Association of weight loss and weight loss maintenance following diabetes diagnosis by screening and incidence of cardiovascular disease and all-cause mortality: An observational analysis of the ADDITION-Europe trial.

AIMS: Short-term weight loss may lead to remission of type 2 diabetes but the effect of maintained weight loss on cardiovascular disease (CVD) is unknown. We quantified the associations between changes in weight 5 years following a diagnosis of diabetes, and incident CVD events and mortality up to 10 years after diagnosis. MATERIALS AND METHODS: Observational analysis of the ADDITION-Europe trial of 2730 adults with screen-detected type 2 diabetes from the UK, Denmark and the Netherlands. We defined weight change based on the maintenance at 5 years of weight loss achieved during the year after diabetes diagnosis, and as 5-year overall change in weight. Incident CVD events (n = 229) and all-cause mortality (n = 225) from 5 to 10 years follow-up were ascertained from medical records. RESULTS: Gaining >2% weight during the year after diabetes diagnosis was associated with higher hazard of all-cause mortality versus maintaining weight [hazard ratio (95% confidence interval): 3.18 (1.30-7.82)]. Losing ≥5% weight 1 year after diagnosis was also associated with mortality, whether or not weight loss was maintained at 5 years: 2.47 (0.99-6.21) and 2.72 (1.17-6.30), respectively. Losing ≥10% weight over 5 years was associated with mortality among those with body mass index <30 kg/m2 [4.62 (1.87-11.42)]. Associations with CVD incidence were inconclusive. CONCLUSIONS: Both weight loss and weight gain after screen-detected diabetes diagnosis were associated with higher mortality, but not CVD events, particularly among participants without obesity. The clinical implications of weight loss following a diagnosis of diabetes probably depend on its magnitude and timing, and may differ by body mass index status. Personalization of weight loss advice and support may be warranted.

Diabetes care providers' opinions and working methods after four years of experience with a diabetes patient web portal; a survey among health care providers in general practices and an outpatient clinic.

BACKGROUND: To gain insight into the opinions and working methods of diabetes care providers after using a diabetes web portal for 4 years in order to understand the role of the provider in patients' web portal use. METHODS: Survey among physicians and nurses from general practices and an outpatient clinic, correlated with data from the common web portal. RESULTS: One hundred twenty-eight questionnaires were analysed (response rate 56.6%). Responders' mean age was 46.2 ± 9.8 years and 43.8% were physicians. The majority was of opinion that the portal improves patients' diabetes knowledge (90.6%) and quality of care (72.7%). Although uploading glucose diary (93.6%) and patient access to laboratory and clinical notes (91.2 and 71.0%) were considered important, these features were recommended to patients in only 71.8 and 19.5% respectively. 64.8% declared they informed their patients about the portal and 45.3% handed-out the information leaflet and website address. The portal was especially recommended to type 1 diabetes patients (78.3%); those on insulin (84.3%) and patients aged< 65 years (72.4%). Few found it timesaving (21.9%). Diabetes care providers' opinions were not associated with patients' portal use. CONCLUSIONS: Providers are positive about patients web portals but still not recommend or encourage the use to all patients. There seems room for improvement in their working methods.

Validity and reliability of a Malay version of the brief illness perception questionnaire for patients with type 2 diabetes mellitus.

