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Johannes A Romijn

Johannes A Romijn

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702
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Introduction
Skills and Expertise

Publications

Publications (702)
Article
Background: Acetaminophen is metabolized through a non-toxic sulfation and glucuronidation pathway and toxic oxidation pathway (via CYP2E1 and CYP1A2). A short-term high-fat diet induces alterations in the steatotic liver and may alter hepatic drug enzyme activity. In the case of acetaminophen, these alterations may result in an increased risk of...
Article
Objectives Physician gaze towards patients is fundamental for medical consultations. Physicians’ use of Electronic Health Records (EHR) affects their gaze towards patients, and may negatively influence this interaction. We aimed to study conversation patterns during gaze shifts of physicians from the patient towards the EHR. Methods Outpatient con...
Article
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Background: Generally, food intake occurs in a three-meal per 24 h fashion with in-between meal snacking. As such, most humans spend more than ∼ 12–16 h per day in the postprandial state. It may be reasoned from an evolutionary point of view, that the human body is physiologically habituated to less frequent meals. Metabolic flexibility (i.e., reci...
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Face gaze is a fundamental non-verbal behaviour and can be assessed using eye-tracking glasses. Methodological guidelines are lacking on which measure to use to determine face gaze. To evaluate face gaze patterns we compared three measures: duration, frequency and dwell time. Furthermore, state of the art face gaze analysis requires time and manual...
Preprint
The patient-physician relationship is a critical determinant for patient health outcomes. Verbal and non-verbal communication, such as eye gaze, are vital aspects of this bond. Neurobiological studies indicate that oxytocin may serve as a link between increased eye gaze and social bonding. Therefore, oxytocin signaling could serve as a key factor i...
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Background Glucagon-like peptide-1 (GLP-1) receptor agonist treatment is beneficial for the human glucose metabolism, and GLP-1 secretion is greatly enhanced following Roux-en-Y gastric bypass (RYGB). Objectives To elucidate the relationship between GLP-1 concentrations and insulin sensitivity in subjects with class II/III obesity without diabetes...
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Animal studies indicate that hypothalamic dysfunction plays a major role in type 2 diabetes mellitus (T2DM) development, and that insulin resistance and inflammation are important mechanisms involved in this disorder. However, it remains unclear how T2DM and antidiabetic treatments affect the human hypothalamus. Here, we characterized the proopiome...
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Purpose of review: The global prevalence of obesity has increased rapidly over the last decades, posing a severe threat to human health. Currently, bariatric surgery is the most effective therapy for patients with morbid obesity. It is unknown whether this treatment is also suitable for patients with obesity due to a confirmed genetic defect (gene...
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Background & aims To investigate the acute effects of intravenous vs enteral meal administration on circulating bile acid and gut hormone responses. Methods In a randomized crossover design, we compared the effects of duodenal (via a nasoduodenal tube) vs parenteral (intravenous) administration over 180 minutes of identical mixed meals on circulat...
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Fasting induces profound changes in the hypothalamus-pituitary-thyroid axis and peripheral thyroid hormone (TH) metabolism, ultimately leading to lower serum thyroid hormone (TH) concentrations. In the present study, we aimed to investigate the regulation of type 3 deiodinase (D3) during fasting in two metabolic tissues: liver and white adipose tis...
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Retinol-binding protein-4 (RBP4) is elevated in serum and adipose tissue (AT) in obesity-induced insulin resistance and correlates inversely with insulin-stimulated glucose disposal. But its role in insulin-mediated suppression of lipolysis, free fatty acids (FFA), and endogenous glucose production (EGP) in humans is unknown. RBP4 mRNA or protein l...
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Background: Bile acids are multifaceted metabolic compounds that signal to cholesterol, glucose, and lipid homeostasis via receptors like the Farnesoid X Receptor (FXR) and transmembrane Takeda G protein-coupled receptor 5 (TGR5). The postprandial increase in plasma bile acid concentrations is therefore a potential metabolic signal. However, this...
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Introduction: There is considerable variability in the rates and extent of drug metabolism between patients due to physiological, genetic, pharmacologic, environmental and nutritional factors such as fasting. This variability in drug metabolism may result in treatment failure or, conversely, in increased side effects or toxicity. Preclinical studie...
