Publications by authors named "Simone J P M Eussen"

55 Publications

Greater daily glucose variability and lower time in range assessed with continuous glucose monitoring are associated with greater aortic stiffness: The Maastricht Study.

Diabetologia 2021 May 15. Epub 2021 May 15.

CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, the Netherlands.

Aims: CVD 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.

Methods: We 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 [SD] and CGM-assessed CV [CV]) and time in range (TIR) 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.

Results: Higher SD was associated with higher cf-PWV after adjusting for demographics, cardiovascular risk factors and lifestyle factors (regression coefficient [B] per 1 mmol/l SD [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 (MSG), SD and MSG 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 CV (B [95% CI] per 10% CV: 0.303 m/s [0.046, 0.559], p = 0.021) and lower TIR (B [95% CI] per 10% TIR: -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.

Conclusions: Our findings show that greater daily glucose variability and lower TIR 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 TIR to prevent CVD.
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http://dx.doi.org/10.1007/s00125-021-05474-8DOI Listing
May 2021

Sex differences in the association of prediabetes and type 2 diabetes with microvascular complications and function: The Maastricht Study.

Cardiovasc Diabetol 2021 05 7;20(1):102. Epub 2021 May 7.

Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Background: Women with type 2 diabetes are disproportionally affected by macrovascular complications; we here investigated whether this is also the case for microvascular complications and retinal microvascular measures.

Methods: In a population-based cohort study of individuals aged 40-75 years (n = 3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated sex-specific associations, and differences therein, of (pre)diabetes (reference: normal glucose metabolism), and of continuous measures of glycemia with microvascular complications and retinal measures (nephropathy, sensory neuropathy, and retinal arteriolar and venular diameters and dilatation). Sex differences were analyzed using regression models with interaction terms (i.e. sex-by- (pre)diabetes and sex-by-glycemia) and were adjusted for potential confounders.

Results: Men with type 2 diabetes (but not those with prediabetes) compared to men with normal glucose metabolism, (and men with higher levels of glycemia), had significantly higher prevalences of nephropathy (odds ratio: 1.58 95% CI (1.01;2.46)) and sensory neuropathy (odds ratio: 2.46 (1.67;3.63)), larger retinal arteriolar diameters (difference: 4.29 µm (1.22;7.36)) and less retinal arteriolar dilatation (difference: - 0.74% (- 1.22; - 0.25)). In women, these associations were numerically in the same direction, but generally not statistically significant (odds ratios: 1.71 (0.90;3.25) and 1.22 (0.75;1.98); differences: 0.29 µm (- 3.50;4.07) and: - 0.52% (- 1.11;0.08), respectively). Interaction analyses revealed no consistent pattern of sex differences in the associations of either prediabetes or type 2 diabetes or glycemia with microvascular complications or retinal measures. The prevalence of advanced-stage complications was too low for evaluation.

Conclusions: Our findings show that women with type 2 diabetes are not disproportionately affected by early microvascular complications.
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http://dx.doi.org/10.1186/s12933-021-01290-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106227PMC
May 2021

Carotid stiffness is associated with retinal microvascular dysfunction-The Maastricht study.

Microcirculation 2021 Apr 27:e12702. Epub 2021 Apr 27.

CARIM School for Cardiovascular Diseases, Maastricht University (UM), Maastricht, The Netherlands.

Objective: This study investigated whether arterial stiffening is a determinant of subtle retinal microvascular changes that precede diabetic retinopathy.

Research Design And Methods: This study used cross-sectional data from the Maastricht Study, a type 2 diabetes-enriched population-based cohort study. We used multivariable linear regression analysis to investigate, in individuals without and with type 2 diabetes, the associations of carotid distensibility coefficient and carotid-femoral pulse wave velocity with retinal microvascular diameters and flicker light-induced dilation and adjusted for cardiovascular and lifestyle risk factors.

Results: The retinal microvascular diameter study population consisted of N = 2434 participants (51.4% men, mean ± SD age 59.8 ± 8.1 years, and 28.1% type 2 diabetes). No measures of arterial stiffness were significantly associated with microvascular diameters. Greater carotid distensibility coefficient (i.e., lower carotid stiffness) was significantly associated with greater retinal arteriolar flicker light-induced dilation (per standard deviation, standardized beta [95% CI] 0.06 [0.00; 0.12]) and non-significantly, but directionally similarly, associated with greater retinal venular flicker light-induced dilation (0.04 [-0.02; 0.10]). Carotid-femoral pulse wave velocity (i.e., aortic stiffness) was not associated with retinal microvascular flicker light-induced dilation. The associations between carotid distensibility coefficient and retinal arteriolar and venular flicker light-induced dilation were two- to threefold stronger in individuals with type 2 diabetes than in those without.

Conclusion: In this population-based study greater carotid, but not aortic, stiffness was associated with worse retinal flicker light-induced dilation and this association was stronger in individuals with type 2 diabetes. Hence, carotid stiffness may be a determinant of retinal microvascular dysfunction.
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http://dx.doi.org/10.1111/micc.12702DOI Listing
April 2021

Associations of Dietary Patterns with Incident Depression: The Maastricht Study.

Nutrients 2021 Mar 23;13(3). Epub 2021 Mar 23.

CARIM School for Cardiovascular Diseases, Maastricht University, 6200 MD Maastricht, The Netherlands.

Our aim was to assess the association between defined dietary patterns and incident depressive symptoms. We used data from The Maastricht Study, a population-based cohort study ( = 2646, mean (SD) age 59.9 (8.0) years, 49.5% women; 15,188 person-years of follow-up). Level of adherence to the Dutch Healthy Diet (DHD), Mediterranean Diet, and Dietary Approaches To Stop Hypertension (DASH) were derived from a validated Food Frequency Questionnaire. Depressive symptoms were assessed at baseline and annually over seven-year-follow-up (using the 9-item Patient Health Questionnaire). We used Cox proportional hazards regression analyses to assess the association between dietary patterns and depressive symptoms. One standard deviation (SD) higher adherence in the DHD and DASH was associated with a lower hazard ratio (HR) of depressive symptoms with HRs (95%CI) of 0.78 (0.69-0.89) and 0.87 (0.77-0.98), respectively, after adjustment for sociodemographic and cardiovascular risk factors. After further adjustment for lifestyle factors, the HR per one SD higher DHD was 0.83 (0.73-0.96), whereas adherence to Mediterranean and DASH diets was not associated with incident depressive symptoms. Higher adherence to the DHD lowered risk of incident depressive symptoms. Adherence to healthy diet could be an effective non-pharmacological preventive measure to reduce the incidence of depression.
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http://dx.doi.org/10.3390/nu13031034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004955PMC
March 2021

Pilot Clinical Trial of Time-Restricted Eating in Patients with Metabolic Syndrome.

Nutrients 2021 Jan 24;13(2). Epub 2021 Jan 24.

Division of Cardiovascular Medicine, University of California San Diego, La Jolla, CA 92037, USA.

