The Association of a Vegan Diet during Pregnancy with Maternal and Child Outcomes: A Systematic Review.

Background: With the increasing prevalence of pregnant women adhering to a vegan diet, gaining insight into their nutritional intake and its association with maternal and fetal outcomes is essential to providing recommendations and developing guidelines for general practice. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review of the available scientific literature in Medline, Embase, and Cochrane was conducted in January 2024. Results: The titles and abstracts of 2211 unique articles were screened. Only six studies were eligible for inclusion and assessed for methodological quality using the (National Institutes of Health Study Quality (NIHSQ) Assessment Tool. The intake of protein and various micronutrients was significantly lower among vegan pregnant women compared to omnivorous women. Vitamin B12 supplements seemed sufficient in optimizing maternal and umbilical cord vitamin B12 levels amongst vegan mothers. Further, women on a vegan diet less often showed excessive pregnancy weight gain. However, children from women on a vegan diet had a significantly lower birth weight than those from women on an omnivorous diet. Conclusion: So far, only a few studies, with a large diversity of (assessment of) outcomes and insufficient power, have been published on this topic, limiting our ability to make firm conclusions about the effects of a vegan diet during pregnancy on maternal and fetal outcomes.

The associations of socioeconomic position with structural brain damage and connectivity and cognitive functioning: The Maastricht Study.

BACKGROUND: Socioeconomic inequalities in cognitive impairment may partly act through structural brain damage and reduced connectivity. This study investigated the extent to which the association of early-life socioeconomic position (SEP) with later-life cognitive functioning is mediated by later-life SEP, and whether the associations of SEP with later-life cognitive functioning can be explained by structural brain damage and connectivity. METHODS: We used cross-sectional data from the Dutch population-based Maastricht Study (n = 4,839; mean age 59.2 ± 8.7 years, 49.8% women). Early-life SEP was assessed by self-reported poverty during childhood and parental education. Later-life SEP included education, occupation, and current household income. Participants underwent cognitive testing and 3-T magnetic resonance imaging to measure volumes of white matter hyperintensities, grey matter, white matter, cerebrospinal fluid, and structural connectivity. Multiple linear regression analyses tested the associations between SEP, markers of structural brain damage and connectivity, and cognitive functioning. Mediation was tested using structural equation modeling. RESULTS: Although there were direct associations between both indicators of SEP and later-life cognitive functioning, a large part of the association between early-life SEP and later-life cognitive functioning was explained by later-life SEP (72.2%). The extent to which structural brain damage or connectivity acted as mediators between SEP and cognitive functioning was small (up to 5.9%). CONCLUSIONS: We observed substantial SEP differences in later-life cognitive functioning. Associations of structural brain damage and connectivity with cognitive functioning were relatively small, and only marginally explained the SEP gradients in cognitive functioning.

Brain structure and connectivity mediate the association between lifestyle and cognition: The Maastricht Study.

Life-course exposure to risk and protective factors impacts brain macro- and micro-structure, which in turn affects cognition. The concept of brain-age gap assesses brain health by comparing an individual's neuroimaging-based predicted age with their calendar age. A higher BAG implies accelerated brain ageing and is expected to be associated with worse cognition. In this study, we comprehensively modelled mutual associations between brain health and lifestyle factors, brain age and cognition in a large, middle-aged population. For this study, cognitive test scores, lifestyle and 3T MRI data for n = 4881 participants [mean age (± SD) = 59.2 (±8.6), 50.1% male] were available from The Maastricht Study, a population-based cohort study with extensive phenotyping. Whole-brain volumes (grey matter, cerebrospinal fluid and white matter hyperintensity), cerebral microbleeds and structural white matter connectivity were calculated. Lifestyle factors were combined into an adapted LIfestyle for BRAin health weighted sum score, with higher score indicating greater dementia risk. Cognition was calculated by averaging z-scores across three cognitive domains (memory, information processing speed and executive function and attention). Brain-age gap was calculated by comparing calendar age to predictions from a neuroimaging-based multivariable regression model. Paths between LIfestyle for BRAin health tertiles, brain-age gap and cognitive function were tested using linear regression and structural equation modelling, adjusting for sociodemographic and clinical confounders. The results show that cerebrospinal fluid, grey matter, white matter hyperintensity and cerebral microbleeds best predicted brain-age gap (R 2 = 0.455, root mean squared error = 6.44). In regression analysis, higher LIfestyle for BRAin health scores (greater dementia risk) were associated with higher brain-age gap (standardized regression coefficient ß = 0.126, P < 0.001) and worse cognition (ß = -0.046, P = 0.013), while higher brain-age gap was associated with worse cognition (ß=-0.163, P < 0.001). In mediation analysis, 24.7% of the total difference in cognition between the highest and lowest LIfestyle for BRAin health tertile was mediated by brain-age gap (ß indirect = -0.049, P < 0.001; ß total = -0.198, P < 0.001) and an additional 3.8% was mediated via connectivity (ß indirect = -0.006, P < 0.001; ß total = -0.150, P < 0.001). Findings suggest that associations between health- and lifestyle-based risk/protective factors (LIfestyle for BRAin health) and cognition can be partially explained by structural brain health markers (brain-age gap) and white matter connectivity markers. Lifestyle interventions targeted at high-risk individuals in mid-to-late life may be effective in promoting and preserving cognitive function in the general public.

