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Contains fulltext : 235311.pdf (Publisher’s version ) (Open Access), BACKGROUND: Closed-loop insulin delivery systems, which integrate continuous glucose monitoring (CGM) and algorithms that continuously guide insulin dosing, have been shown to improve glycaemic control. The ability to predict future glucose values can further optimize such devices. In this study, we used machine learning to train models in predicting future glucose levels based on prior CGM and accelerometry data. METHODS: We used data from The Maastricht Study, an observational population-based cohort that comprises individuals with normal glucose metabolism, prediabetes, or type 2 diabetes. We included individuals who underwent >48h of CGM (n = 851), most of whom (n = 540) simultaneously wore an accelerometer to assess physical activity. A random subset of individuals was used to train models in predicting glucose levels at 15- and 60-minute intervals based on either CGM data or both CGM and accelerometer data. In the remaining individuals, model performance was evaluated with root-mean-square error (RMSE), Spearman's correlation coefficient (rho) and surveillance error grid. For a proof-of-concept translation, CGM-based prediction models were optimized and validated with the use of data from individuals with type 1 diabetes (OhioT1DM Dataset, n = 6). RESULTS: Models trained with CGM data were able to accurately predict glucose values at 15 (RMSE: 0.19mmol/L; rho: 0.96) and 60 minutes (RMSE: 0.59mmol/L, rho: 0.72). Model performance was comparable in individuals with type 2 diabetes. Incorporation of accelerometer data only slightly improved prediction. The error grid results indicated that model predictions were clinically safe (15 min: >99%, 60 min >98%). Our prediction models translated well to individuals with type 1 diabetes, which is reflected by high accuracy (RMSEs for 15 and 60 minutes of 0.43 and 1.73 mmol/L, respectively) and clinical safety (15 min: >99%, 60 min: >91%). CONCLUSIONS: Machine learning-based models are able to accurately and safely predic

Contains fulltext : 218096.pdf (publisher's version ) (Open Access), Within the southern region of the Netherlands, the Maastricht Study is an on-going observational prospective population-based cohort study that focuses on the etiology of Type 2 diabetes mellitus (T2DM). Representativeness of the participating population is a crucial but often an unknown factor in population-based cohort studies such as the Maastricht Study. We therefore aimed to assess the representativeness of the study population by comparing drug utilization of the participants of the Maastricht Study with the general population of the Netherlands.Since T2DM patients were oversampled in this study, a sampling method was applied in order to ensure a similar distribution of T2DM over the study population. Drug use in the study population was compared with drug use in the population of the Netherlands, using a Z-test to compare 2 independent proportions.In general, drug use in the study was similar compared with national data. However, in the age group 65 to 74 years total drug use was lower in the study population (833/1000 persons) versus nationwide data (882/1000 persons). The use of pulmonary medications was lower (104/1000 persons vs 141/1000 persons) and the use of hypnotics/anxiolytics was higher (90/1000 persons vs 36/1000 persons) in the Maastricht Study as compared with national data.Drug use in the Maastricht Study population is largely comparable to that in the total Dutch population aged 45 to 74. Therefore, data on drug use by participants in the Maastricht Study can be used to perform studies assessing outcomes associated with drug use.

