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Background Several studies have investigated the relationship between dietary patterns and the risk of bladder cancer (BC) in different regions including Europe, the United States, and Asia, with no conclusive evidence. A meta-analysis was undertaken to integrate the most recent information on the relationship between a data-driven Western diet (WD), the Mediterranean diet (MD), and dietary-inflammatory-index (DII) and the risk of BC. Method We looked for published research into the relationship between dietary patterns and the incidence of BC in the PubMed/Medline, Cochrane Library, Web of Science, and Scopus databases up until February 2021. Using a multivariate random-effects model, we compared the highest and lowest categories of WD, MD and DII patterns and provided the relative risk (RR) or odds ratios (OR) and 95 percent confidence intervals (CIs) for the relevant relationships. Results The analysis comprised 12 papers that were found to be suitable after scanning the databases. Both case–control (OR 0.73, 95% CI: 0.52, 0.94; I 2  = 49.9%, n  = 2) and cohort studies (RR 0.93, 95% CI: 0.88, 0.97; I 2  = 63%, n  = 4) found a substantial inverse association between MD and BC. In addition, although cohort studies (RR 1.53, 95% CI 1.37, 1.70; I 2  = 0%, n  = 2) showed a direct association between WD and BC, case–control studies (OR 1.33, 95% CI 0.81, 1.88; I 2  = 68.5%, n  = 2) did not. In cohort studies, we found no significant association between DII and BC (RR 1.02, 95% CI 0.93, 1.12; I 2  = 38.5%, n  = 2). In case–control studies, however, a strong direct association between DII and BC was discovered (RR 2.04, 95% CI 1.23, 2.85; I 2  = 0%, n  = 2). Conclusion The current meta-analysis showed that MD and WD have protective and detrimental effects on BC risk, respectively. No significant association between DII and the risk of BC was observed. More research is still needed to confirm the findings. Additional study is warranted to better understand the etiological mechanisms underlying how different dietary patterns affect BC. Trial registration Protocol registration number: CRD42020155353. Database for protocol registration: The international prospective register of systematic reviews database ( PROSPERO ). Data of registration: August 2020.

Aims/hypothesisBiomarkers of endothelial dysfunction and low-grade inflammation are important in the pathogenesis of CVD and can potentially be modified by physical activity and sedentary behaviour. Effects of physical activity on biomarkers of endothelial dysfunction may be especially prominent in type 2 diabetes.MethodsIn the population-based Maastricht Study (n = 2363, 51.5% male, 28.3% type 2 diabetes, 15.1% prediabetes [defined as impaired glucose tolerance and impaired fasting glucose]), we determined biomarkers of endothelial dysfunction and low-grade inflammation, and combined z scores were calculated. Physical activity and sedentary behaviour were measured by activPAL. Linear regression analyses were used with adjustment for demographic, lifestyle and cardiovascular risk factors.ResultsThe association between total, light, moderate-to-vigorous and vigorous intensity physical activity and sedentary time on the one hand and biomarkers of endothelial dysfunction on the other were generally significant and were consistently stronger in prediabetes and type 2 diabetes as compared with normal glucose metabolism status (p for interaction <0.05). Associations between physical activity and sedentary behaviour on the one hand and low-grade inflammation on the other were also significant and were similar in individuals with and without (pre)diabetes (p for interaction >0.05).Conclusions/interpretationPhysical activity and sedentary behaviour are associated with biomarkers of endothelial dysfunction and low-grade inflammation. For biomarkers of endothelial dysfunction, associations between physical activity and sedentary behaviour were consistently stronger in (pre)diabetes than in normal glucose metabolism. Whether increasing physical activity or decreasing sedentary time can positively influence biomarkers of endothelial dysfunction in individuals with prediabetes and type 2 diabetes requires further study.