Metabolic syndrome (MetS) and erratic eating patterns are associated with circadian rhythm disruption which contributes to an increased cardiometabolic risks. Restricting eating period (time-restricted eating, TRE) can restore robust circadian rhythms and improve cardiometabolic health. We describe a protocol of the Time-Restricted Eating on Metabolic and Neuroendocrine homeostasis, Inflammation, and Oxidative Stress (TREMNIOS) pilot clinical trial in Polish adult patients with MetS and eating period of ≥14 h/day. The study aims to test the feasibility of TRE intervention and methodology for evaluating its efficacy for improving metabolic, neuroendocrine, inflammatory, oxidative stress and cardiac biomarkers, and daily rhythms of behavior for such population. Participants will apply 10-h TRE over a 12-week monitored intervention followed by a 12-week self-directed intervention. Changes in eating window, body weight and composition, biomarkers, and rhythms of behavior will be evaluated. Dietary intake, sleep, activity and wellbeing will be monitored with the myCircadianClock application and questionnaires. Adherence to TRE defined as the proportion of days recorded with app during the monitored intervention in which participants satisfied 10-h TRE is the primary outcome. TREMNIOS will also provide an exploratory framework to depict post-TRE changes in cardiometabolic outcomes and behavior rhythms. This protocol extends previous TRE-related protocols by targeting European population with diagnosed MetS and including long-term intervention, validated tools for monitoring dietary intake and adherence, and comprehensive range of biomarkers. TREMNIOS trial will lay the groundwork for a large-scale randomized controlled trial to determine TRE efficacy for improving cardiometabolic health in MetS population.
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http://dx.doi.org/10.3390/nu13020346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7911880PMC
January 2021

Accelerometer-derived sedentary time and physical activity and the incidence of depressive symptoms - The Maastricht Study.

Psychol Med 2020 Dec 18:1-8. Epub 2020 Dec 18.

Department of Social Medicine, Maastricht University, The Netherlands.

Background: This study examined the associations between accelerometer-derived sedentary time (ST), lower intensity physical activity (LPA), higher intensity physical activity (HPA) and the incidence of depressive symptoms over 4 years of follow-up.

Methods: We included 2082 participants from The Maastricht Study (mean ± s.d. age 60.1 ± 8.0 years; 51.2% men) without depressive symptoms at baseline. ST, LPA and HPA were measured with the ActivPAL3 activity monitor. Depressive symptoms were measured annually over 4 years of follow-up with the 9-item Patient Health Questionnaire (PHQ-9). Cox regression analysis was performed to examine the associations between ST, LPA, HPA and incident depressive symptoms (PHQ-9 ⩾ 10). Analyses were adjusted for total waking time per day, age, sex, education level, type 2 diabetes mellitus, body mass index, total energy intake, smoking status and alcohol use.

Results: During 7812.81 person-years of follow-up, 203 (9.8%) participants developed incident depressive symptoms. No significant associations [Hazard Ratio (95% confidence interval)] were found between sex-specific tertiles of ST (lowest v. highest tertile) [1.13 (0.76-1.66], or HPA (highest v. lowest tertile) [1.14 (0.78-1.69)] and incident depressive symptoms. LPA (highest v. lowest tertile) was statistically significantly associated with incident depressive symptoms in women [1.98 (1.19-3.29)], but not in men (p-interaction <0.01).

Conclusions: We did not observe an association between ST or HPA and incident depressive symptoms. Lower levels of daily LPA were associated with an increased risk of incident depressive symptoms in women. Future research is needed to investigate accelerometer-derived measured physical activity and ST with incident depressive symptoms, preferably stratified by sex.
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http://dx.doi.org/10.1017/S0033291720004924DOI Listing
December 2020

The association between cardio-respiratory fitness and incident depression: The Maastricht Study.

J Affect Disord 2021 01 29;279:484-490. Epub 2020 Sep 29.

CARIM School for Cardiovascular Diseases, Maastricht University, Medical Center+, Maastricht, the Netherlands; CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, the Netherlands; Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, the Netherlands. Electronic address:

Background: Moderate to vigorous physical activity (MVPA) can help to prevent depression, but identification of the most important psycho-biological pathways involved is unclear. The improvement of cardio-respiratory fitness (CRF) in response to MVPA can vary markedly, we therefore examined the association between CRF and the incidence of depressive symptoms.

Methods: We used data from The Maastricht Study, a large population-based prospective-cohort study. CRF was estimated at baseline from a graded submaximal exercise protocol and MVPA was measured with accelerometry. Depressive symptoms were assessed using the validated Dutch version of the 9-item Patient Health Questionnaire, both at baseline and during annual follow-up over five years. Cox proportional hazards models were used.

Results: A total of 1,730 individuals without depressive symptoms at baseline were included in the analysis. During the 5-year follow-up, n = 166 (9.6%) of individuals developed depressive symptoms. Compared to individuals with a low CRF, those with a moderate-to-high CRF had a significantly lower risk of developing depressive symptoms, independent of MVPA (medium CRF: HR = 0.49 (95%CI = 0.33-0.72); high CRF: HR = 0.48 (95% CI = 0.30-0.75). These associations were adjusted for age, sex, level of education, diabetes status, smoking status, alcohol use, energy intake, waist circumferences and antidepressant medications.

Limitations: PHQ-9 is a validated screening instrument, but it is not a diagnostic tool of depression.

Conclusions: Higher CRF was strongly associated with a lower risk of incident depressive symptoms over 5-year follow-up, independent of the level of MVPA at baseline, suggesting that interventions aimed at improving CRF could reduce the risk of depression.
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http://dx.doi.org/10.1016/j.jad.2020.09.090DOI Listing
January 2021

Association of the Amount and Pattern of Physical Activity With Arterial Stiffness: The Maastricht Study.

J Am Heart Assoc 2020 10 15;9(20):e017502. Epub 2020 Oct 15.

CAPHRI Care and Public Health Research Institute Maastricht University Maastricht the Netherlands.

Background Arterial stiffness is an independent risk factor for cardiovascular disease and can be beneficially influenced by physical activity. However, it is not clear how an individual's physical activity pattern over a week is associated with arterial stiffness. Therefore, we examined the associations of the amount and pattern of higher intensity physical activity with arterial stiffness. Methods and Results Data from the Maastricht Study (n=1699; mean age: 60±8 years, 49.4% women, 26.9% type 2 diabetes mellitus) were used. Arterial stiffness was assessed by carotid-to-femoral pulse wave velocity and carotid distensibility. The amount (continuous variable as h/wk) and pattern (categorical variable) of higher intensity physical activity were assessed with the activPAL3. Activity groups were: inactive (<75 min/wk), insufficiently active (75-150 min/wk), weekend warrior (>150 min/wk in ≤2 sessions), and regularly active (>150 min/wk in ≥3 sessions). In the fully adjusted model (adjusted for demographic, lifestyle, and cardiovascular risk factors), higher intensity physical activity was associated with lower carotid-to-femoral pulse wave velocity (amount: β = -0.05, 95% CI, -0.09 to -0.01; insufficiently active: β = -0.33, 95% CI, -0.55 to -0.11; weekend warrior: β = -0.38, 95% CI, -0.64 to -0.12; and regularly active: β = -0.46, 95% CI, -0.71 to -0.21 [reference: inactive]). These associations were stronger in those with type 2 diabetes mellitus. There was no statistically significant association between higher intensity physical activity with carotid distensibility. Conclusions Participating in higher intensity physical activity was associated with lower carotid-to-femoral pulse wave velocity, but there was no difference between the regularly actives and the weekend warriors. From the perspective of arterial stiffness, engaging higher intensity physical activity, regardless of the weekly pattern, may be an important strategy to reduce the risk of cardiovascular disease, particularly in individuals with type 2 diabetes mellitus.
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http://dx.doi.org/10.1161/JAHA.120.017502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763372PMC
October 2020

The association of hyperglycaemia and insulin resistance with incident depressive symptoms over 4 years of follow-up: The Maastricht Study.

Diabetologia 2020 11 5;63(11):2315-2328. Epub 2020 Aug 5.

Department of Psychiatry and Neuropsychology, Maastricht University Medical Center (MUMC+), Maastricht, the Netherlands.

Aims/hypothesis: Depression 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.

Methods: We 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, HbA 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.

Results: Fasting plasma glucose, 2 h post-load glucose and HbA 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/interpretation: The 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. Graphical abstract.
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http://dx.doi.org/10.1007/s00125-020-05247-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527373PMC
November 2020

Association of Markers of Microvascular Dysfunction With Prevalent and Incident Depressive Symptoms: The Maastricht Study.