Longitudinal associations of plasma kynurenines and ratios with fatigue and quality of life in colorectal cancer survivors up to 12 months post-treatment.

Fatigue is prevalent in colorectal cancer (CRC) survivors, impacting their health-related quality of life (HRQoL). Inflammation-induced activation of the kynurenine pathway may play a role in cancer-related fatigue and HRQoL, but evidence is scarce. Therefore, we aimed to investigate longitudinal associations of plasma tryptophan, kynurenines, and ratios with fatigue and HRQoL in CRC survivors up to 12 months post-treatment. Repeated measurements at 6 weeks, 6 months, and 12 months post-treatment were performed in 249 stage I-III CRC survivors. Plasma tryptophan and eight kynurenines were analyzed using liquid chromatography-tandem mass spectrometry (LC/MS-MS). Fatigue and HRQoL outcomes were evaluated using validated questionnaires. Confounder-adjusted linear mixed models were conducted to analyze longitudinal associations, with false discovery rate (FDR) correction. Higher tryptophan (Trp), kynurenic acid (KA), and xanthurenic acid (XA) concentrations, as well as a higher kynurenic acid-to-quinolinic acid ratio (KA/QA), were associated with less fatigue and better functioning, while a higher kynurenine-to-tryptophan ratio (KTR) and 3-hydroxykynurenine ratio (HKr) were associated with more fatigue and worse functioning. Finally, higher KA and XA concentrations and a higher KA/QA ratio were associated with a higher overall HRQoL summary score, while a higher HKr was associated with a lower overall HRQoL summary score. In conclusion, we observed that tryptophan and several kynurenines were longitudinally associated with fatigue and HRQoL in CRC survivors up to 12 months post-treatment. Future research is needed to validate our findings and explore the potential of the kynurenine pathway as intervention target for reducing fatigue and enhancing HRQoL after CRC treatment.

Longitudinal associations of diurnal rest-activity rhythms with fatigue, insomnia, and health-related quality of life in survivors of colorectal cancer up to 5 years post-treatment.

BACKGROUND: There is a growing population of survivors of colorectal cancer (CRC). Fatigue and insomnia are common symptoms after CRC, negatively influencing health-related quality of life (HRQoL). Besides increasing physical activity and decreasing sedentary behavior, the timing and patterns of physical activity and rest over the 24-h day (i.e. diurnal rest-activity rhythms) could also play a role in alleviating these symptoms and improving HRQoL. We investigated longitudinal associations of the diurnal rest-activity rhythm (RAR) with fatigue, insomnia, and HRQoL in survivors of CRC. METHODS: In a prospective cohort study among survivors of stage I-III CRC, 5 repeated measurements were performed from 6 weeks up to 5 years post-treatment. Parameters of RAR, including mesor, amplitude, acrophase, circadian quotient, dichotomy index, and 24-h autocorrelation coefficient, were assessed by a custom MATLAB program using data from tri-axial accelerometers worn on the upper thigh for 7 consecutive days. Fatigue, insomnia, and HRQoL were measured by validated questionnaires. Confounder-adjusted linear mixed models were applied to analyze longitudinal associations of RAR with fatigue, insomnia, and HRQoL from 6 weeks until 5 years post-treatment. Additionally, intra-individual and inter-individual associations over time were separated. RESULTS: Data were available from 289 survivors of CRC. All RAR parameters except for 24-h autocorrelation increased from 6 weeks to 6 months post-treatment, after which they remained relatively stable. A higher mesor, amplitude, circadian quotient, dichotomy index, and 24-h autocorrelation were statistically significantly associated with less fatigue and better HRQoL over time. A higher amplitude and circadian quotient were associated with lower insomnia. Most of these associations appeared driven by both within-person changes over time and between-person differences in RAR parameters. No significant associations were observed for acrophase. CONCLUSIONS: In the first five years after CRC treatment, adhering to a generally more active (mesor) and consistent (24-h autocorrelation) RAR, with a pronounced peak activity (amplitude) and a marked difference between daytime and nighttime activity (dichotomy index) was found to be associated with lower fatigue, lower insomnia, and a better HRQoL. Future intervention studies are needed to investigate if restoring RAR among survivors of CRC could help to alleviate symptoms of fatigue and insomnia while enhancing their HRQoL. TRIAL REGISTRATION: EnCoRe study NL6904 ( https://www.onderzoekmetmensen.nl/ ).

