Search

Supplementary Table S2. Scaffold 'Sample view' of all proteins and protein clusters identified in protein band 1 to 5.

Supplementary Figure 1. Standard curve of rabbit monoclonal antibody to recombinant survivin using DAC-ELISA (A) and sandwich ELISA (B). Supplementary Figure 2. Antibody response to recombinant survivin was measured in seven NSCLC sera previously reported to be positive for survivin antibodies and in seven healthy non-smoking control sera. Supplementary Figure 3. Standard curve of rabbit anti-survivin spiked in non-smoking control sera using sandwich ELISA. Supplementary Figure 4. Standard curve of rabbit anti-survivin spiked in NSCLC patient sera using sandwich ELISA. Supplementary Figure 5. Standard curve of human autoantibodies to HuD using sandwich ELISA. Supplementary Figure 6. Results of sandwich ELISA were confirmed by western blot analysis.

The high mortality rate in lung cancer is largely attributable to late diagnosis. Case–control studies suggest that autoantibodies to the survivin protein are potential biomarkers for early diagnosis. We tested the hypothesis that sandwich ELISA can detect autoantibodies to survivin before radiologic diagnosis in patients with early-stage non–small cell lung cancer (NSCLC). Because previous studies assayed survivin autoantibodies with the direct antigen-coating ELISA (DAC-ELISA), we first compared that assay with the sandwich ELISA. Based on the more robust results from the sandwich ELISA, we used it to measure survivin autoantibodies in the serum of 100 individuals from a well-controlled population study [the Dutch–Belgian Lung Cancer Screening Trial (NELSON) trial] composed of current and former smokers (50 patients with NSCLC, both before and after diagnosis, and 50 matched, smoking-habit control subjects), and another 50 healthy nonsmoking control subjects. We found no difference in specific autoantibodies to survivin in NSCLC patients, although nonspecific median optical densities were 24% higher (P < 0.001) in both NSCLC patients and smokers, than in healthy nonsmokers. Finally, we confirmed the ELISA results with Western blot analysis of recombinant and endogenous survivin (HEK-293), which showed no anti-survivin reactivity in patient sera. We conclude that specific anti-survivin autoantibody reactivity is most likely not present in sera before or after diagnosis. Autoantibody studies benefit from a comparison to a well-controlled population, stratified for smoking habit. Cancer Immunol Res; 4(2); 165–72. ©2015 AACR.

ObjectivesOsteoarthritis (OA) of the foot-ankle complex is understudied. Understanding determinants of pain and activity limitations is necessary to improve management of foot OA. The aim of the present study was to investigate demographic, foot-specific and comorbidity-related factors associated with pain and activity limitations in patients with foot OA.MethodsThis exploratory cross-sectional study included 75 patients with OA of the foot and/or ankle joints. Demographic and clinical data were collected with questionnaires and by clinical examination. The outcome variables of pain and activity limitations were measured using the Foot Function Index (FFI). Potential determinants were categorized into demographic factors (e.g., age, sex), foot-specific factors (e.g., plantar pressure and gait parameters), and comorbidity-related factors (e.g., type and amount of comorbid diseases). Multivariable regression analyses with backward selection (p-out≥0.05) were performed in two steps, leading to a final model.ResultsOf all potential determinants, nine factors were selected in the first step. Five of these factors were retained in the second step (final model): female sex, pain located in the hindfoot, higher body mass index (BMI), neurological comorbidity, and Hospital Anxiety and Depression Scale (HADS) score were positively associated with the FFI score. The explained variance (R2) for the final model was 0.580 (adjusted R2 ​= ​0.549).ConclusionFemale sex, pain located in the hindfoot, higher BMI, neurological comorbidity and greater psychological distress were independently associated with a higher level of foot-related pain and activity limitations. By addressing these factors in the management of foot OA, pain and activity limitations may be reduced.

Summary Objectives Weakness of upper leg muscles has a negative impact on future disease and functional status in subjects with knee osteoarthritis (OA). The aims of the present study were to (i) describe the course of muscle strength over 48 months and (ii) identify baseline predictors for a decline in upper leg muscle strength over time in subjects with knee OA. Methods Data were obtained from the Osteoarthritis Initiative (OAI) database, a multicenter, observational study of knee OA. Upper leg muscle strength (in N/kg) was measured at baseline, 24 and 48 months. Potential baseline predictors included demographics, OA-specific and health and lifestyle related factors. Linear mixed model analyses were performed. Results A total of 1390 subjects with knee osteoarthritis were included. A statistically significant decline of muscle strength was found between baseline and 24 months (B = −0.186, 95%CI [-0.358,-0.014], p = 0.03), but not between other time points (24–48 months p = 0.89, and baseline and 48 months p = 0.058). Predictors of a decline in muscle strength over time included demographic predictors (older age, being female, higher body mass index (BMI)), one lifestyle predictor (lower dietary protein intake) and one OA-specific predictor (radiographic severity). Conclusions Muscle strength declined over time in subjects with knee OA. The identified predictors may help clinicians to select and treat subjects with knee OA at risk of a decline in muscle strength.

Aims: We aimed to identify baseline predictors of mortality in patients with a severe mental illness (SMI) over a 6-year period and to describe mortality rates as standardised mortality ratios (SMRs). We hypothesised that cardiovascular diseases, older age, cigarette smoking, more severe psychiatric symptoms and more severe psychotropic side effects, and alcohol or drug use were independent risk factors for mortality. Method: Medical examinations were conducted at baseline in a cohort of 322 SMI patients. SMRs were estimated after 6 years and an evaluation was made of the impact of a wide range of variables on survival time. Results: Almost 11% of the SMI patients had died at the end of the study period. All-cause SMRs were 4.51 (95% CI 3.07–5.95) for all SMI patients (4.89, 95% CI 2.97–6.80 for men, and 3.94, 95% CI 1.78–6.10 for women). Natural causes accounted for 86% of excess mortality and unnatural causes for 14%. Cardiovascular disease was a major contributor to this excess mortality. Multivariate Cox regression analyses showed that premature death was associated with a longer history of tobacco use (HR: 1.03, 95% CI 1.02–1.03) and more severe symptoms of disorganisation (HR: 2.36, 95% CI 2.21–2.52). Conclusions: The high SMR and the incidence of cardiovascular disease-related death in SMI patients in our study justify concern. This study underscores the urgent need for interventions to reduce excess mortality in patients with SMI.