Hypertension 2020 08 8;76(2):342-349. Epub 2020 Jul 8.

Department of Internal Medicine (A.F.J.G., M.J.M.v.A., C.D.A.S., B.M.S., N.C.S., R.M.A.H., C.J.H.v.d.K., T.T.v.S., M.T.S., A.J.H.M.H.), Maastricht University Medical Center (MUMC+), the Netherlands.

The etiology of late-life depression (LLD) is still poorly understood. Microvascular dysfunction (MVD) has been suggested to play a role in the etiology of LLD, but direct evidence of this association is scarce. The aim of this study was to investigate whether direct and indirect markers of early microvascular dysfunction are associated with prevalent and incident LLD in the population-based Maastricht Study cohort. We measured microvascular dysfunction at baseline by use of flicker light-induced retinal vessel dilation response (Dynamic Vessel Analyzer), heat-induced skin hyperemic response (laser- Doppler flowmetry), and plasma markers of endothelial dysfunction (endothelial dysfunction; sICAM-1 [soluble intercellular adhesion molecule-1], sVCAM-1 [soluble vascular adhesion molecule-1], sE-selectin [soluble E-selectin], and vWF [Von Willebrand Factor]). Depressive symptoms were assessed with the 9-item Patient Health Questionnaire (PHQ-9) at baseline and annually over 4 years of follow-up (n=3029; mean age 59.6±8.2 years, 49.5% were women, n=132 and n=251 with prevalent and incident depressive symptoms [PHQ-9≥10]). We used logistic, negative binominal and Cox regression analyses, and adjusted for demographic, cardiovascular, and lifestyle factors. Retinal venular dilatation and plasma markers of endothelial dysfunction were associated with the more prevalent depressive symptoms after full adjustment (PHQ-9 score, RR, 1.05 [1.00-1.11] and RR 1.06 [1.01-1.11], respectively). Retinal venular dilatation was also associated with prevalent depressive symptoms (PHQ-9≥10; odds ratio, 1.42 [1.09-1.84]), after full adjustment. Retinal arteriolar dilatation and plasma markers of endothelial dysfunction were associated with incident depressive symptoms (PHQ-9≥10; HR, 1.23 [1.04-1.46] and HR, 1.19 [1.05-1.35]), after full adjustment. These findings support the concept that microvascular dysfunction in the retina, and plasma markers of endothelial dysfunction is involved in the etiology of LLD and might help in finding additional targets for the prevention and treatment of LLD.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.15260DOI Listing
August 2020

Blood pressure variability and microvascular dysfunction: the Maastricht Study.

J Hypertens 2020 08;38(8):1541-1550

Department of Internal Medicine, Maastricht University Medical Centre.

Background: Microvascular dysfunction (MVD) contributes to stroke, dementia, depression, retinopathy and chronic kidney disease. However, the determinants of MVD are incompletely understood. Greater blood pressure variability (BPV) may be one such determinant.

Methods And Results: We used cross-sectional data of The Maastricht Study (n = 2773, age 59.9 years; 51.9% men) to investigate whether greater very short- to mid-term BPV is associated with various MVD measures. We standardized and averaged within-visit, 24-h and 7-day BPV into a systolic and a diastolic BPV composite score. MVD measures included a composite score of MRI cerebral small vessel disease (CSVD) features (total brain parenchymal volume, white matter hyperintensity volume, lacunar infarcts and cerebral microbleeds), a composite score of flicker light-induced retinal arteriolar and venular dilation response, albuminuria, heat-induced skin hyperemia and a composite score of plasma biomarkers of MVD (sICAM-1, sVCAM-1, sE-selectin and von Willebrand Factor). We used linear regression adjusted for age, sex, glucose metabolism status, mean 24-h systolic or DBP, cardiovascular risk factors and antihypertensive medication. We found that higher systolic and diastolic BPV composite scores (per SD) were associated with higher albuminuria [higher ratio, 1.04 (95% CI 1.00-1.08) and 1.07 (1.03-1.11), respectively], but not with other measures of MVD tested.

Conclusion: Greater systolic and diastolic BPV was associated with higher albuminuria, but not with CSVD features, flicker light-induced retinal arteriolar and venular dilation response, heat-induced skin hyperemia and plasma biomarkers of MVD. This suggests that the microvasculature of the kidneys is most vulnerable to the detrimental effects of greater BPV.
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http://dx.doi.org/10.1097/HJH.0000000000002444DOI Listing
August 2020

Associations of 24-Hour Urinary Sodium and Potassium Excretion with Cardiac Biomarkers: The Maastricht Study.

J Nutr 2020 06;150(6):1413-1424

Division of Nephrology, Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, Netherlands.

Background: It is a matter of debate whether sodium and potassium intake are associated with heart disease. Further, the mechanisms underlying associations of sodium and potassium intake with cardiac events, if any, are not fully understood.

Objectives: We examined cross-sectional associations of 24-h urinary sodium excretion (UNaE) and potassium excretion (UKE), as estimates of their intakes, with high-sensitivity cardiac troponins T (hs-cTnT) and I (hs-cTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP), which are markers of cardiomyocyte injury and cardiac dysfunction.

Methods: We included 2961 participants from the population-based Maastricht Study (mean ± SD age 59.8 ± 8.2 y, 51.9% men), who completed the baseline survey between November 2010 and September 2013. Associations were examined with restricted cubic spline linear regression analyses and ordinary linear regression analyses, adjusted for demographics, lifestyle, and cardiovascular disease (CVD) risk factors.

Results: Median [IQR] 24-h UNaE and UKE were 3.7 [2.8-4.7] g/24 h and 3.0 [2.4-3.6] g/24 h, respectively. After adjustment for potential confounders, 24-h UNaE was not associated with hs-cTnT, hs-cTnI, and NT-proBNP concentrations. In contrast, after adjustment for potential confounders, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. For example, as compared with the third/median quintile of 24-h UKE (range: 2.8-3.2 g/24 h), participants in the first quintile (range: 0.5-2.3 g/24 h) had 1.05 (95% CI: 0.99, 1.11) times higher hs-cTnT and 1.14 (95% CI: 1.03, 1.26) times higher NT-proBNP. Associations were similar after further adjustment for estimated glomerular filtration rate, albuminuria, blood pressure, and serum potassium.

Conclusions: Twenty-four-hour UNaE was not associated with the studied cardiac biomarkers. In contrast, lower 24-h UKE was nonlinearly associated with higher hs-cTnT and NT-proBNP. This finding supports recommendations to increase potassium intake in the general population. In addition, it suggests that cardiac dysfunction and/or cardiomyocyte injury may underlie previously reported associations of lower potassium intake with CVD mortality.
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http://dx.doi.org/10.1093/jn/nxaa080DOI Listing
June 2020

Associations of Arterial Stiffness With Cognitive Performance, and the Role of Microvascular Dysfunction: The Maastricht Study.

Hypertension 2020 06 10;75(6):1607-1614. Epub 2020 Apr 10.

From the CARIM School for Cardiovascular Diseases (S.P.R., C.D.A.S., A.J.H.M.H., C.G.S., A.A.K., R.M.A.H., P.C.D., S.J.P.M.E., K.D.R., M.T.S., T.T.v.S.).

