Maureen van den Donk

Effect of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with type 2 diabetes detected by screening (ADDITION-Europe): a cluster-randomised trial

Summary Background Intensive 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. Methods In 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 practices study group assignment. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00237549. Findings Primary 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. Interpretation An 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. Funding National 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.

Cognition in the Early Stage of Type 2 Diabetes

OBJECTIVE Type 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 METHODS Included 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. RESULTS Relative 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. CONCLUSIONS This 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.

Combined Task Delegation, Computerized Decision Support, and Feedback Improve Cardiovascular Risk for Type 2 Diabetic Patients A cluster randomized trial in primary care

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.

Work Stress, Sense of Coherence, and Risk of Type 2 Diabetes in a Prospective Study of Middle-Aged Swedish Men and Women

OBJECTIVE To investigate the prospective influence of work stress on type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS This 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. RESULTS In 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]). CONCLUSIONS Work 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.

Computerized Decision Support Systems in Primary Care for Type 2 Diabetes Patients Only Improve Patients' Outcomes when Combined with Feedback on Performance and Case Management: A Systematic Review

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. RESULTS Twenty RCTs met inclusion criteria. In 14 studies a CDSS was combined with another intervention. Two studies were left out of the analysis because of low quality. Four studies with a CDSS alone and four studies with a CDSS and reminders showed improvements of the process of care. CDSS with feedback on performance with or without reminders improved the process of care (one study) and patient outcome (two studies). CDSS with case management improved patient outcome (two studies). CDSS with reminders, feedback on performance, and case management improved both patient outcome and the process of care (two studies). CONCLUSIONS CDSSs used by healthcare providers in primary T2DM care are effective in improving the process of care; adding feedback on performance and/or case management may also improve patient outcome.

Intensive multifactorial treatment and cognitive functioning in screen-detected type 2 diabetes — The ADDITION-Netherlands study: A cluster-randomized trial

AIM To assess whether an intensive multifactorial treatment can reduce cognitive decrements and cognitive decline in screen-detected type 2 diabetes. METHODS The multinational ADDITION-study, a cluster-randomized parallel group trial in patients with screen-detected type 2 diabetes, compared the effectiveness of intensive multifactorial treatment (IT; lifestyle advice and strict regulation of metabolic parameters) with routine care (RC) on cardiovascular outcome. In The Netherlands randomization was stratified according to practice organization. Allocation was concealed from patients. The present study assessed the effect of IT on cognition through two neuropsychological assessments (NPA) on two occasions. The assessments took place three and six years after the start of the intervention. Non-diabetic controls served as reference group. The first NPA was performed in 183 patients (IT: 97; RC: 86) and 69 controls. The second NPA was performed in 135 patients (IT: 71; RC: 64) and 55 controls. Primary outcome was a composite score, including the domains memory, information-processing speed and attention and executive function. Comparisons between the treatment groups were performed with multi-level analyses. RESULTS The first NPA showed no differences between the treatment groups (mean difference composite z-score: 0.00; 95%-CI -0.16 to 0.16; IT vs RC). Over the next three years cognitive decline in the diabetic groups was within the range of the reference group and did not differ between the treatment arms (difference decline between diabetic groups -0.12; -0.24 to 0.01; IT vs RC). CONCLUSIONS Six years of IT in screen-detected type 2 diabetes had no benefit on cognitive functioning over RC.

High-sensitivity C-reactive protein to detect metabolic syndrome in a centrally obese population: a cross-sectional analysis.

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.

Effect of Early Multifactorial Therapy Compared With Routine Care on Microvascular Outcomes at 5 Years in People With Screen-Detected Diabetes: A Randomized Controlled Trial The ADDITION-Europe Study