Background Reduced sleep quality is a major concern in patients with chronic widespread pain (CWP).1 2 Poor sleep quality in CWP has received relatively little attention in both multidisciplinary treatment and clinical research in multidisciplinary treatment.3 4 Objectives (i) To investigate the prevalence of poor sleep quality and (ii) to explore the associations between clinical, cognitive and emotional factors and quality of sleep in patients with CWP indicated for multidisciplinary treatment. Methods Baseline data were used from 163 CWP patients referred for multidisciplinary treatment. Linear regression models, adjusted for age and gender, were used to assess the relationship of clinical (pain, fatigue, pain interference and disability), emotional (anxiety, depression and psychological distress) and cognitive factors (catastrophizing, acceptance, self-efficacy, kinesiofobia and illness beliefs) with sleep quality, as measured with the Pittsburgh Sleep Quality Index (PSQI). Results Poor sleep quality was found in 92% of the patients. The multivariate model showed that a higher level of fatigue, psychological distress and more concerns about the illness were independently associated with poorer quality of sleep. The model explained 27.9% of the variance of sleep quality. Conclusions The high prevalence of poor sleep quality in patients with CWP referred for multidisciplinary treatment emphasises the need to target sleep during the treatment program. Poorer quality of sleep is related to a higher level of fatigue, psychological distress and more concerns about the illness. Attention to these factors during multidisciplinary treatment could contribute to improvement in quality of sleep. References [1] Breivik H, Collett B, Ventafridda V, et al. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain2006;10(4):287–333. [2] Arnold LM, Crofford LJ, Mease PJ, et al. Patient perspectives on the impact of fibromyalgia. Patient Educ Couns2008;73(1):114–20. [3] Scascighini L, Toma V, Dober-Spielmann, et al. Multidisciplinary treatment for chronic pain: a review of inter ventions and outcomes. Rheumatology (Oxford)2008;47(5):670–678. [4] Dworkin RH, Turk DC, Farrar JT, et al. core outcome measures for chronic pain clinical trials:IMMPACT recommendation. Pain2005;113(1–2):9–19. Disclosure of Interest None declared

Background There is strong evidence that exercise therapy is effective in reducing pain and activity limitations in knee osteoarthritis (OA), but effect sizes are low to moderate. Stratified exercise therapy tailored to clinically relevant subgroups of patients is expected to optimise treatment effects in a cost-effective manner. Objectives This study aimed to explore the feasibility of a newly developed model of stratified exercise therapy in primary care. Methods A mixed method design was used, consisting of an uncontrolled pretest-posttest design and a process evaluation. Eligible patients visiting a participating primary care physical therapist (PT) were included. Based on our model, participants were allocated to the ‘high muscle strength subgroup’, ‘low muscle strength subgroup’, ‘obesity subgroup’ or ‘depression subgroup’, and received subgroup-specific, protocolised, 4 month exercise therapy. Feasibility of stratified exercise therapy according to this model was evaluated by a process evaluation (process documentation, semi-structured interviews and focus group meeting) and outcome (physical functioning (KOOS-ADL) and knee pain (NRS), assessed at baseline and 4 months follow-up). Results We included 50 patients, of which 3 patients dropped out. The process evaluation suggests that our model is feasible for patients and PTs, with some adaptations for further optimisation. We found clinically relevant improvements on physical functioning (p Conclusions Our model of stratified exercise therapy is feasible in primary care. Minor adaptations could further optimise the feasibility. Future research should determine the (cost-)effectiveness of this model, compared to usual, non-stratified exercise therapy. Disclosure of Interest None declared

BackgroundEndothelial dysfunction (ED), low-grade inflammation (LGI) and oxidative stress (OxS) may be involved in the pathobiology of depression. Previous studies on the association of these processes in depression have yielded contradictory results. We therefore investigated comprehensively, in a population-based cohort study, the association between ED, LGI and OxS on the one hand and depressive symptoms on the other.MethodWe used data from the Hoorn Study and determined biomarkers of ED [flow-mediated dilatation (FMD), von Willebrand factor, soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1, soluble thrombomodulin and soluble endothelial selectin], LGI [C-reactive protein, tumour necrosis factor-α, interleukin 6, interleukin 8, serum amyloid A, myeloperoxidase (MPO) and sICAM-1] and OxS (oxidized low density lipoprotein and MPO). Depressive symptoms were quantified by the Center for Epidemiologic Studies Depression Scale (CES-D) questionnaire (n = 493; age 68 years; 49.9% female). Regression analyses were performed with the use of biomarker Z scores. Adjustments were made for age, sex and glucose metabolism status (cohort stratification variables) and prior cardiovascular disease, hypertension, waist-to-hip ratio, cholesterol levels, education level, physical activity, dietary habits, and the use of antihypertensive and/or lipid-lowering medication and/or metformin (potential confounders).ResultsAfter adjustment for age, sex and glucose metabolism status, one standard deviation increase in the ED Z score was associated with a 1.9 [95% confidence interval (CI) 0.7–3.1] higher CES-D score. Additional adjustments did not materially change this result. LGI and OxS were not associated with the CES-D score.ConclusionsED, as quantified by an array of circulating biomarkers and FMD, was independently associated with depressive symptoms. This study supports the hypothesis that ED plays an important role in the pathobiology of depression.

OBJECTIVE To investigate risk of a recurrent cardiovascular event and its predictors in a population-based cohort. RESEARCH DESIGN AND METHODS Participants of the Hoorn Study who had experienced a first cardiovascular event after baseline (n = 336) were followed with respect to a recurrent event. Absolute risk of a recurrent event was calculated for individuals with normal glucose metabolism, intermediate hyperglycemia, and type 2 diabetes. Cox regression models were used to investigate which variables, measured before the first vascular event, predicted a recurrent event using the stepwise backward procedure. RESULTS During a median follow-up of 4.1 years, 44% (n = 148) of the population developed a recurrent vascular event. The rate of recurrent events per 100 person-years was 7.2 (95% CI 5.8–8.7) in individuals with normal glucose metabolism, compared with 9.8 (6.6–14.0) in individuals with intermediate hyperglycemia and 12.5 (8.5–17.6) in individuals with type 2 diabetes. Higher age (hazard ratio 1.02 [95% CI 1.00–1.04]), male sex (1.56 [1.08–2.25]), waist circumference (1.02 [1.02–1.03]), higher systolic blood pressure (1.01 [1.01–1.02]), higher HbA1c (%, 1.13 [0.97–1.31]/ mmol/mol, 1.01 [1.00–1.03]), and family history of myocardial infarction (1.38 [0.96–2.00]) predicted a recurrent cardiovascular event. CONCLUSIONS Individuals with type 2 diabetes, but not individuals with intermediate hyperglycemia, are at increased risk for a recurrent vascular event compared with individuals with normal glucose metabolism. In people with a history of cardiovascular disease, people at increased risk of a recurrent event can be identified based on the patient’s risk profile before the first event.

Objective. With depression being present in approximately 20% of people with type 2 diabetes mellitus (T2DM), we expect equally frequent prescription of antidepressants, anxiolytics, and hypnotics. Nevertheless, prescription data in people with T2DM is missing and the effect of depression on glycaemic control is contradictory. The aim of this study was to assess the prevalence of antidepressants, anxiolytics, and/or hypnotics use in a large, managed, primary care system cohort of people with T2DM and to determine the sociodemographic characteristics, comorbidities, T2DM medication, and metabolic control associated with its use. Method. The prevalence of antidepressants, anxiolytics, and/or hypnotics use in the years 2007–2012 was assessed in the Hoorn Diabetes Care System Cohort from the Netherlands. Results. From the 7016 people with T2DM, 500 people (7.1%) used antidepressants only, 456 people (6.5%) used anxiolytics and/or hypnotics only, and 254 people (3.6%) used a combination. Conclusion. We conclude that in our managed, primary care system 17% of all people with T2DM used antidepressants, anxiolytics, and/or hypnotics. Users of antidepressants, anxiolytics, and/or hypnotics were more often female, non-Caucasian, lower educated, and more often treated with insulin.

