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Aims/hypothesis: The hyperglycaemic clamp technique and the frequently sampled IVGTT are unsuitable techniques to assess beta cell function (BCF) in large cohorts. Therefore, the aim of this study was to evaluate the discriminatory ability of simple OGTT-based BCF indices for prediction of prediabetes (meaning impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes., Methods: Glucose metabolism status was assessed by 2 h 75 g OGTT at baseline (n = 476, mean age 59.2 years, 38.7% women) and after 7 years of follow-up (n = 416) in the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study (1999-2009). Baseline plasma glucose, insulin and C-peptide values during OGTTs were used to calculate 21 simple indices of BCF. Disposition indices (BCF index × Matsuda index), to compensate for the prevailing level of insulin resistance, were calculated for the BCF indices with the best discriminatory abilities. The discriminatory ability of the BCF indices was estimated by the area under the receiver operating characteristics curve (ROC AUC) with an outcome of incident prediabetes (n = 73) or type 2 diabetes (n = 60 and n = 18 cases, respectively, in individuals who were non-diabetic or had normal glucose metabolism at baseline)., Results: For incident prediabetes (n = 73), all ROC AUCs were less than 70%, whereas for incident type 2 diabetes, I 30 /I 0 , CP 30 /CP 0 , ΔI 30 /ΔG 30 , ΔCP 30 /ΔG 30 (where I, CP and G are the plasma concentrations of insulin, C-peptide and glucose, respectively, at the times indicated), and corrected insulin response at 30 min had ROC AUCs over 70%. In at-baseline non-diabetic individuals, disposition indices ΔI 30 /ΔG 30 , ΔCP 30 /ΔG 30 and corrected insulin response at 30 min had ROC AUCs of over 80% for incident type 2 diabetes. Moreover, these BCF disposition indices had significantly better discriminatory abilities for incident type 2 diabetes than the Matsuda index alone., Conclusions/interpretation: BCF indices reflecting early-phase insulin secretion have the best ability to discriminate individuals who will develop prediabetes and type 2 diabetes. Of these, ΔCP 30 /ΔG 30 , often referred to as the C-peptidogenic index, performed consistently well.

Background: Reduced estimated glomerular filtration rate (eGFR) and albuminuria have been associated with worse cognitive performance. However, few studies have examined whether these associations are confined to older individuals or may be extended to the middle-aged population., Study Design: Cross-sectional analyses of a prospective population-based cohort study., Setting & Participants: 2,987 individuals aged 40 to 75 years from the general population (The Maastricht Study)., Predictor: eGFR and urinary albumin excretion (UAE)., Outcomes: Memory function, information processing speed, and executive function., Measurements: Analyses were adjusted for demographic variables (age, sex, and educational level), lifestyle factors (smoking behavior and alcohol consumption), depression, and cardiovascular disease risk factors (glucose metabolism status, waist circumference, total to high-density lipoprotein cholesterol ratio, triglyceride level, use of lipid-modifying medication, systolic blood pressure, use of antihypertensive medication, and prevalent cardiovascular disease)., Results: UAE was <15mg/24 h in 2,439 (81.7%) participants, 15 to <30 mg/24 h in 309 (10.3%), and ≥30mg/24 h in 239 (8.0%). In the entire study population, UAE≥30mg/24 h was associated with lower information processing speed as compared to UAE<15mg/24 h (β [SD difference] = -0.148; 95% CI, -0.263 to -0.033) after full adjustment, whereas continuous albuminuria was not. However, significant interaction terms (P for interaction < 0.05) suggested that albuminuria was most strongly and extensively associated with cognitive performance in older individuals. Mean (±SD) eGFR, estimated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine-cystatin C equation (eGFR cr-cys ), was 88.4±14.6 mL/min/1.73m 2 . eGFR cr-cys was not associated with any of the domains of cognitive performance after full adjustment. However, significant interaction terms (P for interaction < 0.05) suggested that eGFR cr-cys was associated with cognitive performance in older individuals., Limitations: Cross-sectional design, which limited causal inferences., Conclusions: In the entire study population, albuminuria was independently associated with lower information processing speed, whereas eGFR cr-cys was not associated with cognitive performance. However, both were more strongly and extensively associated with cognitive performance in older individuals., (Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Background/objectives: Elderly with functional disabilities are at increased risk of inadequate dietary intake. Little is known about the effectiveness of interventions aimed at improving their dietary intake and nutritional status, nor about the determinants of successful implementation. We performed a feasibility study to evaluate the implementation and effectiveness of a home delivery service providing nutritious meals., Design: Quasi-experimental, with participants allocated to treatment group based on municipality of residence., Setting and Participants: Functionally disabled home-dwelling elderly receiving home care., Intervention: Three-month daily meal service consisting of dinner and snacks (intervention). The control group sustained habitual food intake., Measurements: Data on satisfaction and problems regarding the meal service were collected by structured interviews. Dietary intake (2-day estimated food diary), nutritional status (anthropometry), handgrip strength, and quality of life (questionnaire-based) was measured at baseline, three months (end of intervention), and six months (follow-up)., Results: Forty-four elderly were included (intervention group: 25, control group: 19). For most aspects of the meal service, approximately 90% of participants indicated being satisfied, and the large majority (70%) was interested in receiving a similar meal service in the future. At the end of the 3-month intervention, the intervention group showed a greater increase than the control group in body weight (P< 0.005), body mass index (P< 0.005), upper leg circumference (P< 0.01) and fat free mass (FFM, P< 0.03). Three months post-intervention, only the increase in FFM remained statistically significant (P< 0.05). Except for calcium intake, no positive intervention effect was observed for any of the other outcomes., Conclusion: Our study stresses the feasibility as well as the potential of healthy and tasteful meals to support home-dwelling elderly, by showing that a high-quality meal service was highly appreciated and had a rapid effect on FFM., Competing Interests: None

Background: Depression is a highly prevalent disease with a high morbidity and mortality risk. Its pathophysiology is not entirely clear. However, type 2 diabetes is an important risk factor for depression. One mechanism that may explain this association may include the formation of advanced glycation end products (AGEs). We therefore investigated the association of AGEs with depressive symptoms and depressive disorder. In addition, we examined whether the potential association was present for somatic and/or cognitive symptoms of depression., Methods: Cross-sectional data were used from the Maastricht Study (N = 862, mean age 59.8 ± 8.5 years, 55% men). AGE accumulation was measured with skin autofluorescence (SAF) by use of the AGE Reader. Plasma levels of protein-bound pentosidine were measured with high-performance liquid chromatography and fluorescence detection. Nε-(carboxymethyl)lysine (CML) and Nε-(carboxyethyl)lysine (CEL) were measured with ultraperformance liquid chromatography and tandem mass spectrometry. Depressive symptoms and depressive disorder were assessed by the nine-item Patient Health Questionnaire and the Mini-International Neuropsychiatric Interview., Results: Higher SAF was associated with depressive symptoms (β = 0.42, 95% CI 0.12-0.73, P = .007) and depressive disorder (OR = 1.42, 95% CI 1.04-1.95, P = .028) after adjustment for age, sex, type 2 diabetes, smoking, BMI, and kidney function. Plasma pentosidine, CML, and CEL were not independently associated with depressive symptoms and depressive disorder., Conclusions: This study shows that AGE accumulation in the skin is independently associated with higher levels of depressive symptoms and depressive disorder. This association is present for both somatic and cognitive symptoms of depression. This might suggest that AGEs are involved in the development of depression., (© 2016 Wiley Periodicals, Inc.)

Aims: To determine the association of verbal intelligence, a core constituent of health literacy, with diabetic complications and walking speed in people with Type 2 diabetes., Methods: This study was performed in 228 people with Type 2 diabetes participating in the Maastricht Study, a population-based cohort study. We examined the cross-sectional associations of score on the vocabulary test of the Groningen Intelligence Test with: 1) determinants of diabetic complications (HbA 1c , blood pressure and lipid level); 2) diabetic complications: chronic kidney disease, neuropathic pain, self-reported history of cardiovascular disease and carotid intima-media thickness; and 3) walking speed. Analyses were performed using linear regression and adjusted in separate models for potential confounders and mediators. Significant age- and sex-adjusted associations were additionally adjusted for educational level in a separate model., Results: After full adjustment, lower verbal intelligence was associated with the presence of neuropathic pain [odds ratio (OR) 1.18, 95% CI 1.02;1.36], cardiovascular disease (OR 1.14, 95% CI 1.01;1.30), and slower walking speed (regression coefficient -0.011 m/s, 95% CI -0.021; -0.002 m/s). These associations were largely explained by education. Verbal intelligence was not associated with blood pressure, glycaemic control, lipid control, chronic kidney disease or carotid intima-media thickness., Conclusions: Lower verbal intelligence was associated with the presence of some diabetic complications and with a slower walking speed, a measure of physical functioning. Educational level largely explained these associations. This implies that clinicians should be aware of the educational level of people with diabetes and should provide information at a level of complexity tailored to the patient., (© 2016 Diabetes UK.)