Item does not contain fulltext, PURPOSE: This cross-sectional study examined the mutual independent associations of sedentary behavior, lower intensity physical activity (LPA) and higher intensity physical activity HPA (an approximation of moderate to vigorous physical activity (MVPA) with cardio-respiratory fitness (CRF). METHODS: 2,024 participants were included from The Maastricht Study (mean+/-SD age: 59.7+/-8.1 years, 49.6% men). With the activPAL3 activity monitor we assessed sedentary time (ST), sedentary pattern variables (number of sedentary breaks, average sedentary bout duration, and number of prolonged sedentary bouts (>/=30 min)), LPA, and HPA. CRF was calculated as maximum power output per kg body mass (Wmax kg) estimated from a sub-maximal cycle ergometer test. Linear regression analyses and isotemporal substitution analyses were used to examine associations of ST, sedentary pattern variables, and HPA with CRF. Analyses were stratified by sex. RESULTS: One hour of ST per day was associated with a lower Wmax kg: Bmen= -0.03 (95% CI: -0.05;-0.01) and Bwomen= -0.02 (-0.04; 0.00), independent of HPA. No statistically significant associations between sedentary patterns variables and CRF were observed. LPA was associated with a higher Wmax kg: Bmen = 0.12 (0.07;0.17) and Bwomen= 0.12 (0.07;0.18). HPA was associated with a higher Wmax kg: Bmen = 0.48 (0.38;0.58) and Bwomen= 0.27 (0.18;0.36). Replacing ST with LPA (Bmen = 0.08 (0.03;0.14), Bwomen= 0.10 (0.05;0.16)) or with HPA (Bmen = 0.49 (0.39;0.59), Bwomen= 0.28 (0.19;0.36)), but not with standing was associated with higher CRF. CONCLUSION: Modest associations between sedentary behavior and CRF were observed. Replacing ST with LPA was associated with higher CRF, which could be of particular importance for individuals who cannot engage in HPA. Nonetheless, replacing ST with HPA was associated with greatest estimated change in CRF.

Item does not contain fulltext, AIMS: To investigate the association between long-term dipeptidyl peptidase-4 (DPP-4) inhibitor use and risk of fracture among people with type 2 diabetes mellitus (T2DM). METHODS: A retrospective population-based cohort study, using data from the Clinical Practice Research Datalink database (2007-2015), was conducted. All those (N = 328 254) with at least one prescription for a non-insulin antidiabetic drug (NIAD), aged >/=18 years at the time of data collection, were included. Cox proportional hazards models were used to estimate the hazard ratios of any fracture, osteoporotic fracture and hip fracture in DPP-4 inhibitor users compared with those using other NIADs. Analyses were stratified by continuous duration of DPP-4 inhibitor use. Time-dependent adjustments were made for age, sex, lifestyle, comorbidity and concomitant drug use. RESULTS: Current use of DPP-4 inhibitors was not associated with risk of any fracture (adjusted hazard ratio [HR] 0.99 [95% confidence interval {CI} 0.93-1.06]) as compared with current other NIAD use. Current use of DPP-4 inhibitors was also not associated with risk of osteoporotic or hip fracture. After stratification by continuous duration of DPP-4 inhibitor use the highest category was not associated with any (>4.0-8.5 years of use, adjusted HR 0.99 [95% CI 0.70-1.41]), osteoporotic (>3.0-8.5 years of use, adjusted HR 0.75 [95% CI 0.52-1.09]) or hip (>2.0-8.5 years of use; adjusted HR 1.24 [95% CI 0.85-1.79]) fracture. CONCLUSION: Continuous long-term DPP-4 inhibitor use (defined as >4.0-8.5 years of DPP-4 inhibitor use for any fracture, >3.0-8.5 years for osteoporotic fracture and >2.0-8.5 years for hip fracture was not associated with risk of any, osteoporotic or hip fracture. These findings may be of value for clinical decisions regarding treatment of patients with T2DM, especially those at high risk of fracture.

Contains fulltext : 174660.pdf (publisher's version ) (Open Access), Background: In an aging population, regular physical activity (PA) and exercise have been recognized as important factors in maintaining physical function and thereby preventing loss of independence and disability. However, (older) adults spent the majority of their day sedentary and therefore insight into the consequences of sedentary behavior on physical function, independent of PA, is warranted. Objective: To examine the associations of objectively measured sedentary time (ST), patterns of sedentary behavior, overall PA, and higher intensity PA (HPA) with objective measures of physical function. Methods: This is a cross-sectional study in 1,932 men and women (aged 40-75 years) participating in The Maastricht Study. The activPAL3 was used to assess daily sedentary behavior: ST (h), sedentary breaks (n), prolonged (>/=30 min) sedentary bouts (n), and to assess time spent in (H)PA (h). Measures of physical function included: covered distance during a 6 min walk test [6MWD (meters)], timed chair rise stand test performance [TCSTtime (seconds)], grip strength (kg kg-1), and elbow flexion and knee extension strength (Nm kg-1). Linear regression analyses were used to examine associations between daily sedentary behavior and PA with physical function. Results: Every additional hour ST was associated with shorter 6MWD [B = -2.69 m (95% CI = -4.69; -0.69)] and lower relative elbow extension strength (B = -0.01 Nm kg-1 (-0.02; 0.00). More sedentary breaks were associated with faster TCSTtime: B = -0.55 s (-0.85; -0.26). Longer average sedentary bout duration was associated with slower TCSTtime [B = 0.17 s (0.09; 0.25)] and lower knee extension strength [B = -0.01 Nm kg-1 (-0.02; 0.00)]. Every hour of PA and HPA were associated with greater 6MWD [BPA = 15.88 m (9.87; 21.89), BHPA = 40.72 m (30.18; 51.25)], faster TCSTtime [BPA = -0.55 s (-1.03; -0.07), BHPA = -2.25 s (-3.09; -1.41)], greater elbow flexion strength [BPA = 0.03 Nm kg-1 (0.01; 0.07)], [BHPA = 0.05 Nm kg-1 (0.01