BACKGROUND: Illness perceptions involve the personal beliefs that patients have about their illness and may influence health behaviours considerably. Since an instrument to measure these perceptions for Malay population in Malaysia is lacking, we translated and examined the psychometric properties of the Malay version of the Brief Illness Perception Questionnaire (MBIPQ) in adult patients with type 2 diabetes mellitus. METHODS: The MBIPQ has nine items, all use a 0-10 response scale, except the ninth item about causal factors, which is an open-ended item. A standard procedure was used to translate and adapt the English BIPQ into Malay language. Construct validity was examined comparing item scores and scores on the Diabetes Management Self-Efficacy Scale, the Morisky Medication Adherence Scale, the World Health Organization Quality of Life-brief, the 9-item Patient Health Questionnaire, the 17-item Diabetes Distress Scale, HbA1c and the presence of complications. In addition, 2-week and 4-week test-retest reliability were studied. RESULTS: A total of 312 patients completed the MBIPQ. Out of this, 97 and 215 patients completed the 2- or 4-weeks test-retest reliability questionnaire, respectively. Moderate inter-items correlations were observed between illness perception dimensions (r = -0.31 to 0.53). MBIPQ items showed the expected correlations with self-efficacy (r = 0.35), medication adherence (r = 0.29), quality of life (r = -0.17 to 0.31) and depressive symptoms (r = -0.18 to 0.21). People with severe diabetes-related distress also were more concern (t-test = 4.01, p < 0.001) and experienced lower personal control (t-test = 2.07, p = 0.031). People with any diabetes-related complication perceived the consequences as more serious (t-test = 2.04, p = 0.044). The 2-week and 4-week test-retest reliabilities varied between ICCagreement 0.39 to 0.70 and 0.58 to 0.78, respectively. CONCLUSIONS: The psychometric properties of items in the MBIPQ are moderate. The MBIPQ showed good cross-cultural validity and moderate construct validity. Test-retest reliability was moderate. Despite the moderate psychometric properties, the MBIPQ may be useful in clinical practice as it is a useful instrument to elicit and communicate on patient's personal thoughts and feelings. Future research is needed to establish its responsiveness and predictive validity. TRIAL REGISTRATION: ClinicalTrials.gov NCT02730754 registered on March 29, 2016; NCT02730078 registered on March 29, 2016.

The effectiveness of a value-based EMOtion-cognition-Focused educatIonal programme to reduce diabetes-related distress in Malay adults with Type 2 diabetes (VEMOFIT): study protocol for a cluster randomised controlled trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) patients experience many psychosocial problems related to their diabetes. These often lead to emotional disorders such as distress, stress, anxiety and depression, resulting in decreased self-care, quality of life and disease control. The purpose of the current study is to evaluate the effectiveness of a brief value-based emotion-focused educational programme in adults with T2DM on diabetes-related distress (DRD), depressive symptoms, illness perceptions, quality of life, diabetes self-efficacy, self-care and clinical outcomes. METHODS: A cluster randomised controlled trial will be conducted in 10 public health clinics in Malaysia, all providing diabetes care according to national clinical practice guidelines. Patients' inclusion criteria: Malay, ≥ 18 years with T2DM for at least 2 years, on regular follow-up with one of three biomarkers HbA1c, systolic blood pressure and LDL-cholesterol sub-optimally controlled, and with a mean 17-item Diabetes Distress Scale (DDS-17) score ≥ 3. The intervention consists of four sessions and one booster over a period of 4 months that provide information and skills to assist patients in having proper perceptions of their T2DM including an understanding of the treatment targets, understanding and managing their emotions and goal-setting. The comparator is an attention-control group with three meetings over a similar period. With an estimated intra-cluster correlation coefficient ρ of 0.015, a cluster size of 20 and 20% non-completion, the trial will need to enroll 198 patients. PRIMARY OUTCOME: the between groups difference in proportion of patients achieving a mean DDS-17 score < 3 (non-significant distress) at 6 months post-intervention. Secondary outcomes will be the differences in the above mentioned variables between groups. DISCUSSION: We hypothesize that primary and secondary outcomes will improve significantly after the intervention compared to the comparator group. The results of this study can contribute to better care for T2DM patients with DRD. TRIAL REGISTRATION: ClinicalTrials.gov NCT02730078 . Registered on 29 March 2016, last updated on 4 January 2017.

Effectiveness of shared goal setting and decision making to achieve treatment targets in type 2 diabetes patients: A cluster-randomized trial (OPTIMAL).