Albuminuria may be a biomarker of generalized (i.e., microvascular and macrovascular) endothelial dysfunction. According to this concept, endothelial dysfunction of the renal microcirculation causes albuminuria by increasing glomerular capillary wall permeability and intraglomerular pressure, the latter eventually leading to glomerular capillary dropout (rarefaction) and further increases in intraglomerular pressure. However, direct evidence for an association between capillary rarefaction and albuminuria is lacking. Therefore, we examined the cross-sectional association between the recruitment of capillaries after arterial occlusion (capillary density during postocclusive peak reactive hyperemia) and during venous occlusion (venous congestion), as assessed with skin capillaroscopy, and albuminuria in 741 participants of the Maastricht Study, including 211 participants with type 2 diabetes. Overall, 57 participants had albuminuria, which was defined as a urinary albumin excretion ≥30 mg/24 h. After adjustment for potential confounders, participants in the lowest tertile of skin capillary recruitment during postocclusive peak reactive hyperemia had an odds ratio for albuminuria of 2.27 (95% confidence interval, 1.07 to 4.80) compared with those in the highest tertile. Similarly, a comparison between the lowest and the highest tertiles of capillary recruitment during venous congestion yielded an odds ratio of 2.89 (95% confidence interval, 1.27 to 6.61) for participants in the lowest tertile. In conclusion, lower capillary density of the skin microcirculation independently associated with albuminuria, providing direct support for a role of capillary rarefaction in the pathogenesis of albuminuria., (Copyright © 2016 by the American Society of Nephrology.)

Objectives: To assess the psychometric properties and identify the best cutoff value of the Patient Health Questionnaire-9 (PHQ-9) for depression screening in individuals with type 2 diabetes mellitus (T2DM)., Design: Observational population-based cohort study., Setting: The Maastricht Study., Participants: Individuals with and without T2DM (mean age 58.6 ± 8.1, 44.6% male) according to an oral glucose tolerance test (N = 2,997)., Measurements: Depressive disorder and depressive symptoms were measured using the Mini-International Neuropsychiatric Interview (MINI) as the reference and the PHQ-9. Cronbach alpha, Cohen's kappa and receiver operating characteristic (ROC) analyses were used. Differences in factorial structure between participants with and without T2DM were tested using multigroup confirmatory factor analysis., Results: Based on the traditional PHQ-9 cutoff value, 133 (4.4%) participants had depressive symptoms (PHQ-9 score ≥10). Internal consistency of the PHQ-9 was good (Cronbach α = 0.87 with T2DM, 0.82 without T2DM), the kappa of agreement between the PHQ-9 and the MINI was moderate (0.40 with T2DM, 0.43 without T2DM). Area under the ROC curve for the PHQ-9 was 0.87 in participants with T2DM and 0.88 in those without. A PHQ-9 cutoff score of 5 provided the best sensitivity (92.3%), with acceptable specificity (70.4%), for T2DM, similar to sensitivity and specificity in individuals without T2DM. Factor analysis suggested a similar two-factor structure in both groups (affective and somatic symptoms)., Conclusion: Patient Health Questionnaire-9 performs well as a screening tool for depressive symptoms in individuals with and without T2DM based on the cutoff value of 5, indicating that the PHQ-9 can be used in two-stage screening in primary care to select individuals with T2DM for further psychological evaluation., (© 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.)

In this cohort of relatively young and well-treated participants with type 2 diabetes, we found no association between diabetes status and a history of previous fractures and recent falls. Furthermore, no association between diabetes severity and previous fractures or recent falls was found., Introduction: In this study, we examined the association between glucose metabolism status and historical fractures or recent falls and the effect of diabetes severity (glucose control, insulin use, and diabetes duration) on falls and fractures in the participants with type 2 diabetes., Methods: Cross-sectional data from 2005 participants of the Maastricht Study. Falls in the past 6 months and fractures ≥age 50 were assessed by questionnaire. Glucose metabolism status (normal glucose metabolism, impaired glucose metabolism, or type 2 diabetes) was based on the oral glucose tolerance test and medication use., Results: In the completely adjusted model, the odds for a fall were not significantly higher in those with impaired glucose metabolism status (OR (95%CI) 1.28 (0.93-1.77)) or with type 2 diabetes (OR (95%CI) 1.21 (0.80-1.81)) compared with the group with normal glucose metabolism. Within the group with type 2 diabetes, there were no significant differences with regard to reported falls between participants with HbA1c >7 % (53 mmol/mol) versus HbA1c ≤7 % (OR (95%CI) 1.05 (0.58-1.90)), insulin users versus non-insulin users (OR (95%CI) 1.51 (0.79-2.89)), and with a diabetes duration >5 versus ≤5 years (OR (95%CI) 0.52 (0.46-1.47)). Similarly, neither glucose metabolism status nor diabetes severity was associated with prior fractures., Conclusions: Glucose metabolism status was not significantly associated with previous fractures and recent falls. In addition, in this cohort of relatively young and well-treated participants with type 2 diabetes, diabetes severity was not associated with previous fractures and recent falls., Competing Interests: Compliance with ethical standards The study has been approved by the institutional medical ethical committee (NL31329.068.10) and the Minister of Health, Welfare and Sports of the Netherlands, on the basis of the Health Council’s opinion (Permit 131088-105234-PG). All participants gave written informed consent. Conflict of interest None.

Background: There has been much debate recently on the best type of thromboprophylaxis following elective total joint replacement surgery., Objective: This study aims to compare rates of venous thromboembolism (VTE), gastro-intestinal (GI) bleeding and mortality events, with use of new oral anticoagulants (NOAC) or low-molecular-weight heparins (LMWHs) compared with aspirin in patients undergoing total joint replacement., Methods: A population-based retrospective cohort study was performed using the Clinical Practice Research Datalink. Patients ≥18 years of age who had undergone total knee (n = 3261) or hip replacement (THR (n = 4016)) between 2008 and 2012 were included. Within this population, three cohorts were selected, based on their first prescription within the 35-day period after surgery: use of NOACs only, LMWHs only and aspirin only. Incidence rates were calculated, and Cox proportional hazard models were fitted to estimate the risk of VTE, GI bleeding and all-cause mortality with the use of NOACs and LMWHs compared with aspirin use after total knee replacement and THR. We statistically adjusted our analyses for lifestyle factors, comorbidities and concomitant drug use., Results: Total knee replacement and THR patients currently on LMWHs had higher risk of VTE (HR = 17.2 (6.9-43.0) and HR = 39.5 (18.0-87.0), respectively), GI bleeding (HR = 20.9 (1.9-232.3) and HR = 2.0 (0.2-17.2), respectively) and all-cause mortality (HR = 4.3 (1.7-12.4) and HR = 4.0 (2.4-6.7), respectively). NOAC use was associated with an increased risk of GI bleeding in patients undergoing THR surgery., Conclusions: In contrast to previous studies, we found an increased risk of VTE, GI bleeding and all-cause mortality with the use of LMWHs compared with aspirin. Risk of GI bleeding was increased with the use of NOACs compared with aspirin use after THR surgery. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Type 2 diabetes (T2DM) is associated with an increased risk of cardiovascular disease. This can be partly explained by large-artery dysfunction, which already occurs in prediabetes ("ticking clock hypothesis"). Whether a similar phenomenon also applies to microvascular dysfunction is not known. We therefore tested the hypothesis that microvascular dysfunction is already present in prediabetes and is more severe in T2DM. To do so, we investigated the associations of prediabetes, T2DM, and measures of hyperglycemia with microvascular function measured as flicker light-induced retinal arteriolar dilation and heat-induced skin hyperemia., Methods: In the Maastricht Study, a T2DM-enriched population-based cohort study (n=2213, 51% men, aged [mean±standard deviation] 59.7±8.2 years), we determined flicker light-induced retinal arteriolar %-dilation (Dynamic Vessel Analyzer), heat-induced skin %-hyperemia (laser-Doppler flowmetry), and glucose metabolism status (oral glucose tolerance test; normal glucose metabolism [n=1269], prediabetes [n=335], or T2DM [n=609]). Differences were assessed with multivariable regression analyses adjusted for age, sex, body mass index, smoking, physical activity, systolic blood pressure, lipid profile, retinopathy, estimated glomerular filtration rate, (micro)albuminuria, the use of lipid-modifying and blood pressure-lowering medication, and prior cardiovascular disease., Results: Retinal arteriolar %-dilation was (mean±standard deviation) 3.4±2.8 in normal glucose metabolism, 3.0±2.7 in prediabetes, and 2.3±2.6 in T2DM. Adjusted analyses showed a lower arteriolar %-dilation in prediabetes (B=-0.20, 95% confidence interval -0.56 to 0.15) with further deterioration in T2DM (B=-0.61 [-0.97 to -0.25]) versus normal glucose metabolism (P for trend=0.001). Skin %-hyperemia was (mean±standard deviation) 1235±810 in normal glucose metabolism, 1109±748 in prediabetes, and 937±683 in T2DM. Adjusted analyses showed a lower %-hyperemia in prediabetes (B=-46 [-163 to 72]) with further deterioration in T2DM (B=-184 [-297 to -71]) versus normal glucose metabolism (P for trend=0.001). In addition, higher glycohemoglobin A1c and fasting plasma glucose were associated with lower retinal arteriolar %-dilation and skin %-hyperemia in fully adjusted models (for glycohemoglobin A1c, standardized B=-0.10 [-0.15 to -0.05], P<0.001 and standardized B=-0.13 [-0.19 to -0.07], P<0.001, respectively; for fasting plasma glucose, standardized B=-0.09 [-0.15 to -0.04], P<0.001 and standardized B=-0.10 [-0.15 to -0.04], P=0.002, respectively)., Conclusion: Prediabetes, T2DM, and measures of hyperglycemia are independently associated with impaired microvascular function in the retina and skin. These findings support the concept that microvascular dysfunction precedes and thus may contribute to T2DM-associated cardiovascular disease and other complications, which may in part have a microvascular origin such as impaired cognition and heart failure., (© 2016 American Heart Association, Inc.)