Associations of between- and within-day patterns of physical activity accumulation with arterial stiffness and indices of microvascular health-Evidence from The Maastricht study.

While physical activity (PA) is understood to promote vascular health, little is known about whether the daily and weekly patterns of PA accumulation associate with vascular health. Accelerometer-derived (activPAL3) 6- or 7-day stepping was analyzed for 6430 participants in The Maastricht Study (50.4% women; 22.4% Type 2 diabetes mellitus (T2DM)). Multivariable regression models examined associations between stepping metrics (average step count, and time spent slower and faster paced stepping) with arterial stiffness (measured as carotid-femoral pulse wave velocity (cfPWV)), and several indices of microvascular health (heat-induced skin hyperemia, retinal vessel reactivity and diameter), adjusting for confounders and moderators. PA pattern metrics were added to the regression models to identify associations with vascular health beyond that of stepping metrics. Analyses were stratified by T2DM status if an interaction effect was present. Average step count and time spent faster paced stepping was associated with better vascular health, and the association was stronger in those with compared to those without T2DM. In fully adjusted models a higher step count inter-daily stability was associated with a higher (worse) cfPWV in those without T2DM (std ß = 0.04, p = 0.007) and retinal venular diameter in the whole cohort (std ß = 0.07, p = 0.002). A higher within-day variability in faster paced stepping was associated with a lower (worse) heat-induced skin hyperemia in those with T2DM (std ß = -0.31, p = 0.008). Above and beyond PA volume, the daily and weekly patterns in which PA was accumulated were additionally associated with improved macro- and microvascular health, which may have implications for the prevention of vascular disease.

Associations of 24 h time-use compositions of sitting, standing, physical activity and sleeping with optimal cardiometabolic risk and glycaemic control: The Maastricht Study.

AIMS/HYPOTHESIS: The associations of sitting, standing, physical activity and sleep with cardiometabolic health and glycaemic control markers are interrelated. We aimed to identify 24 h time-use compositions associated with optimal metabolic and glycaemic control and determine whether these varied by diabetes status. METHODS: Thigh-worn activPAL data from 2388 participants aged 40-75 years (48.7% female; mean age 60.1 [SD = 8.1] years; n=684 with type 2 diabetes) in The Maastricht Study were examined. Compositional isometric log ratios were generated from mean 24 h time use (sitting, standing, light-intensity physical activity [LPA], moderate-to-vigorous physical activity [MVPA] and sleeping) and regressed with outcomes of waist circumference, fasting plasma glucose (FPG), 2 h plasma glucose, HbA1c, the Matsuda index expressed as z scores, and with a clustered cardiometabolic risk score. Overall analyses were adjusted for demographics, smoking, dietary intake and diabetes status, and interaction by diabetes status was examined separately. The estimated difference when substituting 30 min of one behaviour with another was determined with isotemporal substitution. To identify optimal time use, all combinations of 24 h compositions possible within the study footprint (1st-99th percentile of each behaviour) were investigated to determine those cross-sectionally associated with the most-optimal outcome (top 5%) for each outcome measure. RESULTS: Compositions lower in sitting time and with greater standing time, physical activity and sleeping had the most beneficial associations with outcomes. Associations were stronger in participants with type 2 diabetes (p<0.05 for interactions), with larger estimated benefits for waist circumference, FPG and HbA1c when sitting was replaced by LPA or MVPA in those with type 2 diabetes vs the overall sample. The mean (range) optimal compositions of 24 h time use, considering all outcomes, were 6 h (range 5 h 40 min-7 h 10 min) for sitting, 5 h 10 min (4 h 10 min-6 h 10 min) for standing, 2 h 10 min (2 h-2 h 20 min) for LPA, 2 h 10 min (1 h 40 min-2 h 20 min) for MVPA and 8 h 20 min (7 h 30 min-9 h) for sleeping. CONCLUSIONS/INTERPRETATION: Shorter sitting time and more time spent standing, undergoing physical activity and sleeping are associated with preferable cardiometabolic health. The substitutions of behavioural time use were significantly stronger in their associations with glycaemic control in those with type 2 diabetes compared with those with normoglycaemic metabolism, especially when sitting time was balanced with greater physical activity.