OBJECTIVE: About 20% of patients with type 2 diabetes achieve all their treatment targets. Shared decision making (SDM) using a support aid based on the 5-years results of the ADDITION study on multifactorial treatment, could increase this proportion. RESEARCH DESIGN AND METHODS: Cluster-randomized trial in 35 former ADDITION primary care practices. Practices were randomized to SDM or care as usual (1:1). Both ADDITION and non-ADDITION type 2 diabetes patients, 60-80 years, known with diabetes for 8-12 years, were included. In the intervention group, patients were presented evidence about the relationship between treatment intensity and cardiovascular events. They chose intensive or less intensive treatment and prioritized their targets. After 1 year priorities could be rearranged. FOLLOW-UP: 24 months. Intention-to-treat analysis. MAIN OUTCOME MEASURE: proportion of patients that achieved all three treatment targets. RESULTS: At baseline 26.4% in the SDM group (n=72) had already achieved all three treatment goals (CG: 23.5%, n=81). In the SDM group 44 patients chose intensive treatment, 25 continued their former less intensive treatment and three people switched from the more to the less intensive protocol. After 24 months 31.8% of the patients in the SDM group achieved all three treatment targets (CG: 25.3%), RR 1.26 (95% CI 0.81-1.95). Mean systolic blood pressure decreased in the SDM group (-5.4 mm Hg, P<.01), mean HbA1c and total cholesterol did not change. CONCLUSIONS: Despite an already high baseline level of diabetes care, we found strong indications that SDM on both intensity of treatment and prioritizing treatment goals further improved outcomes.

How to choose the most appropriate cognitive test to evaluate cognitive complaints in primary care.

BACKGROUND: Despite the wealth of research devoted to the performance of individual cognitive tests for diagnosing cognitive impairment (including mild cognitive impairment and dementia), it can be difficult for general practitioners to choose the most appropriate test for a patient with cognitive complaints in daily practice. In this paper we present a diagnostic algorithm for the evaluation of cognitive complaints in primary care. The rationale behind this algorithm is that the likelihood of cognitive impairment -which can be determined after history taking and an informant interview- should determine which cognitive test is most suitable. METHODS: We distinguished three likelihoods of cognitive impairment: not likely, possible or likely. We selected cognitive tests based on pre-defined required test features for each of these three situations and a review of the literature. We incorporated the cognitive tests in a practical diagnostic algorithm. RESULTS: Based on the available literature, in patients with complaints but where cognitive impairment is considered to be unlikely the clock-drawing test can be used to rule out cognitive impairment. When cognitive impairment is possible the Montreal cognitive assessment can be used to rule out cognitive impairment or to make cognitive impairment more likely. When cognitive impairment is likely the Mini-Mental State Examination can be used to confirm the presence of cognitive impairment. CONCLUSIONS: We propose a diagnostic algorithm to increase the efficiency of ruling out or diagnosing cognitive impairment in primary care. Further study is needed to validate and evaluate this stepwise diagnostic algorithm.

Oral Hypoglycemic Agents Added to Insulin Monotherapy for Type 2 Diabetes.

CLINICAL QUESTION: Among patients with type 2 diabetes mellitus who do not achieve optimal glycemic control with insulin monotherapy, is the addition of oral hypoglycemic agents associated with benefits (measured by lowering of hemoglobin A1c) or adverse effects? BOTTOM LINE: Adding a sulfonylurea to insulin was associated with more hypoglycemic events compared with insulin alone, but this association was not observed for metformin. Adding a sulfonylurea or metformin to insulin was associated with a decrease in hemoglobin A1c of approximately 1.0%.

Effect of six years intensified multifactorial treatment on levels of hs-CRP and adiponectin in patients with screen detected type 2 diabetes: the ADDITION-Netherlands randomized trial.