As accelerometers are commonly used for 24-h measurements of daily activity, methods for separating waking from sleeping time are necessary for correct estimations of total daily activity levels accumulated during the waking period. Therefore, an algorithm to determine wake and bed times in 24-h accelerometry data was developed and the agreement of this algorithm with self-report was examined. One hundred seventy-seven participants (aged 40-75 years) of The Maastricht Study who completed a diary and who wore the activPAL3™ 24 h/day, on average 6 consecutive days were included. Intraclass correlation coefficient (ICC) was calculated and the Bland-Altman method was used to examine associations between the self-reported and algorithm-calculated waking hours. Mean self-reported waking hours was 15.8 h/day, which was significantly correlated with the algorithm-calculated waking hours (15.8 h/day, ICC = 0.79, P = < 0.001). The Bland-Altman plot indicated good agreement in waking hours as the mean difference was 0.02 h (95% limits of agreement (LoA) = -1.1 to 1.2 h). The median of the absolute difference was 15.6 min (Q1-Q3 = 7.6-33.2 min), and 71% of absolute differences was less than 30 min. The newly developed automated algorithm to determine wake and bed times was highly associated with self-reported times, and can therefore be used to identify waking time in 24-h accelerometry data in large-scale epidemiological studies.

Background and Aims: There is increasing evidence linking arterial (mainly aortic) stiffness and type 2 diabetes, a risk factor for arterial stiffness, to cognitive impairment and dementia. However, data on carotid stiffness, which may be especially relevant for cognitive performance, are scarce, and few studies have addressed the interplay between arterial stiffness, type 2 diabetes, and cognitive performance., Methods: We studied individuals with (n = 197) and without (n = 528) type 2 diabetes, who completed a neuropsychological test battery and underwent applanation tonometry and vascular ultrasound to evaluate aortic (i.e. carotid-to-femoral pulse wave velocity) and carotid stiffness (i.e. distensibility, compliance and Young's elastic modulus). Linear regression analyses were performed and adjusted for demographics, vascular risk factors, and depression., Results: Overall, our results showed that carotid, but not aortic, stiffness was associated with worse cognitive performance, primarily in the domains of processing speed (standardized regression coefficient for distensibility -0.083, p = 0.040; compliance -0.077, p = 0.032) and executive function and attention (distensibility -0.133, p = 0.001; compliance -0.090, p = 0.015; Young's elastic modulus -0.081, p = 0.027). These associations did not differ by diabetes status. The differences in cognitive performance between individuals with and without type 2 diabetes (mean difference in domain scores relative to those without diabetes for free recall memory -0.23, processing speed -0.19, executive function and attention -0.23; all p ≤ 0.009 and adjusted for demographics, traditional vascular risk factors, and depression) were not substantially altered after additional adjustment for carotid stiffness., Conclusions: Our findings suggest that carotid stiffness is associated with cognitive performance in both individuals with and without diabetes, but does not mediate the relationship between type 2 diabetes and cognitive dysfunction., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Arterial stiffening, as characterized by an increase in carotid-femoral pulse-wave velocity or pulse pressure, increases the risk of cardiovascular disease, especially among individuals with type 2 diabetes mellitus. Advanced glycation end products are hypothesized to play a role in the development of arterial stiffness. Therefore, we investigated the association between skin autofluorescence, an estimate of tissue advanced glycation end products, and plasma advanced glycation end products on the one hand and arterial stiffening on the other in 862 participants of The Maastricht Study (mean age of 60 years; 45% women) with normal glucose metabolism (n=469), impaired glucose metabolism (n=140), or type 2 diabetes (n=253). Associations were analyzed with linear regression analysis and adjusted for potential confounders. We found that higher skin autofluorescence as measured by the AGE Reader and plasma pentosidine were independently associated with higher carotid-femoral pulse-wave velocity (sβ 0.10; 95% confidence interval, 0.03-0.17 and 0.10; 0.04-0.16, respectively) and central pulse pressure (sβ 0.08; 95% confidence interval 0.01-0.15 and 0.07; 0.01-0.13, respectively). The associations between skin autofluorescence and pentosidine, and carotid-femoral pulse-wave velocity were more pronounced in individuals with type 2 diabetes mellitus (P-interaction<0.10). These results support the hypothesis that accumulation of advanced glycation end products is involved in arterial stiffening and may explain part of the increased risk of cardiovascular disease in individuals with type 2 diabetes mellitus., (© 2016 American Heart Association, Inc.)

A standardised, national, 160-item FFQ, the FFQ-NL 1.0, was recently developed for Dutch epidemiological studies. The objective was to validate the FFQ-NL 1.0 against multiple 24-h recalls (24hR) and recovery and concentration biomarkers. The FFQ-NL 1.0 was filled out by 383 participants (25-69 years) from the Nutrition Questionnaires plus study. For each participant, one to two urinary and blood samples and one to five (mean 2·7) telephone-based 24hR were available. Group-level bias, correlation coefficients, attenuation factors, de-attenuated correlation coefficients and ranking agreement were assessed. Compared with the 24hR, the FFQ-NL 1.0 estimated the intake of energy and macronutrients well. However, it underestimated intakes of SFA and trans-fatty acids and alcohol and overestimated intakes of most vitamins by >5 %. The median correlation coefficient was 0·39 for energy and macronutrients, 0·30 for micronutrients and 0·30 for food groups. The FFQ underestimated protein intake by an average of 16 % and K by 5 %, relative to their urinary recovery biomarkers. Attenuation factors were 0·44 and 0·46 for protein and K, respectively. Correlation coefficients were 0·43-0·47 between (fatty) fish intake and plasma EPA and DHA and 0·24-0·43 between fruit and vegetable intakes and plasma carotenoids. In conclusion, the overall validity of the newly developed FFQ-NL 1.0 was acceptable to good. The FFQ-NL 1.0 is well suited for future use within Dutch cohort studies among adults.

Context and Objective: Moderate-to-vigorous physical activity (MVPA) and physical fitness (PF) are positively associated with glucose tolerance. Such associations may be partly conditioned by microvascular function, which is a common correlate to MVPA, PF, and glucose tolerance. To test this hypothesis, the present study sought to investigate independent associations of MVPA and PF with glucose tolerance and to what extent these associations are mediated by microvascular function. Design, Setting, Participants, and Outcome Measures: Data from The Maastricht Study were used (n = 512 for MVPA and n = 488 for PF analyses; mean age, 59 [SD = 9] y, 52 % men). Glucose tolerance was assessed by 2-hour postload plasma glucose levels (2hPG). The total number of weekly hours of MVPA was estimated with the Community Healthy Activities Model Program for Seniors questionnaire. Walking speed during the 6-minute walk test was used to evaluate PF. Microvascular function was determined by postocclusive capillary recruitment and flowmotion with capillaroscopy and laser Doppler flowmetry in skin microcirculation., Results: In univariate analyses, MVPA, PF, and microvascular function variables were associated with 2hPG. MVPA (n = 512, β = -0.056, P = .019) and PF (n = 488, β = -0.368, P = .006) remained associated with 2hPG after adjustment for established cardio-metabolic risk factors and history of cardiovascular disease; addition of microvascular function variables as potential mediators did not materially change the associations of MVPA (β = -0.054, P = .024) and PF (β = -0.364, P = .006) with 2hPG. No mediation effects of microvascular function variables were detected., Conclusions: MVPA and PF were independently associated with 2hPG, irrespective of established risk factors and generalized microvascular function. The possibility that specific microvascular functions, eg, insulin-mediated vasodilation, influence the association of MVPA and PF with 2hPG needs further investigation.

Background: The pathogenesis of depression may involve low-grade inflammation and endothelial dysfunction. We aimed to evaluate the independent associations of inflammation and endothelial dysfunction with depressive symptoms and depressive disorder, and the role of lifestyle factors in this association., Methods: In The Maastricht Study, a population-based cohort study (n=852, 55% men, m=59.8±8.5years), depressive symptoms were assessed with the Patient Health Questionnaire-9 and (major and minor) depressive disorder with the Mini-International Neuropsychiatric Interview. Plasma biomarkers of inflammation (hsCRP, SAA, sICAM-1, IL-6, IL-8, TNF-α) and endothelial dysfunction (sVCAM-1, sICAM-1, sE-selectin, vWF) were measured with sandwich immunoassays and combined into two standardized sum scores., Results: Biomarkers of inflammation (hsCRP, TNF-α, SAA, sICAM-1) and endothelial dysfunction (sICAM-1, sE-Selectin) were univariately associated with depressive symptoms and depressive disorder. The sum scores of inflammation and endothelial dysfunction were associated with depressive disorder after adjustment for age, sex, type 2 diabetes, kidney function and prior cardiovascular disease (OR 1.54, p=0.001 and 1.40, p=0.006). Both sum scores remained significantly associated with depressive disorder after additional adjustment for lifestyle factors smoking, alcohol consumption and body mass index. The sum score of inflammation was also independently associated with depressive symptoms, while the sum score of endothelial dysfunction was not., Conclusions: Inflammation and endothelial dysfunction are both associated with depressive disorder, independent of lifestyle factors. Our results might suggest that inflammation and endothelial dysfunction are involved in depression., (Copyright © 2016. Published by Elsevier Inc.)

