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Contains fulltext : 292525.pdf (Publisher’s version ) (Open Access), BACKGROUND: Detrimental associations of sedentary behaviour (time spent sitting) with musculoskeletal pain (MSP) conditions have been observed. However, findings on those with, or at risk of, type 2 diabetes (T2D) have not been reported. We examined the linear and non-linear associations of device-measured daily sitting time with MSP outcomes according to glucose metabolism status (GMS). METHODS: Cross-sectional data from 2827 participants aged 40-75 years in the Maastricht Study (1728 with normal glucose metabolism (NGM); 441 with prediabetes; 658 with T2D), for whom valid data were available on activPAL-derived daily sitting time, MSP [neck, shoulder, low back, and knee pain], and GMS. Associations were examined by logistic regression analyses, adjusted serially for relevant confounders, including moderate-to-vigorous intensity physical activity (MVPA) and body mass index (BMI). Restricted cubic splines were used to further examine non-linear relationships. RESULTS: The fully adjusted model (including BMI, MVPA, and history of cardiovascular disease) showed daily sitting time to be significantly associated with knee pain in the overall sample (OR = 1.07, 95%CI: 1.01-1.12) and in those with T2D (OR = 1.11, 95%CI: 1.00-1.22); this was not statistically significant in those with prediabetes (OR = 1.04, 95%CI: 0.91-1.18) or NGM (OR = 1.05, 95%CI: 0.98-1.13). There were no statistically significant associations between daily sitting time and neck, shoulder, or low back pain in any of the models. Furthermore, the non-linear relationships were statistically non-significant. CONCLUSION: Among middle-aged and older adults with T2D, daily sitting time was significantly associated with higher odds of knee pain, but not with neck, shoulder, or low back pain. No significant association was observed in those without T2D for neck, shoulder, low back, or knee pain. Future studies, preferably those utilising prospective designs, could examine additional attributes of daily sitting

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with an estimated heritability between 40 and 50%. DNA methylation patterns can serve as proxies of (past) exposures and disease progression, as well as providing a potential mechanism that mediates genetic or environmental risk. Here, we present a blood-based epigenome-wide association study meta-analysis in 9706 samples passing stringent quality control (6763 patients, 2943 controls). We identified a total of 45 differentially methylated positions (DMPs) annotated to 42 genes, which are enriched for pathways and traits related to metabolism, cholesterol biosynthesis, and immunity. We then tested 39 DNA methylation–based proxies of putative ALS risk factors and found that high-density lipoprotein cholesterol, body mass index, white blood cell proportions, and alcohol intake were independently associated with ALS. Integration of these results with our latest genome-wide association study showed that cholesterol biosynthesis was potentially causally related to ALS. Last, DNA methylation at several DMPs and blood cell proportion estimates derived from DNA methylation data were associated with survival rate in patients, suggesting that they might represent indicators of underlying disease processes potentially amenable to therapeutic interventions.

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Contains fulltext : 283464.pdf (Publisher’s version ) (Open Access), Whether older adults need more protein than younger adults is debated. The population reference intake for adults set by the European Food Safety Authority is 0.83 g/kg body weight (BW)/d based primarily on nitrogen balance studies, but the underlying data on health outcomes are outdated. An expert committee of the Health Council of the Netherlands conducted a systematic review (SR) of randomized controlled trials (RCTs) examining the effect of increased protein intake on health outcomes in older adults from the general population with an average habitual protein intake ≥0.8 g/(kg BW · d). Exposures were the following: 1) extra protein compared with no protein and 2) extra protein and physical exercise compared with physical exercise. Outcomes included lean body mass, muscle strength, physical performance, bone health, blood pressure, serum glucose and insulin, serum lipids, kidney function, and cognition. Data of >1300 subjects from 18 RCTs were used. Risk of bias was judged as high (n = 9) or "some concerns" (n = 9). In 7 of 18 RCTs, increased protein intake beneficially affected ≥1 of the tested outcome measures of lean body mass. For muscle strength, this applied to 3 of 8 RCTs in the context of physical exercise and in 1 of 7 RCTs without physical exercise. For the other outcomes, <30% (0-29%) of RCTs showed a statistically significant effect. The committee concluded that increased protein intake has a possible beneficial effect on lean body mass and, when combined with physical exercise, muscle strength; likely no effect on muscle strength when not combined with physical exercise, or on physical performance and bone health; an ambiguous effect on serum lipids; and that too few RCTs were available to allow for conclusions on the other outcomes. This SR provides insufficiently convincing data that increasing protein in older adults with a protein intake ≥0.8 g/(kg BW · d) elicits health benefits.