BACKGROUND: Levels of high-sensitivity C-reactive protein (hs-CRP) and adiponectin, reflecting chronic inflammation, are associated with cardiovascular disease in type 2 diabetes. The long-term effects of multifactorial therapy in type 2 diabetes patients on CRP and adiponectin are unknown. METHODS: The ADDITION-NL study is a randomized clinical trial among screen-detected type 2 diabetes patients, randomized to intensive treatment (HbA1c <7.0% (53 mmol/mol), blood pressure ≤135/85 mmHg, total cholesterol ≤3.5 mmol/L) or routine care. Hs-CRP and adiponectin were measured before and 1, 2 and 6 years after inclusion. We analysed the effectiveness of the intervention on hs-CRP and adiponectin levels using a mixed effects model, taking into account practice, baseline levels and different medications. RESULTS: A total of 424 patients were included (intensive care n = 235; routine care n = 189). Both groups were well matched. Body mass index, systolic blood pressure, total cholesterol and HbA1c improved significantly more in the intensive care group compared to routine care group. Levels of hs-CRP decreased significantly in both treatment groups over time. Mean hs-CRP in the routine care group was 24% higher (p = 0.0027) than in the intensive treatment group during follow-up. After an initial increase the adiponectin values levelled off to nearly baseline values in both groups. The difference between the two groups after 6 years was 0.44 µg/mL (p = 0.27). CONCLUSIONS: Intensified multifactorial treatment in type 2 diabetes results in an enhanced decrease in hs-CRP. Whether this is clinically meaningful remains uncertain. The link to adiponectin seems to be more complex.

Comparison of perceptions of obesity among adults with central obesity with and without additional cardiometabolic risk factors and among those who were formally obese, 3 years after screening for central obesity.

BACKGROUND: Perceptions of illness are important determinants of health behaviour. A better understanding of perceptions of obesity might allow more effective interventions that challenge these perceptions through lifestyle modification programs. Although several studies have evaluated causal attributions with regard to obesity, other domains of illness perception, such as the perceived consequences of obesity and perceived controllability, have not yet been studied. The aim of the current study was to explore perceptions regarding causes, consequences, control, concerns and time course of obesity of centrally obese adults, with and without an elevated cardiometabolic risk and with or without weight loss, 3 years after screening for metabolic syndrome, and to compare these perceptions. METHODS: Three groups were selected from a longitudinal study dependent on the baseline and 3-year follow-up profiles: individuals with central obesity and metabolic syndrome at both time points ('persistent cardiometabolic-risk group', n = 80), those with central obesity but without metabolic syndrome on either occasion ('persistent obese group', n = 63), and formerly obese individuals ('improved cardiometabolic-risk group', n = 49). Perceptions of obesity were assessed using an adapted version of the Brief Illness Perception Questionnaire (BIPQ, range 0-10). Chi-square and Kruskal-Wallis tests were performed to compare the 'persistent cardiometabolic risk' group with the other two groups with regard to patient characteristics and BIPQ scores. RESULTS: Both males and females who improved their cardiometabolic risk perceived their obesity as shorter (median (IQR): 3.0 (4.0) vs. 6.0 (3.0), p < 0.001) and experienced greater personal control over their weight (7.0 (3.0) vs. 5.0 (3.0), p = 0.002) compared to those who did not improve. Females who improved their cardiometabolic risk experienced fewer identity and illness concerns, this was not found for males. Other scores did not differ between groups. CONCLUSION: Obese adults with an improved cardiometabolic risk profile felt greater personal control and considered their obesity to be of shorter duration. Persistence of central obesity with additional cardiometabolic risk factors had a larger impact on female than male participants with respect to identity and illness concerns. Whether discussing 'personal control' is a favourable element in lifestyle intervention should now be assessed in the setting of a controlled trial.

Shared decision making in type 2 diabetes with a support decision tool that takes into account clinical factors, the intensity of treatment and patient preferences: design of a cluster randomised (OPTIMAL) trial.

