Guy E.H.M. Rutten

Effect of valsartan on the incidence of diabetes and cardiovascular events

BACKGROUND It is not known whether drugs that block the renin-angiotensin system reduce the risk of diabetes and cardiovascular events in patients with impaired glucose tolerance. METHODS In this double-blind, randomized clinical trial with a 2-by-2 factorial design, we assigned 9306 patients with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors to receive valsartan (up to 160 mg daily) or placebo (and nateglinide or placebo) in addition to lifestyle modification. We then followed the patients for a median of 5.0 years for the development of diabetes (6.5 years for vital status). We studied the effects of valsartan on the occurrence of three coprimary outcomes: the development of diabetes; an extended composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, arterial revascularization, or hospitalization for unstable angina; and a core composite outcome that excluded unstable angina and revascularization. RESULTS The cumulative incidence of diabetes was 33.1% in the valsartan group, as compared with 36.8% in the placebo group (hazard ratio in the valsartan group, 0.86; 95% confidence interval [CI], 0.80 to 0.92; P<0.001). Valsartan, as compared with placebo, did not significantly reduce the incidence of either the extended cardiovascular outcome (14.5% vs. 14.8%; hazard ratio, 0.96; 95% CI, 0.86 to 1.07; P=0.43) or the core cardiovascular outcome (8.1% vs. 8.1%; hazard ratio, 0.99; 95% CI, 0.86 to 1.14; P=0.85). CONCLUSIONS Among patients with impaired glucose tolerance and cardiovascular disease or risk factors, the use of valsartan for 5 years, along with lifestyle modification, led to a relative reduction of 14% in the incidence of diabetes but did not reduce the rate of cardiovascular events. (ClinicalTrials.gov number, NCT00097786.)

Effect of nateglinide on the incidence of diabetes and cardiovascular events

BACKGROUND The ability of short-acting insulin secretagogues to reduce the risk of diabetes or cardiovascular events in people with impaired glucose tolerance is unknown. METHODS In a double-blind, randomized clinical trial, we assigned 9306 participants with impaired glucose tolerance and either cardiovascular disease or cardiovascular risk factors to receive nateglinide (up to 60 mg three times daily) or placebo, in a 2-by-2 factorial design with valsartan or placebo, in addition to participation in a lifestyle modification program. We followed the participants for a median of 5.0 years for incident diabetes (and a median of 6.5 years for vital status). We evaluated the effect of nateglinide on the occurrence of three coprimary outcomes: the development of diabetes; a core cardiovascular outcome that was a composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure; and an extended cardiovascular outcome that was a composite of the individual components of the core composite cardiovascular outcome, hospitalization for unstable angina, or arterial revascularization. RESULTS After adjustment for multiple testing, nateglinide, as compared with placebo, did not significantly reduce the cumulative incidence of diabetes (36% and 34%, respectively; hazard ratio, 1.07; 95% confidence interval [CI], 1.00 to 1.15; P=0.05), the core composite cardiovascular outcome (7.9% and 8.3%, respectively; hazard ratio, 0.94, 95% CI, 0.82 to 1.09; P=0.43), or the extended composite cardiovascular outcome (14.2% and 15.2%, respectively; hazard ratio, 0.93, 95% CI, 0.83 to 1.03; P=0.16). Nateglinide did, however, increase the risk of hypoglycemia. CONCLUSIONS Among persons with impaired glucose tolerance and established cardiovascular disease or cardiovascular risk factors, assignment to nateglinide for 5 years did not reduce the incidence of diabetes or the coprimary composite cardiovascular outcomes. (ClinicalTrials.gov number, NCT00097786.)

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.

The ADDITION study : proposed trial of the cost-effectiveness of an intensive multifactorial intervention on morbidity and mortality among people with Type 2 diabetes detected by screening

OBJECTIVE: The overall aims of the ADDITION study are to evaluate whether screening for prevalent undiagnosed Type 2 diabetes is feasible, and whether subsequent optimised intensive treatment of diabetes, and associated risk factors, is feasible and beneficial.DESIGN: Population-based screening in three European countries followed by an open, randomised controlled trial.SUBJECTS AND METHODS: People aged 40–69 y in the community, without known diabetes, will be offered a random capillary blood glucose screening test by their primary care physicians, followed, if equal to or greater than 5.5 mmol/l, by fasting and 2-h post-glucose-challenge blood glucose measurements. Three thousand newly diagnosed patients will subsequently receive conventional treatment (according to current national guidelines) or intensive multifactorial treatment (lifestyle advice, prescription of aspirin and ACE-inhibitors, in addition to protocol-driven tight control of blood glucose, blood pressure and cholesterol). Patients allocated to intensive treatment will be further randomised to centre-specific interventions to motivate adherence to lifestyle changes and medication. Duration of follow-up is planned for 5 y. Endpoints will include mortality, macrovascular and microvascular complications, patient health status and satisfaction, process-of-care indicators and costs.