Item does not contain fulltext, The aim of the present study was to estimate the effect of incretins on fracture risk in the real-world situation by meta-analysis of the available population-based cohort data. Pubmed and Embase were searched for original articles investigating use of incretin agents, and fracture risk up to December 2015. Adjusted results were extracted and pooled by use of generic inverse variance methods, assuming a random-effects model. Neither current dipeptidyl peptidase 4-inhibitor use nor current glucagon-like peptide 1 receptor agonist use was associated with a decreased risk of fracture: pooled relative risk (pooled RR [95% confidence interval]: 1.02 [0.91-1.13] and 1.03 [0.87-1.22]), respectively. This meta-analysis demonstrated that current use of incretin agents, was not associated with decreased fracture risk. Our findings show the value of representative real-world populations, and the risks associated with suggesting benefits for medications on the basis of safety reporting in randomized controlled trials.

Item does not contain fulltext, Type 2 diabetes mellitus (T2DM) has been associated with an increased risk of fractures, despite normal to increased bone mineral density (BMD). Insulin use is one of the factors linked to this increased fracture risk. However, direct negative effects of insulin on bone quality are not expected since insulin is thought to be anabolic to bone. In this cross-sectional study the association between insulin use and volumetric BMD (vBMD), bone micro-architecture and bone strength of the distal radius, as measured with HR-pQCT, was examined. Data from 50 participants with T2DM of The Maastricht Study (mean age 62+/-7.5years, 44% women) was used. Participants were classified as insulin user (n=13) or non-insulin user (n=37) based on prescription data. Linear regression analysis was used to estimate the association between current insulin use and HR-pQCT derived parameters. After adjustment for age, sex, body mass index, glycated hemoglobin A1c and T2DM duration, insulin use was associated with lower total vBMD (standardized beta (beta):-0.56 (95% CI:-0.89 to -0.24)), trabecular vBMD (beta:-0.58 (95% CI:-0.87 to -0.30)), trabecular thickness (beta:-0.55 (95% CI:-0.87 to -0.23)), cortical thickness (beta:-0.41 (95% CI:-0.74 to -0.08)), log cortical pore volume (beta:-0.43 (95% CI:-0.73 to -0.13)), bone stiffness (beta:-0.39 (95% CI:-0.62 to -0.17)) and failure load (beta:-0.39 (95% CI:-0.60 to -0.17)) when compared to the non-insulin users. Insulin use was not associated with cortical vBMD, trabecular number, trabecular separation, cortical porosity and cortical pore diameter. This study indicates that insulin use is negatively associated with bone density, bone micro-architectural and bone strength parameters. These findings may partly explain the previously observed increased fracture risk in insulin users, although there may be residual confounding by other factors related to disease severity in insulin users.

