SummaryBackgroundIntensive treatment of multiple cardiovascular risk factors can halve mortality among people with established type 2 diabetes. We investigated the effect of early multifactorial treatment after diagnosis by screening.MethodsIn a pragmatic, cluster-randomised, parallel-group trial done in Denmark, the Netherlands, and the UK, 343 general practices were randomly assigned screening of registered patients aged 40–69 years without known diabetes followed by routine care of diabetes or screening followed by intensive treatment of multiple risk factors. The primary endpoint was first cardiovascular event, including cardiovascular mortality and morbidity, revascularisation, and non-traumatic amputation within 5 years. Patients and staff assessing outcomes were unaware of the practice's study group assignment. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00237549.FindingsPrimary endpoint data were available for 3055 (99·9%) of 3057 screen-detected patients. The mean age was 60·3 (SD 6·9) years and the mean duration of follow-up was 5·3 (SD 1·6) years. Improvements in cardiovascular risk factors (HbA1c and cholesterol concentrations and blood pressure) were slightly but significantly better in the intensive treatment group. The incidence of first cardiovascular event was 7·2% (13·5 per 1000 person-years) in the intensive treatment group and 8·5% (15·9 per 1000 person-years) in the routine care group (hazard ratio 0·83, 95% CI 0·65–1·05), and of all-cause mortality 6·2% (11·6 per 1000 person-years) and 6·7% (12·5 per 1000 person-years; 0·91, 0·69–1·21), respectively.InterpretationAn intervention to promote early intensive management of patients with type 2 diabetes was associated with a small, non-significant reduction in the incidence of cardiovascular events and death.FundingNational Health Service Denmark, Danish Council for Strategic Research, Danish Research Foundation for General Practice, Danish Centre for Evaluation and Health Technology Assessment, Danish National Board of Health, Danish Medical Research Council, Aarhus University Research Foundation, Wellcome Trust, UK Medical Research Council, UK NIHR Health Technology Assessment Programme, UK National Health Service R&D, UK National Institute for Health Research, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Novo Nordisk, Astra, Pfizer, GlaxoSmithKline, Servier, HemoCue, Merck.

OBJECTIVEType 2 diabetes is known to be associated with decrements in memory and executive functions and information-processing speed. It is less clear, however, at which stage of diabetes these cognitive decrements develop and how they progress over time. In this study, we investigated cognitive functioning of patients with recent screen-detected type 2 diabetes, thus providing insight into the nature and severity of cognitive decrements in the early stage of the disease. Possible risk factors were also addressed.RESEARCH DESIGN AND METHODSIncluded in this study were 183 diabetic patients from a previously established study cohort and 69 control subjects. A full neuropsychological assessment, addressing six cognitive domains, was made for each participant. Raw test scores were standardized into z scores per domain and compared between the groups. Possible risk factors for cognitive decrements were examined with multivariate linear regression.RESULTSRelative to scores for the control group, mean z scores were between 0.01 and 0.2 lower in the diabetic group across all domains, but after adjustment for differences in IQ between patients and control subjects, only memory performance was significantly reduced (mean difference −0.15 [95% CI −0.28 to −0.03]). A history of macrovascular disease and current smoking were significant determinants of slower information-processing speed in patients with diabetes.CONCLUSIONSThis study shows that modest cognitive decrements are already present at the early stage of type 2 diabetes. A history of macrovascular disease and smoking are significant risk factors for some early decrements.

OBJECTIVETo investigate the prospective influence of work stress on type 2 diabetes (T2D).RESEARCH DESIGN AND METHODSThis population-based cohort included 3,205 women and 2,227 men, aged 35–56 years, with baseline normal glucose tolerance measured with oral glucose tolerance test. At follow-up 8–10 years later, T2D was diagnosed in 60 women and 111 men. Work stress factors evaluated by questionnaire (i.e., demands, decision latitude, job strain, shift work, overtime work, and also sense of coherence) were studied in association with T2D. Odds ratios (ORs) and 95% CIs adjusted for age, education, BMI, physical activity, smoking, family history of diabetes, and psychological distress were calculated.RESULTSIn women, low decision latitude was associated with T2D on its own (OR 2.4 [95% CI 1.1–5.2]) and combined with high demands: job strain (OR 4.2 [2.0–8.7]), adjusted for all available potential confounders. Also, shift work increased the risk of T2D in women (OR 2.2 [1.0–4.7]) when adjusted for age, education, and psychological distress, although this risk was diluted after multifactor adjustment (OR 1.9 [0.8–4.4]). In men, high work demands and high strain decreased the risk of T2D (OR 0.5 [0.3–0.9]) for both measures, as did an active job (high demands and high decision latitude, OR 0.4 [0.2–0.9]).CONCLUSIONSWork stress and shift work may contribute to the development of T2D in women. In men, the risk was decreased by high work demands, high strain, and an active job.

