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Introduction
Skills and Expertise
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August 2002 - present
Publications
Publications (684)
Objective: Pernicious anaemia (PA) is characterised by vitamin B12 deficiency due to autoimmune-mediated loss of gastric parietal cells and intrinsic factor. The Pernicious Anaemia Society (PAS) identified 10 research priorities for PA through a James-Lind Alliance Priority Setting Partnership (JLA-PSP). This study aimed to survey PAS members to id...
We aimed to assess the association of SAF with cardiovascular mortality in the general population and the possible association between SAF with other disease-specific mortality rates. We evaluated 77,143 participants without known diabetes or cardiovascular disease. The cause of death was ascertained by the municipality database. The associations b...
Objective
To address the relationship between tissue accumulation of advanced glycation end-products, assessed by skin autofluorescence (SAF), and subclinical atherosclerosis quantified with coronary artery calcium score (CACS) in the general Dutch population.
Methods
A total of 3,839 participants of the LifeLines Cohort Study without diabetes or...
Leucine aminoacyl tRNA‐synthetase 1 (LARS1)‐deficiency (infantile liver failure syndrome type 1 (ILFS1)) has a multisystemic phenotype including fever‐associated acute liver failure (ALF), chronic neurologic abnormalities, and encephalopathic episodes. In order to better characterize encephalopathic episodes and MRI changes, 35 cranial MRIs from 13...
Purpose
The ‘Biomarkers of heterogeneity in type 1 diabetes’ study cohort was set up to identify genetic, physiological and psychosocial factors explaining the observed heterogeneity in disease progression and the development of complications in people with long-standing type 1 diabetes (T1D).
Participants
Data and samples were collected in two su...
Background
An increasing number of adult individuals are at risk of vitamin B12 deficiency, either from reduced nutritional intake or impaired gastrointestinal B12 absorption.
Objective
This study aims to review the current best practices for the diagnosis and treatment of individuals with vitamin B12 deficiency.
Methods
A narrative literature re...
We aimed to assess the association of SAF with cardiovascular mortality in the general population and the possible association between SAF with other disease-specific mortality rates. We evaluated 77,143 participants without known diabetes or cardiovascular disease. The cause of death was ascertained by the municipality database. The associations b...
Autoimmune gastritis (AIG) is characterized by the destruction of gastric parietal cells, resulting in hypochlorhydria and eventual achlorhydria, as oxyntic glands in the corpus are destroyed and become atrophic. The permanent loss of gastric acid has many impacts—both theoretical and documented. The most concerning of these are hypergastrinemia an...
This study investigates impaired awareness of hypoglycaemia (IAH), a complication of insulin therapy affecting 20–40% of individuals with type 1 diabetes. The exact pathophysiology is unclear, therefore we sought to identify metabolic signatures in IAH to elucidate potential pathophysiological pathways. Plasma samples from 578 individuals of the Du...
Background
Overweight and obesity rates among the general population of the Netherlands keep increasing. Combined lifestyle interventions (CLIs) focused on physical activity, nutrition, sleep, and stress management can be effective in reducing weight and improving health behaviors. Currently available CLIs for weight loss (CLI-WLs) in the Netherlan...
To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT...
Objectives
Cardiovascular disease (CVD) is a precarious complication of type 1 diabetes (T1D). Alongside glycaemic control, lipid and blood pressure (BP) management are essential for the prevention of CVD. However, age-specific differences in lipid and BP between individuals with T1D and the general population are relatively unknown.
Design
Cross-...
During the last decades, gestational diabetes mellitus (GDM) prevalence has been on the rise. While insulin remains the gold standard treatment for GDM, metformin use during pregnancy is controversial. This review aimed to comprehensively assess the available data on the efficacy and safety of metformin during pregnancy, both for the mother and the...
Hypothyroidism is associated with a decreased health-related quality of life (HRQoL). We hypothesized that individuals with hypothyroidism (defined as use of thyroid hormone (TH)) and especially those having an impaired HRQoL are characterized by a high prevalence of comorbid disorders, and that the impact of hypothyroidism and comorbidity on HRQoL...
Background
Type 2 diabetes disproportionately affects individuals of non-White ethnicity through a complex interaction of multiple factors. Therefore, early disease detection and prediction are essential and require tools that can be deployed on a large scale. We aimed to tackle this problem by developing questionnaire-based prediction models for t...