Type 2 diabetes is associated with cognitive decrements, accelerated cognitive decline, and increased risk for dementia. Patients with the metabolic syndrome, a major risk factor for diabetes, may display comparable cognitive decrements as seen in type 2 diabetes. Currently, the impact of diabetes and prediabetes on cognition and the underlying organization of functional brain networks still remain to be elucidated. This study investigated whether functional brain networks are affected in type 2 diabetes and prediabetes. Forty-seven participants with diabetes, 47 participants with prediabetes, and 45 control participants underwent detailed cognitive testing and 3-Tesla resting state functional MRI. Graph theoretical network analysis was performed to investigate alterations in functional cerebral networks. Participants with diabetes displayed altered network measures, characterized by a higher normalized cluster coefficient and higher local efficiency, compared with control participants. The network measures of the participants with prediabetes fell between those with diabetes and control participants. Lower processing speed was associated with shorter path length and higher global efficiency. Participants with type 2 diabetes have altered functional brain networks. This alteration is already apparent in the prediabetic stage to a somewhat lower level, hinting at functional reorganization of the cerebral networks as a compensatory mechanism for cognitive decrements., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Background: P waves reported in electrocardiology literature uniformly appear smooth. Computer simulation and signal analysis studies have shown much more complex shapes., Objective: We systematically investigated P-wave complexity in normal volunteers using high-fidelity electrocardiographic techniques without filtering., Methods: We recorded 5-min multichannel ECGs in 16 healthy volunteers. Noise and interference were reduced by averaging over 300 beats per recording. In addition, normal P waves were simulated with a realistic model of the human atria., Results: Measured P waves had an average of 4.1 peaks (range 1-10) that were reproducible between recordings. Simulated P waves demonstrated similar complexity, which was related to structural discontinuities in the computer model of the atria., Conclusion: The true shape of the P wave is very irregular and is best seen in ECGs averaged over many beats., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background/objectives: The few prospective studies that examined lung, female breast and prostate cancer risk in vegetarians have yielded mixed results, whereas none have studied the effects of low meat diets. Moreover, little is known about the explanatory role of (non-) dietary factors associated with these diets., Subjects/methods: The Netherlands Cohort Study-Meat Investigation Cohort (NLCS-MIC)- is an analytical cohort of 11 082 individuals including 1133 self-reported vegetarians (aged 55-69 years at baseline). At baseline (1986), subjects completed a questionnaire on dietary habits and other risk factors for cancer and were classified into vegetarians (n=691), pescetarians (n=389), 1 day per week (n=1388), 2-5 days per week (n=2965) and 6-7 days per week meat consumers (n=5649)., Results: After 20.3 years of follow-up, 279 lung, 312 postmenopausal breast and 399 prostate cancer cases (including 136 advanced) were available for analyses. After adjustment for confounding variables, we found no statistically significant association between meat consumption groups and the risk of lung cancer. As well, no significant associations were observed for postmenopausal breast and overall prostate cancer. After adjustment for confounders, individuals consuming meat 1 day per week were at a 75% increased risk of advanced prostate cancer compared with 6-7 days per week meat consumers (95%CI 1.03-2.97)., Conclusions: Vegetarians, pescetarians and 1 day per week meat consumers did not have a reduced risk of lung, postmenopausal breast and overall prostate cancer compared with individuals consuming meat on a daily basis after taking confounders into account.

Background: Both obesity and the metabolic syndrome are associated with increased risk of cardiovascular diseases and type 2 diabetes. Although both frequently occur together in the same individual, obesity and the metabolic syndrome can also develop independently from each other. The (patho)physiology of "metabolically healthy obese" (i.e. obese without metabolic syndrome) and "metabolically unhealthy non-obese" phenotypes (i.e. non-obese with metabolic syndrome) is not fully understood, but physical activity and sedentary behavior may play a role., Objective: To examine objectively measured physical activity and sedentary behavior across four groups: I) "metabolically healthy obese" (MHO); II) "metabolically unhealthy obese" (MUO); III)"metabolically healthy non-obese" (MHNO); and IV) "metabolically unhealthy non-obese" (MUNO)., Methods: Data were available from 2,449 men and women aged 40-75 years who participated in The Maastricht Study from 2010 to 2013. Participants were classified into the four groups according to obesity (BMI≥30kg/m2) and metabolic syndrome (ATPIII definition). Daily activity was measured for 7 days with the activPAL physical activity monitor and classified as time spent sitting, standing, and stepping., Results: In our study population, 562 individuals were obese. 19.4% of the obese individuals and 72.7% of the non-obese individuals was metabolically healthy. After adjustments for age, sex, educational level, smoking, alcohol use, waking time, T2DM, history of CVD and mobility limitation, MHO (n = 107) spent, per day, more time stepping (118.2 versus 105.2 min; p<0.01) and less time sedentary (563.5 versus 593.0 min., p = 0.02) than MUO (n = 440). In parallel, MHNO (n = 1384) spent more time stepping (125.0 versus 115.4 min; p<0.01) and less time sedentary (553.3 versus 576.6 min., p<0.01) than MUNO (n = 518)., Conclusion: Overall, the metabolically healthy groups were less sedentary and more physically active than the metabolically unhealthy groups. Therefore, physical activity and sedentary time may partly explain the presence of the metabolic syndrome in obese as well as non-obese individuals.

It is generally thought that people with diabetes mellitus (DM) are more likely to suffer from osteoarthritis (OA) due to an increased body mass index (BMI), resulting in mechanical destruction of cartilage. However, previous studies have suggested a coexisting metabolic causality.To evaluate the risk of hip or knee replacement, as a proxy for severe OA, in patients with DM. We additionally evaluated the risk of total joint replacement (TJR) with various proxies for increased DM severity.A population-based case-control study was performed, using the Clinical Practice Research Datalink (CPRD). Cases (n = 94,609) were defined as patients >18 years who had undergone TJR between 2000 and 2012. Controls were matched by age, gender, and general practice. Conditional logistic regression was used to estimate the risk of total knee (TKR) and total hip replacement (THR) surgery associated with use of antidiabetic drugs (ADs). We additionally stratified current AD users by proxies for DM severity.Current AD use was significantly associated with a lower risk of TKR (OR = 0.86 (95% CI = 0.78-0.94)) and THR (OR = 0.90 (95% CI = 0.82-0.99)) compared to patients not using ADs. Moreover, risk of TKR and THR was decreased with increasing HbA1c.This study does not support the theory that DM patients are more likely to suffer from severe OA as compared to patients without diabetes. Moreover, risk of severe OA necessitating TJR decreases with increasing DM severity. This is possibly due to dissimilarities in methodology, a decrease in eligibility for surgery, or variability of OA phenotypes.

Aims/hypothesis: The study investigated cross-sectional associations of total amount and patterns of sedentary behaviour with glucose metabolism status and the metabolic syndrome., Methods: We included 2,497 participants (mean age 60.0 ± 8.1 years, 52% men) from The Maastricht Study who were asked to wear an activPAL accelerometer 24 h/day for 8 consecutive days. We calculated the daily amount of sedentary time, daily number of sedentary breaks and prolonged sedentary bouts (≥30 min), and the average duration of the sedentary bouts. To determine glucose metabolism status, participants underwent an oral glucose tolerance test. Associations of sedentary behaviour variables with glucose metabolism status and the metabolic syndrome were examined using multinomial logistic regression analyses., Results: Overall, 1,395 (55.9%) participants had normal glucose metabolism, 388 (15.5%) had impaired glucose metabolism and 714 (28.6%) had type 2 diabetes. The odds ratio per additional hour of sedentary time was 1.22 (95% CI 1.13, 1.32) for type 2 diabetes and 1.39 (1.27, 1.53) for the metabolic syndrome. No significant or only weak associations were seen for the number of sedentary breaks, number of prolonged sedentary bouts or average bout duration with either glucose metabolism status or the metabolic syndrome., Conclusions/interpretation: An extra hour of sedentary time was associated with a 22% increased odds for type 2 diabetes and a 39% increased odds for the metabolic syndrome. The pattern in which sedentary time was accumulated was weakly associated with the presence of the metabolic syndrome. These results suggest that sedentary behaviour may play a significant role in the development and prevention of type 2 diabetes, although longitudinal studies are needed to confirm our findings.

Observational studies suggest an inverse association between total dairy product intake and diabetes risk. However, there is a lack of information on the relationship of specific dairy products with impaired glucose metabolism (IGM) and type 2 diabetes mellitus (T2DM). Individuals aged 40-75 years were recruited for the Maastricht Study. All the participants filled out a 253-food item FFQ, covering fifty specific dairy items that captured differences between full-fat, semi-skimmed and skimmed products, as well as fermented and non-fermented products. Glucose metabolism status was assessed by an oral glucose tolerance test, and participants were informed on their glucose metabolism status after returning the FFQ. Data of 2391 individuals were available to estimate OR (95 % CI) for IGM (n 470) and newly diagnosed (ND) T2DM (n 125), with adjustment for age, sex, BMI, physical activity, smoking status, education, energy intake and intakes of vegetables, fruits, meat and fish. For IGM, fully adjusted analyses revealed inverse associations, with OR comparing the highest with the lowest tertile of intake of 0·73 (95 % CI 0·55, 0·96) for skimmed products and 0·74 (95 % CI 0·54, 0·99) for fermented products. These dairy products were not associated with ND T2DM. In contrast, full-fat products were positively associated with ND T2DM (OR 2·01; 95 % CI 1·16, 3·47), whereas total dairy product intake was inversely associated with ND T2DM (OR 0·50; 95 % CI 0·26, 0·93). In conclusion, individuals with a high consumption of skimmed and fermented products had lower odds of having IGM, and individuals with a high consumption of total dairy products had lower odds of having ND T2DM. High intake of full-fat products was not related to IGM but was positively related to ND T2DM.