Item does not contain fulltext, INTRODUCTION: Sedentary time has been associated with detrimental health effects, so in some countries, guidelines to reduce sedentary time have been developed. As reducing sedentary time inevitably results in more nonsedentary time, effects of this reduction may depend on the activity with which it is replaced. PURPOSE: This study aimed to examine associations of theoretical reallocations of sedentary time to standing or stepping with cardiometabolic outcomes and type 2 diabetes. METHODS: We included 2213 participants (51% men, mean +/- SD age = 60.0 +/- 8.1 yr) of the Maastricht Study who were asked to wear an accelerometer 24 h.d for a week. We calculated daily sedentary, standing, and stepping time. An isotemporal substitution modeling approach was applied to examine effects on waist circumference; body mass index; cholesterol, triacylglycerol, glucose, and insulin levels; metabolic syndrome; and type 2 diabetes. RESULTS: Replacement of sedentary time (30 min.d) with stepping was associated with lower odds for metabolic syndrome (odds ratio [OR] = 0.72, 95% confidence interval [CI] = 0.66-0.78) and type 2 diabetes (OR = 0.79, 95% CI = 0.72-0.87), more favorable waist circumference (B = -1.42, 95% CI = -1.78 to -1.06), and body mass index (B = -0.48, 95% CI = -0.62 to -0.35) and improved cholesterol, triacylglycerol, glucose, and insulin levels. Replacing sedentary time with standing was associated with lower odds for metabolic syndrome and type 2 diabetes and favorable outcomes in waist circumference, cholesterol, triacylglycerol, and insulin levels. CONCLUSION: Theoretical replacements of sedentary time with nonsedentary time (both standing and stepping) were associated with lower odds for metabolic syndrome, type 2 diabetes, and beneficial metabolic outcomes. These results could be important for the general population, including those who cannot meet physical activity guidelines. Consideration should be given to developing recommendations for daily reallocatin

Aims Tailored, patient-centred innovations are needed in the care for persons with type 2 diabetes mellitus (T2DM), in particular those with insufficient glycaemic control. Therefore, this study sought to assess their biopsychosocial characteristics and explore whether distinct biopsychosocial profiles exist within this subpopulation, which differ in health-related quality of life (HRQoL). Methods Cross-sectional study based on data from The Maastricht Study, a population-based cohort study focused on the aetiology, pathophysiology, complications, and comorbidities of T2DM. We analysed associations and clustering of glycaemic control and HRQoL with 38 independent variables (i.e. biopsychosocial characteristics) in different subgroups and using descriptive analyses, latent class analysis (LCA), and logistic regressions. Results Included were 840 persons with T2DM, mostly men (68.6%) and with a mean age of 62.6 (±7.7) years. Mean HbA1c was 7.1% (±3.2%); 308 patients (36.7%) had insufficient glycaemic control (HbA1c>7.0% [53 mmol/mol]). Compared to those with sufficient control, these patients had a significantly worse-off status on multiple biopsychosocial factors, including self-efficacy, income, education and several health-related characteristics. Two ‘latent classes’ were identified in the insufficient glycaemic control subgroup: with low respectively high HRQoL. Of the two, the low HRQoL class comprised about one-fourth of patients and had a significantly worse biopsychosocial profile. Conclusions Insufficient glycaemic control, particularly in combination with low HRQoL, is associated with a generally worse biopsychosocial profile. Further research is needed into the complex and multidimensional causal pathways explored in this study, so as to increase our understanding of the heterogeneous care needs and preferences of persons with T2DM, and translate this knowledge into tailored care and support arrangements.

Contains fulltext : 171731.pdf (publisher's version ) (Open Access), In the present study, we used national health care databases to estimate fracture incidence rates (IRs) and compared these IRs based on imputed data. We showed that imputation could lead to both over- and underestimation of IRs, and future research should therefore focus on how to improve those imputations. INTRODUCTION: Osteoporosis is a major public health burden through associated (osteoporotic) fractures. In Denmark, the incidence rates (IRs) of hip fracture are widely available. However, there is limited data about other fracture sites. A recent report could only provide imputed IRs, although nationwide data is readily available in electronic healthcare databases. Therefore, our aim was to estimate fracture site-specific IRs for Denmark in 2011 and to compare those to the previously reported imputed data. METHODS: Data from the Danish National Hospital Discharge Register was used to estimate age- and gender-specific IRs for any fracture as well as for different fracture sites in the Danish population aged 20 years and older in 2011. Hip fracture IRs were stratified to sub-sites, and IRs were determined for all hip fractures which were confirmed by surgery. RESULTS: The total number of incident fractures in 2011 was 80,760 (IR 191, 95 % confidence interval (CI) 190-192 (per 10,000 person-years)), of which 35,398 (43.8 %, IR 171, 95 % CI 169-173) occurred in men and 45,362 (56.2 %, IR 211, 95 % CI 209-213) in women. The majority of the fractures occurred in the population aged 50 years and older (n = 50,470, IR 249, 95 % CI 247-251). The numbers of any hip fracture were lower than the previously imputed estimates, whereas the number of forearm fractures was higher. CONCLUSION: We showed age- and gender-specific fracture rates for any fracture as well as for different fracture sites. The IRs of most fracture sites increased with age. Estimating the number of fractures for Denmark based on imputation of data from other countries led to both over- and underestimatio