The mechanisms underlying cognitive impairment are incompletely understood but may include arterial stiffness and microvascular dysfunction. In the population-based Maastricht Study, we investigated the association between arterial stiffness and cognitive performance, and whether any such association was mediated by microvascular dysfunction. We included cross-sectional data of 2544 participants (age, 59.7 years; 51.0% men; 26.0% type 2 diabetes mellitus). We used carotid-femoral pulse wave velocity and carotid distensibility coefficient as measures of aortic and carotid stiffness, respectively. We calculated a composite score of microvascular dysfunction based on magnetic resonance imaging features of cerebral small vessel disease, flicker light-induced retinal arteriolar and venular dilation response, albuminuria, and plasma biomarkers of microvascular dysfunction (sICAM-1 [soluble intercellular adhesion molecule-1], sVCAM-1 [soluble vascular adhesion molecule-1], sE-selectin [soluble E-selectin], and vWF [von Willebrand factor]). Cognitive domains assessed were memory, processing speed, and executive function. A cognitive function score was calculated as the average of these domains. Higher aortic stiffness (per m/s) was associated with lower cognitive function (β, -0.018 SD [95% CI, -0.036 to -0.000]) independent of age, sex, education, and cardiovascular risk factors, but higher carotid stiffness was not. Higher aortic stiffness (per m/s) was associated with a higher microvascular dysfunction score (β, 0.034 SD [95% CI, 0.014 to 0.053]), and a higher microvascular dysfunction score (per SD) was associated with lower cognitive function (β, -0.089 SD [95% CI, -0.124 to -0.053]). Microvascular dysfunction significantly explained 16.2% of the total effect of aortic stiffness on cognitive function. The present study showed that aortic stiffness, but not carotid stiffness, is independently associated with worse cognitive performance, and that this association is in part explained by microvascular dysfunction.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.14307DOI Listing
June 2020

Metabolic profiling of tissue-specific insulin resistance in human obesity: results from the Diogenes study and the Maastricht Study.

Int J Obes (Lond) 2020 06 17;44(6):1376-1386. Epub 2020 Mar 17.

Department of Epidemiology, Maastricht University, Maastricht, The Netherlands.

Background: Recent evidence indicates that insulin resistance (IR) in obesity may develop independently in different organs, representing different etiologies toward type 2 diabetes and other cardiometabolic diseases. The aim of this study was to investigate whether IR in the liver and IR in skeletal muscle are associated with distinct metabolic profiles.

Methods: This study includes baseline data from 634 adults with overweight or obesity (BMI ≥ 27 kg/m) (≤65 years; 63% women) without diabetes of the European Diogenes Study. Hepatic insulin resistance index (HIRI) and muscle insulin sensitivity index (MISI), were derived from a five-point OGTT. At baseline 17 serum metabolites were identified and quantified by nuclear-magnetic-resonance spectroscopy. Linear mixed model analyses (adjusting for center, sex, body mass index (BMI), waist-to-hip ratio) were used to associate HIRI and MISI with these metabolites. In an independent sample of 540 participants without diabetes (BMI ≥ 27 kg/m; 40-65 years; 46% women) of the Maastricht Study, an observational prospective population-based cohort study, 11 plasma metabolites and a seven-point OGTT were available for validation.

Results: Both HIRI and MISI were associated with higher levels of valine, isoleucine, oxo-isovaleric acid, alanine, lactate, and triglycerides, and lower levels of glycine (all p < 0.05). HIRI was also associated with higher levels of leucine, hydroxyisobutyrate, tyrosine, proline, creatine, and n-acetyl and lower levels of acetoacetate and 3-OH-butyrate (all p < 0.05). Except for valine, these results were replicated for all available metabolites in the Maastricht Study.

Conclusions: In persons with obesity without diabetes, both liver and muscle IR show a circulating metabolic profile of elevated (branched-chain) amino acids, lactate, and triglycerides, and lower glycine levels, but only liver IR associates with lower ketone body levels and elevated ketogenic amino acids in circulation, suggestive of decreased ketogenesis. This knowledge might enhance developments of more targeted tissue-specific interventions to prevent progression to more severe disease stages.
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http://dx.doi.org/10.1038/s41366-020-0565-zDOI Listing
June 2020

Higher levels of daily physical activity are associated with better skin microvascular function in type 2 diabetes-The Maastricht Study.

Microcirculation 2020 05 10;27(4):e12611. Epub 2020 Mar 10.

CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.

Objective: Physical activity may provide a means for the prevention of cardiovascular disease via improving microvascular function. Therefore, this study investigated whether physical activity is associated with skin and retinal microvascular function.

Methods: In The Maastricht Study, a population-based cohort study enriched with type 2 diabetes (n = 1298, 47.3% women, aged 60.2 ± 8.1 years, 29.5% type 2 diabetes), we studied whether accelerometer-assessed physical activity and sedentary time associate with skin and retinal microvascular function. Associations were studied by linear regression and adjusted for major cardiovascular risk factors. In addition, we investigated whether associations were stronger in type 2 diabetes.

Results: In individuals with type 2 diabetes, total physical activity and higher-intensity physical activity were independently associated with greater heat-induced skin hyperemia (regression coefficients per hour), respectively, 10 (95% CI: 1; 18) and 36 perfusion units (14; 58). In individuals without type 2 diabetes, total physical activity and higher-intensity physical activity were not associated with heat-induced skin hyperemia. No associations with retinal arteriolar %-dilation were identified.

Conclusion: Higher levels of total and higher-intensity physical activity were associated with greater skin microvascular vasodilation in individuals with, but not in those without, type 2 diabetes.
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http://dx.doi.org/10.1111/micc.12611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317394PMC
May 2020

Evaluating the Validity of a Food Frequency Questionnaire in Comparison with a 7-Day Dietary Record for Measuring Dietary Intake in a Population of Survivors of Colorectal Cancer.

J Acad Nutr Diet 2020 02 3;120(2):245-257. Epub 2019 Dec 3.

Background: Food frequency questionnaires (FFQs) are a commonly used method to assess dietary intake in epidemiological studies. It is important to evaluate the validity of FFQs in the population of interest.

Objective: To evaluate the validity of an FFQ for measuring dietary intake in survivors of colorectal cancer (CRC), relative to a 7-day dietary record.

Design: Dietary intake was assessed 1 year after the end of CRC treatment. Participants first completed a 7-day dietary record and 2 weeks later a 253-item FFQ that measured intake in the preceding month.

Participants/setting: Data were used from a subsample of participants (n=100) enrolled in an ongoing prospective study (EnCoRe study) in the Netherlands, from 2015 to 2018.

Main Outcome Measures: Estimated intakes of total energy, 19 nutrients, and 20 food groups as well as scoring adherence to the dietary recommendations of the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) were compared between both dietary assessment methods.

Statistical Analyses Performed: Means and standard deviations, Spearman rank correlations corrected for within-person variation and total energy, and κ agreement between quintiles were assessed.

Results: The median Spearman correlation corrected for within-person variation for nutrients and total energy was 0.60. Correlations >0.50 were found for 15 of 19 nutrients, with highest agreement for vitamin B-12 (0.74), polysaccharides (0.75), and alcohol (0.91). On average, 73% (range=60% to 84%) of participants were classified into the exact same or adjacent nutrient quintile. The median Spearman correlation corrected for within-person variation for food groups was 0.62. Correlations >0.50 were found for 17 of 20 food groups, with highest agreement for cereals and cereal products (0.96), fish (0.96), and potatoes (0.99). The Spearman correlation between total scores of the WCRF/AICR dietary recommendations was 0.53.

Conclusions: Relative to a 7-day dietary record, the validity of an FFQ for measuring dietary intake among survivors of CRC appeared moderate to good for most nutrients and food groups.
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http://dx.doi.org/10.1016/j.jand.2019.09.008DOI Listing
February 2020

Adverse differences in cardiometabolic risk factor levels between individuals with pre-diabetes and normal glucose metabolism are more pronounced in women than in men: the Maastricht Study.

BMJ Open Diabetes Res Care 2019 15;7(1):e000787. Epub 2019 Nov 15.

Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, The Netherlands.

Objective: To investigate whether adverse differences in levels of cardiovascular risk factors in women than men, already established when comparing individuals with and without diabetes, are also present before type 2 diabetes onset.

Research Design And Methods: In a population-based cohort study of individuals aged 40-75 years (n=3410; 49% women, 29% type 2 diabetes (oversampled by design)), we estimated associations with cardiometabolic and lifestyle risk factors of (1) pre-diabetes and type 2 diabetes (reference category: normal glucose metabolism) and (2) among non-diabetic individuals, of continuous levels of hemoglobin A1c (HbA1c). Age-adjusted sex differences were analyzed using linear and logistic regression models with sex interaction terms.

Results: In pre-diabetes, adverse differences in cardiometabolic risk factors were greater in women than men for systolic blood pressure (difference, 3.02 mm Hg; 95% CI:-0.26 to 6.30), high-density lipoprotein (HDL) cholesterol (difference, -0.10 mmol/L; 95% CI: -0.18 to -0.02), total-to-HDL cholesterol ratio (difference, 0.22; 95% CI: -0.01 to 0.44), triglycerides (ratio: 1.11; 95% CI: 1.01 to 1.22), and inflammation markers Z-score (ratio: 1.18; 95% CI: 0.98 to 1.41). In type 2 diabetes, these sex differences were similar in direction, and of greater magnitude. Additionally, HbA1c among non-diabetic individuals was more strongly associated with several cardiometabolic risk factors in women than men: per one per cent point increase, systolic blood pressure (difference, 3.58 mm Hg; 95% CI: -0.03 to 7.19), diastolic blood pressure (difference, 2.10 mm Hg; 95% CI: -0.02 to 4.23), HDL cholesterol (difference, -0.09 mmol/L; 95% CI: -0.19 to 0.00), and low-density lipoprotein cholesterol (difference, 0.26 mmol/L; 95% CI: 0.05 to 0.47). With regard to lifestyle risk factors, no consistent pattern was observed.

Conclusion: Our results are consistent with the concept that the more adverse changes in cardiometabolic risk factors in women (than men) arise as a continuous process before the onset of type 2 diabetes.
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http://dx.doi.org/10.1136/bmjdrc-2019-000787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6861068PMC
September 2020

The oral glucose tolerance test-derived incremental glucose peak is associated with greater arterial stiffness and maladaptive arterial remodeling: The Maastricht Study.

Cardiovasc Diabetol 2019 11 14;18(1):152. Epub 2019 Nov 14.

Department of Internal Medicine, Maastricht University Medical Center+, Maastricht, The Netherlands.

Background: Daily glucose variability may contribute to vascular complication development irrespective of mean glucose values. The incremental glucose peak (IGP) during an oral glucose tolerance test (OGTT) can be used as a proxy of glucose variability. We investigated the association of IGP with arterial stiffness, arterial remodeling, and microvascular function, independent of HbA and other confounders.

Methods: IGP was calculated as the peak minus baseline plasma glucose value during a seven-point OGTT in 2758 participants (age: 60 ± 8 years; 48% women) of The Maastricht Study, an observational population-based cohort. We assessed the cross-sectional associations between IGP and arterial stiffness (carotid-femoral pulse wave velocity [cf-PWV], carotid distensibility coefficient [carDC]), arterial remodeling (carotid intima-media thickness [cIMT]; mean [CWS] and pulsatile [CWS] circumferential wall stress), and microvascular function (retinal arteriolar average dilatation; heat-induced skin hyperemia) via multiple linear regression with adjustment for age, sex, HbA, cardiovascular risk factors, lifestyle factors, and medication use.

Results: Higher IGP was independently associated with higher cf-PWV (regression coefficient [B]: 0.054 m/s [0.020; 0.089]) and with higher CWS (B: 0.227 kPa [0.008; 0.446]). IGP was not independently associated with carDC (B: - 0.026 10/kPa [- 0.112; 0.060]), cIMT (B: - 2.745 µm [- 5.736; 0.245]), CWS (B: 0.108 kPa [- 0.054; 0.270]), retinal arteriolar average dilatation (B: - 0.022% [- 0.087; 0.043]), or heat-induced skin hyperemia (B: - 1.380% [- 22.273; 19.513]).

Conclusions: IGP was independently associated with aortic stiffness and maladaptive carotid remodeling, but not with carotid stiffness, cIMT, and microvascular function measures. Future studies should investigate whether glucose variability is associated with cardiovascular disease.
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http://dx.doi.org/10.1186/s12933-019-0950-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857146PMC
November 2019

Subcutaneous Adipose Tissue and Systemic Inflammation Are Associated With Peripheral but Not Hepatic Insulin Resistance in Humans.

Diabetes 2019 12 6;68(12):2247-2258. Epub 2019 Sep 6.

Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands

Obesity-related insulin resistance (IR) may develop in multiple organs, representing various etiologies for cardiometabolic diseases. We identified abdominal subcutaneous adipose tissue (ScAT) transcriptome profiles in liver or muscle IR by means of RNA sequencing in overweight or obese participants of the Diet, Obesity, and Genes (DiOGenes) (NCT00390637, ClinicalTrials.gov) cohort ( = 368). Tissue-specific IR phenotypes were derived from a 5-point oral glucose tolerance test. Hepatic and muscle IR were characterized by distinct abdominal ScAT transcriptome profiles. Genes related to extracellular remodeling were upregulated in individuals with primarily hepatic IR, while genes related to inflammation were upregulated in individuals with primarily muscle IR. In line with this, in two independent cohorts, the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) ( = 325) and the Maastricht Study ( = 685), an increased systemic low-grade inflammation profile was specifically related to muscle IR but not to liver IR. We propose that increased ScAT inflammatory gene expression may translate into an increased systemic inflammatory profile, linking ScAT inflammation to the muscle IR phenotype. These distinct IR phenotypes may provide leads for more personalized prevention of cardiometabolic diseases.
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http://dx.doi.org/10.2337/db19-0560DOI Listing
December 2019

Association of artificially sweetened and sugar-sweetened soft drinks with β-cell function, insulin sensitivity, and type 2 diabetes: the Maastricht Study.

Eur J Nutr 2020 Jun 5;59(4):1717-1727. Epub 2019 Sep 5.

Department of Epidemiology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.

Purpose: Artificially sweetened and sugar-sweetened beverage consumptions have both been reported to be associated with type 2 diabetes mellitus (T2D) risk. The aim of the current study was to investigate the potential underlying associations with dynamic pancreatic β-cell function (BCF) and insulin sensitivity.

Methods: We evaluated cross-sectional associations in 2240 individuals (mean ± SD age 59.6 ± 8.18, 49.4% male, 21.9% T2D) participating in a diabetes-enriched population-based cohort. Artificially sweetened and sugar-sweetened soft drinks and juice consumption were assessed by a food-frequency questionnaire. Glucose metabolism status, insulin sensitivity, and BCF were measured by a seven-point oral glucose tolerance test. Regression analyses were performed to assess associations of artificially and sugar-sweetened beverage consumption with measures of glucose homeostasis. Associations were adjusted for potential confounders, and additionally with and without total energy intake and BMI, as these variables could be mediators.

Results: Moderate consumption of artificially sweetened soft drink was associated with lower β-cell glucose sensitivity [standardized beta (95% CI), - 0.06 (- 0.11, - 0.02)], total insulin secretion [β - 0.06 (- 0.10, - 0.02)], and with lower β-cell rate sensitivity [odds ratio (95% CI), 1.29 (1.03, 1.62)] compared to abstainers. Daily artificially sweetened soft drink consumption was associated with lower β-cell glucose sensitivity [β - 0.05 (- 0.09, 0.00)], and total insulin secretion [β - 0.05 - 0.09, - 0.01)] compared to abstainers.