Objective: The 99th percentile upper reference limit of high-sensitivity cardiac troponin (hs-cTn) from a healthy reference population is used for diagnosing acute myocardial infarction (AMI). Accepted current thresholds of hs-cTnT (Roche) and hs-cTnI (Abbott) are 14 and 26 ng/L, respectively. Since thresholds for hs-cTnT and hs-cTnI were derived from different reference cohorts it is unclear whether they are biologically equivalent. We directly assessed sex-specific and age-specific 99th percentile upper reference limits of hs-cTnT and hs-cTnI in a single reference cohort, to investigate whether current divergent thresholds of hs-cTnT and hs-cTnI stem from intrinsic assay differences or reflect cohort variation., Methods: A healthy reference population was derived from a population-based cohort (the Maastricht Study: n=3451; age: 40-75 years). Individuals with diabetes mellitus, a history of cardiovascular disease, cardiac ischaemia on ECG, N-terminal pro-brain natriuretic peptide >125 ng/L or estimated glomerular filtration rate <60 mL/min/1.73 m(2) were excluded. Non-parametric analyses were performed to assess 99th percentile upper reference limits., Results: 1540 individuals were included in the healthy reference population (age 57±8 years, 52.4% women). Overall 99th percentile upper reference limits of hs-cTnT and hs-cTnI were 15 and 13 ng/L, respectively. Upper reference limits were higher in men than women (hs-cTnT: 16 vs 12 ng/L), (hs-cTnI: 20 vs 11 ng/L) and increased with age., Conclusions: Direct comparison reveals numerically similar thresholds for hs-cTnT and hs-cTnI assays. This finding is in line with recently reported underdiagnosis of AMI with the current decision limit of 26 ng/L for hs-cTnI, especially among women. Downwards adjustment of the hs-cTnI threshold, differentiated for sex, would equalise clinical decision limits for both assays, and may prevent further underdiagnosis of AMI., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Aims: Osteoarthritis (OA) is the most common musculoskeletal condition in the elderly population. However, no disease modifying drug exists for this disease. In vivo animal studies have suggested that thiazolidinediones (TZD) may be used as disease modifying osteoarthritis drugs (DMOADs). To our knowledge, this has not yet been examined in humans before. The aim was to determine the risk of total joint replacement (TJR) in patients using TZDs compared with diabetic patients using other antidiabetic drugs., Methods: A population based case-control study was performed using the Clinical Practice Research Datalink (CPRD). Cases (n = 94 609) were defined as patients >18 years of age who had undergone total knee (TKR) or hip replacement (THR) between 2000 and 2012. Controls were matched by age, gender and practice/surgery. Conditional logistic regression analyses were used to estimate the risk of TKR and THR with the use of TZDs in patients currently using one or more antidiabetic drugs. In order to determine effect with prolonged use, we also stratified TZD users by total number of prescriptions prior to surgery. We statistically adjusted our analyses for lifestyle factory, comorbidities and concomitant drug use., Results: There was no difference in risk of TKR (OR 1.09, 95% CI 0.93, 1.27) and THR (OR 0.92, 95% CI 0.76, 1.10) when TZD users were compared with other AD users. Furthermore, we did not find an association with prolonged use of TZDs and TJR., Conclusion: Despite promising results from animal in vivo studies, this study did not find any evidence for a disease modifying osteoarthritic effect of TZDs., (© 2015 The British Pharmacological Society.)

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 and have different personality traits compared to individuals without type 2 diabetes. Future longitudinal analyses within The Maastricht Study will increase our understanding of biological and behavioral mechanisms that link psychological distress to morbidity and mortality in type 2 diabetes.

Objective: To evaluate among stakeholders the support for the new, dynamic concept of health, as published in 2011: 'Health as the ability to adapt and to self-manage', and to elaborate perceived indicators of health in order to make the concept measurable., Design: A mixed methods study: a qualitative first step with interviews and focus groups, followed by a quantitative survey., Participants: Representatives of seven healthcare stakeholder domains, for example, healthcare providers, patients with a chronic condition and policymakers. The qualitative study involved 140 stakeholders; the survey 1938 participants., Results: The new concept was appreciated, as it addresses people as more than their illness and focuses on strengths rather than weaknesses. Caution is needed as the concept requires substantial personal input of which not everyone is capable. The qualitative study identified 556 health indicators, categorised into six dimensions: bodily functions, mental functions and perception, spiritual/existential dimension, quality of life, social and societal participation, and daily functioning, with 32 underlying aspects. The quantitative study showed all stakeholder groups considering bodily functions to represent health, whereas for other dimensions there were significant differences between groups. Patients considered all six dimensions almost equally important, thus preferring a broad concept of health, whereas physicians assessed health more narrowly and biomedically. In the qualitative study, 78% of respondents considered their health indicators to represent the concept., Conclusions: To prevent confusion with health as 'absence of disease', we propose the use of the term 'positive health' for the broad perception of health with six dimensions, as preferred by patients. This broad perception deserves attention by healthcare providers as it may support shared decision-making in medical practice. For policymakers, the broad perception of 'positive health' is valuable as it bridges the gap between healthcare and the social domain, and by that it may demedicalise societal problems., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Type D personality - the combination of negative affectivity (NA) and social inhibition (SI) - has been associated with depression but little is known about underlying mechanisms. We examined whether (1) Type D is a vulnerability factor for depression in general, (2) Type D is associated with inflammation or endothelial dysfunction, and (3) these biomarkers alter the possible association between Type D and depression., Methods: In the Maastricht Study, 712 subjects underwent assessment of NA, SI and Type D personality (DS14), depressive disorder (Mini-International Neuropsychiatric Interview) and depressive symptoms (Patient Health Questionnaire-9). Plasma biomarkers of inflammation (hsCRP, SAA, sICAM-1, IL-6, IL-8, TNF-α) and endothelial dysfunction (sVCAM-1, sICAM-1, E-selectin, vWF) were measured with sandwich immunoassays or ELISA and combined into standardized sumscores., Results: Regarding personality, 49% of the study population was low in NA and SI, 22% had SI only, 12% NA only and 17% had Type D. Depressive disorder and depressive symptoms were significantly more prevalent in Type D versus the other three personality subgroups. Multivariable regression analyses showed that Type D was associated with inflammation (β=0.228, p=0.014) and endothelial dysfunction (β=0.216, p=0.022). After adjustment for these biomarkers, Type D remained independently associated with increased vulnerability to depressive disorder (OR=13.20, p<0.001) and depressive symptoms (β=3.87, p<0.001)., Limitations: The cross-sectional design restrained us to draw any conclusions on causality. The relatively low prevalence of depressive disorder restrained us to adjust for more potential confounders., Conclusions: Type D personality may be a vulnerability factor for depression, irrespective of levels of inflammation or endothelial dysfunction. Future research should examine possible underlying mechanisms., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The aim of this study was to validate an ultra-performance liquid chromatography tandem mass-spectrometry (UPLC-MS/MS) method for the determination of advanced glycation endproducts (AGEs) in food items and to analyze AGEs in a selection of food items commonly consumed in a Western diet. N(ε)-(carboxymethyl)lysine (CML), N(ε)-(1-carboxyethyl)lysine (CEL) and N(δ)-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were quantified in the protein fractions of 190 food items using UPLC-MS/MS. Intra- and inter-day accuracy and precision were 2-29%. The calibration curves showed perfect linearity in water and food matrices. We found the highest AGE levels in high-heat processed nut or grain products, and canned meats. Fruits, vegetables, butter and coffee had the lowest AGE content. The described method proved to be suitable for the quantification of three major AGEs in food items. The presented dietary AGE database opens the possibility to further quantify actual dietary exposure to AGEs and to explore its physiological impact on human health., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: To prospectively investigate the presence and counts of archaea in feces of 472 children in association with weight development from 6 to 10 years of age., Methods: Within the KOALA Birth Cohort Study, a single fecal sample from each child was analyzed by quantitative polymerase chain reaction to quantify archaea (Methanobrevibacter smithii, Methanosphera stadtmanae). Anthropometric outcomes (overweight [body mass index {BMI} ≥ 85th percentile], age- and sex-standardized BMI, weight, and height z-scores) were repeatedly measured at ages (mean ± SD) of 6.2 ± 0.5, 6.8 ± 0.5, 7.8 ± 0.5, and 8.8 ± 0.5 years. Generalized estimating equation was used for statistical analysis while controlling for confounders., Results: Methanobrevibacter smithii colonization was associated with an increased risk of overweight (adjusted odds ratio [OR] = 2.69; 95% confidence interval [CI] 0.96-7.54) from 6 to 10 years of age. Children with high levels (>7 log10 copies/g feces) of this archaeon were at highest risk for overweight (OR = 3.27; 95% CI 1.09-9.83). Moreover, M. smithii colonization was associated with higher weight z-scores (adj. β 0.18; 95% CI 0.00-0.36), but not with height. For BMI z-scores, the interaction (P = 0.008) between M. smithii and age was statistically significant, implying children colonized with M. smithii had increasing BMI z-scores with age., Conclusions: Presence and higher counts of M. smithii in the gut of children are associated with higher weight z-scores, higher BMI z-scores, and overweight., (© 2015 The Obesity Society.)

