c) screening, 6,803 subjects free of diabetes were classified as non-diabetic, pre-diabetic and possibly diabetic by FPG (<100, 100-125 and >125 mg/dl) and HbA(1c) (<5.7, 5.7-6.4 and >6.4%). Hazard ratios, sensitivity and specificity were estimated for individuals with pre-diabetes with respect to incident diabetes in the following 5 years. Areas under the receiver operating characteristic curves (AUC) were estimated for levels of FPG ≤ 125 mg/dl and HbA(1c) ≤ 6.4% in diabetes prediction. Although FPG and HbA(1c) screenings poorly agreed in classifying individuals as pre-diabetic, hazard ratios [95% confidence interval] for incident diabetes were similarly increased in univariate models in the two pre-diabetic groups: FPG 100-125 mg/dl, 4.72 [3.69; 6.05]; HbA(1c) 5.7-6.4%, 3.97 [3.05; 5.23]. HbA(1c) and FPG had comparable AUCs (FPG, 0.732; HbA(1c), 0.725) and consequently similar 5-year sensitivities and specificities for their pre-diabetes definitions (when the lower cut-off for HbA(1c)-defined pre-diabetes was increased to a level between 5.8 and 5.9%). Combining HbA(1c) and FPG increased the AUC to 0.778, and a further increase to 0.817 was seen with additional inclusion of conventional risk factors. FPG and HbA(1c) have comparable (yet insufficient) abilities in identifying individuals at high risk for diabetes. Effectiveness of a diabetes screening program could be improved by a risk score including FPG and HbA(1c).
[Show abstract][Hide abstract] ABSTRACT: The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over a 1,000 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy ). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods.
European Journal of Epidemiology 08/2011; 26(8):657-86. DOI:10.1007/s10654-011-9610-5 · 5.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To assess the cardiovascular risk of diabetic subjects with chronic kidney disease (CKD) based on different estimated glomerular filtration rate (eGFR) equations and to evaluate which definition of CKD best improves cardiovascular risk prediction of the Framingham Cardiovascular Risk Score (Framingham-CV-RS).
CKD was defined as eGFR <60 mL/min/1.73 m(2), estimated by the creatinine-based Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations and a cystatin C-based equation (CKD-CysC). Cox regression was used to estimate hazard ratios (HRs) of subjects with CKD for incident cardiovascular events in a cohort of 1,153 individuals with diabetes (baseline age 50-74 years). Furthermore, the CKD definitions were added individually to a reference model comprising the Framingham-CV-RS variables and HbA(1c), and measures of model discrimination and reclassification were assessed.
During 5 years of follow-up, 95 individuals had a primary cardiovascular event. Crude HRs were increased for all CKD definitions. However, after adjusting for established cardiovascular risk factors, HRs for both creatinine-based CKD definitions were attenuated to point estimates of 1.03, whereas the HRs for the cystatin C-based CKD definition remained significantly increased (HR 1.75 [95% CI 1.07-2.87]). Extension of the reference model by the different CKD definitions resulted in an increase in the c statistic only when adding CKD-CysC (from 0.638 to 0.644) along with a net reclassification improvement of 8.9%.
Only the cystatin C-based CKD definition was an independent risk predictor for cardiovascular events in our diabetic study cohort and indicated a potentially better clinical utility for cardiovascular risk prediction than creatinine-based equations.
Diabetes care 02/2012; 35(4):879-86. DOI:10.2337/dc11-1998 · 8.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Excess total and cardiovascular morbidity and mortality remain very high among those with type 2 diabetes versus those without diabetes. Clinical trials to lower blood glucose have been disappointing probably because the participants were too late in the natural history of diabetes and already had extensive vascular disease. Insulin resistance measured simply by elevated fasting blood insulin is an early marker of β-cell stress and peripheral insulin resistance. Metformin will prevent development of diabetes among patients with impaired fasting glucose but only for the short term. Metformin reduces risk of coronary heart disease. The drug is safe, low cost, and may also prevent cancer. The combination of diet and exercise followed by metformin in the early phase of "insulin resistance" may reduce or delay both atherosclerosis and arteriosclerosis complications associated with diabetes. Preventive therapy must begin much earlier than before clinical diagnosis of diabetes and aim to initially lower blood insulin levels or insulin resistance.
Current Diabetes Reports 03/2012; 12(3):265-73. DOI:10.1007/s11892-012-0263-x · 3.08 Impact Factor
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