Background
Type 2 diabetes disproportionately affects individuals of non-White ethnicity through a complex interaction of multiple factors. Therefore, early disease detection and prediction are essential and require tools that can be deployed on a large scale. We aimed to tackle this problem by developing questionnaire-based prediction models for t...
Purpose: The "Biomarkers of heterogeneity in type 1 diabetes" study cohort was set up to identify genetic, physiological and psychosocial factors explaining the observed heterogeneity in disease progression and the development of complications in people with long-standing type 1 diabetes (T1D). Data and samples are available for new studies and col...
Several research groups have attempted to describe the heterogeneity of type 2 diabetes by creating specific subtypes. A Swedish study evaluating subtypes of type 2 diabetes soon after diagnosis has proposed the existence of 5 clusters. Subtyping can lead to a better understanding of the underlying pathophysiology, better prediction of the developm...
The growing public interest in genetic risk scores for various health conditions can be harnessed to inspire preventive health action. However, current commercially available genetic risk scores can be deceiving as they do not consider other, easily attainable risk factors, such as sex, BMI, age, smoking habits, parental disease status and physical...
Aims/hypothesis:
Optimal diabetes care and risk factor management are important to delay micro- and macrovascular complications in individuals with type 1 diabetes (T1D). Ongoing improvement of management strategies requires the evaluation of target achievement and identification of risk factors in individuals who do (or do not) achieve these targ...
Background
Neurobehavioural disorder diagnoses have been increasing over the last decades, leading to heightened interest in the aetiological factors involved. Endocrine disrupting chemicals, such as parabens and bisphenols, have been suggested as one of those factors. It is unknown whether exposure during adolescence may affect neurobehavioural de...
Background
Cardiovascular disease (CVD) is a precarious complication of type 1 diabetes (T1D). Alongside glycaemic control, lipid and blood pressure (BP) management are essential for the prevention of CVD. However, age-specific differences in lipid and BP between individuals with T1D and the general population are relatively unknown. We therefore c...
Introduction:
SURE Netherlands (NCT03929679) evaluated the use of once-weekly (OW) semaglutide, a glucagon-like peptide 1 receptor agonist (GLP-1RA), in routine clinical care for individuals with type 2 diabetes (T2D).
Methods:
Adults (age ≥ 18 years) with T2D were enrolled into the single-arm study. The primary endpoint was change from baseline...
Background
Skin autofluorescence (SAF) is a non-invasive measure reflecting accumulation of advanced glycation endproducts (AGEs) in the skin. Higher SAF levels are associated with an increased risk of developing type 2 diabetes and cardiovascular disease. An earlier genome-wide association study (GWAS) revealed a strong association between NAT2 va...
Increased skin autofluorescence (SAF) predicts the development of diabetes-related complications and cardiovascular disease. We assessed the performance of a simple model which includes SAF to identify individuals at high risk for undiagnosed and incident type 2 diabetes, in 58,377 participants in the Lifelines Cohort Study without known diabetes....
Vitamin B 12 is an essential nutrient that is not made by plants; consequently, unfortified plant-based foods are not a reliable supply. Recent estimates suggest high rates of vitamin B 12 deficiency among the vegetarian and vegan populations, particularly in pregnant women or women of child-bearing age who, for ethical and health reasons, are shif...
Aims:
This study aims to evaluate the stability of C-peptide over time and to compare fasting C-peptide and C-peptide response after Mixed-Meal Tolerance Test (MMTT) at T90 or T120 with C-peptide area under the curve (AUC) in long-standing type 1 diabetes.
Methods:
We included 607 type 1 diabetes individuals with diabetes duration >5 years. C-pe...
BACKGROUND
Overweight and obesity rates amongst the general population of The Netherlands keep increasing. In 2021, almost 50% of Dutch adults were living with overweight, including 13% with obesity. Combined lifestyle interventions (CLIs) focused on physical activity, nutrition, and other lifestyle pillars can be effective in reducing weight and i...
In the Netherlands, abnormal New-Born Screening (NBS) results are communicated to parents by the general practitioner (GP). Good communication and consequential trust in professionals is of the utmost importance in the treatment of phenylketonuria (PKU). The aim of this study was to assess parental satisfaction regarding the communication of an abn...