BACKGROUND: No more than 10-15% of type 2 diabetes mellitus (T2DM) patients achieve all treatment goals regarding glycaemic control, lipids and blood pressure. Shared decision making (SDM) should increase that percentage; however, not all support decision tools are appropriate. Because the ADDITION-Europe study demonstrated two (almost) equally effective treatments but with slightly different intensities, it may be a good starting point to discuss with the patients their diabetes treatment, taking into account both the intensity of treatment, clinical factors and patients' preferences. We aim to evaluate whether such an approach increases the proportion of patients that achieve all three treatment goals. METHODS: In a cluster-randomised trial including 40 general practices, that participated until 2009 in the ADDITION Study, 150 T2DM patients 60-80 years, known with T2DM for 8-15 years, will be included. Practices are randomised a second time, i.e. intervention practices in the ADDITION study could be control practices in the current study and vice versa. For the GPs from the intervention group a 2-hour training in SDM was developed as well as a decision support tool to be used during the consultation. GPs plan the first visit with the patients to decide on the intensity of the treatment, personalised targets and the priorities of treatment. The control group will continue with the treatment they were allocated to in the ADDITION study. FOLLOW-UP: 24 months. The primary outcome is the proportion of patients who achieve all three treatment goals. Secondary outcomes are the proportion of patients who achieve five treatment goals (HbA1c, blood pressure, total cholesterol, body weight, not smoking), evaluation of the SDM process (SDM-Q9 and CPS), satisfaction with the treatment (DTSQ), wellbeing and quality of life (W-BQ12, ADD QoL-19), health status (SF-36, EQ-5D) and coping (DCMQ). The proportions of achieved treatment goals will be compared between both groups. For the secondary outcomes mixed models will be used. The Medical Research Ethics Committee of the University Medical Centre Utrecht has approved the study protocol (Protocol number: 11-153). DISCUSSION: This trial will provide evidence whether an intervention with a multi-faceted decision support tool increases the proportion of achieved personalised goals in type 2 diabetes patients. TRIAL REGISTRATION: NCT02285881, November 4, 2014.

Repeat prescriptions of guideline-based secondary prevention medication in patients with type 2 diabetes and previous myocardial infarction in Dutch primary care.

BACKGROUND: Secondary prevention is efficient in reducing morbidity and mortality after a myocardial infarction (MI). However, both short-term and long-term mortality after MI remains relativity high in type 2 diabetes patients. OBJECTIVE: To evaluate repeat prescriptions of secondary prevention medication (anti-thrombotic agent, beta-blocker and statin) in type 2 diabetes patients with a previous MI. METHODS: Data of 1009 type 2 diabetes patients with a previous MI were extracted from the Julius General Practitioners' Network database. The proportion of patients with recent repeat prescriptions of guideline-based medication was determined. Furthermore, repeat prescriptions was determined 6 months, 1 year, 2 years and 5 years after MI. Generalized linear models were used to examine changes over time. Multivariate logistic regression analysis was used to analyse the association between patient characteristics and prescription. RESULTS: Only 46% of all type 2 diabetes patients with a previous MI had a recent repeat prescription for all three medicines. An increase in prescription over time was found for statins (P = 0.001). Older aged people [odds ratio (OR): 0.99, 95% confidence interval (CI): 0.98-1.00] were less likely to receive the combination of all three. CONCLUSION: A substantial proportion of type 2 diabetes patients with a previous MI did not receive guideline-based secondary prevention. Prescription rates were quite stable over time. This study confirms the need for a different approach to achieve an improvement of secondary prevention in type 2 diabetes patient with a previous MI. GPs can play an important role in this respect by being extra alert that prescription occurs according to the guidelines.

Living with diabetes: a group-based self-management support programme for T2DM patients in the early phases of illness and their partners, study protocol of a randomised controlled trial.

BACKGROUND: The present article presents the protocol for a randomised controlled trial to test the effectiveness of a group-based self-management support programme for recently diagnosed type 2 diabetes mellitus (T2DM) patients (one to three years post-diagnosis) and their partners. The course aims to support T2DM patients and their partners in successfully integrating diabetes care into their daily lives and hereby enhance self-management and diabetes-specific health-related quality of life. The content of the course is based on the Common-Sense Model of Self-Regulation (CSM). Furthermore, principles from the Social Cognitive Theory (SCT) and social support theories are integrated. METHODS/DESIGN: We aim to recruit 160 recently diagnosed T2DM patients and their partners from general practices in six different regions in the Netherlands. Patients need to be diagnosed with T2DM for one to three years and have to experience some degree of diabetes-related difficulties, as measured with a three-item screener. Participating patients and their partners are randomly allocated to the intervention or control condition. Participants in the intervention condition receive three monthly group sessions and a booster session three months later. Participants in the control condition receive a single information meeting. Data will be collected at baseline (T0), directly after the programme (T1) and six months post-programme (T2), including: self-management, diabetes-specific health-related quality of life, illness perceptions, attitudes, social support and empowerment. A three-level multilevel model will be used to compare change-scores between the conditions (intervention/control) on each outcome. DISCUSSION: Our study will be the first to determine whether a group-based support programme based on the CSM is effective in enhancing self-management and diabetes-specific health-related quality of life in recently diagnosed T2DM patients. The important role of patients' partners in effective diabetes care is also acknowledged in the study. TRIAL REGISTRATION: Netherlands National Trial Register (NTR) NTR3302.