Diabetes, hyperglycaemia, and acute ischaemic stroke

Diabetes and ischaemic stroke often arise together. People with diabetes have more than double the risk of ischaemic stroke after correction for other risk factors, relative to individuals without diabetes. Multifactorial treatment of risk factors for stroke-in particular, lifestyle factors, hypertension, and dyslipidaemia-will prevent a substantial number of these disabling strokes. Hyperglycaemia occurs in 30-40% of patients with acute ischaemic stroke, also in individuals without a known history of diabetes. Admission hyperglycaemia is associated with poor functional outcome, possibly through aggravation of ischaemic damage by disturbing recanalisation and increasing reperfusion injury. Uncertainty surrounds the question of whether glucose-lowering treatment for early stroke can improve clinical outcome. Achievement of normoglycaemia in the early stage of stroke can be difficult, and the possibility of hypoglycaemia remains a concern. Phase 3 studies of glucose-lowering therapy in acute ischaemic stroke are underway.

NHG-Standaard Diabetes mellitus type 2

nog sterkere nadruk op de noodzaak van structurering van de diabeteszorg; andere afkappunten voor het stellen van de diagnose; richtlijnen voor de opsporing van personen met diabetes in hoog-risicogroepen; vervallen van onderscheid tussen eerste en tweede generatie sulfonylureumderivaten; voorkeur voor metformine bij mensen met een Quetelet index > 27; opname van facultatieve richtlijnen voor behandeling met insuline; opname van richtlijnen voor de behandeling van hypertensie en vetstofwisselingsstoornissen bij patienten met diabetes.

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.

Patient characteristics do not predict poor glycaemic control in type 2 diabetes patients treated in primary care

Many diabetic patients in general practice do not achieve good glycaemic control. The aim of this study was to assess which characteristics of type 2 diabetes patients treated in primary care predict poor glycaemic control (HbA1c≥ 7%). Data were collected from the medical records. 1641 patients were included who had mean HbA1c 7.1(SD 1.7)%, and 42% had HbA1c≥ 7%. On univariate analysis younger age; longer duration of diabetes; higher levels of blood glucose at diagnosis; most recent fasting blood glucose (FBG), total cholesterol, and triglyceride; higher body mass index (BMI); treatment with oral hypoglycaemic agents (OHA); treatment with insulin; more GP-visits for diabetes in the last year; and lower educational level were associated with poor control. Both in multiple linear regression and in multiple logistic regression higher levels of FBG (odds ratio (OR):= 1.6, 95% confidence interval (CI): 1.49, 1.70), treatment with OHA (OR: 2.1, 95% CI: 1.41, 3.04), treatment with insulin (OR: 7.2, 95% CI: 4.18, 12.52), lower educational level (OR: 1.26, 95% CI: 1.01, 1.56) were independently associated with poor levels of HbA1c. When FBG levels were excluded from the model, higher blood glucose at diagnosis, higher values for triglyceride and total cholesterol, and younger age predicted poor glycaemic control, but these variables explained only 15% of the variation in HbA1c. In conclusion prediction of poor glycaemic control from patient characteristics in diabetic patients in general practice is hardly possible. FBG appeared to be a strong predictor of HbA1c, which underlines the usefulness of this simple test in daily diabetes care. The worse metabolic control in those treated with either OHA or insulin suggests that current treatment regimes might be not sufficiently applied to reach the targets of care. Providers of diabetes care should be attentive to patients with lower educational level.

Beyond good intentions: The role of proactive coping in achieving sustained behavioural change in the context of diabetes management

This study examines the effectiveness of a brief self-management intervention to support patients recently diagnosed with type-2 diabetes to achieve sustained improvements in their self-care behaviours. Based on proactive coping, the intervention emphasizes the crucial role of anticipation and planning in maintaining self-care behaviours. In a randomised controlled trial among recent screen-detected patients, participants who received the intervention were compared with usual-care controls, examining changes in proximal outcomes (intentions, self-efficacy and proactive coping), self-care behaviour (diet, physical activity and medication) and weight over time (0, 3 and 12 months). Subsequently, the contribution of proactive coping in predicting maintenance of behavioural change was analysed using stepwise hierarchical regression analyses, controlling for baseline self-care behaviour, patient characteristics, and intentions and self-efficacy as measured after the course. The intervention was effective in improving proximal outcomes and behaviour with regard to diet and physical activity, resulting in significant weight loss at 12 months. Furthermore, proactive coping was a better predictor of long-term self-management than either intentions or self-efficacy. Proactive coping thus offers new insights into behavioural maintenance theory and can be used to develop effective self-management interventions.

Manipulation of patient–provider interaction: discussing illness representations or action plans concerning adherence

According to Leventhals Self-Regulatory Model of Illness, patients have ideas and action plans related to the management of their disease. The aim of this study is to examine whether ideas and action plans relating to hypertension change as a result of general practitioners (GPs) discussing them during consultation, and whether these changed ideas and actions plans affect adherence. The study employed an experimental design, highlighting three conditions: (0) care-as-usual consultation; (1) discussing patients ideas about their disorder; and (2) discussing patients action plans. Ten GP-trainees performed care-as-usual consultations, were subsequently assigned to a training in either Condition 1 or 2, and performed the trained conversations. Hundred and eight patients with hypertension were consecutively assigned to the conditions, and completed questionnaires a week before, immediately after the consultation, and 1 month later. The training resulted in two new, feasible and different types of conversations that managed to affect some of the patients ideas and action plans. It is concluded that the study provided GPs with a tool to discuss illness representations and actions plan of patients with hypertension. Implications for the management of hypertension adherence in primary care are discussed.