De Gezondheidsraad heeft nieuwe voedingsnormen voor energie (referentiewaarden voor de dagelijkse calorische inname) opgesteld voor zuigelingen, kinderen en volwassenen van diverse leeftijden, zwangere vrouwen en vrouwen die borstvoeding geven. Dit advies is een deeladvies binnen de evaluatie van de Nederlandse voedingsnormen. Harmonisatie van voedingsnormen binnen Europa is daarbij het streven. Daarom heeft de Commissie Voeding van de raad geëvalueerd in hoeverre de voedingsnormen van de Europese voedselveiligheidsautoriteit (European Food Safety Authority (EFSA)) overgenomen kunnen worden in Nederland. Daarbij heeft zij ook zes rapporten van andere nationale en internationale organisaties betrokken die relevant zijn voor Nederland.

Nutri-Score is een logo op de verpakking van voedingsmiddelen dat op basis van de samenstelling ervan een score geeft: van donkergroene A tot rode E. Het logo dat nu al in de winkels te vinden is (vanwege een proef met het logo en via producten uit het buitenland) klopt te vaak niet met de voedingsaanbevelingen zoals de Schijf van Vijf. Daarom is de manier waarop de Nutri-Score wordt berekend herzien. De Gezondheidsraad heeft de herziene berekening geëvalueerd. De raad stelt vast dat deze vooral beter zichtbaar maakt welke producten een ongezondere samenstelling hebben: die krijgen een gele, oranje of rode score (C, D of E). Bij de groene scores (A en B) maakt Nutri-Score vaak wel, maar nog niet altijd genoeg onderscheid, bijvoorbeeld tussen witte en volkoren varianten van pasta en rijst. Ook zouden meer plantaardige oliën en zachte margarines en halvarines een groene score moeten krijgen en laat de nieuwe systematiek van Nutri-Score soms nog veel ruimte voor ongezonde toevoegingen als zout en suiker. De raad ziet meerwaarde voor het logo, als middel om producten met elkaar te vergelijken. Dit geldt in het bijzonder voor mensen die met de huidige voorlichting moeilijk te bereiken zijn en die vaker een ongezond voedingspatroon hebben. Het logo is een aanvulling op de bestaande voedingsvoorlichting die van groot belang blijft voor een volwaardig, duurzaam en veilig voedingspatroon. Het logo is niet perfect, maar de raad ziet voldoende mogelijkheden het verder te verbeteren. Essentieel is dat de tekortkomingen daadwerkelijk worden opgelost. Verder vindt de raad het noodzakelijk bij invoering van het logo te onderzoeken welk effect het heeft op het gedrag van consumenten en producenten om te bezien in hoeverre het daadwerkelijk bijdraagt aan een gezonder voedingspatroon.