Reasons and barriers for using a patient portal: survey among patients with diabetes mellitus.

BACKGROUND: The use of a Web portal for patients with diabetes mellitus to access their own personal health record may result in improved diabetes outcomes. However, the adoption by patients is slow. This may be caused by patient characteristics, but also by the content, layout, and promotion of the portal. Detailed knowledge about this could help increase patients' participation in Web portals. OBJECTIVE: The aim was to study the opinions of patients with diabetes and identify perceived barriers to using a Web portal to optimize its use. METHODS: We conducted a survey among patients with type 1 and type 2 diabetes mellitus from 62 primary care practices and 1 outpatient hospital clinic in the central area of the Netherlands who all used the same electronic health record with a Web portal. Questionnaires about patient characteristics, opinions about reasons for use or nonuse, and about portal content were sent to 1500 patients with a login and 3000 patients without a login to the Web portal. Patient groups were stratified according to login frequency. Demographic and diabetes-related variables were analyzed with multivariable regression analysis. RESULTS: The total response rate was 66.63% (2391/4399); 1390 of 4399 patients (31.60%) were eligible for analysis. There were 413 regular users (login frequency more than once) and 758 nonusers (no login). Most nonusers (72.4%) stated that the main reason for not requesting a login was that they were unaware of the existence of the portal. Other barriers reported by patients were disinterest in managing their own disease (28.5%, 216/758) and feelings of inadequacy with the use of computers and Internet (11.6%, 88/758). Patients treated by a general practitioner were more frequently nonusers compared to patients treated by an internist (78.8%, 666/846 vs 28.3%, 92/325; P<.001) and more users than nonusers became aware of the Web portal through their physician (94.9%, 392/413 vs 48.8%, 102/209; P<.001). Nonusers perceived specific portal content as not as useful as regular users did, especially access to laboratory values (71.7%, 383/534 vs 92.3%, 372/403), rereading clinic visits (61.3%, 320/522 vs 89.6%, 360/402), e-messaging (52.0%, 262/504 vs 74.6%, 299/401), and uploading results to the glucose diary (45.3%, 229/506 vs 74.0%, 288/400; all P<.001). CONCLUSIONS: Our study shows that unawareness of the patient portal is the main barrier of enrollment. Users and nonusers perceive the usefulness of the portal differently and do not have the same recommendations for additional functionalities. To increase patients' participation in a Web portal, the unawareness of its existence and its possibilities need to be addressed by their health care professionals.

Effect of early intensive multifactorial therapy compared with routine care on self-reported health status, general well-being, diabetes-specific quality of life and treatment satisfaction in screen-detected type 2 diabetes mellitus patients (ADDITION-Europe): a cluster-randomised trial.