Objectives: We aimed to design and test a method to extract information on antithrombotic therapy from anonymised free-text notes in the Clinical Practice Research Datalink (CPRD)., Setting: General practice database representative of the UK., Participants: All patients undergoing total hip replacement (THR, n=25,898) or total knee replacement (TKR, n=22,231) between January 2008 and October 2012 were included. Antithrombotic drug use related to THR or TKR was identified using anonymised free text and prescription data., Primary and Secondary Outcome Measures: Internal validity of our newly designed method was determined by calculating positive predictive values (PPVs) of hits for predefined keywords in a random sample of anonymised free-text notes. In order to determine potential detection bias, total joint replacement (TJR) patient characteristics were compared as per their status of exposure to antithrombotics., Results: PPVs ranging between 97% and 99% for new oral anticoagulants (NOAC) or low-molecular weight heparins (LMWH) exposure related to TJR were obtained with our method. Our search strategy increased detection rates by 57%, yielding a total proportion of 18.5% of all THR and 18.6% of all TKR surgeries. Identified users of NOACs and LMWHs were largely similar with regards to age, sex, lifestyle, disease and drug history compared to patients without identified drug use., Conclusions: We have developed a useful method to identify additional exposure to NOACs or LMWHs with TJR surgery., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

To study how a vegetarian or low meat diet influences the risk of colorectal cancer compared to a high meat diet, and to assess the explanatory role of factors associated with these diets. In the Netherlands Cohort Study - Meat Investigation Cohort (NLCS-MIC) (cohort of 10,210 individuals including 1040 self-defined vegetarians), subjects completed a baseline questionnaire in 1986, based on which they were classified into vegetarians (n = 635), pescetarians (n = 360), 1 day/week- (n = 1259), 2-5 day/week- (n = 2703), and 6-7 day/week meat consumers (n = 5253). After 20.3 years of follow-up, 437 colorectal cancer cases (307 colon, 92 rectal) were available. A non-significantly decreased risk of CRC for vegetarians, pescetarians, and 1 day/week compared to 6-7 day/week meat consumers was observed (age/sex adjusted Hazard Ratios (HR): 0.73(0.47-1.13), 0.80(0.47-1.39), and 0.72(0.52-1.00), respectively). Most of the differences in HR between these groups could be explained by intake of dietary fiber and soy products. Other (non-)dietary factors characteristic for a vegetarian or low meat diet had negligible individual effects, but attenuated the HRs towards the null when combined. Vegetarians, pescetarians, and 1 day/week meat eaters showed a non-significantly decreased risk of colorectal cancer compared to 6-7 day/week meat consumers, mainly due to differences in dietary pattern other than meat intake.

Evidence from developing countries demonstrates a mixed relationship of overweight/obesity with socioeconomic status (SES) and place of residence. Theory of nutrition transition suggests that over the course of development, overweight first emerges among rich and urban people before spreading among rural and poor people. India is currently experiencing a rapid rise in the proportion of overweight and obese population especially among adult women. Under the backdrop of huge socio-economic heterogeneity across the states of India, the inter-state scenario of overweight and obesity differs considerably. Hence, this paper investigates the evolution over time of overweight and obesity among ever-married Indian women (15-49 years) from selected 'underweight states' (Bihar, Orissa and Madhya Pradesh, where underweight proportion is predominant) and 'overweight states' (Kerala, Delhi and Punjab, where overweight is the prime concern), in relation to a few selected socio-economic and demographic indicators. This study analysed National Family Health Surveys- NFHS-2 (1998-99) and NFHS-3 (2005-06) following Asian population specific BMI cut-offs for overweight and obesity. The results confirm that within India itself the relationship of overweight and obesity with place of residence and SES cannot be generalized. Results from 'overweight states' show that the overweight problem has started expanding from urban and well-off women to the poor and rural people, while the rural-urban and rich-poor difference has disappeared. On the other hand in 'underweight states' overweight and obesity have remained socially segregated and increasing strongly among urban and richer section of the population. The rate of rise of overweight and obesity has been higher in rural areas of 'OW states' and in urban areas of 'UW states'. Indian policymakers thus need to design state-specific approaches to arrest the rapid growth of overweight and its penetration especially towards under-privileged section of the society., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Arterial stiffness may be a mechanism to explain the association between uric acid and cardiovascular disease. We aimed to analyse associations between serum uric acid and regional and local arterial stiffness, and assess potential differences related to sex and glucose metabolism status., Methods: A cross-sectional study was performed in 614 adults [52.6% men; mean age 58.7 ± 8.5 years; 23.2% type 2 diabetes mellitus (by design)] from The Maastricht Study. Arterial stiffness was assessed by carotid-femoral pulse wave velocity (cfPWV), distensibility, and compliance coefficient of the carotid and femoral artery, and carotid artery Young's elastic modulus., Results: Higher uric acid (per SD of 74 μmol/l) was associated with greater stiffness indicated by a significantly higher cfPWV [β = 0.216 (95% confidence interval 0.061, 0.372); P = 0.006] and lower carotid distensibility coefficient [β = -0.633 (95% confidence interval -1.099, -0.166); P = 0.008] after adjustment for sex, age, and glucose metabolism status. Associations lost significance after adjusting for mean arterial pressure, BMI, waist, smoking status, heart rate, total : high-density lipoprotein cholesterol ratio, triglycerides, estimated glomerular filtration rate, use of lipid-lowering, antihypertensive, and diabetes medication, and use of secondary uricosurics. No associations were found between uric acid and carotid compliance coefficient, carotid Young's elastic modulus, or stiffness of the femoral artery. A significant interaction (P < 0.10) with glucose metabolism status was found for cfPWV. However, none of the stratified associations were significant. There was no interaction with sex., Conclusion: Uric acid was not significantly associated with stiffness of the aorta, or the carotid or femoral artery among adults aged 40-75 years without and with type 2 diabetes mellitus.

Objective: Microvascular dysfunction has been suggested as a possible underlying mechanism for the association between uric acid and various diseases, such as hypertension, renal disease and cardiomyopathies. We therefore analysed the association between serum uric acid and skin microvascular function, a model of generalized microvascular function., Methods: A cross-sectional study was performed in 610 individuals [51.8% men; mean age 58.7 ± 8.6 years; 23.6% with type 2 diabetes (by design)] from The Maastricht Study. We assessed skin capillary density (capillaries/mm) by capillaroscopy at baseline, after 4 min of arterial occlusion, and after 2 min of venous congestion. Capillary recruitment after arterial occlusion and during venous congestion was expressed as the absolute change in capillary density after recruitment and as the percentage change in capillary density from baseline., Results: Crude linear regression analyses showed that serum uric acid [per +1 standard deviation (SD) of 74 μmol/l] was not associated with baseline capillary density [β = -0.21 (95% confidence interval, 95% CI -1.61 to 1.19) P = 0.765], while an inverse association was found between uric acid and absolute change in capillary density after arterial occlusion [β = -1.15 (95% CI -2.36 to 0.06) P = 0.062] and during venous congestion [β = -1.41 (95% CI -2.68 to -0.14) P = 0.029]. However, after adjustment for sex, age and glucose metabolism status, these associations were no longer statistically significant. In addition, we found no association between uric acid and percentage capillary recruitment after arterial occlusion [β = -1.66 (95% CI -3.97 to 0.65) P = 0.159] or during venous congestion [β = -2.02 (95% CI -4.46 to 0.42) P = 0.104] in unadjusted analyses; multivariable analyses gave similar results., Conclusion: These results do not support the hypothesis that generalized microvascular dysfunction (as estimated in skin microcirculation) is the underlying mechanism for the association between uric acid and cardiovascular and renal diseases. The possibility that uric acid is associated with microvascular dysfunction in specific end-organs, for example heart or kidney, needs further investigation.

Objective: Hypertension and diabetes are both risk factors for cognitive decline, and individuals with both might have an especially high risk. We therefore examined linear and nonlinear (quadratic) associations of 24-h blood pressure (BP) with cognitive performance in participants with and without type 2 diabetes. We also tested the association of nocturnal dipping status with cognitive performance., Research Design and Methods: This study was performed as part of the Maastricht Study, an ongoing population-based cohort study. Cross-sectional associations of 24-h BP (n = 713, of whom 201 had type 2 diabetes) and nocturnal dipping status (n = 686, of whom 196 had type 2 diabetes) with performance on tests for global cognitive functioning, information processing speed, verbal memory (immediate and delayed word recall), and response inhibition were tested using linear regression analysis and adjusted for demographics, vascular risk factors, cardiovascular disease, depression, and lipid-modifying and antihypertensive medication use., Results: After full adjustment, we found quadratic (inverted U-shaped) associations of 24-h diastolic blood pressure (DBP) with information processing speed (b for quadratic term = -0.0267, P < 0.01) and memory (immediate word recall: b = -0.0180, P < 0.05; delayed word recall: b = -0.0076, P < 0.01) in participants with diabetes, but not in those without. No clear pattern was found for dipping status., Conclusions: This study shows that both low and high 24-h DBP are associated with poorer performance on tests of information processing speed and memory in individuals with type 2 diabetes., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

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: Arterial stiffness is not associated with skin microvascular function, irrespective of the presence of T2DM., (© American Journal of Hypertension, Ltd 2014. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

We hypothesized that early life exposure to nucleotides and nucleosides lowers the risk of recurrent wheeze, atopic dermatitis, and allergic sensitization among n = 429 children. Concentrations in breast milk were established by high-performance liquid chromatography; concentrations in formula milks were obtained from manufacturers. Questionnaires and home visits were used to assess outcomes. Adjusted odds ratios in the highest tertile compared with those in the lowest tertile of exposure ranged from 1.11 to 1.99 in predominantly formula-fed children, and from 0.40 to 0.53 in predominantly breast-fed children, but were not significant. Thus, we found no evidence for association between nucleotide and nucleoside exposure and the development of atopic outcomes in children up to 2 years.