Background: Dicarbonyls are highly reactive compounds and major precursors of advanced glycation end products (AGEs). Both dicarbonyls and AGEs are associated with development of age-related diseases. Dicarbonyls are formed endogenously but also during food processing. To what extent dicarbonyls from the diet contribute to circulating dicarbonyls and AGEs in tissues is unknown.Objectives: To examine cross-sectional associations of dietary dicarbonyl intake with plasma dicarbonyl concentrations and skin AGEs.Methods: In 2566 individuals of the population-based Maastricht Study (age: 60 +/- 8 y, 50% males, 26% with type 2 diabetes), we estimated habitual intake of the dicarbonyls methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG) by combining FFQs with our dietary dicarbonyl database of MGO, GO, and 3-DG concentrations in> 200 commonly consumed food products. Fasting plasma concentrations of MGO, GO, and 3-DG were measured by ultra-performance liquid chromatography-tandem mass spectrometry. Skin AGEs were measured as skin autofluorescence (SAF), using theAGE Reader. Associations of dietary dicarbonyl intake with their respective plasma concentrations and SAF (all standardized) were examined using linear regression models, adjusted for age, sex, potential confounders related to cardiometabolic risk factors, and lifestyle.Results: Median intake of MGO, GO, and 3-DG was 3.6, 3.5, and 17 mg/d, respectively. Coffee was the main dietary source of MGO, whereas this was bread for GO and 3-DG. In the fully adjusted models, dietary MGO was associated with plasma MGO (beta: 0.08; 95% CI: 0.02, 0.13) and SAF (beta: 0.12; 95% CI: 0.07, 0.17). Dietary GO was associated with plasma GO (beta: 0.10; 95% CI: 0.04, 0.16) but not with SAF. 3-DG was not significantly associated with either plasma 3-DG or SAF.Conclusions: Higher habitual intake of dietary MGO and GO, but not 3-DG, was associated with higher corresponding plasma concentrations. Higher intake of MGO was also a

Item does not contain fulltext, OBJECTIVE: Obesity and liver fat are associated with decreased levels of serum sex hormone binding globulin (SHBG). Laboratory studies suggest that hepatic de novo lipogenesis (DNL) is involved in the downregulation of SHBG synthesis. The aim of the present study was to address the role of DNL on serum SHBG in humans. DESIGN: A cross-sectional study examining the association between DNL, measured by stable isotopes, and serum SHBG, stratified by sex. PARTICIPANTS: Healthy men (n = 34) and women (n = 21) were combined from two cross-sectional studies. Forty-two per cent of participants had hepatic steatosis, and the majority were overweight (62%) or obese (27%). RESULTS: DNL was inversely associated with SHBG in women (β: -0.015, 95% CI: -0.030; 0.000), but not in men (β: 0.007, 95% CI: -0.005; 0.019) (p for interaction = .068). Adjustment for study population, age and body mass index did not materially change these results, although statistical significance was lost after adjustment for serum insulin. CONCLUSIONS: An inverse association between DNL and SHBG may explain the decreased SHBG levels that are observed in obesity, at least in women.

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

Contains fulltext : 232027.pdf (Publisher’s version ) (Open Access), AIM: To describe the prevalence and characteristics of polypharmacy in a Dutch cohort of individuals with type 2 diabetes. METHODS: We included people with type 2 diabetes from the Diabetes Pearl cohort, of whom 3886 were treated in primary care and 2873 in academic care (secondary/tertiary). With multivariable multinomial logistic regression analyses stratified for line of care, we assessed which sociodemographic, lifestyle and cardiometabolic characteristics were associated with moderate (5-9 medications) and severe polypharmacy (≥10 medications) compared with no polypharmacy (0-4 medications). RESULTS: Mean age was 63 ± 10 years, and 40% were women. The median number of daily medications was 5 (IQR 3-7) in primary care and 7 (IQR 5-10) in academic care. The prevalence of moderate and severe polypharmacy was 44% and 10% in primary care, and 53% and 29% in academic care respectively. Glucose-lowering and lipid-modifying medications were most prevalent. People with severe polypharmacy used a relatively large amount of other (i.e. non-cardiovascular and non-glucose-lowering) medication. Moderate and severe polypharmacy across all lines of care were associated with higher age, low educational level, more smoking, longer diabetes duration, higher BMI and more cardiovascular disease. CONCLUSIONS: Severe and moderate polypharmacy are prevalent in over half of people with type 2 diabetes in primary care, and even more in academic care. People with polypharmacy are characterized by poorer cardiometabolic status. These results highlight the significance of polypharmacy in type 2 diabetes.