Aim. This study explored the association of depressive symptoms with indices of insulin sensitivity and insulin secretion in a cohort of non-diabetic men and women aged 30 to 64 years.Methods. The study population was derived from the 3-year follow-up of the Relationship between Insulin Sensitivity and Cardiovascular Disease Risk (RISC) study. Presence of significant depressive symptoms was defined as a Center for Epidemiologic Studies Depression Scale (CES-D) score >= 16. Standard oral glucose tolerance tests were performed. Insulin sensitivity was assessed with the oral glucose insulin sensitivity (OGIS) index. Insulin secretion was estimated using three model-based parameters of insulin secretion (beta-cell glucose sensitivity, the potentiation factor ratio, and beta-cell rate sensitivity).Results. A total of 162 out of 1027 participants (16%) had significant depressive symptoms. Having significant depressive symptoms was not related to either OGIS [standardized beta (beta) -0.033; P=0.24] or beta-cell glucose sensitivity ([3 0.007; P=0.82). Significant depressive symptoms were related to decreased beta-cell rate sensitivity (odds ratio for significant depressive symptoms of the lowest vs. highest quartile of beta-cell rate sensitivity was 2.04; P =0.01). Also, significant depressive symptoms were associated with a statistically significant decrease in the potentiation factor ratio in unadjusted models, but not in the fully adjusted model.Conclusion. Depressive symptoms were not related to insulin sensitivity and tended to be weakly associated to some parameters of insulin secretion in non-diabetic individuals. Prospective studies are needed to study the temporal association between depression and insulin secretion. (C) 2012 Elsevier Masson SAS. All rights reserved.

Context: The BclI polymorphism in the glucocorticoid receptor (GR) gene is associated with enhanced glucocorticoid (GC) sensitivity. Objective: Our objective was to investigate the association of the BclI polymorphism with body fatness and insulin resistance. Design and Setting: We conducted an observational cohort study, combining data from 2 cohort studies enriched with individuals with impaired glucose metabolism and/or diabetes mellitus type 2 (DM2). Patients and Methods: We examined 1228 participants (mean age 64.7 years, 45% women) from the Cohort Study on Diabetes and Atherosclerosis Maastricht (CODAM, n = 543) and the Hoorn Study (n = 685). Body mass index (BMI), waist and hip circumferences, and waist-to-hip ratio (WHR) were obtained; insulin resistance was estimated using the homeostasis model assessment for insulin resistance (HOMA2-IR). Results: We identified 519 noncarriers (CC), 540 heterozygous (CG) carriers, and 169 homozygous (GG) carriers of the G-allele of the BclI polymorphism. Homozygous carriers had a higher BMI (28.9 vs 27.9 kg/m(2)) and waist (99.6 vs 97.2 cm) and hip (105.5 vs 103.2 cm) circumference compared with noncarriers, also after adjustment for age, sex, cohort, glucose tolerance, and lifestyle risk factors: beta = 0.94 kg/m(2) (95% confidence interval, 0.24-1.63), beta = 2.84 cm (0.95; 4.73) and beta = 2.38 cm (0.88-3.87), respectively. Similar results were obtained when comparing homozygous carriers with heterozygous carriers: beta = 1.03 kg/m(2) (0.34-1.72), beta = 2.20 cm (0.31-4.08) and beta = 1.99 cm (0.51-3.48), respectively. There were no differences in WHR. Ln-HOMA2-IR was higher in GG carriers compared with CG carriers; 0.29 vs 0.17 [beta = 0.09 (0.01-0.17)], but this effect was attenuated after adjustment for BMI [beta = 0.04 (-0.04 to 0.11)]. Conclusion: Homozygous carriers of the BclI polymorphism of the GR gene have significantly greater total body fatness, contributing to higher HOMA2-IR, compared with heterozygous carriers and noncarriers. (J Clin Endocrinol Metab 98: E595-E599, 2013)

BACKGROUND/OBJECTIVES:Lower circulating polyunsaturated fatty acids (PUFAs) may induce loss of heart function. We investigated whether lower concentrations of n-3 and n-6 PUFAs were associated with less favourable echocardiographic measures and higher heart rate in older Caucasians, cross-sectionally and after 7 years of follow-up.SUBJECTS/METHODS:We used data from the Hoorn Study, a population-based cohort. Cross-sectional data were available for 621 participants and longitudinal data for 336 participants. Mean age was 68.6±6.8 years at baseline. We performed linear regression analyses using n-3 and n-6 PUFAs quartiles - assayed by gas liquid chromatography - with left ventricular ejection fraction (LVEF), left ventricular mass index, left atrial volume index and heart rate.RESULTS:In multivariable analyses (regression coefficient (95% confidence interval)), the lowest eicosapentaenoic acid and docosahexaenoic acid quartiles compared with the highest quartiles were cross-sectionally associated with lower LVEF. Lower eicosapentaenoic acid and docosahexaenoic acid concentrations were associated with higher heart rate: 3.7 b.p.m. (1.5, 6.0; P for trend

Aims: Tobacco smoking is known to increase the long-term risk of developing Type 2 diabetes mellitus, but the mechanisms involved are poorly understood. This observational, cross-sectional study aims to compare measures of insulin sensitivity and β-cell function in current, ex- and never-smokers. Methods: The study population included 1246 people without diabetes (mean age 44 years, 55% women) from the EGIR-RISC population, a large European multicentre cohort. Insulin sensitivity was measured using a hyperinsulinaemic, euglycaemic clamp and the homeostatic model assessment – insulin resistance (HOMA-IR) index. Two β-cell function parameters were derived from measures during an oral glucose tolerance test: the early insulin response index and β-cell glucose sensitivity. Additionally, the areas under the curve during the oral glucose tolerance test were calculated for glucose, insulin and C-peptide. Results: According to smoking habits, there were differences in insulin sensitivity, which was lower in women who smoked, and in β-cell glucose sensitivity, which was lower in men who smoked, but these associations lost significance after adjustment. However, after adjustment, the areas under the glucose and the C-peptide curves during the oral glucose tolerance test were significantly higher in men who smoked. Conclusions: Smoking habits were not independently associated with insulin sensitivity or β-cell function in a healthy middle-aged European population. Health-selection bias, methodological shortcomings or a true lack of causal links between smoking and impaired insulin sensitivity/secretion are possible explanations. The mechanisms behind the observed increased glucose and C-peptide areas under the curve during the oral glucose tolerance test in male smokers need to be further evaluated.