Association of kidney function with physical performance: the Maastricht study.

BACKGROUND: Kidney failure has been associated with decreased physical capacity, although evidence regarding the physical performance of individuals with earlier stages of chronic kidney disease (CKD) remains limited. METHODS: Cross-sectional data were derived from the prospective, population-based Maastricht Study. Multivariate linear regression models were fitted to assess the association of estimated glomerular filtration rate (eGFR) and albuminuria categories with physical performance test outcomes. RESULTS: Overall, 7396 participants were included. Compared to eGFR 60-90 ml/min/1.73 m2, values < 60 ml/min/1.73 m2 were associated with significantly shorter 6-min walk distance (ß: - 13.04 m, 95% confidence intervals-CI - 19.95; - 6.13), worse timed chair rise stand test time (ß: 0.91 s, 95% CI 0.36; 1.47), lower maximal grip (ß: - 0.83 kg, 95% CI - 1.50; - 0.15) and elbow flexion (ß: - 3.64 Nm, 95% CI - 7.11; - 0.16) strength. Additionally, eGFR > 90 ml/min/1.73 m2 was linked to significantly shorter 6-min walk distance (ß: - 6.13 m, 95% CI - 9.44; - 2.82). Urinary albumin excretion > 30 mg/24 h was associated with shorter 6-min walk distance (ß: - 12.48 m, 95% CI - 18.28; - 6.68), worse timed chair rise stand test time (ß: 0.51 s, 95% CI 0.11; 1.06), lower maximal grip (ß: - 1.34 kg, 95% CI - 1.91; - 0.76) and elbow flexion strength (ß: - 3.31 Nm, 95% CI - 5.80; - 0.82). CONCLUSIONS: Reduced eGFR and higher albuminuria levels were associated with worse physical performance, especially shorter 6-min walk distance and lower muscle strength. The relationship between eGFR and physical function was non-linear, with also high eGFR values being associated with worse performance, especially in the six-minute walk test.

Retinal microvascular function and incidence and trajectories of clinically relevant depressive symptoms: the Maastricht Study.

BACKGROUND: Cerebral microvascular dysfunction may contribute to depression via disruption of brain structures involved in mood regulation, but evidence is limited. We investigated the association of retinal microvascular function, a proxy for microvascular function in the brain, with incidence and trajectories of clinically relevant depressive symptoms. METHODS: Longitudinal data are from The Maastricht Study of 5952 participants (59.9 ± 8.5 years/49.7% women) without clinically relevant depressive symptoms at baseline (2010-2017). Central retinal arteriolar equivalent and central retinal venular equivalent (CRAE and CRVE) and a composite score of flicker light-induced retinal arteriolar and venular dilation were assessed at baseline. We assessed incidence and trajectories of clinically relevant depressive symptoms (9-item Patient Health Questionnaire score ⩾10). Trajectories included continuously low prevalence (low, n = 5225 [87.8%]); early increasing, then chronic high prevalence (early-chronic, n = 157 [2.6%]); low, then increasing prevalence (late-increasing, n = 247 [4.2%]); and remitting prevalence (remitting, n = 323 [5.4%]). RESULTS: After a median follow-up of 7.0 years (range 1.0-11.0), 806 (13.5%) individuals had incident clinically relevant depressive symptoms. After full adjustment, a larger CRAE and CRVE were each associated with a lower risk of clinically relevant depressive symptoms (hazard ratios [HRs] per standard deviation [s.d.]: 0.89 [95% confidence interval (CI) 0.83-0.96] and 0.93 [0.86-0.99], respectively), while a lower flicker light-induced retinal dilation was associated with a higher risk of clinically relevant depressive symptoms (HR per s.d.: 1.10 [1.01-1.20]). Compared to the low trajectory, a larger CRAE was associated with lower odds of belonging to the early-chronic trajectory (OR: 0.83 [0.69-0.99]) and a lower flicker light-induced retinal dilation was associated with higher odds of belonging to the remitting trajectory (OR: 1.23 [1.07-1.43]). CONCLUSIONS: These findings support the hypothesis that cerebral microvascular dysfunction contributes to the development of depressive symptoms.

Tolerance development in cow's milk-allergic children receiving amino acid-based formula with synbiotics: 36-Months follow-up of a randomized controlled trial (PRESTO Study).