Introduction: Lifestyle Triple P is a general parenting intervention which focuses on preventing further excessive weight gain in overweight and obese children. The objective of the current study was to assess the effectiveness of the Lifestyle Triple P intervention in the Netherlands., Method: We used a parallel randomized controlled design to test the effectiveness of the intervention. In total, 86 child-parent triads (children 4-8 years old, overweight or obese) were recruited and randomly assigned (allocation ratio 1:1) to the Lifestyle Triple P intervention or the control condition. Parents in the intervention condition received a 14-week intervention consisting of ten 90-minute group sessions and four individual telephone sessions. Primary outcome measure was the children's body composition (BMI z-scores, waist circumference and skinfolds). The research assistant who performed the measurements was blinded for group assignment. Secondary outcome measures were the children's dietary behavior and physical activity level, parenting practices, parental feeding style, parenting style, and parental self-efficacy. Outcome measures were assessed at baseline and 4 months (short-term) and 12 months (long-term) after baseline. Multilevel multiple regression analyses were conducted to determine the effect of the intervention on primary and secondary outcome measures., Results: No intervention effects were found on children's body composition. Analyses of secondary outcomes showed positive short-term intervention effects on children's soft-drink consumption and parental responsibility regarding physical activity, encouragement to eat, psychological control, and efficacy and satisfaction with parenting. Longer-term intervention effects were found on parent's report of children's time spent on sedentary behavior and playing outside, parental monitoring food intake, and responsibility regarding nutrition., Conclusion: Although the Lifestyle Triple P intervention showed positive effects on some parent reported child behaviors and parenting measures, no effects were visible on children's body composition or objectively measured physical activity. Several adjustments of the intervention content are recommended, for example including a booster session., Trial Registration: Nederlands Trial Register NTR 2555.

Context: Advanced glycation end-products (AGEs) are thought to be involved in the pathogenesis of Alzheimer's disease. AGEs are products resulting from nonenzymatic chemical reactions between reduced sugars and proteins, which accumulate during natural aging, and their accumulation is accelerated in hyperglycemic conditions such as type 2 diabetes mellitus., Objective: The objective of the study was to examine associations between AGEs and cognitive functions., Design, Setting, and Participants: This study was performed as part of the Maastricht Study, a population-based cohort study in which, by design, 215 participants (28.1%) had type 2 diabetes mellitus., Main Outcome Measures: We examined associations of skin autofluorescence (SAF) (n = 764), an overall estimate of skin AGEs, and specific plasma protein-bound AGEs (n = 781) with performance on tests for global cognitive functioning, information processing speed, verbal memory (immediate and delayed word recall), and response inhibition., Results: After adjustment for demographics, diabetes, smoking, alcohol, waist circumference, total cholesterol/high-density lipoprotein cholesterol ratio, triglycerides, and lipid-lowering medication use, higher SAF was significantly associated with worse delayed word recall (regression coefficient, b = -0.44; P = .04), and response inhibition (b = 0.03; P = .04). After further adjustment for systolic blood pressure, cardiovascular disease, estimated glomerular filtration rate, and depression, associations were attenuated (delayed word recall, b = -0.38, P = .07; response inhibition, b = 0.02, P = .07). Higher pentosidine levels were associated with worse global cognitive functioning (b = -0.61; P = .04) after full adjustment, but other plasma AGEs were not. Associations did not differ between individuals with and without diabetes., Conclusion: We found inverse associations of SAF (a noninvasive marker for tissue AGEs) with cognitive performance, which were attenuated after adjustment for vascular risk factors and depression.

Studies on the occurrence of gout show a large range in estimates. However, a clear insight into the factors responsible for this variation in estimates is lacking. Therefore, our aim was to review the literature on the prevalence and incidence of gout systematically and to obtain insight into the degree of and factors contributing to the heterogeneity. We searched MEDLINE, EMBASE, and Web of Science (January 1962 to July 2012) to identify primary studies on the prevalence and incidence of gout in the general population. Data were extracted by two persons on sources of clinical heterogeneity, methodological heterogeneity, and variation in outcome reporting. Meta-analysis and meta-regression analysis were performed for the prevalence of gout. Of 1,466 articles screened, 77 articles were included, of which 71 reported the prevalence and 12 the incidence of gout. The pooled prevalence (67 studies; N = 12,226,425) based on a random effects model was 0.6% (95% CI 0.4; 0.7), however there was a high level of heterogeneity (I(2) = 99.9%). Results from a mixed-effects meta-regression model indicated that age (p = 0.019), sex (p < 0.001), continent (p < 0.001), response rate (p = 0.016), consistency in data collection (p = 0.002), and case definition (p < 0.001) were significantly associated with gout prevalence and jointly accounted for 88.7% of the heterogeneity. The incidence in the total population ranged from 0.06 to 2.68 per 1,000 person-years. In conclusion, gout is a common disease and the large variation in the prevalence data on gout is explained by sex, continent on which the study was performed, and the case definition of gout.

Objective: Skin microvascular flow motion (SMF)--blood flow fluctuation attributed to the rhythmic contraction and dilation of arterioles--is thought to be an important component of the microcirculation, by ensuring optimal delivery of nutrients and oxygen to tissue and regulating local hydraulic resistance. There is some evidence that SMF is altered in obesity, type 2 diabetes mellitus, and hypertension. Nevertheless, most studies of SMF have been conducted in highly selected patient groups, and evidence how SMF relates to other cardiovascular risk factors is scarce. Therefore, the aim of the present study was to examine in a population-based setting which cardiovascular risk factors are associated with SMF., Methods: We measured SMF in 506 participants of the Maastricht Study without prior cardiovascular event. SMF was investigated using Fourier transform analysis of skin laser Doppler flowmetry at rest within five frequency intervals in the 0.01-1.6-Hz spectral range. The associations with SMF of the cardiovascular risk factors age, sex, waist circumference, total-to-high-density lipoprotein cholesterol, fasting plasma glucose, 24-h SBP, and cigarette smoking were analysed by use of multiple linear regression analysis., Results: Per 1 SD higher age, waist circumference and 24-h SBP, SMF was 0.16 SD higher [95% confidence interval (CI) 0.07, 0.25; P < 0.001), -0.14 SD lower (95% CI -0.25, -0.04; P = 0.01), and 0.16 SD higher (95% CI 0.07, 0.26; P < 0.001), respectively, in fully adjusted analyses. We found no significant associations of sex, fasting plasma glucose levels, total-to-high-density lipoprotein cholesterol ratio, or pack years of smoking with SMF., Conclusion: Age and 24-h SBP are directly, and waist circumference is inversely associated with SMF in the general population. The exact mechanisms underlying these findings remain elusive. We hypothesize that flow motion may be an important component of the microcirculation by ensuring optimal delivery of nutrients and oxygen to tissue and regulating local hydraulic resistance not only under physiological conditions but also under pathophysiological conditions when microcirculatory perfusion is reduced, such as occurs with ageing and higher blood pressure. In addition, obesity may result in an impaired flow motion with negative effects on the delivery of nutrients and oxygen to tissue and local hydraulic resistance.