AIMS: To identify HbA1c trajectories after the start of insulin treatment and to identify clinically applicable predictors of the response to insulin therapy.METHODS: The study population comprised 1203 people with Type 2 diabetes included in the Hoorn Diabetes Care System (n = 9849). Inclusion criteria were: age ≥ 40 years; initiation of insulin during follow-up after failure to reach HbA1c levels ≤ 53 mmol/mol (7%) with oral glucose-lowering agents; and a follow up ≥ 2 years after initiating insulin. Latent class growth modelling was used to identify trajectories of HbA1c . Subjects considered to be 'off target' had HbA1c levels ≥ 53 mmol/mol (7.0%) during one-third or more of the follow-up time, and those considered to be 'on target' had HbA1c levels ≥ 53 mmol/mol (7.0%) during less than one-third of the follow-up time.RESULTS: Four HbA1c trajectories were identified. Most people (88.7%) were classified as having a stable HbA1c trajectory of ~57 mmol/mol (7.4%). Only 24.4% of the people were on target in response to insulin; this was associated with lower HbA1c levels and a higher age at the start of insulin treatment.CONCLUSIONS: Using latent class growth modelling, four HbA1c trajectories were identified. A quarter of the people starting insulin were on target. Low HbA1c levels and advanced age at the start of insulin therapy were associated with better response to insulin therapy. Initiating insulin earlier improves the likelihood of achieving and sustaining glycaemic control.

Background and Aims: To investigate associations between baseline serum 25-hydroxyvitamin D [25(OH)D] levels and myocardial structure and function after 8 years of follow-up in older Dutch subjects. Methods: We included 256 subjects of the Hoorn Study, a population-based cohort. They underwent a standardized 2-dimensional echocardiogram at baseline between 2000 and 2001, and again between 2007 and 2009. We studied the association of 25(OH)D quartiles with echocardiographic measures of the left ventricular mass index (LVMI), left ventricular systolic function and markers of diastolic function using linear regression analyses. Results: At baseline, subjects had a mean age of 67.4 ± 5.2 years and 41.4% had prior cardiovascular disease (CVD). Low serum 25(OH)D levels were only associated with higher LVMI at 8-year follow-up in subjects without prior CVD and in subjects with low kidney function (median estimated glomerular filtration rate ≤77.5 ml/min/1.73m2). The associations attenuated after adjustments for parathyroid hormone (PTH), which was associated with higher LVMI (g/m2.7) in subjects with low kidney function (regression coefficient highest quartile 6.3, 95% CI: 0.2, 12.5). Conclusion: This study showed no strong associations of 25(OH)D with myocardial structure and function. However, PTH - a possible modifiable mediator in the relation between 25(OH)D and myocardial structure - was positively associated with LVMI in subjects with low kidney function.

Aims/hypothesis In this study we aimed to replicate the previously reported association between the glycaemic response to metformin and the SNP rs11212617 at a locus that includes the ataxia telangiectasia mutated (ATM) gene in multiple additional populations. Methods Incident users of metformin selected from the Diabetes Care System West-Friesland (DCS, n = 929) and the Rotterdam Study (n = 182) from the Netherlands, and the CARDS Trial (n = 254) from the UK were genotyped for rs11212617 and tested for an association with both HbA1c reduction and treatment success, defined as the ability to reach the treatment target of an HbA1c ≤7 % (53 mmol/mol). Finally, a meta-analysis including data from literature was performed. Results In the DCS cohort, we observed an association between rs11212617 genotype and treatment success on metformin (OR 1.27, 95% CI 1.03, 1.58, p = 0.028); in the smaller Rotterdam Study cohort, a numerically similar but non-significant trend was observed (OR 1.45, 95% CI 0.87, 2.39, p = 0.15); while in the CARDS cohort there was no significant association. In meta-analyses of these three cohorts separately or combined with the previously published cohorts, rs11212617 genotype is associated with metformin treatment success (OR 1.24, 95% CI 1.04, 1.49, p = 0.016 and OR 1.25, 95% CI 1.33, 1.38, p = 7.8 × 10−6, respectively). Conclusions/interpretation A gene variant near ATM is significantly associated with metformin treatment response in type 2 diabetic patients from the Netherlands and the UK. This is the first robustly replicated common susceptibility locus found to be associated with metformin treatment response. Electronic supplementary material The online version of this article (doi:10.1007/s00125-012-2537-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Aims/hypothesis: The Finnish diabetes risk questionnaire is a widely used, simple tool for identification of those at risk for drug-treated type 2 diabetes. We updated the risk questionnaire by using clinically diagnosed and screen-detected type 2 diabetes instead of drug-treated diabetes as an endpoint and by considering additional predictors.Methods: Data from 18,301 participants in studies of the Evaluation of Screening and Early Detection Strategies for Type 2 Diabetes and Impaired Glucose Tolerance (DETECT-2) project with baseline and follow-up information on oral glucose tolerance status were included. Incidence of type 2 diabetes within 5 years was used as the outcome variable. Improvement in discrimination and classification of the logistic regression model was assessed by the area under the receiver-operating characteristic (ROC) curve and by the net reclassification improvement. Internal validation was by bootstrapping techniques.Results: Of the 18,301 participants, 844 developed type 2 diabetes in a period of 5 years (4.6%). The Finnish risk score had an area under the ROC curve of 0.742 (95% CI 0.726–0.758). Re-estimation of the regression coefficients improved the area under the ROC curve to 0.766 (95% CI 0.750–0.783). Additional items such as male sex, smoking and family history of diabetes (parent, sibling or both) improved the area under the ROC curve and net reclassification. Bootstrapping showed good internal validity.Conclusions/interpretation: The predictive value of the original Finnish risk questionnaire could be improved by adding information on sex, smoking and family history of diabetes. The DETECT-2 update of the Finnish diabetes risk questionnaire is an adequate and robust predictor for future screen-detected and clinically diagnosed type 2 diabetes in Europid populations.

Background There is strong evidence that exercise therapy is effective in reducing pain and activity limitations in knee osteoarthritis (OA), but effect sizes are low to moderate. Stratified exercise therapy tailored to clinically relevant subgroups of patients is expected to optimise treatment effects in a cost-effective manner. Objectives This study aimed to explore the feasibility of a newly developed model of stratified exercise therapy in primary care. Methods A mixed method design was used, consisting of an uncontrolled pretest-posttest design and a process evaluation. Eligible patients visiting a participating primary care physical therapist (PT) were included. Based on our model, participants were allocated to the ‘high muscle strength subgroup’, ‘low muscle strength subgroup’, ‘obesity subgroup’ or ‘depression subgroup’, and received subgroup-specific, protocolised, 4 month exercise therapy. Feasibility of stratified exercise therapy according to this model was evaluated by a process evaluation (process documentation, semi-structured interviews and focus group meeting) and outcome (physical functioning (KOOS-ADL) and knee pain (NRS), assessed at baseline and 4 months follow-up). Results We included 50 patients, of which 3 patients dropped out. The process evaluation suggests that our model is feasible for patients and PTs, with some adaptations for further optimisation. We found clinically relevant improvements on physical functioning (p Conclusions Our model of stratified exercise therapy is feasible in primary care. Minor adaptations could further optimise the feasibility. Future research should determine the (cost-)effectiveness of this model, compared to usual, non-stratified exercise therapy. Disclosure of Interest None declared