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Background: Dicarbonyls are highly reactive compounds and major precursors of advanced glycation end products (AGEs). Both dicarbonyls and AGEs are associated with development of age-related diseases. Dicarbonyls are formed endogenously but also during food processing. To what extent dicarbonyls from the diet contribute to circulating dicarbonyls and AGEs in tissues is unknown.Objectives: To examine cross-sectional associations of dietary dicarbonyl intake with plasma dicarbonyl concentrations and skin AGEs.Methods: In 2566 individuals of the population-based Maastricht Study (age: 60 +/- 8 y, 50% males, 26% with type 2 diabetes), we estimated habitual intake of the dicarbonyls methylglyoxal (MGO), glyoxal (GO), and 3-deoxyglucosone (3-DG) by combining FFQs with our dietary dicarbonyl database of MGO, GO, and 3-DG concentrations in> 200 commonly consumed food products. Fasting plasma concentrations of MGO, GO, and 3-DG were measured by ultra-performance liquid chromatography-tandem mass spectrometry. Skin AGEs were measured as skin autofluorescence (SAF), using theAGE Reader. Associations of dietary dicarbonyl intake with their respective plasma concentrations and SAF (all standardized) were examined using linear regression models, adjusted for age, sex, potential confounders related to cardiometabolic risk factors, and lifestyle.Results: Median intake of MGO, GO, and 3-DG was 3.6, 3.5, and 17 mg/d, respectively. Coffee was the main dietary source of MGO, whereas this was bread for GO and 3-DG. In the fully adjusted models, dietary MGO was associated with plasma MGO (beta: 0.08; 95% CI: 0.02, 0.13) and SAF (beta: 0.12; 95% CI: 0.07, 0.17). Dietary GO was associated with plasma GO (beta: 0.10; 95% CI: 0.04, 0.16) but not with SAF. 3-DG was not significantly associated with either plasma 3-DG or SAF.Conclusions: Higher habitual intake of dietary MGO and GO, but not 3-DG, was associated with higher corresponding plasma concentrations. Higher intake of MGO was also a

Objective : An exaggerated exercise SBP, which is potentially modifiable, may be associated with incident depressive symptoms via an increased pulsatile pressure load on the brain. However, the association between exaggerated exercise SBP and incident depressive symptoms is unknown. Therefore, we examined whether exaggerated exercise SBP is associated with a higher risk of depressive symptoms over time. Methods : We used longitudinal data from the population-based Maastricht Study, with only individuals free of depressive symptoms at baseline included (n = 2121; 51.3% men; age 59.5 +/- 8.5 years). Exercise SBP was measured at baseline with a submaximal exercise cycle test. We calculated a composite score of exercise SBP based on four standardized exercise SBP measures: SBP at moderate workload, SBP at peak exercise, SBP change per minute during exercise and SBP 4 min after exercise. Clinically relevant depressive symptoms were determined annually at follow-up and defined as a Patient Health Questionnaire score of at least 10. Results : After a mean follow-up of 3.9 years, 175 participants (8.3%) had incident clinically relevant depressive symptoms. A 1 SD higher exercise SBP composite score was associated with a higher incidence of clinically relevant depressive symptoms [hazard ratio: 1.27 (95% confidence interval: 1.04-1.54)]. Results were adjusted for age, sex, education level, glucose metabolism status, lifestyle, cardiovascular risk factors, resting SBP and cardiorespiratory fitness. Conclusion : A higher exercise SBP response is associated with a higher incidence of clinically relevant depressive symptoms.