Recent epidemiological studies have shown varying associations between coffee consumption and bladder cancer (BC). This research aims to elucidate the association between coffee consumption and BC risk by bringing together worldwide cohort studies on this topic. Coffee consumption in relation to BC risk was examined by pooling individual data from 12 cohort studies, comprising of 2601 cases out of 501,604 participants. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs), were obtained using multilevel Weibull regression models. Furthermore, dose–response relationships were examined using generalized least squares regression models. The association between coffee consumption and BC risk showed interaction with sex ( P -interaction < 0.001) and smoking ( P -interaction = 0.001). Therefore, analyses were stratified by sex and smoking. After adjustment for potential confounders, an increased BC risk was shown for high (> 500 ml/day, equivalent to > 4 cups/day) coffee consumption compared to never consumers among male smokers (current smokers: HR = 1.75, 95% CI 1.27–2.42, P -trend = 0.002; former smokers: HR = 1.44, 95% CI 1.12–1.85, P -trend = 0.001). In addition, dose–response analyses, in male smokers also showed an increased BC risk for coffee consumption of more than 500 ml/day (4 cups/day), with the risk of one cup (125 ml) increment as 1.07 (95% CI 1.06–1.08). This research suggests that positive associations between coffee consumption and BC among male smokers but not never smokers and females. The inconsistent results between sexes and the absence of an association in never smokers indicate that the associations found among male smokers is unlikely to be causal and is possibly caused by residual confounding of smoking.

Aims/hypothesisDepression is twice as common in individuals with type 2 diabetes as in the general population. However, it remains unclear whether hyperglycaemia and insulin resistance are directly involved in the aetiology of depression. Therefore, we investigated the association of markers of hyperglycaemia and insulin resistance, measured as continuous variables, with incident depressive symptoms over 4 years of follow-up.MethodsWe used data from the longitudinal population-based Maastricht Study (n = 2848; mean age 59.9 ± 8.1 years, 48.8% women, 265 incident depression cases, 10,932 person-years of follow-up). We assessed hyperglycaemia by fasting and 2 h post-load OGTT glucose levels, HbA1c and skin autofluorescence (reflecting AGEs) at baseline. We used the Matsuda insulin sensitivity index and HOMA-IR to calculate insulin resistance at baseline. Depressive symptoms (nine-item Patient Health Questionnaire score ≥10) were assessed at baseline and annually over 4 years. We used Cox regression analyses, and adjusted for demographic, cardiovascular and lifestyle risk factors.ResultsFasting plasma glucose, 2 h post-load glucose and HbA1c levels were associated with an increased risk for incident depressive symptoms after full adjustment (HR 1.20 [95% CI 1.08, 1.33]; HR 1.25 [1.08, 1.44]; and HR 1.22 [1.09, 1.37] per SD, respectively), while skin autofluorescence, insulin sensitivity index and HOMA-IR were not (HR 0.99 [0.86, 1.13]; HR 1.02 [0.85, 1.25]; and HR 0.93 [0.81, 1.08], per SD, respectively).Conclusions/interpretationThe observed temporal association between hyperglycaemia and incident depressive symptoms in this study supports the presence of a mechanistic link between hyperglycaemia and the development of depressive symptoms.

The purpose of this study is to determine if healthier neighbourhood food environments are associated with healthier diet quality. This was a cross-sectional study using linear regression models to analyse data from the Maastricht Study. Diet quality was assessed using data collected with a FFQ to calculate the Dutch Healthy Diet (DHD). A buffer zone encompassing a 1000 m radius was created around each participant home address. The Food Environment Healthiness Index (FEHI) was calculated using a Kernel density analysis within the buffers of available food outlets. The association between the FEHI and the DHD score was analysed and adjusted for socio-economic variables. The region of Maastricht including the surrounding food retailers in the Netherlands. 7367 subjects aged 40-75 years in the south of the Netherlands. No relationship was identified between either the FEHI (B = 0·62; 95 % CI = -2·54, 3·78) or individual food outlets, such as fast food (B = -0·07; 95 % CI = -0·20, 0·07) and diet quality. Similar null findings using the FEHI were identified at the 500 m (B = 0·95; 95 % CI = -0·85, 2·75) and 1500 m (B = 1·57; 95 % CI = -3·30, 6·44) buffer. There was also no association between the food environment and individual items of the DHD including fruits, vegetables and sugar-sweetened beverages. The food environment in the Maastricht area appeared marginally unhealthy, but the differences in the food environment were not related to the quality of food that participants reported as intake.