Conclusions: Moderate and daily consumption of artificially sweetened soft drinks was associated with lower BCF, but not with insulin sensitivity. No evidence was found for associations of sugar-sweetened soft drink and juice consumption with BCF or insulin sensitivity in this middle-aged population. Prospective studies are warranted to further investigate the associations of artificially and sugar-sweetened beverage consumption with non-fasting insulin sensitivity and multiple BCF aspects.
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http://dx.doi.org/10.1007/s00394-019-02026-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230048PMC
June 2020

Vitamin B12 Intake From Animal Foods, Biomarkers, and Health Aspects.

Front Nutr 2019 28;6:93. Epub 2019 Jun 28.

Department of Epidemiology, CARIM School for Cardiovascular Diseases Maastricht University, Maastricht, Netherlands.

The EAT-Lancet commission recently suggested that transformation to healthy diets by 2050 will require a reduction of at least 50% in consumption of foods such as red meat and sugar, and a doubling in the global consumption of fruits, vegetables, nuts, and legumes. A diet rich in plant-based foods and with fewer animal source foods confers both improved health and environmental benefits. Notably, the risk of vitamin B12 deficiency increases when consuming a diet low in animal products. Humans are dependent on animal foods such as dairy products, meat, fish and eggs. Vitamin B12 deficiency is common worldwide, especially in populations with low consumption of animal foods because of low socioeconomic status, ethical reasons, or because of their lifestyle (i.e., vegans). According to the European Food Safety Authoroty, the recommended adequate intake of vitamin B12 is 4.0 μg/d for adults, and vitamin B12 requirements are higher during pregnancy and lactation. Infants and children from deficient mothers and elderly people are at risk for vitamin B12 deficiency. Diagnosis of vitamin B12 deficiency is hampered by low specificity of available biomarkers, and there is no consensus yet regarding the optimal definition of low vitamin B12 status. In general, a combination of at least two biomarkers is recommended. Therefore, this review presents an overview of vitamin B12 biochemistry and its biomarkers. We further summarize current recommendations of vitamin B12 intake, and evidence on the associations of vitamin B12 intake from different nutrient-dense animal foods with vitamin B12 status markers. Finally, potential consequences of low vitamin B12 status on different health outcomes for pregnant women, infants and elderly are presented.
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http://dx.doi.org/10.3389/fnut.2019.00093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6611390PMC
June 2019

Intakes of Vitamin B-12 from Dairy Food, Meat, and Fish and Shellfish Are Independently and Positively Associated with Vitamin B-12 Biomarker Status in Pregnant Dutch Women.

J Nutr 2019 01;149(1):131-138

Departments of Epidemiology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.

Background: The effect of vitamin B-12 from different animal foods on vitamin B-12 biomarker status has not previously been evaluated in pregnant women.

Objective: We examined the association of vitamin B-12 intake from dairy, meat, fish (including shellfish), and eggs with circulating concentrations of vitamin B-12 biomarkers and with the presence of vitamin B-12 deficiency in 1266 pregnant women participating in the KOALA Birth Cohort Study.

Methods: Blood samples were collected in weeks 34-36 of pregnancy, and vitamin B-12 intake from foods and supplements was estimated with a semiquantitative food-frequency questionnaire (FFQ). Total vitamin B-12, holotranscobalamin (holoTC), and methylmalonic acid (MMA) were determined in plasma. Vitamin B-12 deficiency was defined as holoTC <35 pmol/L and MMA >0.45 μmol/L. Associations were evaluated with linear and logistic regression analyses, adjusting for potential confounders.

Results: Significant dose-response relations were observed between vitamin B-12 intake from dairy, meat, and fish and plasma vitamin B-12, holoTC, and MMA [P-trend for (shell)fish with MMA = 0.002; P-trend for dairy, meat, and fish with all other markers < 0.001]. The OR (95% CI) of vitamin B-12 deficiency in the third compared with the first tertile of dairy-derived vitamin B-12 was 0.13 (0.04, 0.49), and the ORs for vitamin B-12 from meat and fish were 0.33 (0.11, 0.97) and 0.25 (0.08, 0.82), respectively. Egg-derived vitamin B-12 was only associated with holoTC. Additional analyses showed that self-defined vegetarians and FFQ-defined lacto-ovo-vegetarians had lower median total dietary vitamin B-12 intake and considerably worse vitamin B-12 biomarker status than omnivores and pescatarians.

Conclusions: In pregnant Dutch women, higher intakes of vitamin B-12 from dairy, meat, and fish were positively associated with vitamin B-12 status, suggesting that dairy, meat, and fish are good sources of bioactive vitamin B-12 in pregnancy. Nevertheless, for (lacto-)vegetarians, vitamin B-12 supplementation is recommended.
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http://dx.doi.org/10.1093/jn/nxy233DOI Listing
January 2019

Consumption of dairy products in relation to the presence of clinical knee osteoarthritis: The Maastricht Study.

Eur J Nutr 2019 Oct 21;58(7):2693-2704. Epub 2018 Sep 21.

Department of Epidemiology, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands.

Purpose: Observational studies showed inverse associations between milk consumption and knee osteoarthritis (knee OA). There is lack of information on the role of specific dairy product categories. We explored the association between dairy consumption and the presence of knee osteoarthritis in 3010 individuals aged 40-75 years participating in The Maastricht Study.

Methods: The presence of knee OA was defined according to a slightly modified version of the American College of Rheumatology (ACR) clinical classification criteria. Data on dairy consumption were appraised by a 253-item FFQ covering 47 dairy products with categorization on fat content, fermentation or dairy type. Multivariable logistic regression analyses were performed to estimate odd ratios (ORs) and 95% confidence intervals (95%CI), while correcting for relevant factors.

Results: 427 (14%) participants were classified as having knee OA. Significant inverse associations were observed between the presence of knee OA and intake of full-fat dairy and Dutch, primarily semi-hard, cheese, with OR for the highest compared to the lowest tertile of intake of 0.68 (95%CI 0.50-0.92) for full-fat dairy, and 0.75 (95%CI 0.56-0.99) for Dutch cheese. No significant associations were found for other dairy product categories.

Conclusion: In this Dutch population, higher intake of full-fat dairy and Dutch cheese, but not milk, was cross-sectionally associated with the lower presence of knee OA. Prospective studies need to assess the relationship between dairy consumption, and in particular semi-hard cheeses, with incident knee OA.
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http://dx.doi.org/10.1007/s00394-018-1818-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6768906PMC
October 2019

Efficacy of Nutritional Intervention in Elderly After Hip Fracture: A Multicenter Randomized Controlled Trial.

J Gerontol A Biol Sci Med Sci 2018 09;73(10):1429-1437

Department of Epidemiology, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, The Netherlands.

Background: Malnutrition after hip fracture is associated with increased rehabilitation time, complications, and mortality. We assessed the effect of intensive 3 month nutritional intervention in elderly after hip fracture on length of stay (LOS).

Methods: Open-label, randomized controlled trial. Exclusion criteria: age < 55 years, bone disease, life expectancy < 1 year, bedridden, using oral nutritional supplements (ONS) before hospitalization, and cognitive impairment. Intervention: weekly dietetic consultation, energy-protein-enriched diet, and ONS (400 mL per day) for 3 months. Control: usual nutritional care. Primary outcome: total LOS in hospital and rehabilitation clinic, including readmissions over 6 months (Cox regression adjusted for confounders); hazard ratio (HR) < 1.0 reflects longer LOS in the intervention group. Secondary outcomes: nutritional and functional status, cognition, quality of life, postoperative complications (6 months); subsequent fractures and all-cause mortality (1 and 5 years). Effect modification by baseline nutritional status was also tested.