Background Strong longitudinal evidence exists that psychological distress is associated with a high morbidity and mortality risk in type 2 diabetes. Little is known about the biological and behavioral mechanisms that may explain this association. Moreover, the role of personality traits in these associations is still unclear. In this paper, we first describe the design of the psychological part of The Maastricht Study that aims to elucidate these mechanisms. Next, we present exploratory results on the prevalence of depression, anxiety and personality traits in type 2 diabetes. Finally, we briefly discuss the importance of these findings for clinical research and practice. Methods We measured psychological distress and depression using the MINI diagnostic interview, the PHQ-9 and GAD-7 questionnaires in the first 864 participants of The Maastricht Study, a large, population-based cohort study. Personality traits were measured by the DS14 and Big Five personality questionnaires. Type 2 diabetes was assessed by an oral glucose tolerance test. Logistic regression analyses were used to estimate the associations of depression, anxiety and personality with type 2 diabetes, adjusted for age, sex and education level. Results Individuals with type 2 diabetes had higher levels of depressive and anxiety symptoms, odds ratios (95 % CI) were 3.15 (1.49; 6.67), 1.73 (0.83–3.60), 1.50 (0.72–3.12), for PHQ-9 ≥ 10, current depressive disorder and GAD-7 ≥ 10, respectively. Type D personality, social inhibition and negative affectivity were more prevalent in type 2 diabetes, odds ratios were 1.95 (1.23–3.10), 1.35 (0.93–1.94) and 1.70 (1.14–2.51), respectively. Individuals with type 2 diabetes were less extraverted, less conscientious, less agreeable and less emotionally stable, and similar in openness to individuals without type 2 diabetes, although effect sizes were small. Conclusions Individuals with type 2 diabetes experience more psychological distress

BACKGROUND: It has been hypothesized that arterial stiffness leads to generalized microvascular dysfunction and that individuals with type 2 diabetes mellitus (T2DM) are particularly prone to the detrimental effects of arterial stiffness. However, evidence for an association between stiffness and markers of generalized microvascular dysfunction is lacking. We therefore investigated the association between arterial stiffness and skin microvascular function in individuals without and with T2DM. METHODS: Cross-sectional data were used of The Supplementation en Vitamines et Mineraux Antioxydants 2 (SUVIMAX2) Study (n = 284/62.2 years/48.6% women/0% T2DM (by design)) and The Maastricht Study (n = 737/59.7 years/45.2% women/28.8% T2DM (by design)). Arterial stiffness was determined by carotid-femoral pulse wave velocity (cfPWV). Skin capillaroscopy was used to determine capillary density at baseline, and during reactive hyperemia and venous congestion. Laser Doppler flowmetry was used to assess acetylcholine- and local heating-induced vasoreactivity, and skin flowmotion. RESULTS: In The SUVIMAX2 Study, cfPWV (per +1 SD) was not associated with baseline capillary density (regression coefficient: -0.48 (95% confidence interval: 2.37; 1.41)) or capillary recruitment during venous congestion (0.54% (-0.74; 1.81%)). In addition, cfPWV was not associated with acetylcholine (-0.02% (-0.14; 0.10%)) or local heating-induced vasoreactivity (0.03% (-0.07; 0.12%)). In The Maastricht Study, in individuals without T2DM, cfPWV was not associated with baseline capillary density (-1.20 (-3.17; 0.77)), and capillary recruitment during reactive hyperemia (1.22% (-0.41; 2.84%)) or venous congestion (1.50% (-0.25; 3.25%)). In addition, cfPWV was not associated with flowmotion (-0.01 (-0.07; 0.06)). Results were adjusted for age and sex. Additional adjustments for confounders did not materially change these results. Results were qualitatively similar in individuals with T2DM. CONCLUSIONS: Arte