AIMS/HYPOTHESIS: The study aimed to examine the effects of intensive treatment (IT) vs routine care (RC) on patient-reported outcomes after 5 years in screen-detected diabetic patients. METHODS: In a pragmatic, cluster-randomised, parallel-group trial, 343 general practices in Denmark, Cambridge and Leicester (UK) and the Netherlands were randomised to screening for type 2 diabetes mellitus plus IT of multiple risk factors in people 40-69 years without known diabetes (n = 1,678 patients) or screening plus RC (n = 1,379 patients). Practices were randomised in a 1:1 ratio according to a computer-generated list. Diabetes mellitus was diagnosed according to WHO criteria. Exclusions were: life expectancy <1 year, housebound, pregnant or lactating, or psychological or psychiatric problems. Treatment targets for IT were: HbA1c <7.0% (53 mmol/mol), BP ≤135/85 mmHg, cholesterol <5 mmol/l in the absence of a history of coronary heart disease and <4.5 mmol/l in patients with cardiovascular (CV) disease; prescription of aspirin to people taking antihypertensive medication and, in cases of CV disease or BP >120/80 mmHg, ACE inhibitors were recommended. After 2003, the treatment algorithm recommended statins to all patients with cholesterol of ≥3.5 mmol/l. Outcome measures were: health status (Euroqol 5 Dimensions [EQ-5D]) at baseline and at follow-up; and health status (36-item Short Form Health Survey [SF-36] and Euroquol Visual Analogue Scale [EQ-VAS]), well-being (12-item Short Form of the Well-Being Questionnaire), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life) and satisfaction with diabetes treatment (Diabetes Treatment Satisfaction Questionnaire) at follow-up. At baseline, standardised self-report questionnaires were used to collect information. Questionnaires were completed at the same health assessment visit as the anthropometric and biochemical measurements. The patients and the staff assessing the outcomes were unaware of the group assignments. Participants were followed for a mean of 5.7 years. Outcome data were available for 1,250 participants in the intensive treatment group (74%) and 967 participants in the routine care group (70%). The estimated differences in means from the four centres were pooled using random effects meta-analysis. Baseline EQ-5D level was used as a covariate in all analyses. RESULTS: EQ-5D values did not change between diagnosis and follow-up, with a median (interquartile range) of 0.85 (0.73-1.00) at baseline and 0.85 (0.73-1.00) at 5 year follow-up. Health status, well-being, diabetes-specific quality of life and treatment satisfaction did not differ between the intensive treatment and routine care groups. There was some heterogeneity between centres (I 2 being between 13% [SF-36 physical functioning] and 73% [EQ-VAS]). CONCLUSIONS/INTERPRETATION: There were no differences in health status, well-being, quality of life and treatment satisfaction between screen-detected type 2 diabetes mellitus patients receiving intensive treatment and those receiving routine care. These results suggest that intensive treatment does not adversely affect patient-reported outcomes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT00237549 FUNDING: ADDITION-Denmark was supported by the National Health Services, the Danish Council for Strategic Research, the Danish Research Foundation for General Practice, Novo Nordisk Foundation, the Danish Centre for Evaluation and Health Technology Assessment, the Diabetes Fund of the National Board of Health, the Danish Medical Research Council and the Aarhus University Research Foundation. In addition, unrestricted grants from pharmaceutical companies were received. ADDITION-Cambridge was supported by the Wellcome Trust, the Medical Research Council, the NIHR Health Technology Assessment Programme, National Health Service R&D support funding and the National Institute for Health Research. SJG received support from the Department of Health NIHR grant funding scheme. ADDITION-Leicester was supported by Department of Health, the NIHR Health Technology Assessment Programme, National Health Service R&D support funding and the National Institute for Health Research. ADDITION-Netherlands was supported by unrestricted grants from Novo Nordisk, Glaxo Smith Kline and Merck, and by the Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht.

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 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.)

Incidence of atrial fibrillation in a population with impaired glucose tolerance: the contribution of glucose metabolism and other risk factors. A post hoc analysis of the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research trial.

BACKGROUND: The role of dysglycemia as an additional risk factor for atrial fibrillation (AF) is controversial. Therefore, it was of interest to assess risk factors for incident AF in a large, representative population of patients with cardiovascular risk factors and impaired glucose tolerance but not overt diabetes in NAVIGATOR. METHODS: Predictors of incident AF were analyzed in 8,943 patients without AF at baseline by Cox proportional hazards regression. Study treatments (valsartan vs no valsartan and nateglinide vs no nateglinide) and the time-dependent covariate for progression to type 2 diabetes mellitus were added separately to the model. RESULTS: The median age of the 8,943 patients included in the present analysis of the NAVIGATOR trial was 63 years. Half of those patients were men, 6,922 (77.4%) had a history of hypertension, and 255 (2.9%) had heart failure. The median glycated hemoglobin was 6%. During the study, 613 of the 8,943 patients without AF at baseline presented with at least 1 episode of AF (6.9% 5-year incidence). Besides established predictors of incident AF, a 1 mmol/L increment of baseline fasting glucose, but not progression to diabetes, was found to be associated with a 33% increased risk of incident AF. Neither valsartan nor nateglinide affected AF incidence. CONCLUSIONS: In a trial population with impaired glucose tolerance, fasting plasma glucose and well-known risk factors (age, hypertension, and elevated body weight), but not progression to diabetes, predict risk of AF.