Background: Lesions of cerebral small vessel disease, such as white matter hyperintensities (WMHs) in individuals with cardiometabolic risk factors, interfere with the trajectories of the white matter and eventually contribute to cognitive decline. However, there is no consensus yet about the precise underlying topological mechanism.Purpose: To examine whether WMH and cognitive function are associated and whether any such association is mediated or explained by structural connectivity measures in an adult population. In addition, to investigate underlying local abnormalities in white matter by assessing the tract-specific WMH volumes and their tract-specific association with cognitive function.Materials and Methods: In the prospective type 2 diabetes-enriched population-based Maastricht Study, structural and diffusion-tensor MRI was performed (December 2013 to February 2017). Total and tract-specific WMH volumes; network measures; cognition scores; and demographic, cardiovascular, and lifestyle characteristics were determined. Multivariable linear regression and mediation analyses were used to investigate the association of WMH volume, tract-specific WMH volumes, and network measures with cognitive function. Associations were adjusted for age, sex, education, diabetes status, and cardiovascular risk factors.Results: A total of 5083 participants (mean age, 59 years +/- 9 [standard deviation]; 2592 men; 1027 with diabetes) were evaluated. Larger WMH volumes were associated with stronger local (standardized beta coefficient, 0.065; PConclusion: White matter hyperintensity volume, local network efficiency, and information processing speed scores are interrelated, and local network properties explain lower cognitive performance due to white matter network alterations. (C) RSNA, 2020

Contains fulltext : 218687.pdf (publisher's version ) (Open Access), OBJECTIVE: Familial combined hyperlipidemia (FCHL) is common among survivors of a premature myocardial infarction. FCHL patients are characterized by visceral obesity, fatty liver, and insulin resistance. The aim of the present study was to determine the incidence and determinants of type 2 diabetes (T2D) in a longitudinal cohort of FCHL pedigrees. RESEARCH DESIGN AND METHODS: FCHL patients, their unaffected relatives and spouses included in our baseline cohort in 1998-2005 (n=596) were re-invited to determine the incidence of self-reported T2D (that was confirmed by medical records), used as the primary outcome measure. The Fatty Liver Index (FLI) and Homeostasis Model Assessment Insulin Resistance (HOMA2-IR) were used as markers of fatty liver and insulin resistance, respectively. A subset of the original cohort underwent ultrasound of the liver, and subcutaneous and visceral fat in 2002-2005 (n=275; 'ultrasound subcohort'). RESULTS: Follow-up data (median: 15 years) was acquired for 76%. The incidence rate of T2D was significantly higher in FCHL patients compared with spouses (19.2 per 1000 person-years vs 2.8 per 1000 person-years; HR : 6.3, 95% CI: 2.4 to 16.8), whereas no differences were observed between unaffected relatives and spouses (HR: 0.9, 95% CI: 0.3 to 2.6). Cox's proportional hazard regression analyses showed that baseline HOMA2-IR and FLI>/=60, but not waist circumference, BMI, or the FCHL affected state, were independently associated with incident T2D. Similar results were obtained in the ultrasound subcohort (median follow-up: 11 years), in which baseline HOMA2-IR and fatty liver (assessed by ultrasound) were independently associated with incident T2D. CONCLUSION: This study further corroborates the suggestion that the liver plays a central role in the pathogenesis of cardiometabolic complications in FCHL. It supports periodical screening for T2D in this high-risk population.

Contains fulltext : 218277.pdf (publisher's version ) (Open Access), OBJECTIVE: People with type 2 diabetes on insulin are at risk for hypoglycemia. Recurrent hypoglycemia can cause impaired awareness of hypoglycemia (IAH), and increase the risk for severe hypoglycemia. The aim of this study was to assess the prevalence and determinants of self-reported IAH and severe hypoglycemia in a Dutch nationwide cohort of people with insulin-treated type 2 diabetes. RESEARCH DESIGN AND METHODS: Observational study of The Dutch Diabetes Pearl, a cohort of people with type 2 diabetes treated in primary, secondary and tertiary diabetes care centers. The presence of IAH and the occurrence of severe hypoglycemia in the past year, defined as an event requiring external help to recover, were assessed using the validated Dutch version of the Clarke questionnaire. In addition, clinical variables were collected including age, diabetes duration, hemoglobin A1c, ethnicity and education. RESULTS: 2350 people with type 2 diabetes on insulin were included: 59.1% men, mean age 61.1+/-10.4 years, mean diabetes duration 14.8+/-9.2 years and 79.5% on basal-bolus therapy. A total of 229 patients (9.7%) were classified as having IAH and 742 patients (31.6%) reported severe hypoglycemia. Increased odds for IAH were found with complex insulin regimens and lower odds with having a partner and body mass index >/=30 kg/m(2). Severe hypoglycemia was associated with complex insulin regimens, non-Caucasian ethnicity and use of psychoactive drugs, and inversely with metformin use. CONCLUSIONS: In this nationwide cohort, almost one out of ten people with type 2 diabetes on insulin had IAH and >30% had a history of severe hypoglycemia in the past year.