Contains fulltext : 154664.pdf (publisher's version ) (Open Access), Glucagon-like Peptide-1 receptor agonists (GLP1-ra) are a relatively new class of anti-hyperglycemic drugs which may positively affect bone metabolism and thereby decrease (osteoporotic) bone fracture risk. Data on the effect of GLP1-ra on fracture risk are scarce and limited to clinical trial data only. The aim of this study was to investigate, in a population-based cohort, the association between the use of GLP1-ra and bone fracture risk. We conducted a population-based cohort study, with the use of data from the Clinical Practice Research Datalink (CPRD) database (2007-2012). The study population (N = 216,816) consisted of all individuals with type 2 diabetes patients with at least one prescription for a non-insulin anti-diabetic drug and were over 18 years of age. Cox proportional hazards models were used to estimate the hazard ratio of fracture in GLP1-ra users versus never-GLP1-ra users. Time-dependent adjustments were made for age, sex, lifestyle, comorbidity and the use of other drugs. There was no decreased risk of fracture with current use of GLP1-ra compared to never-GLP1-ra use (adjusted HR 0.99, 95 % CI 0.82-1.19). Osteoporotic fracture risk was also not decreased by current GLP1-ra use (adjusted HR 0.97; 95 % CI 0.72-1.32). In addition, stratification according to cumulative dose did not show a decreased bone fracture risk with increasing cumulative GLP1-ra dose. We showed in a population-based cohort study that GLP1-ra use is not associated with a decreased bone fracture risk compared to users of other anti-hyperglycemic drugs. Future research is needed to elucidate the potential working mechanisms of GLP1-ra on bone.

Item does not contain fulltext, INTRODUCTION: Although patients with type 2 diabetes mellitus have an increased bone mineral density as compared to healthy patients, their risk of fracture is elevated. Incretins, new anti-diabetic drugs, may have a protective effect on bone mineral density. However, data on the effect of incretins on fracture risk are limited. Therefore the aim of this study was to investigate the association between the use of DPP4-I and the risk of fracture. METHODS: A retrospective population based cohort study, using data from the Clinical Practice Research Datalink (CPRD) database (2007-2012), was conducted. Patients (N=216,816) with at least one prescription for a non-insulin anti-diabetic drug (NIAD), aged 18+ during data collection, were matched to one control patient. Cox proportional hazards models were used to estimate the hazard ratio of any fracture in DPP4 inhibitor (DPP4-I) users versus controls and versus other NIAD patients. Time-dependent adjustments were made for age, sex, life style, comorbidity and drug use. RESULTS: The actual duration of DPP4-I use was 1.3years. There was no different risk of fracture comparing current DPP4-I users to controls (adjusted hazard ratio (adj. HR) 0.89, 95% confidence interval (CI) 0.71-1.13). There was also no increased risk comparing current DPP4-I users to other NIAD users, adj. HR 1.03 (95% CI 0.92-1.15). CONCLUSIONS: DPP4-I use was not associated with fracture risk compared to controls and to other NIAD users. However, the duration of DPP4-I use in our database might have been too short to show an association with fracture risk.