Results: One hundred fifty-two patients were randomized (73 intervention, 79 control). Median total LOS was 34.0 days (range 4-185 days) in the intervention group versus control 35.5 days (3-183 days; plogrank = .80; adjusted hazard ratio (adjHR): 0.98; 95% CI: 0.68-1.41). Hospital LOS: 12.0 days (4-56 days) versus 11.0 days (3-115 days; p = .19; adjHR: 0.75; 95% CI: 0.53-1.06) and LOS in rehabilitation clinics: 19.5 days (0-174 days) versus 18.5 days (0-168 days; p = .82; adjHR: 1.04; 95% CI: 0.73-1.48). The intervention improved nutritional intake/status at 3, but not at 6 months, and did not affect any other outcome. No difference in intervention effect between malnourished and well-nourished patients was found.

Conclusions: Intensive nutritional intervention after hip fracture improved nutritional intake and status, but not LOS or clinical outcomes. Paradigms underlying nutritional intervention in elderly after hip fracture may have to be reconsidered.
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http://dx.doi.org/10.1093/gerona/gly030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132112PMC
September 2018

Which is more important for cardiometabolic health: sedentary time, higher intensity physical activity or cardiorespiratory fitness? The Maastricht Study.

Diabetologia 2018 12 10;61(12):2561-2569. Epub 2018 Sep 10.

CAPHRI Care and Public Health Research Institute, Maastricht University, Maastricht, the Netherlands.

Aims/hypotheses: Our aim was to examine the independent and combined (cross-sectional) associations of sedentary time (ST), higher intensity physical activity (HPA) and cardiorespiratory fitness (CRF) with metabolic syndrome and diabetes status.

Methods: In 1933 adults (aged 40-75 years) ST and HPA (surrogate measure for moderate to vigorous physical activity) were measured with the activPAL3. CRF was assessed by submaximal cycle-ergometer testing. Metabolic syndrome was defined according to the Adult Treatment Panel (ATP) III guidelines. Diabetes status (normal, prediabetes [i.e. impaired glucose tolerance and/or impaired fasting glucose] or type 2 diabetes) was determined from OGTT. (Multinomial) logistic regression analyses were used to calculate likelihood for the metabolic syndrome, prediabetes and type 2 diabetes according to ST, HPA and CRF separately and combinations of ST-CRF and HPA-CRF.

Results: Higher ST, lower HPA and lower CRF were associated with greater odds for the metabolic syndrome and type 2 diabetes independently of each other. Compared with individuals with high CRF and high HPA (CRF-HPA), odds for the metabolic syndrome and type 2 diabetes were higher in groups with a lower CRF regardless of HPA. Individuals with low CRF and low HPA (CRF-HPA) had a particularly high odds for the metabolic syndrome (OR 5.73 [95% CI 3.84, 8.56]) and type 2 diabetes (OR 6.42 [95% CI 3.95, 10.45]). Similarly, compared with those with high CRF and low ST (CRF-ST), those with medium or low CRF had higher odds for the metabolic syndrome, prediabetes and type 2 diabetes, irrespective of ST. In those with high CRF, high ST was associated with significantly high odds for the metabolic syndrome (OR 2.93 [95% CI 1.72, 4.99]) and type 2 diabetes (OR 2.21 [95% CI 1.17, 4.17]). The highest odds for the metabolic syndrome and type 2 diabetes were observed in individuals with low CRF and high ST (CRF-ST) (OR [95% CI]: the metabolic syndrome, 9.22 [5.74, 14.80]; type 2 diabetes, 8.38 [4.83, 14.55]).

Conclusions/interpretation: These data suggest that ST, HPA and CRF should all be targeted in order to optimally reduce the risk for the metabolic syndrome and type 2 diabetes.
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http://dx.doi.org/10.1007/s00125-018-4719-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6223836PMC
December 2018

A systematic review of methods to assess intake of saturated fat (SF) among healthy European adults and children: a DEDIPAC (Determinants of Diet and Physical Activity) study.

BMC Nutr 2018 8;4:21. Epub 2018 May 8.

1School of Public Health, University College Cork, Western Road, Cork, Ireland.

Background: Dietary fat is an essential macronutrient. However, saturated fact has been associated with negative health outcomes including cardiovascular disease. Shifting consumption from saturated fat to unsaturated fats and limiting the level of saturated fat in the diet has been recommended. Currently, there is no standard method to measure saturated fat intake in etiologic studies. Therefore, it is difficult to obtain a reliable picture of saturated fat intake in Europe. To inform the development of the DEDIPAC (DEterminants of DIet and Physical Activity) toolbox of methods, we aimed to identify the assessment methods and specific instruments which have been used to assess saturated fat intake among children or adults in pan-European studies.

Methods: Three electronic databases were searched for English language studies of any design which assessed intake of saturated fat. Reference lists were hand-searched. Studies were included if they were conducted in two or more European countries, and involved healthy, free-living children and adults.

Results: The review identified 20 pan-European studies which assessed saturated fat intake. Food Frequency Questionnaires ( = 8) and diet records ( = 7) were most common, followed by 24-h recalls ( = 5). Methods differed in portion size estimation and the composition data which was used to calculate nutrient intake. Of the instruments used in more than two European countries, five Food Frequency Questionnaires had been specifically tested for validity to assess saturated fat intake; four among adults (Food4me, PURE, IMMIDIET, Health, Alcohol and Psychosocial factors in Eastern Europe (HAPIEE)) and one among children (used by Piqueras et al.).

Conclusions: A standardised approach to portion size estimation and a common source of food composition data are required to measure saturated fat intake across Europe effectively. Only five instruments had been used in more than two European countries and specifically tested for validity to assess saturated fat intake. These instruments may be most appropriate to evaluate intake of saturated fat in future pan-European studies. However, only two instruments had been tested for validity in more than one European country. Future work is needed to assess the validity of the identified instruments across European countries.
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http://dx.doi.org/10.1186/s40795-018-0231-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7050932PMC
May 2018

Amount and pattern of physical activity and sedentary behavior are associated with kidney function and kidney damage: The Maastricht Study.

PLoS One 2018 4;13(4):e0195306. Epub 2018 Apr 4.

Department of Social Medicine, Maastricht University, Maastricht, the Netherlands.

Background: Chronic kidney disease, which is defined as having a reduced kidney function (estimated glomerular filtration rate (eGFR)) and/or signs of kidney damage (albuminuria), is highly prevalent in Western society and is associated with adverse health outcomes, such as cardiovascular disease. This warrants a search for risk factors of lower eGFR and higher albuminuria. Physical activity and sedentary behavior may be such risk factors.

Objective: To examine associations of physical activity (total, high, low), sedentary time and sedentary behavior patterns (breaks, prolonged bouts, average bout duration) with eGFR and albuminuria.

Methods: We examined these associations in 2,258 participants of the Maastricht Study (average age 60.1±8.1 years; 51.3% men), who wore an accelerometer 24h/day on 7 consecutive days. Associations with continuous eGFR and categories of urinary albumin excretion (UAE; <15 [reference category], 15-<30, ≥30 mg/24h) were evaluated with linear regression analyses and multinomial logistic regression analyses, respectively.

Results: After adjustment for potential confounders, each extra hour of total physical activity was associated with a more favorable kidney function (betaeGFR = 2.30 (95%CI = 1.46; 3.14)), whereas each extra hour of sedentary behavior was associated with a more adverse kidney function (betaeGFR = -0.71 (-1.08; -0.35)). Also, compared to individuals with the lowest levels of total physical activity, individuals with the highest levels had less kidney damage (OR15-<30mg/24h = 0.63 (0.41; 0.96), OR≥30mg/24h = 0.84 (0.53; 1.35). An extra hour of sedentary behavior was associated with more kidney damage (OR15-<30 mg/24h = 1.11 (1.01; 1.22), OR≥30 mg/24h = 1.10 (0.99; 1.22)). Further, a highly sedentary pattern was associated with a more adverse kidney function, but no association was seen with kidney damage.