Defining and improving quality management in Dutch diabetes care groups and outpatient clinics: design of the study.

BACKGROUND: Worldwide, the organisation of diabetes care is changing. As a result general practices and diabetes teams in hospitals are becoming part of new organisations in which multidisciplinary care programs are implemented. In the Netherlands, 97 diabetes care groups and 104 outpatient clinics are working with a diabetes care program. Both types of organisations aim to improve the quality of diabetes care. Therefore, it is essential to understand the comprehensive elements needed for optimal quality management at organisational level. This study aims to assess the current level of diabetes quality management in both care groups and outpatient clinics and its improvement after providing feedback on their quality management system and tailored support. METHODS/DESIGN: This study is a before-after study with a one-year follow-up comparing the levels of quality management before and after an intervention to improve diabetes quality management. To assess the status of quality management, online questionnaires were developed based on current literature. They consist of six domains: organisation of care, multidisciplinary teamwork, patient centeredness, performance management, quality improvement policy and management strategies. Based on the questionnaires, respondents will receive feedback on their score in a radar diagram and an elucidating table. They will also be granted access to an online toolbox with instruments that proved to be effective in quality of care improvement and with practical examples. If requested, personal support in implementing these tools will be available. After one year quality management will be measured again using the same questionnaire. DISCUSSION: This study will reveal a nationwide picture of quality management in diabetes care groups and outpatient clinics in the Netherlands and evaluate the effect of offering tailored support. The operationalisation of quality management on organisational level may be of interest for other countries as well.

Satisfaction of well-controlled type 2 diabetes patients with three-monthly and six-monthly monitoring.

BACKGROUND: Patient's satisfaction with monitoring frequency is of interest when implementing six-monthly monitoring for well-controlled type 2 diabetes patients. Here we want to determine the satisfaction of well-controlled type 2 diabetes patients with either three-monthly or six-monthly diabetes monitoring and their future preference. METHODS: Survey among 2215 well-controlled type 2 diabetes patients (not using insulin, HbA1c ≤58 mmol/mol, systolic blood pressure ≤145 mmHg and total cholesterol ≤5.2 mmol/l) who participated in the EFFIMODI study, a randomised controlled patient-preference equivalence trial. At baseline, participants were asked whether they had a strong preference for three-monthly or six-monthly monitoring or not. If not, they were randomised to either three-monthly or six-monthly monitoring, while the others were monitored according to their preference. After eighteen months, all participants were asked whether they were satisfied with the monitoring frequency and about their future preference. Patient characteristics associated with satisfaction were also examined. RESULTS: Most patients (70.8%) would like to continue their monitoring frequency. Patients from the preference groups were more often satisfied than randomised patients (92.7% and 88.1%, respectively) and patients monitored three-monthly were more often satisfied than patients monitored six-monthly (93.5% and 88.5%, respectively). Higher age, better physical health, less diabetes-related distress, higher diabetes treatment satisfaction and less perceived hyper- and hypoglycaemias were associated with a higher monitoring satisfaction. CONCLUSIONS: Most well-controlled type 2 diabetes patients were satisfied with their monitoring frequency and would like to continue it. Although the satisfaction for three-monthly monitoring was slightly higher, the satisfaction with six-monthly monitoring was still rather high (88.5%). TRIAL REGISTRATION: Current controlled trials ISRCTN93201802.

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.

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 practice's 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 (HbA(1c) 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.