Objective: This brief report presents initial data from the Amsterdam Study of Acute Psychiatry (ASAP-I) about factors associated with the decision to admit patients compulsorily (involuntarily) to emergency psychiatric services in the Amsterdam region of the Netherlands. Methods: The study was a prospective cohort study of 1,970 consecutive patients who came into contact with the Psychiatric Emergency Service Amsterdam. Results: A history of more than 14 outpatient contacts the previous year was associated with a low risk of compulsory admission (OR=.3). An involuntary admission in the previous five years was associated with a higher risk (OR=3.7). Referral by a general practitioner was associated with a low risk compared with referral by police (OR= 2.4) or by mental health services (OR=2.3). Conclusions: The hypothesis that outpatient treatment may help to prevent compulsory admission found some support in this study. More research is needed to understand the mechanisms of the associations so that an intervention study can be developed to test this hypothesis. (Psychiatric Services 60:1543–1546, 2009)

Objective Vitamin D deficiency is common among the elderly and may contribute to cardiovascular disease. The aim of our study was to elucidate whether low serum levels of 25-hydroxyvitamin D [25(OH)D] are associated with an increased risk of all-cause and cardiovascular mortality. Design and patients The Hoorn Study is a prospective population-based study among older men and women. Measurements Fasting serum 25(OH)D was determined in 614 study participants at the follow-up visit in 2000-2001, the baseline for the present analysis. To account for sex differences and seasonal variations of 25(OH)D levels we formed sex-specific quartiles, which were calculated from the 25(OH)D values of each season. Results After a mean follow-up period of 6·2 years, 51 study participants died including 20 deaths due to cardiovascular causes. Unadjusted Cox proportional hazard ratios (HRs; with 95% confidence intervals) for all-cause and cardiovascular mortality in the first when compared with the upper three 25(OH)D quartiles were 2·24 (1·28- 3·92; P = 0·005) and 4·78 (1·95-11·69; P = 0·001), respectively. After adjustment for age, sex, diabetes mellitus, smoking status, arterial hypertension, high-density lipoprotein-cholesterol, glomerular filtration rate and waist-to-hip ratio, the HRs remained significant for all-cause [1·97 (1·08-3·58; P = 0·027)] and for cardiovascular mortality [5·38 (2·02-14·34; P = 0·001)]. Conclusions Low 25(OH)D levels are associated with all-cause mortality and even more pronounced with cardiovascular mortality, but it remains unclear whether vitamin D deficiency is a cause or a consequence of a poor health status. Therefore, intervention studies are warranted to evaluate whether vitamin D supplementation reduces mortality and cardiovascular diseases. © 2009 Blackwell Publishing Ltd.

The metabolic syndrome (MetS) increases cardiovascular disease (CVD) risk. How MetS increases CVD risk is incompletely understood, but increasing arterial stiffness is one candidate link, which in turn could be explained by (low-grade) inflammation, endothelial dysfunction (ED) or insulin resistance (IR). However, MetS-related increases in stiffness may not be uniformly distributed over muscular and elastic arteries. Therefore, the purpose of this study was to determine: (1) the associations between the MetS, and muscular and elastic arterial stiffness, and (2) whether any such associations could be explained by inflammation, ED or IR. These questions were addressed in the Hoorn Study. MetS was defined according to the NCEP (National Cholesterol Education Program) criteria. Arterial stiffness was determined by ultrasound, tonometry and echocardiography. Inflammation, ED and IR were estimated by C-reactive protein, flow-mediated vasodilation and the homoeostatic model for the assessment of IR, respectively. The results showed that MetS was associated with both femoral and brachial arterial stiffness, significantly so for the distensibility coefficients and for the femoral compliance coefficient. In the carotid artery and aorta, no particular pattern emerged. Additional adjustment for either inflammation, ED or IR did not materially alter the results. The results therefore indicate that muscular arteries may stiffen preferentially over elastic arteries and that distensibility is affected to a greater extent than compliance, thus maintaining volume compliance over vessel wall stiffening. Additionally, the increase in stiffness was not explained by inflammation, ED or IR and suggests that stiffening of the muscular arteries in MetS may not be the consequence of these phenomena.Journal of Human Hypertension advance online publication, 12 March 2009; doi:10.1038/jhh.2009.8.

Early insulin secretion following a meal is representative for normal physiology and may depend on meal composition. To compare the effects of a fat-rich and a carbohydrate-rich mixed meal on insulinogenic index as a measure of early insulin secretion in normoglycemic women (NGM) and in women with type 2 diabetes mellitus (DM2), and to assess the relationship of anthropometric and metabolic factors with insulinogenic index.Postmenopausal women, 76 with NGM and 64 with DM2, received a fat-rich meal and a carbohydrate-rich meal on separate occasions. Early insulin response was estimated as insulinogenic index ( big up tri, Deltainsulin(0-30 min)/ big up tri, Deltaglucose(0-30 min)) for each meal. Associations of fasting and postprandial triglycerides, body mass index, waist and hip circumference and alanine aminotransferase with insulinogenic indices were determined.Women with NGM present with higher insulinogenic index than women with DM2. The insulinogenic index following the fat-rich meal ( big up tri, DeltaI(30)/ big up tri, DeltaG(30) (fat)) was higher than the index following the carbohydrate-rich meal (big up tri, DeltaI(30)/ big up tri, DeltaG(30) (CH)) (P0.05 in women with DM2, and not significant in women with NGM). In women with DM2, homeostasis model assessment for insulin resistance was positively associated with big up tri, DeltaI(30)/ big up tri, DeltaG(30) (CH). In women with NGM, waist circumference was independently and inversely associated with big up tri, DeltaI(30)/ big up tri, DeltaG(30) (fat) and with big up tri, DeltaI(30)/ big up tri, DeltaG(30) (CH); hip circumference was positively associated with big up tri, DeltaI(30)/ big up tri, DeltaG(30) (fat).The insulinogenic index following the fat-rich meal was higher than following the isocaloric carbohydrate-rich meal, which might favorably affect postprandial glucose excursions, especially in women with DM2. The association between a larger waist circumference and a lower meal-induced insulinogenic index in women with NGM requires further mechanistic studies.

Background: We hypothesized that acarbose would delay conversion from impaired glucose tolerance (IGT) to type 2 diabetes by alleviating postprandial hyperglycaemia. Our study's main objective was to investigate the effect of acarbose in IGT-persons on their 2-h plasma glucose level and beta-cell function. Subjects and Methods: The study included a random sample of 45-70-year-old residents of Hoorn, Netherlands, with mean fasting plasma glucose

To evaluate whether the metabolic syndrome (MetS) defined by the International Diabetes Federation (IDF) criteria, which has abdominal adiposity as a mandatory element, predicts cardiovascular disease (CVD) mortality better than the cluster of other IDF-defined abnormalities not including abdominal adiposity.Data from nine European population-based studies, including 7782 men and 7739 women (aged 30-89 years), with a median follow-up of 8.55 years, were jointly analyzed. Hazard ratios for CVD mortality were calculated with Cox regression models.In total, 41% of the men and 38% of the women had the IDF MetS. Individuals with the IDF MetS were by definition more obese and had a higher prevalence of diabetes than non-obese subjects withor = 2 IDF abnormalities; whereas non-obese men withor = 3 factors had more atherogenic lipid profiles. Multivariate adjusted hazard ratio for CVD death in men and women with the IDF MetS was 2.44 (1.69-2.98) and 2.32 (1.27-4.23); in non-obese men with 2 andor = 3 factors the hazard ratio was 1.60 (1.12-2.30) and 2.44 (1.62-3.66), respectively, and in non-obese women with 2 factors the hazard ratio was 2.41 (1.09-5.33).The cluster of the CVD risk factors predicted CVD mortality regardless of the presence or absence of the abdominal adiposity. Inclusion of abdominal adiposity as a prerequisite will miss those non-obese individuals who have increased CVD mortality.