The objective of the present study is to assess the rates of acquired tolerance to cow's milk (CM) after 36 months in subjects who consumed amino acid-based formula with synbiotics (AAF-S) or amino acid-based formula without synbiotics (AAF) during a 1-year intervention period in early life as part of the PRESTO study (Netherlands Trial Register number NTR3725). Differences in CM tolerance development between groups were analysed using a logistic regression model. Results show that the proportion of subjects (mean [±SD] age, 3.8 ± 0.27 years) who developed CM tolerance after 36 months was similar in the group receiving AAF-S (47/60 [78%]) and in the group receiving AAF (49/66 [74%]) (p = 0.253), that is, figures comparable to natural outgrowth of CM allergy. Our data suggest that the consumption of AAF and absence of exposure to CM peptides do not slow down CM tolerance acquisition.

Dietary composition of adult eosinophilic esophagitis patients is related to disease severity.

BACKGROUND: In addition to the elimination diet, dietary composition may influence disease severity in patients with eosinophilic esophagitis (EoE) through modulation of the immune response. AIM: To explore the immunomodulatory role of nutrition before and during elimination diet in adult EoE patients. METHODS: Nutritional intake was assessed in 39 Dutch adult EoE patients participating in the Supplemental Elemental Trial (Dutch trial registry NL6014, NTR6778) using 3-day food diaries. In this randomized controlled trial, diagnosed patients received either a four-food elimination diet alone (FFED) or FFED with addition of an amino acid-based formula for 6 weeks. Multiple linear regression analyses were performed to assess associations between the intake of nutrients and food groups per 1000 kCal and peak eosinophil count/high power field (PEC), both at baseline and after 6 weeks. RESULTS: At baseline, we found a statistically significant negative (thus favorable) relationship between the intake of protein, total fat, phosphorus, zinc, vitamin B12, folate, and milk products and PEC (p < .05), while calcium (p = .058) and full-fat cheese/curd (p = .056) were borderline (favorably) significant. In contrast, total carbohydrates, prepacked fruit juice, and white bread were significantly positively (unfavorable) related to PEC (p < .05), while ultra-processed meals (p = .059) were borderline (unfavorably) significant. After dietary intervention, coffee/tea were significantly negatively (favorably) related to PEC, hummus/legumes were significantly positively (unfavorably) related with PEC, while peanuts were borderline significantly positively related (p = .058). CONCLUSION: Dietary composition may be related to inflammation in adult EoE patients. High-quality and anti-inflammatory diets may be a promising adjuvant therapy in the dietary management of EoE.

Dietary intake of dicarbonyl compounds and changes in body weight over time in a large cohort of European adults.

Dicarbonyl compounds are highly reactive precursors of advanced glycation end products (AGE), produced endogenously, present in certain foods and formed during food processing. AGE contribute to the development of adverse metabolic outcomes, but health effects of dietary dicarbonyls are largely unexplored. We investigated associations between three dietary dicarbonyl compounds, methylglyoxal (MGO), glyoxal (GO) and 3-deoxyglucosone (3-DG), and body weight changes in European adults. Dicarbonyl intakes were estimated using food composition database from 263 095 European Prospective Investigation into Cancer and Nutrition-Physical Activity, Nutrition, Alcohol, Cessation of Smoking, Eating Out of Home in Relation to Anthropometry participants with two body weight assessments (median follow-up time = 5·4 years). Associations between dicarbonyls and 5-year body-weight changes were estimated using mixed linear regression models. Stratified analyses by sex, age and baseline BMI were performed. Risk of becoming overweight/obese was assessed using multivariable-adjusted logistic regression. MGO intake was associated with 5-year body-weight gain of 0·089 kg (per 1-sd increase, 95 % CI 0·072, 0·107). 3-DG was inversely associated with body-weight change (-0·076 kg, -0·094, -0·058). No significant association was observed for GO (0·018 kg, -0·002, 0·037). In stratified analyses, GO was associated with body-weight gain among women and older participants (above median of 52·4 years). MGO was associated with higher body-weight gain among older participants. 3-DG was inversely associated with body-weight gain among younger and normal-weight participants. MGO was associated with a higher risk of becoming overweight/obese, while inverse associations were observed for 3-DG. No associations were observed for GO with overweight/obesity. Dietary dicarbonyls are inconsistently associated with body weight change among European adults. Further research is needed to clarify the role of these food components in overweight and obesity, their underlying mechanisms and potential public health implications.

Longitudinal associations of plasma kynurenines and ratios with anxiety and depression scores in colorectal cancer survivors up to 12 months post-treatment.