OBJECTIVE -The Diabetes Care Protocol combines task delegation (a practice nurse), computerized decision support, and feedback every 3 months. We studied the effect of the Diabetes Care Protocol on A1C and cardiovascular risk factors in type 2 diabetic patients in primary care.RESEARCH DESIGN AND METHODS -In a cluster randomized trial, mean changes in cardiovascular risk factors between the intervention and control groups after 1 year were calculated by generalized linear models.RESULTS -Throughout the Netherlands, 26 intervention practices included 1,699 patients and 29 control practices 1,692 patients. The difference in A1C change was not significant, whereas total cholesterol, LDL cholesterol, and blood pressure improved significantly more in the intervention group. The 10-year coronary heart disease risk estimate of the UK Prospective Diabetes Study improved 1.4% more in the intervention group.CONCLUSIONS -Delegation of routine diabetes care to a practice nurse combined with computerized decision support and feedback did not improve A1C but reduced cardiovascular risk in type 2 diabetes patients.

To find out whether ultrasound-guided fine-needle aspiration (FNA) and ultrasound and stereotactic-guided large core needle biopsy (LCNB) are reliable alternatives to needle-localised open breast biopsy (NLBB) in daily practice, we performed a retrospective study and evaluated the validity of these methods. In all, 718 women with 749 nonpalpable breast lesions from three Dutch Hospitals were included, and the validity of the various methods for diagnosis was assessed. This was carried out according to a method described by Burbank and Parker for evaluating the quality of an image-guided breast intervention. We compared our results with the outcome of the COBRA study. Overall, all diagnostic strategies (NLBB, FNA, LCNB ultrasound and stereotactic guided) show comparable agreement rates. However, the miss rates differ: 2% for NLBB, 3% for COBRA (LCNB in study setting), 5% for FNA and 8 -12% for LCNB in practice. Fine-needle aspiration was nonconclusive in 29%, and shows an overestimation for DCIS in 9%. The DCIS underestimate rate in NLBB was 8%. For the assessment of lesions consisting of microcalcifications only and to exclude malignancy in all other lesions, a 14-gauge needle should be used. Ultrasound-guided intervention can be performed in a large percentage of nonpalpable lesions. Lesions consisting only of microcalcifications on mammography need special attention. Needle-localised open breast biopsy (NLBB) is considered the gold standard procedure for the diagnosis of nonpalpable breast lesions (NPBL) (Jackman and Marzoni, 1997). Needle-localised open breast biopsy is a surgical procedure with high costs and for most of the patients, is a traumatic experience. In the past few decades, less traumatic and cost-saving nonoperative image-guided techniques, such as fine-needle aspiration (FNA) and large-core needle biopsy (LCNB), have been advocated as an alternative to surgery to obtain material for a microscopic diagnosis. For guidance, ultrasound or stereotaxis are advocated.Recently, a large prospective study on stereotactic-guided LCNB was performed in the Netherlands to evaluate the diagnostic accuracy of this method (COBRA study) (Verkooijen, 2002). This study included 973 patients with 1029 nonpalpable breast lesions and showed a sensitivity rate of 97% and a specificity rate of 99% for stereotactic-guided LCNB. These figures are comparable to NLBB (Jackman and Marzoni, 1997). In the Dutch study, the stereotactic LCNB was always performed on a dedicated prone table, in an optimal setting. The dedicated equipment appears to be highly reliable but has the disadvantage of high initial expense. Therefore, it is not widely available in the Netherlands. The other alternatives for NLBB, such as stereotactic-guided LCNB with upright mammography machine and add on digital attachment, ultrasound-guided FNA and LCNB are more widely available. To find out whether FNA (ultrasound-guided) and LCNB (ultrasound and stereotactic-guided) are reliable alternatives to NLBB in daily practice, a retrospective study on the dia...