Objective To study the prevalence and risk factors of depressive symptoms, comparing subjects with normal glucose metabolism (NGM), impaired glucose metabolism (IGM) or Type 2 diabetes mellitus (DM2). Research design and methods Cross-sectional data from a population-based cohort study conducted among 550 residents (276 men and 274 women) of the Hoorn region, the Netherlands. Levels of depressive symptoms were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D score ≥ 16). Glucose metabolism status was determined by means of fasting and post-load glucose levels. Results The prevalence of depressive symptoms in men with NGM, IGM and DM2 was 7.7, 7.0 and 15.0% (P = 0.19) and for women 7.7, 23.1 and 19.7% (P

Alanine aminotransferase (ALT) is a marker of non-alcoholic fatty liver disease (NAFLD) and predicts incident type 2 diabetes mellitus (DM2). Recently, ALT was shown to be also associated with endothelial dysfunction and carotid atherosclerosis. We studied the predictive value of ALT for all-cause mortality, incident cardiovascular disease (CVD) and coronary heart disease (CHD) events in a population-based cohort of Caucasian men and women aged 50-75 years, at baseline. The 10-year risk of all-cause mortality, fatal and non-fatal CVD and CHD events in relation to ALT was assessed in 1439 subjects participating in the Hoorn Study, using Cox survival analysis. Subjects with prevalent CVD/CHD and missing data were excluded. As compared with the first tertile, the age- and sex-adjusted hazard ratios (95% confidence intervals) for all-cause mortality, CVD events and CHD events were 1.30 (0.92-1.83), 1.40 (1.09-1.8 1) and 2.04 (1.35-3. 10), respectively, for subjects in the upper tertile of ALT. After adjustment for components of the metabolic syndrome and traditional risk factors, the association of ALT and CHD events remained significant for Subjects in the third relative to those in the first tertile, with a hazard ratio of 1.88 (1.21-2.92) and 1.75 (1.12-2.73), respectively. In conclusion, the predictive value of ALT for coronary events, seems independent of traditional risk factors and the features of the metabolic syndrome in a population-based cohort. Further studies should confirm these findings and elucidate the pathophysiological mechanisms.

Aims: To study the association between alanine aminotransferase (ALT) and the 6-year risk of the metabolic syndrome in a population-based study in Caucasian men and women. Methods: The association of ALT with the 6-year risk of the metabolic syndrome in 1097 subjects, aged 50-75 years, was assessed in the Hoorn Study with logistic regression analysis. Subjects with the metabolic syndrome at baseline, defined according to the Adult Treatment Panel III of the National Cholesterol Education Program, were excluded. Results: After 6.4 (range 4.4-8.1) years follow-up, 226 subjects (20.6%) had developed the metabolic syndrome. The odds ratio (95% confidence interval) for developing the metabolic syndrome, adjusted for age, sex, alcohol intake and follow-up duration was 2.25 (1.50-3.37) for subjects in the upper tertile compared with those in the lower tertile of ALT. This association persisted after additional adjustment for all the baseline metabolic syndrome features [1.62 (1.02-2.58)]. Among the individual components of the metabolic syndrome, ALT was significantly associated only with fasting plasma glucose at follow-up. Conclusions: These data suggest that ALT is associated with risk of the metabolic syndrome in a general population of middle-aged Caucasian men and women, further strengthening the role of ALT as an indicator for future metabolic derangement. These findings warrant further studies to elucidate the role of non-adipose tissue fat accumulation in the pathogenesis of complications related to the metabolic syndrome.

OBJECTIVE: A high monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) intake is associated with lower plasma low-density lipoprotein (LDL)-cholesterol. However, PUFA may increase the susceptibility of LDL to undergo oxidative modifications. The aim of this study was to analyze the association of habitual dietary fat intake with LDL size and oxidizability. DESIGN: Cross-sectional. SETTING: Cohort study. SUBJECTS: Seven hundred and fifty-eight subjects with normal, impaired glucose metabolism and type II diabetes. INTERVENTIONS: Mean LDL size was measured by high-performance gel-filtration chromatography. In vitro oxidizability of LDL was determined by measuring lag time, reflecting the resistance of LDL to copper-induced oxidation. Information about dietary fat intake was obtained by a validated food frequency questionnaire. RESULTS: PUFA intake (energy percent) was significantly and negatively associated with LDL size in subjects with type II diabetes (standardized beta (95% confidence interval) -0.17 (-0.28;-0.06)) and impaired glucose metabolism - although not statistically significant - (-0.09 (-0.24;0.05)), but not in subjects with normal glucose metabolism (0.01 (-0.10;0.12)) (P-value for interaction=0.02). No significant associations were observed for total, saturated fat and MUFA intake with LDL size. Intake of fat was associated with lag time; however, the small magnitude of the associations suggested that the composition of dietary fat is not a major factor affecting lag time. The same association with lag time was observed in all three glucose metabolism categories. CONCLUSIONS: In individuals with abnormal glucose metabolism, higher PUFA intake is associated with smaller LDL particle size, but does not alter the susceptibility of LDL to in vitro oxidation. SPONSORSHIP: Dutch Diabetes Research Foundation, and the Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO).

The category of IFG was introduced in the late 1990s to denote a state of non-diabetic hyperglycaemia defined by a fasting plasma glucose (FPG) concentration between 6.1 and 6.9 mmol/l. In 2003 the American Diabetes Association recommended that this diagnostic threshold be lowered to 5.6 mmol/l. The justification for lowering the threshold has been questioned. This simple change in cut-off value creates a pandemic of IFG, with a two- to five-fold increase in the prevalence of IFG across the world. Such a change in threshold has far-reaching public health implications. The European Diabetes Epidemiology Group (EDEG) has reviewed the evidence for this lower cut-off point for the definition of IFG and concludes that the previous definition should not be altered. EDEG further recommends that the value of all categorical definitions of non-diabetic hyperglycaemia should be reconsidered.

Objective. Homocysteine and cardiovascular autonomic function are both predictors of cardiovascular disease and death, particularly in patients with diabetes. The mechanism by which homocysteine causes disease is unknown. The objective of our study was to determine whether hyperhomocysteinaemia is associated with impaired cardiovascular autonomic function in an age-, sex-, and glucose tolerance-stratified sample of an elderly Caucasian population. Methods. We studied 609 subjects, 252 with normal glucose metabolism, 173 with impaired glucose metabolism, and 184 with type 2 diabetes. Cardiac cycle duration (RR interval) and continuous finger arterial pressure were measured under three conditions: during (i) spontaneous breathing, (ii) six deep breaths over 1 min, and (iii) an active change in position from lying to standing. From these readings, 10 parameters of autonomic function were assessed (three Ewing tests, six heart rate variability tests and one test of baroreflex sensitivity). These 10 measurements were summarized in a single cardiovascular autonomic dysfunction score (CADS). Results. Comparing values of autonomic function measures in the lowest versus the highest quartile of homocysteine revealed no significant association between homocysteine level and autonomic function in the whole study group, nor in the individual glucose tolerance groups. Multiple adjustment for age, sex, waist-to-hip ratio, serum creatinine, use of antihypertensives and fasting insulin, confirmed this result. We found no evidence of effect modification of glucose tolerance status on the association between homocysteine and autonomic dysfunction (P for interaction for CADS = 0.79). Conclusions. There is no evidence for an association between homocysteine levels and cardiovascular autonomic function in either diabetic or nondiabetic subjects. Cardiovascular autonomic dysfunction does not help explain why hyperhomocysteinaemia is related to cardiovascular mortality. © 2005 Blackwell Publishing Ltd.