Contains fulltext : 229476.pdf (Publisher’s version ) (Closed access), The large number of pharmacological agents available to treat type 2 diabetes (T2D) makes choosing the optimal drug for any given patient a complex task. Because newer agents offer several advantages, whether and when sulphonylureas (SUs) should still be used to treat T2D is controversial. Published treatment guidelines and recommendations should govern the general approach to diabetes management. However, expert opinions can aid in better understanding local practices and in formulating individual choices. The current consensus paper aims to provide additional guidance on the use of SUs in T2D. We summarize current local treatment guidelines in European countries, showing that SUs are still widely proposed as second-line treatment after metformin and are often ranked at the same level as newer glucose-lowering medications. Strong evidence now shows that sodium-glucose co-transporter-2 inhibitors (SGLT-2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with low hypoglycaemia risk, promote weight loss, and exert a positive impact on vascular, cardiac and renal endpoints. Thus, using SUs in place of SGLT-2is and GLP-1RAs may deprive patients of key advantages and potentially important cardiorenal benefits. In subjects with ascertained cardiovascular disease or at very high cardiovascular risk, SGLT-2is and/or GLP-1RAs should be used as part of diabetes management, in the absence of contraindications. Routine utilization of SUs as second-line agents continues to be acceptable in resource-constrained settings.

The original version of the Supplementary Information associated with this Article included an incorrect Supplementary Data 1 file, in which additional delimiters were included in the first column for a number of rows, resulting in column shifts for some of these rows. The HTML has been updated to include a corrected version of Supplementary Data 1; the original incorrect version of Supplementary Data 1 can be found as Supplementary Information associated with this Correction. In addition, the original version of this Article contained an error in the author affiliations. An affiliation of Abdel Abdellaoui with Department of Psychiatry, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.

Progress in high-throughput metabolic profiling provides unprecedented opportunities to obtain insights into the effects of drugs on human metabolism. The Biobanking BioMolecular Research Infrastructure of the Netherlands has constructed an atlas of drug-metabolite associations for 87 commonly prescribed drugs and 150 clinically relevant plasma-based metabolites assessed by proton nuclear magnetic resonance. The atlas includes a meta-analysis of ten cohorts (18,873 persons) and uncovers 1,071 drug-metabolite associations after evaluation of confounders including co-treatment. We show that the effect estimates of statins on metabolites from the cross-sectional study are comparable to those from intervention and genetic observational studies. Further data integration links proton pump inhibitors to circulating metabolites, liver function, hepatic steatosis and the gut microbiome. Our atlas provides a tool for targeted experimental pharmaceutical research and clinical trials to improve drug efficacy, safety and repurposing. We provide a web-based resource for visualization of the atlas (http://bbmri.researchlumc.nl/atlas/).

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

Metabolomics examines the small molecules involved in cellular metabolism. Approximately 50% of total phenotypic differences in metabolite levels is due to genetic variance, but heritability estimates differ across metabolite classes. We perform a review of all genome-wide association and (exome-) sequencing studies published between November 2008 and October 2018, and identify >800 class-specific metabolite loci associated with metabolite levels. In a twin-family cohort (N = 5117), these metabolite loci are leveraged to simultaneously estimate total heritability (h2 total), and the proportion of heritability captured by known metabolite loci (h2 Metabolite-hits) for 309 lipids and 52 organic acids. Our study reveals significant differences in h2 Metabolite-hits among different classes of lipids and organic acids. Furthermore, phosphatidylcholines with a high degree of unsaturation have higher h2 Metabolite-hits estimates than phosphatidylcholines with low degrees of unsaturation. This study highlights the importance of common genetic variants for metabolite levels, and elucidates the genetic architecture of metabolite classes.