Conclusions: Physical activity and sedentary behavior were associated with kidney function and kidney damage. Additionally, sedentary behavior patterns were associated with kidney function. Causal studies are required to examine whether this indeed implicates that prevention strategies should focus not only on increasing physical activity, but on reducing sedentary behavior as well.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0195306PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884554PMC
July 2018

Prospective associations of dietary carbohydrate, fat, and protein intake with β-cell function in the CODAM study.

Eur J Nutr 2019 Mar 10;58(2):597-608. Epub 2018 Mar 10.

Department of Epidemiology, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.

Purpose: Type 2 diabetes mellitus (T2DM) is characterized by both impaired pancreatic β-cell function (BCF) and insulin resistance. In the etiology of T2DM, BCF basically determines whether a person with a certain degree of insulin resistance develops T2DM, as β-cells are able to compensatorily increase insulin secretion. The effects of dietary intake on BCF are largely unknown. Our study aim was to investigate whether dietary macronutrient intake predicts BCF.

Methods: Prospective data (median follow-up 7 years) of 303 individuals recruited from the CODAM study population (aged 40-70 years, 39% women) were analyzed. BCF was measured by C-peptide deconvolution and physiological modeling of data from a 5-point, 75-g, 2-h oral glucose tolerance test. Macronutrient intake was estimated by a 178-item Food Frequency Questionnaire.

Results: Associations adjusted for relevant covariates of baseline macronutrient intake with model-derived parameters describing BCF (glucose sensitivity, rate sensitivity or potentiation) or C-peptidogenic index were detected for trans fat [standardized regression coefficient (95%-CI) glucose sensitivity - 0.14 (- 0.26, - 0.01)] per g, cholesterol [potentiation 0.20 (0.02, 0.37)] per 100 mg, dietary fiber [glucose sensitivity 0.21 (0.08, 0.33)] per 10 g, MUFA glucose sensitivity 0.16 (0.02, 0.31) per 10 g, and polysaccharide [potentiation - 0.24 (- 0.43, - 0.05), C-peptidogenic index - 0.16 (- 0.29 - 0.03); odds ratio lowest versus highest tertile (95%-CI) rate sensitivity 1.51 (1.06, 2.15)) per 50 g.

Conclusions: In this population at high risk for developing T2DM, polysaccharide and trans fat intake were associated with worse BCF, whereas increased intake of MUFA, dietary cholesterol, and fiber were associated with better BCF.
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http://dx.doi.org/10.1007/s00394-018-1644-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437317PMC
March 2019

Associations of Dietary Glucose, Fructose, and Sucrose with β-Cell Function, Insulin Sensitivity, and Type 2 Diabetes in the Maastricht Study.

Nutrients 2017 Apr 13;9(4). Epub 2017 Apr 13.

Department of Epidemiology, Maastricht University, Maastricht MD 6200, The Netherlands.

The associations of glucose, fructose, and sucrose intake with type 2 diabetes mellitus (T2DM) have been inconsistent. Furthermore, there is a lack of studies focusing on early markers of T2DM that provide insight into the process of T2DM progression: impaired pancreatic β-cell function (BCF) and insulin sensitivity. This study evaluated associations cross-sectionally in a population-based cohort consisting of 2818 individuals (mean ± SD age 59.7 ± 8.18, 49.5% male, = 120 newly diagnosed T2DM). Glucose, fructose, and sucrose intake were assessed by a food frequency questionnaire. Glucose metabolism status, insulin sensitivity, and BCF were measured by a seven-points oral glucose tolerance test. Linear regression analysis revealed a positive association of glucose intake with insulin sensitivity in the fully adjusted model (standardized beta (95% CI) 0.07 (0.05, 0.14) SD for ≥23 g vs. <10 g of glucose). Fructose and sucrose intake were not associated with insulin sensitivity after full adjustments. In addition, no associations of dietary glucose, fructose, and sucrose with BCF were detected. In conclusion, higher intake of glucose, not fructose and sucrose, was associated with higher insulin sensitivity, independent of dietary fibre. No convincing evidence was found for associations of dietary glucose, fructose, and sucrose with BCF in this middle-aged population.
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http://dx.doi.org/10.3390/nu9040380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5409719PMC
April 2017

Sedentary Behavior, Physical Activity, and Fitness-The Maastricht Study.

Med Sci Sports Exerc 2017 08;49(8):1583-1591

1Department of Human Movement Sciences, Maastricht University, Maastricht, THE NETHERLANDS; 2NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, THE NETHERLANDS; 3Division of Endocrinology, Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Maastricht, THE NETHERLANDS; 4CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, THE NETHERLANDS; 5Department of Social Medicine, Maastricht University, Maastricht, THE NETHERLANDS; 6CAPHRI School for Public Health and Primary Care, Maastricht University, Maastricht, THE NETHERLANDS; 7Radboud Institute for Health Sciences, Radboud University Medical Center, Nijmegen, THE NETHERLANDS; 8Department of Internal Medicine, Maastricht University Medical Centre (MUMC+), Maastricht, THE NETHERLANDS; 9Department of Epidemiology, Maastricht University, Maastricht, THE NETHERLANDS; and 10Heart and Vascular Centre, Maastricht University Medical Centre (MUMC+), Maastricht, THE NETHERLANDS.

Purpose: This cross-sectional study examined the mutual independent associations of sedentary behavior, lower intensity physical activity (LPA) and higher intensity physical activity (HPA) (an approximation of moderate to vigorous physical activity with cardiorespiratory fitness (CRF).

Methods: Two thousand twenty-four participants were included from The Maastricht Study (mean ± SD age, 59.7 ± 8.1 yr; 49.6% men). With the activPAL3 activity monitor, we assessed sedentary time (ST), sedentary pattern variables (number of sedentary breaks, average sedentary bout duration, and number of prolonged sedentary bouts [≥30 min]), LPA, and HPA. CRF was calculated as maximum power output per kilogram body mass (Wmax·kg) estimated from a submaximal cycle ergometer test. Linear regression analyses and isotemporal substitution analyses were used to examine associations of ST, sedentary pattern variables, and HPA with CRF. Analyses were stratified by sex.

Results: One hour of ST per day was associated with a lower Wmax·kg: Bmen = -0.03 (95% confidence interval [CI], -0.05 to -0.01) and Bwomen = -0.02 (95% CI, -0.04 to 0.00), independent of HPA. No statistically significant associations between sedentary patterns variables and CRF were observed. LPA was associated with a higher Wmax·kg: Bmen = 0.12 (95% CI, 0.07-0.17) and Bwomen = 0.12 (95% CI, 0.07-0.18). HPA was associated with a higher Wmax·kg: Bmen = 0.48 (95% CI, 0.38-0.58) and Bwomen = 0.27 (95% CI, 0.18-0.36). Replacing ST with LPA (Bmen, 0.08; 95% CI, 0.03-0.14; Bwomen, 0.10; 95% CI, 0.05-0.16) or with HPA (Bmen, 0.49; 95% CI, 0.39-0.59; Bwomen = 0.28; 95% CI, 0.19-0.36), but not with standing was associated with higher CRF.

Conclusions: Modest associations between sedentary behavior and CRF were observed. Replacing ST with LPA was associated with higher CRF, which could be of particular importance for individuals who cannot engage in HPA. Nonetheless, replacing ST with HPA was associated with greatest estimated change in CRF.
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http://dx.doi.org/10.1249/MSS.0000000000001262DOI Listing
August 2017