INTRODUCTION: Colorectal cancer (CRC) survivors often experience neuropsychological symptoms, including anxiety and depression. Mounting evidence suggests a role for the kynurenine pathway in these symptoms due to potential neuroprotective and neurotoxic roles of involved metabolites. However, evidence remains inconclusive and insufficient in cancer survivors. Thus, we aimed to explore longitudinal associations of plasma tryptophan, kynurenines, and their established ratios with anxiety and depression in CRC survivors up to 12 months post-treatment. METHODS: In 249 stage I-III CRC survivors, blood samples were collected at 6 weeks, 6 months, and 12 months post-treatment to analyze plasma concentrations of tryptophan and kynurenines using liquid-chromatography tandem-mass spectrometry (LC/MS-MS). At the same timepoints, anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS). Confounder-adjusted linear mixed models were used to analyze longitudinal associations. Sensitivity analyses with false discovery rate (FDR) correction were conducted to adjust for multiple testing. RESULTS: Higher plasma tryptophan concentrations were associated with lower depression scores (ß as change in depression score per 1 SD increase in the ln-transformed kynurenine concentration: -0.31; 95%CI: -0.56,-0.05), and higher plasma 3-hydroxyanthranilic acid concentrations with lower anxiety scores (-0.26; -0.52,-0.01). A higher 3-hydroxykynurenine ratio (HKr; the ratio of 3-hydroxykynurenine to the sum of kynurenic acid, xanthurenic acid, anthranilic acid, and 3-hydroxyanthranilic acid) was associated with higher depression scores (0.34; 0.04,0.63) and higher total anxiety and depression scores (0.53; 0.02,1.04). Overall associations appeared to be mainly driven by inter-individual associations, which were statistically significant for tryptophan with depression (-0.60; -1.12,-0.09), xanthurenic acid with total anxiety and depression (-1.04; -1.99,-0.10), anxiety (-0.51; -1.01,-0.01), and depression (-0.56; -1.08,-0.05), and kynurenic-acid-to-quinolinic-acid ratio with depression (-0.47; -0.93,-0.01). In sensitivity analyses, associations did not remain statistically significant after FDR adjustment. CONCLUSION: We observed that plasma concentrations of tryptophan, 3-hydroxyanthranilic acid, xanthurenic acid, 3-hydroxykynurenine ratio, and kynurenic-acid-to-quinolinic-acid ratio tended to be longitudinally associated with anxiety and depression in CRC survivors up to 12 months post-treatment. Future studies are warranted to further elucidate the association of plasma kynurenines with anxiety and depression.

Disease severity-based subgrouping of type 2 diabetes does not parallel differences in quality of life: the Maastricht Study.

AIMS/HYPOTHESIS: Type 2 diabetes is a highly heterogeneous disease for which new subgroups ('clusters') have been proposed based on disease severity: moderate age-related diabetes (MARD), moderate obesity-related diabetes (MOD), severe insulin-deficient diabetes (SIDD) and severe insulin-resistant diabetes (SIRD). It is unknown how disease severity is reflected in terms of quality of life in these clusters. Therefore, we aimed to investigate the cluster characteristics and cluster-wise evolution of quality of life in the previously defined clusters of type 2 diabetes. METHODS: We included individuals with type 2 diabetes from the Maastricht Study, who were allocated to clusters based on a nearest centroid approach. We used logistic regression to evaluate the cluster-wise association with diabetes-related complications. We plotted the evolution of HbA1c levels over time and used Kaplan-Meier curves and Cox regression to evaluate the cluster-wise time to reach adequate glycaemic control. Quality of life based on the Short Form 36 (SF-36) was also plotted over time and adjusted for age and sex using generalised estimating equations. The follow-up time was 7 years. Analyses were performed separately for people with newly diagnosed and already diagnosed type 2 diabetes. RESULTS: We included 127 newly diagnosed and 585 already diagnosed individuals. Already diagnosed people in the SIDD cluster were less likely to reach glycaemic control than people in the other clusters, with an HR compared with MARD of 0.31 (95% CI 0.22, 0.43). There were few differences in the mental component score of the SF-36 in both newly and already diagnosed individuals. In both groups, the MARD cluster had a higher physical component score of the SF-36 than the other clusters, and the MOD cluster scored similarly to the SIDD and SIRD clusters. CONCLUSIONS/INTERPRETATION: Disease severity suggested by the clusters of type 2 diabetes is not entirely reflected in quality of life. In particular, the MOD cluster does not appear to be moderate in terms of quality of life. Use of the suggested cluster names in practice should be carefully considered, as the non-neutral nomenclature may affect disease perception in individuals with type 2 diabetes and their healthcare providers.

Socioeconomic inequalities in health-related functioning among people with type 2 Diabetes: longitudinal analyses in the Maastricht Study.

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 HbA1c-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, HbA1c-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 HbA1c-levels and lifestyle patterns, more attention is needed for socioeconomic differences in health-related functioning for people living with T2DM.