Background
As a clinical and non-invasive tool, the AGE Reader measures skin autofluorescence (SAF) to estimate the accumulation of advanced glycation end products (AGEs) in the skin. Accumulation of AGEs has been implicated in several inflammation-associated diseases, including diabetes and cardio-metabolic diseases. This study aimed to assess SAF...
Introduction
Cardiovascular disease (CVD) is the leading cause of mortality in individuals with type 1 diabetes mellitus (T1DM). Cardiovascular risk management is therefore essential in the management of individuals with T1DM. This study describes the performance of lipid and blood pressure management in individuals with T1DM using three guidelines...
Background: Optimal diabetes care and risk factor management are important to delay micro- and macrovascular complications in individuals with type 1 diabetes (T1D) . Ongoing improvement of management strategies requires the evaluation of target achievement and identification of determinants in individuals who do (or do not) achieve these targets....
The growing public interest in genetic risk scores for various health conditions may inspire preventive health action. However, these risk scores can be deceiving as they do not consider other, easily attainable risk factors, such as sex, BMI, age, smoking habits, parental disease status and physical activity. We show improved performance in identi...
Background
Individuals with type 2 diabetes mellitus (T2DM) have an increased risk for developing macrovascular disease (MVD) manifested by atherosclerosis. Phenotypically and functionally different monocyte subsets (classical; CD14⁺⁺CD16⁻, non-classical; CD14⁺CD16⁺⁺, and intermediate; CD14⁺⁺CD16⁺) including pro-angiogenic monocytes expressing Tie2...
Background
Measurement of thyroid peroxidase autoantibodies (TPOAb) is used to confirm a diagnosis of Hashimoto’s hypothyroidism. Presence of TPOAb may predict future thyroid dysfunction, and is also associated with adverse pregnancy outcomes and worse quality of life.
Methods
We evaluated the performance of four TPOAb and two thyroglobulin antibo...
Maintaining an adequate micronutrient status can be achieved by following a complete, diverse diet. Yet, food trends in Western countries show suboptimal consumption of healthy nutrients. In this study, we explored the prevalence of vitamin and mineral imbalances in a general population cohort of Dutch adults and evaluated the effect of a digital l...
Background: Cardiovascular disease (CVD) is the main reason for morbidity and mortality of patients in hemodialyis. Skin autofluorescence (SAF), a noninvasive measurement method, reflects tissue accumulation of advanced glycation end products (AGEs) that has been implicated in CVD as a strong marker. The aim of this study was to evaluate SAF profil...
Maintaining an adequate micronutrient status can be achieved by following a complete, diverse diet. Yet, food trends in Western countries show suboptimal consumption of healthy nutrients. In this study we explored the prevalence of vitamin and mineral imbalances in a general population cohort of Dutch adults, and evaluated the effect of a digital l...
Gestational diabetes mellitus (GDM) is associated with a high risk of obstetric and neonatal complications. Adequate diagnosis and appropriate treatment are key to prevention of these complications. Most international guidelines have adopted the IADPSG 2010/WHO 2013 diagnostic criteria, for the diagnosis of GDM by recommending the following glycemi...
Background
Skin autofluorescence (SAF) is a non-invasive measure reflecting accumulation of advanced glycation endproducts (AGEs) in the skin. Higher SAF levels are associated with an increased risk of developing type 2 diabetes and cardiovascular disease. An earlier genome-wide association study (GWAS) revealed a strong association between NAT2 va...
Background
We evaluated the performance of skin autofluorescence to select groups at risk for undiagnosed and incident DM2 in a simple and fast risk model.
Methods
We evaluated 58,377 participants without known diabetes of whom SAF measurements. Newly diagnosed diabetes was defined as fasting blood glucose ≥7.0 mmol/l and/or HbA1c ≥48 mmol/mol (≥6....
Increased skin autofluorescence (SAF) predicts the development of diabetes-related complications and cardiovascular disease. We assessed the performance of a simple model which includes SAF to identify individuals at high risk for undiagnosed and incident type 2 diabetes, in 58,377 participants in the Lifelines Cohort Study without known diabetes....