Objectives: The aims of this study were to investigate (i) associations between uric acid and prevalent cardiovascular disease (CVD), ankle-arm blood pressure index (AAIx) and carotid intima-media thickness (CIMT) in the total population and in predefined subgroups according to glucose metabolism status and (ii) the extent to which these associations are explained by low-grade inflammation., Methods: Cross-sectional analyses were conducted among 530 individuals [60.6% men, mean age 58.9 years (s.d. 6.9), 52.6% normal glucose metabolism (NGM)] at increased risk of CVD from the Cohort of Diabetes and Atherosclerosis Maastricht study. A low-grade inflammation score was computed by averaging the z-scores of eight inflammation markers [CRP, TNF-α, IL-6, IL-8, serum amyloid A, intercellular adhesion molecule 1 (ICAM-1), ceruloplasmin and haptoglobin]., Results: After adjustment for traditional CVD risk factors, plasma uric acid (per s.d. of 81 μmol/l) was associated with CVD in individuals with NGM [odds ratio (OR) = 1.66, 95% CI 1.06, 2.58] but not with disturbed glucose metabolism (DGM) (OR = 0.81, 95% CI 0.55, 1.19, P interaction = 0.165). Uric acid was associated with CIMT in the total population (β = 0.024, 95% CI 0.007, 0.042) and slightly more strongly in individuals with NGM (β = 0.030, 95% CI 0.006, 0.054) than DGM (β = 0.018, 95% CI -0.009, 0.044, P interaction = 0.443). There was no association between uric acid and AAIx in any group (P interaction = 0.058). Uric acid was associated with low-grade inflammation in the total population (β = 0.074, 95% CI 0.013, 0.134, P interaction = 0.737). Adding low-grade inflammation to the models did not attenuate any of the associations., Conclusion: The associations for uric acid with CIMT, and with CVD in NGM only, were not explained by low-grade inflammation. A difference in the strength of the associations between individuals with NGM and DGM was suggested., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Several studies have shown a positive association between maternal fish intake in pregnancy and pregnancy duration and child birth weight (BW), probably due to fish n-3 (ω-3) long-chain polyunsaturated fatty acids (LC-PUFAs). n-3 LC-PUFAs can also be synthesized endogenously, and their synthesis depends on single nucleotide polymorphisms (SNPs) in the fatty acid desaturase (FADS) gene encoding for FADS. We assessed the associations of maternal docosahexaenoic acid (DHA) intake in pregnancy with pregnancy duration and BW and investigated whether these associations are modified by maternal or fetal FADS SNP genotypes. We hypothesized that we would find stronger associations in minor allele homozygous mothers or fetuses due to their lower n-3 LC-PUFA endogenous synthesis and hence higher dependence on dietary supply. Data on maternal diet, pregnancy duration, and BW were available for 2622 mother-child pairs from the KOALA (Kind, Ouders en gezondheid: Aandacht voor Leefstijl en Aanleg) Birth Cohort Study. The rs174556 FADS SNP was genotyped in 1516 mothers and 1515 children. Associations and gene-diet interactions were tested with linear regression adjusting for potential confounders, including intake of other PUFAs. Women at the 75th percentile of DHA intake had 0.7-d longer pregnancies (P = 0.016) and 28-g heavier infants (P = 0.039) than did women at the 25th percentile of intake. Associations with arachidonic acid intake were of the same order but in the opposite direction. Mothers who were homozygous for the minor allele had 2-d shorter pregnancies (P = 0.035) and infants who were nearly 140 g lighter (P = 0.006) than did mothers who were major allele homozygotes. Post hoc analyses revealed that they had higher prepregnancy BMI (P = 0.020). Among the women homozygous for the minor allele, those at the 75th percentile of DHA intake had 226-g heavier infants than those at the 25th percentile of intake (P = 0.030), whereas DHA intake was not significantly associated with BW in major allele carriers. These findings suggest that maternal and fetal fatty acid requirements during pregnancy depend on maternal genetic variation in LC-PUFA synthesis., (© 2014 American Society for Nutrition.)

Research on parenting practices has focused on individual behaviors while largely failing to consider the context of their use, i.e., general parenting. We examined the extent to which food parenting practices predict children's dietary behavior (classified as unhealthy: snacking, sugar-sweetened beverage; and healthy: water and fruit intake). Furthermore, we tested the moderating role of general parenting on this relationship. Within the KOALA Birth Cohort Study, in the Netherlands, questionnaire data were collected at 6 and 8 years (N = 1654). Correlations were computed to assess the association between food parenting practices and general parenting (i.e., nurturance, behavioral control, structure, coercive control, and overprotection). Linear regression models were fitted to assess whether food parenting practices predict dietary behavior. Instrumental and emotional feeding, and pressure to eat were found to have associations with undesirable child dietary behavior (increased unhealthy intake/decreased healthy intake), whereas associations were in the desirable direction for covert control, encouragement and restriction. Moderation analyses were performed by evaluating interactions with general parenting. The associations of encouragement and covert control with desirable child dietary behaviors were found to be stronger for children who were reared in a positive parenting context. Future research should assess the influence of contextual parenting factors moderating the relationships between food parenting and child dietary behavior as the basis for the development of more effective family-based interventions., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

The Maastricht Study is an extensive phenotyping study that focuses on the etiology of type 2 diabetes (T2DM), its classic complications, and its emerging comorbidities. The study uses state-of-the-art imaging techniques and extensive biobanking to determine health status in a population-based cohort of 10,000 individuals that is enriched with T2DM individuals. Enrollment started in November 2010 and is anticipated to last 5-7 years. The Maastricht Study is expected to become one of the most extensive phenotyping studies in both the general population and T2DM participants world-wide. The Maastricht study will specifically focus on possible mechanisms that may explain why T2DM accelerates the development and progression of classic complications, such as cardiovascular disease, retinopathy, neuropathy and nephropathy and of emerging comorbidities, such as cognitive decline, depression, and gastrointestinal, musculoskeletal and respiratory diseases. In addition, it will also examine the association of these variables with quality of life and use of health care resources. This paper describes the rationale, overall study design, recruitment strategy and methods of basic measurements, and gives an overview of all measurements that are performed within The Maastricht Study.

Background: Alternative lifestyles are often associated with distinct practices with respect to nutrition, physical activity, smoking, alcohol use and usage of complementary medicine. Evidence concerning effects of these lifestyle-related practices on health status is still fragmentary., Objective: To describe maternal health characteristics related to alternative lifestyles, with emphasis on body-weight status, during pregnancy and maternity periods., Methods: We compared self-reported health-related features of mothers with alternative lifestyles and conventional lifestyles during pregnancy and maternity period in the KOALA Birth Cohort Study. This cohort comprises two recruitment groups of mother-infant pairs, one with a conventional (no selection based on lifestyle, n = 2333), the other with an alternative lifestyle (selected via organic food shops, anthroposophic clinicians and midwives, anthroposophic under-five clinics, Rudolf Steiner schools and relevant magazines, n = 485). Mothers in the alternative group more frequently chose organic foods, adhered to specific living rules, practised vegetarianism and identified themselves with anthroposophy., Results: Mothers in the alternative group showed lower BMI and lower prevalence of overweight and obesity than the conventional group, before pregnancy as well as 4-5 years after delivery. This difference was partly retained after adjusting for potential confounders. Furthermore, women in the alternative group had a lower prevalence of pregnancy-related hypertension, more often started breastfeeding and gave exclusive and prolonged breastfeeding for a longer period. Finally, they smoked less often, but more often drunk alcohol during pregnancy., Conclusion: The results suggest that an alternative lifestyle is associated with favourable body weight and with several differences in other health features.

Background: Parents often fail to correctly perceive their children's weight status, but no studies have examined the association between parental weight status perception and longitudinal BMIz change (BMI standardized to a reference population) at various ages. We investigated whether parents are able to accurately perceive their child's weight status at age 5. We also investigated predictors of accurate weight status perception. Finally, we investigated the predictive value of accurate weight status perception in explaining children's longitudinal weight development up to the age of 9, in children who were overweight at the age of 5., Methods: We used longitudinal data from the KOALA Birth Cohort Study. At the child's age of 5 years, parents filled out a questionnaire regarding child and parent characteristics and their perception of their child's weight status. We calculated the children's actual weight status from parental reports of weight and height at ages 2, 5, 6, 7, 8, and 9 years. Regression analyses were used to identify factors predicting which parents accurately perceived their child's weight status. Finally, regression analyses were used to predict subsequent longitudinal BMIz change in overweight children., Results: Eighty-five percent of the parents of overweight children underestimated their child's weight status at age 5. The child's BMIz at age 2 and 5 were significant positive predictors of accurate weight status perception (vs. underestimation) in normal weight and overweight children. Accurate weight status perception was a predictor of higher future BMI in overweight children, corrected for actual BMI at baseline., Conclusions: Children of parents who accurately perceived their child's weight status had a higher BMI over time, probably making it easier for parents to correctly perceive their child's overweight. Parental awareness of the child's overweight as such may not be sufficient for subsequent weight management by the parents, implying that parents who recognize their child's overweight may not be able or willing to adequately manage the overweight.

Complement factor 3 (C3) has been identified as a novel risk factor for obesity-associated cardiometabolic diseases. Data in the literature suggest that C3 concentrations may be influenced by diet. Therefore, we investigated the associations of intake of total fat, specific fatty acids, and fat-soluble vitamin E (and individual tocopherols) and vitamin A (and its dietary precursors) with circulating C3. In a white cohort [Cohort on Diabetes and Atherosclerosis Maastricht (CODAM); n = 501; 59.4 ± 7.1 y; 61% men], associations of habitual nutrient intake (assessed by a food-frequency questionnaire) with circulating C3 were evaluated by using cross-sectional multiple linear regression analyses. Adjustments were first performed for age, sex, glucose metabolism status (i.e., impaired glucose metabolism or type 2 diabetes), and energy intake and subsequently for BMI, waist circumference, alcohol intake, smoking behavior, and season of blood collection. No associations with C3 were observed for total dietary fat intake or intake of specific fatty acids [saturated, monounsaturated, polyunsaturated, n-6 (ω-6), and n-3 (ω- 3) fatty acids], vitamin E, or individual tocopherols. We observed an inverse association with intake of provitamin A carotenoids α-carotene (in μg/d; regression coefficient β = -0.075; 95% CI: -0.140, -0.010; P = 0.025) and β-carotene (in μg/d; β = -0.021; 95% CI: -0.044, 0.002; P = 0.068) with C3 (in mg/L). In contrast, and only in women, dietary retinol intake (in μg/d) was positively associated with C3 (β = 0.116; 95% CI: 0.014, 0.218; P = 0.026; n = 196). In conclusion, these data suggest that fasting concentrations of C3 may, in a complex manner, be modifiable by variation in dietary provitamin A carotenoids and/or retinol content of the usual diet but most likely not by variations in fat composition and vitamin E content.