Thinner inner retinal layers are associated with lower cognitive performance, lower brain volume, and altered white matter network structure-The Maastricht Study.

INTRODUCTION: The retina may provide non-invasive, scalable biomarkers for monitoring cerebral neurodegeneration. METHODS: We used cross-sectional data from The Maastricht study (n = 3436; mean age 59.3 years; 48% men; and 21% with type 2 diabetes [the latter oversampled by design]). We evaluated associations of retinal nerve fiber layer, ganglion cell layer, and inner plexiform layer thicknesses with cognitive performance and magnetic resonance imaging indices (global grey and white matter volume, hippocampal volume, whole brain node degree, global efficiency, clustering coefficient, and local efficiency). RESULTS: After adjustment, lower thicknesses of most inner retinal layers were significantly associated with worse cognitive performance, lower grey and white matter volume, lower hippocampal volume, and worse brain white matter network structure assessed from lower whole brain node degree, lower global efficiency, higher clustering coefficient, and higher local efficiency. DISCUSSION: The retina may provide biomarkers that are informative of cerebral neurodegenerative changes in the pathobiology of dementia.

Relation of the kynurenine pathway with normal age: A systematic review.

BACKGROUND: The kynurenine pathway (KP) is gaining more attention as a common pathway involved in age-related conditions. However, which changes in the KP occur due to normal ageing is still largely unclear. The aim of this systematic review was to summarize the available evidence for associations of KP metabolites with age. METHODS: We used an broad search strategy and included studies up to October 2023. RESULTS: Out of 8795 hits, 55 studies were eligible for the systematic review. These studies suggest that blood levels of tryptophan decrease with age, while blood and cerebrospinal fluid levels of kynurenine and its ratio with tryptophan increase. Studies investigating associations between cerebrospinal fluid and blood levels of kynurenic acid and quinolinic acid with age reported either positive or non-significant findings. However, there is a large heterogeneity across studies. Additionally, most studies were cross-sectional, and only few studies investigated associations with other downstream kynurenines. CONCLUSIONS: This systematic review suggests that levels of kynurenines are positively associated with age. Larger and prospective studies are needed that also investigate a more comprehensive panel of KP metabolites and changes during the life-course.

Longitudinal associations of circadian eating patterns with sleep quality, fatigue and inflammation in colorectal cancer survivors up to 24 months post-treatment.

Fatigue and insomnia, potentially induced by inflammation, are distressing symptoms experienced by colorectal cancer (CRC) survivors. Emerging evidence suggests that besides the nutritional quality and quantity, also the timing, frequency and regularity of dietary intake (chrono-nutrition) could be important for alleviating these symptoms. We investigated longitudinal associations of circadian eating patterns with sleep quality, fatigue and inflammation in CRC survivors. In a prospective cohort of 459 stage I-III CRC survivors, four repeated measurements were performed between 6 weeks and 24 months post-treatment. Chrono-nutrition variables included meal energy contribution, frequency (a maximum of six meals could be reported each day), irregularity and time window (TW) of energetic intake, operationalised based on 7-d dietary records. Outcomes included sleep quality, fatigue and plasma concentrations of inflammatory markers. Longitudinal associations of chrono-nutrition variables with outcomes from 6 weeks until 24 months post-treatment were analysed by confounder-adjusted linear mixed models, including hybrid models to disentangle intra-individual changes from inter-individual differences over time. An hour longer TW of energetic intake between individuals was associated with less fatigue (ß: -6·1; 95 % CI (-8·8, -3·3)) and insomnia (ß: -4·8; 95 % CI (-7·4, -2·1)). A higher meal frequency of on average 0·6 meals/d between individuals was associated with less fatigue (ß: -3·7; 95 % CI (-6·6, -0·8)). An hour increase in TW of energetic intake within individuals was associated with less insomnia (ß: -3·0; 95 % CI (-5·2, -0·8)) and inflammation (ß: -0·1; 95 % CI (-0·1, 0·0)). Our results suggest that longer TWs of energetic intake and higher meal frequencies may be associated with less fatigue, insomnia and inflammation among CRC survivors. Future studies with larger contrasts in chrono-nutrition variables are needed to confirm these findings.

Associations of an individual's need for cognition with structural brain damage and cognitive functioning/impairment: cross-sectional population-based study.