In clinical practice, the finding of an elevated serum B 12 concentration is often the consequence of supplementation with B 12 in either oral form or injections. Also, elevated serum B 12 may be associated with underlying disorders, like liver diseases or a (haematologic) malignancy. Only a few studies have shown that it may also be the consequenc...
Introduction
C-peptide is an important marker to assess residual insulin production in individuals with type 1 diabetes (T1D), The accuracy and detection limits of C-peptide assays are important to detect C-peptide microsecretion and to reliably observe changes over time in these patients. We compared and verified two commercially available assays...
Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated...
Elevated serum urate levels, a complex trait and major risk factor for incident gout, are correlated with cardiometabolic traits via incompletely understood mechanisms. DNA methylation in whole blood captures genetic and environmental influences and is assessed in transethnic meta-analysis of epigenome-wide association studies (EWAS) of serum urate...
Many predictive models exist that predict risk of common cardiometabolic conditions. However, a vast majority of these models do not include genetic risk scores and do not distinguish between clinical risk requiring medical or pharmacological interventions and pre-clinical risk, where lifestyle interventions could be first-choice therapy. In this s...
Myelodysplastic syndromes (MDS) are in the majority of cases characterized by anemia. Both anemia and MDS per se may directly contribute to impairments in health-related quality of life (HRQoL). In this study, we aimed to investigate the anemia-independent impact of MDS on HRQoL. We evaluated participants (≥ 50 years) from the large population-base...
Background
Dietary treatment in Phenylketonuria (PKU) is known to cause eating problems, but knowledge on both prevalence and magnitude, especially on social restrictions, is scarce. Our aim is to evaluate the social restrictions and eating problems PKU children and their caregivers experience due to dietary treatment.
Methods
A web-based question...
Introduction
This study aimed to assess the association between fasting serum C-peptide levels and the presence of impaired awareness of hypoglycemia (IAH) in people with type 1 diabetes.
Research design and methods
We performed a cross-sectional study among 509 individuals with type 1 diabetes (diabetes duration 5–65 years). Extensive clinical da...
Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of Europe...
Alkaptonuria (AKU, OMIM 203500) is a rare congenital disorder caused by a deficiency of the enzyme homogentisate-1,2,-dioxygenase. The long-term consequences of AKU are joint problems, cardiac valve abnormalities and renal problems. Landmark intervention studies with nitisinone 10 mg daily, suppressing an upstream enzyme activity, demonstrated its...
We conducted genome-wide association studies (GWAS) of relative intake from the macronutrients fat, protein, carbohydrates, and sugar in over 235,000 individuals of European ancestries. We identified 21 unique, approximately independent lead SNPs. Fourteen lead SNPs are uniquely associated with one macronutrient at genome-wide significance (P < 5 ×...
Aims/hypothesis
We aimed to assess and contextualise 134 potential risk variables for the development of type 2 diabetes and to determine their applicability in risk prediction.
Methods
A total of 96,534 people without baseline diabetes (372,007 person-years) from the Dutch Lifelines cohort were included. We used a risk variable-wide association s...
Background
A wide range of predictive models exist that predict risk of common lifestyle conditions. However, these have not focused on identifying pre-clinical higher risk groups that would benefit from lifestyle interventions and do not include genetic risk scores. In this study, we developed, validated, and compared the performance of three deci...
A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21276-3
Endocrine disrupting chemicals (EDCs) include non-persistent exogenous substances such as parabens, bisphenols and phthalates which have been associated with a range of metabolic disorders and disease. It is unclear if exposure remains consistent over time. We investigated change in indicators of EDC exposure between 2009 and 2016 and assessed its...
Reproductive longevity is critical for fertility and impacts healthy ageing in women, yet insights into the underlying biological mechanisms and treatments to preserve it are limited. Here, we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in ~200,000 women of European ancestry...
Abstract Background Skin autofluorescence (SAF) is a non-invasive marker of tissue accumulation of advanced glycation endproducts (AGE). Recently, we demonstrated in the general population that elevated SAF levels predict the development of type 2 diabetes (T2D), cardiovascular disease (CVD) and mortality. We evaluated whether elevated SAF may pred...
Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women...
Complete blood cell counts, including differentials, are widely available and change on aging. Peripheral blood cell counts outside the normal range have previously been associated with increased mortality rates and a number of comorbid conditions. However, data about the association between blood cell count abnormalities, other than anemia, and he...