AIMS: We investigated whether low subcutaneous thigh fat is an independent risk factor for unfavourable glucose and lipid levels, and whether these associations differ between sexes, and between white and black adults. Our secondary aim was to investigate which body composition characteristics (lean tissue, fat tissue) are reflected by anthropometric measures (waist and thigh circumference).METHODS: Anthropometric measurements and computed tomography of the abdomen and of the thigh were performed for all participants of the Health, Aging and Body Composition Study, who were aged 70-79 years. Fasting glucose, triglycerides and HDL-cholesterol, and 2-h postload glucose were determined.RESULTS: After excluding those already diagnosed with diabetes or dyslipidaemia, we analysed data from 2,106 participants. After adjustment for abdominal subcutaneous and visceral fat, and intermuscular thigh fat, larger thigh subcutaneous fat area was statistically significantly associated with lower ln-transformed triglycerides [standardised beta (95% CI) -0.12 (-0.20 to -0.04) in men and -0.13 (-0.21 to -0.05) in women] and higher ln-HDL-cholesterol [0.10 (0.02 to 0.19) and 0.09 (0.01 to 0.18), respectively]. The associations with lower glucose levels were strong in men [-0.11 (-0.20 to -0.02) for fasting and -0.14 (-0.23 to -0.05) for postload glucose], but not statistically significant in women [-0.02 (-0.10 to 0.07) and -0.04 (-0.13 to 0.05), respectively]. There were no differences in the associations between white and black persons. Waist circumference was more strongly associated with abdominal subcutaneous fat, and this association became stronger with increasing BMI, whereas the association with visceral fat became weaker. Thigh circumference was equally dependent on thigh fat and thigh muscle in men, whereas in women the fat component was the main contributor.CONCLUSION: Larger subcutaneous thigh fat is independently associated with more favourable glucose (in men) and lipid levels (in both sexes) after accounting for abdominal fat depots, which are associated with unfavourable glucose and lipid levels. Anthropometric measures reflect different fat depots at different levels of BMI at the abdomen, and reflect both fat and lean tissue at the thigh. These results emphasise the importance of accurate measures of regional body composition when investigating potential health risks.

Background: Hyperhomocysteinemia (HHCY) is a risk factor for cardiovascular diseases (CVD). HHCY may interact with hypertension (HTEN) and an unfavorable cholesterol profile (UNFAVCHOL) to alter the risk of CVD. Objectives: To estimate the prevalences of HHCY (1) isolated and (2) in combination with UNFAVCHOL and/or HTEN in different age categories. To provide information that may improve the screening and treatment of subjects at risk of CVD. Design: Cross-sectional data on 12 541 men and 12 948 women aged 20 + y were used from nine European studies. Results: The prevalence of isolated HHCY was 8.5% in subjects aged 20-40 y, 4.7% in subjects aged 40-60 y and 5.9% in subjects aged over 60 y. When combining all age groups, 5.3% had isolated HHCY and an additional 5.6% had HHCY in combination with HTEN and/or UNFAVCHOL. The combinations of risk factors increased with age and, except for HHCY&UNFAVCHOL, were more prevalent than predicted by chance. Of the young subjects (20-40 y), 24% suffered from one or more of the investigated CVD risk factors. This figure was 75.1% in the old subjects (60 + years). Conclusions: A substantial number of subjects in selected European populations have HHCY (10.9%). In half of these cases, subjects suffer also from other CVD risk factors like UNFAVCHOL and HTEN. Older people in particular tend to have more than one risk factor. Healthcare professionals should be aware of this when screening and treating older people not only for the conventional CVD risk factors like UNFAVCHOL and HTEN but also HHCY, as this can easily be reduced through increased intake of folic acid via supplement or foods fortified with folic acid. © 2005 Nature Publishing Group All rights reserved.

Objective— To explore to what extent homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine, total folate, 5-methyltetrahydrofolate (5-MTHF), vitamin B12, and vitamin B6 are associated with endothelium-dependent, flow-mediated vasodilation (FMD), and whether these associations are stronger in individuals with diabetes or other cardiovascular risk factors. Methods and Results— In this population-based study of 608 elderly people, FMD and endothelium-independent nitroglycerin-mediated dilation (NMD) were ultrasonically estimated from the brachial artery (absolute change in diameter [μm]). High SAM and low 5-MTHF were significantly associated with high and low FMD, respectively (linear regression coefficient, [95% confidence interval]): 48.57 μm (21.16; 75.98) and −32.15 μm (−59.09; −5.20), but high homocysteine was not (−15.11 μm (−42.99; 12.78). High SAM and low 5-MTHF were also significantly associated with high and low NMD, respectively. NMD explained the association of 5-MTHF with FMD but not of SAM. No interactions were observed for diabetes or cardiovascular risk factors. Conclusions— In this elderly population, both SAM and 5-MTHF are associated with endothelial and smooth muscle cell function. The effect of homocysteine on endothelial function is relatively small compared with SAM and 5-MTHF. The relative impact of SAM, 5-MTHF, and homocysteine, and the mechanisms through which these moieties may affect endothelial and smooth muscle cell function need clarification.

Prevalence of macrovascular disease amongst type 2 diabetic patients detected by targeted screening and patients newly diagnosed in general practice: the Hoorn Screening Study.Spijkerman AM, Henry RM, Dekker JM, Nijpels G, Kostense PJ, Kors JA, Ruwaard D, Stehouwer CD, Bouter LM, Heine RJ.Institutes for Research in Extramural Medicine, VU University Medical Center, Amsterdam, The Netherlands. amw.spijkerman@vumc.nlOBJECTIVES: Screening for type 2 diabetes has been recommended and targeted screening might be an efficient way to screen. The aim was to investigate whether diabetic patients identified by a targeted screening procedure differ from newly diagnosed diabetic patients in general practice with regard to the prevalence of macrovascular complications. DESIGN: Cross-sectional population-based study. SETTING: Population study, primary care. SUBJECTS: Diabetic patients identified by a population-based targeted screening procedure (SDM patients), consisting of a screening questionnaire and a fasting capillary glucose measurement followed by diagnostic testing, were compared with newly diagnosed diabetic patients in general practice (GPDM patients). Ischaemic heart disease and prior myocardial infarction were assessed by ECG recording. Peripheral arterial disease was assessed by the ankle-arm index. Intima-media thickness of the right common carotid artery was measured with ultrasound. RESULTS: A total of 195 SDM patients and 60 GPDM patients participated in the medical examination. The prevalence of MI was 13.3% (95% CI 9.3-18.8%) and 3.4% (1.0-11.7%) in SDM patients and GPDM patients respectively. The prevalence of ischaemic heart disease was 39.5% (95% CI 32.9-46.5%) in SDM patients and 24.1% (15.0-36.5%) in GPDM patients. The prevalence of peripheral arterial disease was similar in both groups: 10.6% (95% CI 6.9-15.9%) and 10.2% (4.7-20.5%) respectively. Mean intima-media thickness was 0.85 mm (+/-0.17) in SDM patients and 0.90 mm (+/-0.20) in GPDM patients. The difference in intima-media thickness was not statistically significant. CONCLUSIONS: Targeted screening identified patients with a prevalence of macrovascular complications similar to that of patients detected in general practice, but with a lower degree of hyperglycaemia

