Bruce HR Wolffenbuttel

Bruce HR Wolffenbuttel
University of Groningen | RUG · Department of Endocrinology

MD PhD

About

633
Publications
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26,334
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Introduction
Additional affiliations
August 2002 - present
University of Groningen

Publications

Publications (633)
Article
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....
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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...
Preprint
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 antib...
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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...
Preprint
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...
Chapter
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...
Preprint
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...
Preprint
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 HbA 1c ≥48 mmol/mol (≥6...
Preprint
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....
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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...
Article
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...
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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...
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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...
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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...
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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...
Article
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...
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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...
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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...
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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...
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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 ×...
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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...
Preprint
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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...
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A Correction to this paper has been published: https://doi.org/10.1038/s41467-021-21276-3
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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...
Preprint
Full-text available
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...
Article
Full-text available
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 predict the...
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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...
Article
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...
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Background Thyroid hormone plays a pivotal role in human metabolism. In epidemiologic studies, adequate registration of thyroid disorders is warranted. We examined the prevalence of thyroid disorders, reported thyroid medication use, thyroid hormone levels, and validity of thyroid data obtained from questionnaires in the Lifelines Cohort Study. Me...
Article
Sensortechnologie biedt aan mensen met type 1-diabetes de mogelijkheid om het verloop van de glucosewaarde nauwgezet te volgen. Bij bepaalde typen sensoren is er tevens de mogelijkheid van alarmering bij (dreigende) hypoglykemie. Wij onderzochten in een retrospectieve studieopzet of de kwaliteit van leven van mensen met type 1-diabetes veranderd is...
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Background: There is conflicting evidence in the literature on the association between (elevated) serum B12 concentrations and subsequent disease or mortality. We evaluated in the NHANES general population the association of serum B12 concentrations as well as vitamin B12 supplement intake with all-cause, cardiovascular, and cancer-related mortali...
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Introduction: Sex differences in cardiometabolic risk factors and their management in type 2 diabetes (T2D) have not been fully identified. Therefore, we aimed to examine differences in cardiometabolic risk factor levels, pharmacological treatment and achievement of risk factor control between women and men with T2D. Research design and methods:...
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The link between exposure to endocrine disrupting chemicals (EDCs) and the rapid increase in prevalence of obesity has recently been suggested. However, the magnitude and health impact of EDC exposure in at-risk populations remain largely unclear. In this study, we investigated the effect of a dietary intervention driven reduction in adipose tissue...
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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 an...
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Background: Exposure to environmental endocrine disrupting chemicals (EDCs) may play an important role in the epidemic of metabolic diseases. Epigenetic alterations may functionally link EDCs with gene expression and metabolic traits. Objectives: We aimed to evaluate metabolic-related effects of the exposure to endocrine disruptors including fiv...
Article
Background: Environmental stressors such as transport noise may contribute to development of obesity through increased levels of stress hormones, sleep deprivation and endocrine disruption. Epidemiological evidence supporting an association of road traffic noise with obesity markers is still relatively scant and confined to certain geographical reg...
Article
Biallelic variants in LARS1, coding for the cytosolic leucyl-tRNA synthetase, cause infantile liver failure syndrome 1 (ILFS1). Since its description in 2012, there has been no systematic analysis of the clinical spectrum and genetic findings. Individuals with biallelic variants in LARS1 were included through an international, multicenter collabora...
Article
We conducted an epigenome-wide association study meta-analysis on blood pressure (BP) in 4820 individuals of European and African ancestry aged 14 to 69. Genome-wide DNA methylation data from peripheral leukocytes were obtained using the Infinium Human Methylation 450k BeadChip. The epigenome-wide association study meta-analysis identified 39 BP-re...
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Endocrine Disrupting Chemicals (EDCs) have been linked to a variety of cardiometabolic diseases. Yet, few studies have investigated the exposure to EDCs and cardiometabolic health taking lifestyle into account. We aimed to assess exposure to five parabens, three bisphenols and thirteen metabolites of in total eight phthalates in a general Dutch pop...
Article
Background: Patients with primary hypothyroidism are treated with levothyroxine in order to normalize their serum TSH. Finding the optimal dosage is a long-lasting process and a small change can have major impact. Currently, limited data are available on the impact of dose equivalent substitution between brands. This study aimed to determine the e...
Article
Introduction: Diagnosis of vitamin B12 deficiency is difficult, as there is no conclusive single test for this disorder. We evaluated the association of serum B12 and methylmalonic acid (MMA) with haematologic parameters and physical and cognitive functioning in an effort to use such clinical parameters to improve the interpretation of serum value...
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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 peop...
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Background: Severe obesity is a growing, worldwide burden and conventional therapies including radical change of diet and/or increased physical activity have limited results. Bariatric surgery has been proposed as an alternative therapy showing promising results. It leads to substantial weight loss and improvement of comorbidities such as type 2 d...
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Objective Choosing therapies for type 2 diabetes that are both effective and cost-effective is vital as healthcare systems worldwide aim to maximize health of the population. The present analysis assessed the cost-effectiveness of once-weekly semaglutide (a novel glucagon-like peptide-1 (GLP-1) receptor agonist) versus insulin glargine U100 (the mo...
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Phenylketonuria (PKU) is treated with dietary restrictions and sometimes tetrahydrobiopterin (BH4). PKU patients are at risk for developing micronutrient deficiencies, such as vitamin B12 and folic acid, likely due to their diet. Tyrosinemia type 1 (TT1) is similar to PKU in both pathogenesis and treatment. TT1 patients follow a similar diet, but n...
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Although cobalamin (vitamin B12) deficiency was described over a century ago, it is still difficult to establish the correct diagnosis and prescribe the right treatment. Symptoms related to vitamin B12 deficiency may be diverse and vary from neurologic to psychiatric. A number of individuals with vitamin B12 deficiency may present with the classic...
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Objective: Roux-en-Y gastric bypass (RYGB) is an effective way to induce sustainable weight loss and can be complicated by postprandial hyperinsulinemic hypoglycaemia (PHH). To study the prevalence and the mechanisms behind the occurrence of hypoglycaemia after a mixed meal tolerance test (MMTT) in patients with primary RYGB. Design: This is a c...
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People are constantly exposed to a wide variety of chemicals. Some of these compounds, such as parabens, bisphenols and phthalates, are known to have endocrine disrupting potencies. Over the years, these endocrine disrupting chemicals (EDCs) have been a rising cause for concern. In this study, we describe setup and validation of two methods to meas...
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Aims/hypothesis: Earlier studies have shown that skin autofluorescence measured with an AGE reader estimates the accumulation of AGEs in the skin, which increases with ageing and is associated with the metabolic syndrome and type 2 diabetes. In the present study, we examined whether the measurement of skin autofluorescence can predict 4 year risk...
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C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 100...
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Inborn errors of metabolism in adults are still largely unexplored. Despite the fact that adult‐onset phenotypes have been known for many years, little attention is given to these disorders in neurological practice. The adult‐onset presentation differs from childhood‐onset phenotypes, often leading to considerable diagnostic delay. The identificati...
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Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of g...