OBJECTIVE - Heart failure is common in individuals with type 2 diabetes, and early detection of individuals at risk may offer opportunities for prevention. We aimed to explore 1) prospective associations of B-type natriuretic peptide (BNP) levels in a non-heart failure range with changes in markers of left ventricular (LV) function and 2) possible effect modification by type 2 diabetes in a population-based cohort. RESEARCH DESIGN AND METHODS - Echocardiographic measurements were performed at baseline (2000-2001) and follow-up (2007-2009), together with standardized physical examinations and BNP measurements on 300 individuals (mean age 66 years, 32% with type 2 diabetes) of the longitudinal Hoorn Study. Multivariate linear regression analyses were performed to investigate associations of baseline BNP (<100 pg/mL) in individuals without prevalent heart failure at baseline with changes in LV mass index, LV ejection fraction, left atrial volume index, and ratio of early diastolic LVinflowvelocity (E) to early diastolic lengthening velocity (e′) (E/e′). RESULTS - In all individuals, higher BNP was associated with 8-year increases in left atrial volume index. Higher BNP was also associated with increasing LV mass index and E/e′. These associations were significantly stronger in individuals with type 2 diabetes compared with the nonsignificant associations in individuals without type 2 diabetes. CONCLUSIONS - This 8-year follow-up study shows that higher BNP levels in a non-heart failure range were associated with an increased LV mass and deteriorated LV diastolic function, particularly in individuals with type 2 diabetes. This implies that the presence or absence of type 2 diabetes should be taken into account if BNP levels are used to assess future heart failure risk.

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/1.73m

AIMS: We evaluated the associations of diabetic complications and underlying pathology with daily walking activity in type 2 diabetic patients without manifest mobility limitations. METHODS: 100 persons with type 2 diabetes (mean age 64.5+/-9.4 years) were studied. Persons with manifest mobility limitations were excluded. Possible determinants measured: peripheral neuropathy, neuropathic pain, peripheral arterial disease, cardiovascular disease, decreased muscle strength (handgrip strength), BMI, depression, falls and fear of falling. Walking activity was measured during one week with a pedometer. Functional capacity was measured with the 6min walk test, the timed "up and go" test and a stair climbing test. RESULTS: Prevalence of neuropathy (40%) and obesity (53%) was high. Persons took a median of 6429 steps/day. In multivariate regression analysis, adjusted for age and sex, neuropathy was associated with a reduction of 1967 steps/day, decreased muscle strength with 1782 steps/day, and an increase in BMI of 1kg/m(2) with a decrease of 210 steps/day (all p<0.05). Decreased muscle strength and BMI, but not neuropathy, were associated with outcome of functional capacity tests in multiple regression analysis. CONCLUSIONS: Peripheral neuropathy, decreased muscle strength and obesity are strongly associated with walking in persons with type 2 diabetes without manifest mobility limitations.

Endothelial dysfunction and low-grade inflammation are associated with cardiovascular disease. Arterial stiffening plays an important role in cardiovascular disease and, thus, may be a mechanism through which endothelial dysfunction and/or low-grade inflammation lead to cardiovascular disease. We investigated the associations between, on the one hand, biomarkers of endothelial dysfunction (soluble endothelial selectin, thrombomodulin, and both vascular and intercellular adhesion molecules 1 and von Willebrand factor) and of low-grade inflammation (C-reactive protein, serum amyloid A, interleukin 6, interleukin 8, tumor necrosis factor-alpha and, soluble intercellular adhesion molecule 1) and, on the other hand, arterial stiffness over a 6-year period, in 293 healthy adults (155 women). Biomarkers were combined into mean z scores. Carotid, femoral, and brachial arterial stiffness and carotid-femoral pulse wave velocity were determined by ultrasonography. Measurements were obtained when individuals were 36 and 42 years of age. Associations were analyzed with generalized estimating equation and adjusted for sex, height, and mean arterial pressure. The endothelial dysfunction z score was inversely associated with femoral distensibility (beta: -0.51 [95% CI: -0.95 to -0.06]) and compliance coefficients (beta: -0.041 [95% CI: -0.076 to -0.006]) but not with carotid or brachial stiffness or carotid-femoral pulse wave velocity. The low-grade inflammation z score was inversely associated with femoral distensibility (beta: -0.51 [95% CI: -0.95 to -0.07]) and compliance coefficients (beta: -0.050 [95% CI: -0.084 to -0.016]) and with carotid distensibility coefficient (beta: -0.910 [95% CI: -1.810 to -0.008]) but not with brachial stiffness or carotid-femoral pulse wave velocity. Biomarkers of endothelial dysfunction and low-grade inflammation are associated with greater arterial stiffness. This provides evidence that arterial stiffening may be a mechanism through which endothe