BACKGROUND: High cognitive activity possibly reduces the risk of cognitive decline and dementia. AIMS: To investigate associations between an individual's need to engage in cognitively stimulating activities (need for cognition, NFC) and structural brain damage and cognitive functioning in the Dutch general population with and without existing cognitive impairment. METHOD: Cross-sectional data were used from the population-based cohort of the Maastricht Study. NFC was measured using the Need For Cognition Scale. Cognitive functioning was tested in three domains: verbal memory, information processing speed, and executive functioning and attention. Values 1.5 s.d. below the mean were defined as cognitive impairment. Standardised volumes of white matter hyperintensities (WMH), cerebrospinal fluid (CSF) and presence of cerebral small vessel disease (CSVD) were derived from 3T magnetic resonance imaging. Multiple linear and binary logistic regression analyses were used adjusted for demographic, somatic and lifestyle factors. RESULTS: Participants (n = 4209; mean age 59.06 years, s.d. = 8.58; 50.1% women) with higher NFC scores had higher overall cognition scores (B = 0.21, 95% CI 0.17-0.26, P < 0.001) and lower odds for CSVD (OR = 0.74, 95% CI 0.60-0.91, P = 0.005) and cognitive impairment (OR = 0.60, 95% CI 0.48-0.76, P < 0.001) after adjustment for demographic, somatic and lifestyle factors. The association between NFC score and cognitive functioning was similar for individuals with and without prevalent cognitive impairment. We found no significant association between NFC and WMH or CSF volumes. CONCLUSIONS: A high need to engage in cognitively stimulating activities is associated with better cognitive functioning and less presence of CSVD and cognitive impairment. This suggests that, in middle-aged individuals, motivation to engage in cognitively stimulating activities may be an opportunity to improve brain health.

Longitudinal associations of macronutrient and micronutrient intake with plasma kynurenines in colorectal cancer survivors up to 12 months posttreatment.

BACKGROUND: The tryptophan-kynurenine pathway is increasingly recognized to play a role in health-related quality of life (HRQoL) after cancer. Because tryptophan is an essential amino acid, and vitamins and minerals act as enzymatic cofactors in the tryptophan-kynurenine pathway, a link between diet and kynurenines is plausible. OBJECTIVES: This study aimed to investigate the longitudinal associations of macronutrient and micronutrient intake with metabolites of the kynurenine pathway in colorectal cancer (CRC) survivors up to 12 mo posttreatment. METHODS: In a prospective cohort of stage I-III CRC survivors (n = 247), repeated measurements were performed at 6 wk, 6 mo, and 12 mo posttreatment. Macronutrient and micronutrient intake was measured by 7-d dietary records. Plasma concentrations of tryptophan and kynurenines were analyzed using liquid chromatography tandem mass spectrometry (LC/MS-MS). Longitudinal associations were analyzed using linear mixed models adjusted for sociodemographic, clinical, and lifestyle factors. RESULTS: After adjustment for multiple testing, higher total protein intake was positively associated with kynurenic acid (KA) (ß as standard deviation [SD] change in KA concentration per 1 SD increase in total protein intake: 0.12; 95% CI: 0.04, 0.20), xanthurenic acid (XA) (standardized ß: 0.22; 95% CI: 0.11, 0.33), 3-hydroxyanthranilic acid (HAA) (standardized ß: 0.15; 95% CI: 0.04, 0.27) concentrations, and the kynurenic acid-to-quinolinic acid ratio (KA/QA) (standardized ß: 0.12; 95% CI: 0.02,0.22). In contrast, higher total carbohydrate intake was associated with lower XA concentrations (standardized ß: -0.18; 95% CI: -0.30, -0.07), a lower KA/QA (standardized ß: -0.23; 95% CI: -0.34, -0.13), and a higher kynurenine-to-tryptophan ratio (KTR) (standardized ß: 0.20; 95% CI: 0.10, 0.30). Higher fiber intake was associated with a higher KA/QA (standardized ß: 0.11; 95% CI: 0.02, 0.21) and a lower KTR (standardized ß: -0.12; 95% CI: -0.20, -0.03). Higher total fat intake was also associated with higher tryptophan (Trp) concentrations (standardized ß: 0.18; 95% CI: 0.06, 0.30) and a lower KTR (standardized ß: -0.13; 95% CI: -0.22, -0.03). For micronutrients, positive associations were observed for zinc with XA (standardized ß: 0.13; 95% CI: 0.04, 0.21) and 3-hydroxykynurenine (HK) (standardized ß: 0.12; 95% CI: 0.03, 0.20) concentrations and for magnesium with KA/QA (standardized ß: 0.24; 95% CI: 0.13, 0.36). CONCLUSIONS: Our findings show that intake of several macronutrients and micronutrients is associated with some metabolites of the kynurenine pathway in CRC survivors up to 12 mo posttreatment. These results may be relevant for enhancing HRQoL after cancer through potential diet-induced changes in kynurenines. Further studies are necessary to confirm our findings.