OBJECTIVE To determine the benefit of multifactorial treatment on microvascular complications among people with type 2 diabetes detected by screening. RESEARCH DESIGN AND METHODS This study was a multicenter cluster randomized controlled trial in primary care with randomization at the practice level. In four centers in Denmark; Cambridge, U.K.; the Netherlands; and Leicester, U.K., 343 general practices participated in the trial. Eligible for follow-up were 2,861 of the 3,057 people with diabetes detected by screening included in the original trial. Biomedical data on nephropathy were collected in 2,710 (94.7%) participants, retinal photos in 2,190 (76.6%), and questionnaire data on peripheral neuropathy in 2,312 (80.9%). The prespecified microvascular end points were analyzed by intention to treat. Results from the four centers were pooled using fixed-effects meta-analysis. RESULTS Five years after diagnosis, any kind of albuminuria was present in 22.7% of participants in the intensive treatment (IT) group and in 24.4% in the routine care (RC) group (odds ratio 0.87 [95% CI 0.72–1.07]). Retinopathy was present in 10.2% of the IT group and 12.1% of the RC group (0.84 [0.64–1.10]), and severe retinopathy was present in one patient in the IT group and seven in the RC group. Neuropathy was present in 4.9% and 5.9% (0.95 [0.68–1.34]), respectively. Estimated glomerular filtration rate increased between baseline and follow-up in both groups (4.31 and 6.44 mL/min, respectively). CONCLUSIONS Compared with RC, an intervention to promote target-driven, intensive management of patients with type 2 diabetes detected by screening was not associated with significant reductions in the frequency of microvascular events at 5 years.

Cost-Effectiveness of the Diabetes Care Protocol, a Multifaceted Computerized Decision Support Diabetes Management Intervention That Reduces Cardiovascular Risk

OBJECTIVE The Diabetes Care Protocol (DCP), a multifaceted computerized decision support diabetes management intervention, reduces cardiovascular risk of type 2 diabetic patients. We performed a cost-effectiveness analysis of DCP from a Dutch health care perspective. RESEARCH DESIGN AND METHODS A cluster randomized trial provided data of DCP versus usual care. The 1-year follow-up patient data were extrapolated using a modified Dutch microsimulation diabetes model, computing individual lifetime health-related costs, and health effects. Incremental costs and effectiveness (quality-adjusted life-years [QALYs]) were estimated using multivariate generalized estimating equations to correct for practice-level clustering and confounding. Incremental cost-effectiveness ratios (ICERs) were calculated and cost-effectiveness acceptability curves were created. Stroke costs were calculated separately. Subgroup analyses examined patients with and without cardiovascular disease (CVD+ or CVD− patients, respectively). RESULTS Excluding stroke, DCP patients lived longer (0.14 life-years, P = NS), experienced more QALYs (0.037, P = NS), and incurred higher total costs (€1,415, P = NS), resulting in an ICER of €38,243 per QALY gained. The likelihood of cost-effectiveness given a willingness-to-pay threshold of €20,000 per QALY gained is 30%. DCP had a more favorable effect on CVD+ patients (ICER = €14,814) than for CVD− patients (ICER = €121,285). Coronary heart disease costs were reduced (€−587, P < 0.05). CONCLUSIONS DCP reduces cardiovascular risk, resulting in only a slight improvement in QALYs, lower CVD costs, but higher total costs, with a high cost-effectiveness ratio. Cost-effective care can be achieved by focusing on cardiovascular risk factors in type 2 diabetic patients with a history of CVD.

Insulin therapy in type 2 diabetes is no longer a secondary care activity in the Netherlands.

AIM Because Dutch health care organisations did want to establish well-defined diabetes shared care groups, we investigated the organisation of insulin therapy in general practice in the Netherlands and assessed factors that were associated with providing insulin therapy in type 2 diabetes (DM2) patients. METHODS Questionnaire to half of the Dutch general practitioners (GPs) (n=3848). We compared GPs who both start insulin treatment and monitor the dosages with those who always refer patients requiring insulin therapy or only monitor insulin dosages. RESULTS Total response was 42% (n=1621). 67% of the GPs start insulin therapy in patients with DM2, especially male GPs and those above the age of 40, as well as GPs working in a health centre and those working together with a practice nurse. GPs working in urban regions less often start insulin. The most often mentioned barriers for starting and/or monitoring insulin therapy are lack of knowledge of insulin therapy, lack of time and insufficient financial incentives. CONCLUSION This nation-wide overview shows that insulin therapy is no longer a secondary care based activity. However, there is still need to enlarge the practice staff and to overcome the perceived skills deficit.