Aims/hypothesis. There is accumulating evidence that depression is common in people with Type 2 diabetes. However, most prevalence-studies are uncontrolled and could also be inaccurate from selection-bias, as they are conducted in specialized treatment settings. We studied the prevalence and risk factors of co-morbid depression in a community-based sample of older adults, comparing Type 2 diabetic patients with healthy control subjects. Methods. A large (n=3107) community-based study in Dutch adults (55-85 years of age) was conducted. Pervasive depression was defined as a CES-D score greater than 15. Diagnosis of Type 2 diabetes was obtained from self-reports and data from general practitioners. Results. A number of 216 patients (7%) were identified as having Type 2 diabetes. The prevalence of pervasive depression was increased in people with Type 2 diabetes and co-morbid chronic disease (20%) but not in patients with Type 2 diabetes only (8%), compared with the healthy control subjects (9%). Regression analyses in diabetic patients yielded that being single, being female, having functional limitations, receiving instrumental support and having an external locus of control were associated with higher levels of depression. Conclusions/interpretation. The Results suggest that the prevalence of pervasive depression is increased in patients with Type 2 diabetes and co-morbid disease(s), but not in patients with Type 2 diabetes only. Functional limitations that often accompany co-morbid chronic disease could play an essential role in the development of depression in Type 2 diabetes. These findings can enable clinicians and researchers to identify high-risk groups and set up prevention and treatment programs.

Objectives. Amongst nondiabetic individuals, a high serum homocysteine concentration is an independent but relatively weak risk factor for coronary events. However, it is not known whether homocysteine increases risk of coronary events in type 2 diabetes. Therefore, we examined the combined effect of homocysteine and type 2 diabetes on risk of fatal and nonfatal coronary events. Subjects. We assessed the 10-year risk of coronary events associated with homocysteine amongst diabetic (n = 140) and nondiabetic (n = 361) individuals. Design. We did this in the Hoorn Study, a population-based study of glucose tolerance and related complications in Caucasian men and women aged 50-75 years. Results. The incidence rate for coronary events was 2.63 (29 of 140) per 100 person-years amongst diabetic and 1.29 (42 of 361) amongst nondiabetic individuals. Amongst diabetic individuals, risk of coronary events increased 28% for each 5-μmol L-1 increment of homocysteine (hazard ratio, 1.28:95% CI, 1.02-1.58). This risk was independent of age, sex, hypertension, total cholesterol, HDL-cholesterol, cigarette smoking, body mass index and glomerular filtration rate. In nondiabetic participants, homocysteine was not associated with an increased risk of coronary events (hazard ratio for each 5-μmol L-1 increment of homocysteine, 0.86; 0.52-1.41). Conclusions. These data suggest that homocysteine is significantly associated with coronary events in individuals with type 2 diabetes, independent of traditional cardiovascular risk factors. Investigation of the effect of treatment with vitamin B on prognosis of individuals with type 2 diabetes is warranted.

OBJECTIVE—To report the age- and sex-specific prevalences of diabetes and impaired glucose regulation (IGR) according to the revised 1999 World Health Organization criteria for diabetes in Europe. RESEARCH DESIGN AND METHODS—A total of 13 studies from nine European countries with 7,680 men and 9,251 women aged 30–89 years were included in the data analysis. RESULTS—In most of the study populations, the age-specific prevalences of diabetes were 70 years of age). More than half of the diabetes was undiagnosed in subjects younger than 50 years of age. CONCLUSIONS—Most European populations have a moderate to low prevalence of diabetes and IGR. Diabetes and IGR will be underestimated in Europe, particularly in women and in elderly men, if diagnoses are based on fasting glucose determination alone.

Studies on the efficacy of available methods of treatment for hemiplegic shoulder pain are reviewed in an attempt to identify the most effective treatment for this problem. Because of the poor quality of the 14 selected studies, no definite conclusion can be drawn about the most effective method of treatment. However, functional electrical stimulation and intra-articular triamcinolone acetonide injections seem to be the most promising treatment options.

Keywords Epidemiology.Prediction.Risk scores.Type 2 diabetesAbbreviationADDITION Anglo–Danish–Dutch Study of IntensiveTreatment in People with Screen DetectedDiabetes in Primary CareTo the Editor: In a recent commentary related to our paperon the performance of a risk score questionnaire forpredicting future diabetes [1], Wareham and Griffin makean interesting point about the effect of real life responserates on the true performance of a risk assessment [2]. Inour paper we evaluated the performance of the originalFinnish diabetes risk questionnaire to predict future

Abeer Ahmad,1 M Ruth Mast,1 Giel Nijpels,2 Petra JM Elders,2 Jacqueline M Dekker,3 Jacqueline G Hugtenburg1 1Department of Clinical Pharmacology and Pharmacy, 2Department of General Practice, 3Departments of Epidemiology and Biostatistics, EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, the Netherlands Background: Drug-related problems (DRP) following hospital discharge are common among elderly patients using multiple drugs for the treatment of chronic diseases. The aim of this study was to investigate the occurrence of DRP in these patients using a specific tool for the identification of DRP by community pharmacists. Methods: An observational study involving 340 patients aged over 60 years using at least five prescription drugs and discharged from hospital. The occurrence of DRP was assessed by means of an identification tool specifically developed for use by community pharmacists, including a semistructured patient interview and a checklist of common DRP. Results: In total, 992 potential DRP were observed in the 340 patients (mean 2.9 ± 1.7). No drug prescribed but clear indication, an unnecessarily long duration of treatment, dose too low, and incorrect drug selection were the DRP most commonly observed. Ten percent of DRP occurring in 71 patients were drug–drug interactions. The number of DRP was related to the number of drugs prescribed. Frequently occurring DRP found using the patient interview were fear of side effects and no or insufficient knowledge of drug use. Medication of patients discharged from the pulmonary department and of those with type 2 diabetes was particularly associated with occurrence of DRP. Conclusion: Following hospital discharge, DRP occur frequently among elderly patients using five or more drugs for the treatment of chronic disease. The number of DRP increased with the number of drugs used. An important task for community pharmacists is to identify, resolve, and prevent the occurrence of DRP among this patient group. Since DRP are associated with an increased risk of hospital readmissions, morbidity, and mortality, it is very important to develop intervention strategies to resolve and prevent DRP. Keywords: drug-related problems, elderly, discharge from hospital, community pharmacy