Aims/hypothesisStudies investigating associations between kynurenines and cognitive function have generally been small, restricted to clinical samples or have found inconsistent results, and associations in the general adult population, and in individuals with type 2 diabetes in particular, are not clear. Therefore, the aim of the present study was to investigate cross-sectional associations between plasma kynurenines and cognitive function in a cohort of middle-aged participants with normal glucose metabolism, prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes.MethodsPlasma kynurenines were quantified in 2358 participants aged 61 ± 8 years. Cross-sectional associations of kynurenines with cognitive impairment and cognitive domain scores were investigated using logistic, multiple linear and restricted cubic spline regression analyses adjusted for several confounders.ResultsEffect modification by glucose metabolism status was found for several associations with cognitive impairment, hence analyses were stratified. In individuals with prediabetes, 3-hydroxykynurenine (OR per SD 0.59 [95% CI 0.37, 0.94]) and 3-hydroxyanthranilic acid (0.67 [0.47, 0.96]) were associated with lower odds of cognitive impairment after full adjustment. In individuals with type 2 diabetes, kynurenine (0.80 [0.66, 0.98]), 3-hydroxykynurenine (0.82 [0.68, 0.99]), kynurenic acid (0.81 [0.68, 0.96]), xanthurenic acid (0.73 [0.61, 0.87]) and 3-hydroxyanthranilic acid (0.73 [0.60, 0.87]) were all associated with lower odds of cognitive impairment. Kynurenic acid (β per SD 0.07 [95% CI 0.02, 0.13]) and xanthurenic acid (0.06 [0.01, 0.11]) were also associated with better executive function/attention. No associations were observed in individuals with normal glucose metabolism.Conclusions/interpretationSeveral kynurenines were cross-sectionally associated with lower odds of cognitive impairment and better cognitive functioning in type 2 diabetes, while less widespread associations were seen in prediabetes. Low levels of kynurenines might be involved in the pathway of type 2 diabetes and cognitive decline but this needs further studies.

AimsCVD is the main cause of morbidity and mortality in individuals with diabetes. It is currently unclear whether daily glucose variability contributes to CVD. Therefore, we investigated whether glucose variability is associated with arterial measures that are considered important in CVD pathogenesis.MethodsWe included participants of The Maastricht Study, an observational population-based cohort, who underwent at least 48 h of continuous glucose monitoring (CGM) (n = 853; age: 59.9 ± 8.6 years; 49% women, 23% type 2 diabetes). We studied the cross-sectional associations of two glucose variability indices (CGM-assessed SD [SDCGM] and CGM-assessed CV [CVCGM]) and time in range (TIRCGM) with carotid–femoral pulse wave velocity (cf-PWV), carotid distensibility coefficient, carotid intima–media thickness, ankle–brachial index and circumferential wall stress via multiple linear regression.ResultsHigher SDCGM was associated with higher cf-PWV after adjusting for demographics, cardiovascular risk factors and lifestyle factors (regression coefficient [B] per 1 mmol/l SDCGM [and corresponding 95% CI]: 0.413 m/s [0.147, 0.679], p = 0.002). In the model additionally adjusted for CGM-assessed mean sensor glucose (MSGCGM), SDCGM and MSGCGM contributed similarly to cf-PWV (respective standardised regression coefficients [st.βs] and 95% CIs of 0.065 [−0.018, 0.167], p = 0.160; and 0.059 [−0.043, 0.164], p = 0.272). In the fully adjusted models, both higher CVCGM (B [95% CI] per 10% CVCGM: 0.303 m/s [0.046, 0.559], p = 0.021) and lower TIRCGM (B [95% CI] per 10% TIRCGM: −0.145 m/s [−0.252, −0.038] p = 0.008) were statistically significantly associated with higher cf-PWV. Such consistent associations were not observed for the other arterial measures.ConclusionsOur findings show that greater daily glucose variability and lower TIRCGM are associated with greater aortic stiffness (cf-PWV) but not with other arterial measures. If corroborated in prospective studies, these results support the development of therapeutic agents that target both daily glucose variability and TIRCGM to prevent CVD.