Adequate folate availability is necessary to sustain normal DNA synthesis and normal patterns of DNA methylation and these features of DNA can be modified by methylenetetrahydrofolate reductase (MTHFR) C677T genotype. This study investigated the effect of MTHFR C677T genotype and daily supplementation with 5 mg folic acid and 1.25 mg vitamin B-12 on uracil misincorporation into DNA and promoter methylation. Subjects (n = 86) with a history of colorectal adenoma and MTHFR CC or TT genotype were randomly assigned to receive folic acid plus vitamin B-12 or placebo for 6 mo. Uracil misincorporation and promoter methylation of 6 tumor suppressor and DNA repair genes were assessed in DNA from rectal biopsies at baseline and after the intervention. The biomarkers did not differ between the treated group and the placebo group after 6 mo compared with baseline. The uracil concentration of DNA increased in the treated group (5.37 fmol/microg DNA, P = 0.02), whereas it did not change in the placebo group (P = 0.42). The change from baseline of 4.01 fmol uracil/microg DNA tended to differ between the groups (P = 0.16). An increase in promoter methylation tended to occur more often in the intervention group than in the placebo group (OR = 1.67; P = 0.08). This study suggests that supplementation with high doses of folic acid and vitamin B-12 may not favorably influence uracil incorporation and promoter methylation in subjects with previous colorectal adenomas. Because such alterations may potentially increase the risk of neoplastic transformation, more research is needed to fully define the consequences of these molecular alterations.

Purpose: Computerized decision support systems (CDSSs) are often part of a multifaceted intervention to improve diabetes care. We reviewed the effects of CDSSs alone or in combination with other supportive tools in primary care for type 2 diabetes mellitus (T2DM). Materials and Methods: A systematic literature search was conducted for January 1990-July 2011 in PubMed, Embase, and the Cochrane Database and by consulting reference lists. Randomized controlled trials (RCTs) in general practice were selected if the interventions consisted of a CDSS alone or combined with a reminder system and/or feedback on performance and/or case management. The intervention had to be compared with usual care. Two pairs of reviewers independently abstracted all available data. The data were categorized by process of care and patient outcome measures.

BackgroundPeople with central obesity have an increased risk for developing the metabolic syndrome, type 2 diabetes and cardiovascular disease. However, a substantial part of obese individuals have no other cardiovascular risk factors, besides their obesity. High sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation and a predictor of type 2 diabetes and cardiovascular disease, is associated with the metabolic syndrome and its separate components. We evaluated the use of hs-CRP to discriminate between centrally obese people with and without the metabolic syndrome.Methods1165 people with central obesity but without any previous diagnosis of hypertension, dyslipidemia, diabetes or cardiovascular disease, aged 20-70 years, underwent a physical examination and laboratory assays to determine the presence of the metabolic syndrome (NCEP ATP III criteria). Multivariable linear regression analyses were performed to assess which metabolic syndrome components were independently associated with hs-CRP. A ROC curve was drawn and the area under the curve was calculated to evaluate whether hs-CRP was capable to predict the presence of the metabolic syndrome.ResultsMedian hs-CRP levels were significantly higher in individuals with central obesity with the metabolic syndrome (n = 417; 35.8%) compared to individuals with central obesity without the metabolic syndrome (2.2 mg/L (IQR 1.2-4.0) versus 1.7 mg/L (IQR 1.0-3.4); p < 0.001). Median hs-CRP levels increased with an increasing number of metabolic syndrome components present. In multivariable linear regression analyses, waist circumference and triglycerides were the only components that were independently associated with hs-CRP after adjusting for smoking, gender, alcohol consumption and the other metabolic syndrome components. The area under the ROC curve was 0.57 (95%-CI 0.53-0.60).ConclusionsHs-CRP has limited capacity to predict the presence of the metabolic syndrome in a population with central obesity.