Background Type 2 diabetes mellitus (T2DM) is a common chronic disease that disproportionally affects disadvantaged groups. People with a low socioeconomic position (SEP) have increased risk of T2DM and people with a low SEP and T2DM have higher HbA 1c -levels compared to people with T2DM and high SEP. The aim of this study is to analyze longitudinal socioeconomic differences in health-related functioning in people with T2DM. Methods Longitudinal data from 1,537 participants of The Maastricht Study with T2DM were used (32.6% female, mean (SD) age 62.9 (7.7) years). SEP was determined by baseline measures of education, occupation and income. Health-related functioning (physical, mental and social) was measured with the Short-Form Health Survey and the Impact on Participation and Autonomy survey (all scored from 0 to 100). Associations of SEP and health-related functioning were studied annually over a 10-year period (median (IQR) 7.0 (5.0) years, baseline 2010–2018) using linear mixed methods adjusting for demographics, HbA 1c -levels and lifestyle factors. Results Participants with a low SEP had significantly worse health-related functioning compared to those with a high SEP. For example, participants with low income had lower scores for physical (-4.49[CI -5.77;-3.21]), mental (-2.61[-3.78,-1.44]) and social functioning (-9.76[-12.30;-7.23]) compared to participants with high income on a scale from 0 to 100. In addition, participants with a low education significantly declined more over time in mental (score for interaction education with time − 0.23[-0.37;-0.09]) and social functioning (-0.44[-0.77;-0.11]) compared to participants with high education. Participants with low and intermediate incomes significantly declined more over time in physical functioning (-0.17 [-0.34, -0.01 and − 0.18 [-0.36, 0.00]) compared to participants with high income. Conclusions Among people with T2DM, those with a lower SEP had worse health-related functioning in general than people with a higher SEP. Additionally, people with T2DM and low education developed poorer mental and social functioning over time compared to people with T2DM and high education. People with T2DM and low or intermediate income declined more in physical functioning over time than those with high incomes. In addition to HbA 1c -levels and lifestyle patterns, more attention is needed for socioeconomic differences in health-related functioning for people living with T2DM.

Purpose The role of diet in bladder carcinogenesis has yet to be established. To date most studies have investigated dietary components individually, rather than as dietary patterns, which may provide stronger evidence for any influence of diet on bladder carcinogenesis. The Mediterranean diet has been associated with many health benefits, but few studies have investigated its association with bladder cancer risk. Methods We investigated the potential association between the Mediterranean diet score (MDS) and risk of developing bladder cancer by pooling 13 prospective cohort studies included in the BLadder cancer Epidemiology and Nutritional Determinants (BLEND) study and applying a Cox regression analysis. Results Dietary data from 646,222 study participants, including 3639 incident bladder cancer cases, were analysed. We observed an inverse association between Mediterranean diet and bladder cancer risk (HR high 0.85 [95% CI 0.77, 0.93]). When stratifying the results on non-muscle-invasive or muscle-invasive disease or sex the association remained similar and the HR estimate was consistently below 1.00 both for medium and high adherence to the Mediterranean diet. A consistent association was observed when disregarding fat or alcohol intake. Conclusion We found evidence that adherence to the Mediterranean diet was associated with reduced risk of developing bladder cancer, suggesting a positive effect of the diet as a whole and not just one component.