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Aims/hypothesis The central pacemaker of the mammalian biological timing system is located within the suprachiasmatic nucleus (SCN) in the anterior hypothalamus. Together with the peripheral clocks, this central brain clock ensures a timely, up-to-date and proper behaviour for an individual throughout the day–night cycle. A mismatch between the cen...
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The Christmas season can have a major impact on human health. Especially increased contact with in-laws during the holiday season is an important environmental factor known to affect both physical and mental health (Mirza et al., 2004). However, the mechanism through which in-laws influence host health is not yet understood. Emerging evidence has i...
Article
Context: Bile acids, glucagon-like peptide-1 (GLP-1) and fibroblast growth factor 19 (FGF19) play an important role in postprandial metabolism. In this study, we investigated the postprandial bile acid response in plasma and its relation to insulin, GLP-1 and FGF19. Objective: First, we investigated the postprandial response to 40-hour fasting....
Article
Background and aims: Placement of the duodenal-jejunal bypass liner (DJBL) leads to rapid weight loss and restoration of insulin sensitivity in a similar fashion to bariatric surgery. Increased systemic bile acid levels are candidate effectors for these effects through postprandial activation of their receptors TGR5 and FXR. We aimed to quantify p...
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Background and Objectives Previous studies have shown that nutritional status can alter drug metabolism which may result in treatment failure or untoward side effects. This study assesses the effect of two nutritional conditions, short-term fasting, and a short-term high fat diet (HFD) on cytochrome P450 3A4 (CYP3A4) and uridine 5′-diphospho-glucur...
Article
Bile acids can function in the postprandial state as circulating signaling molecules in the regulation of glucose and lipid metabolism via the transmembrane receptor TGR5 and nuclear receptor FXR. Both receptors are present in the central nervous system, but their function in the brain is unclear. Therefore, we investigated the effects of intracere...
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Desynchronization between the master clock in the brain, which is entrained by (day) light, and peripheral organ clocks, which are mainly entrained by food intake, may have negative effects on energy metabolism. Bile acid metabolism follows a clear day/night rhythm. We investigated whether in rats on a normal chow diet the daily rhythm of plasma bi...
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Background and objectives: Short-term fasting differentially alters cytochrome P450 (CYP) mediated drug metabolism. This has been established by using CYP-enzyme selective probe drugs. However, the observed effects of fasting on the pharmacokinetics of these probe drugs may also include the effects of altered plasma protein binding of these drugs....
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Objective: Fructose consumption has been implicated in the development of obesity and insulin resistance. Emerging evidence shows that fibroblast growth factor 21 (FGF21) has beneficial effects on glucose, lipid, and energy metabolism and may also mediate an adaptive response to fructose ingestion. Fructose acutely stimulates circulating FGF21 cons...
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Hepatic lipid accumulation has been implicated in the development of insulin resistance, but translational evidence in humans is limited. We investigated the relationship between liver fat and tissue-specific insulin sensitivity in 133 obese subjects. Although the presence of hepatic steatosis in obese subjects was associated with hepatic, adipose...
Article
Background & aims Bile acids (BAs) play a key role in lipid uptake and metabolic signalling in different organs including gut, liver, muscle and brown adipose tissue. Portal and peripheral plasma BA concentrations increase after a meal. However, the exact kinetics of postprandial BA metabolism have never been described in great detail. We used a co...
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Background and Objective Short-term fasting can alter drug exposure but it is unknown whether this is an effect of altered oral bioavailability and/or systemic clearance. Therefore, the aim of our study was to assess the effect of short-term fasting on oral bioavailability and systemic clearance of different drugs. Methods In a randomized, controll...
Article
Background: Hepatotoxicity after ingestion of high-dose acetaminophen (N-acetyl-para-aminophenol, APAP) is caused by the metabolites of the drug. To gain more insight in factors influencing susceptibility to APAP hepatotoxicity, quantification of APAP and metabolites is important. A few methods have been developed to simultaneously quantify APAP a...
Article
Background: The metabolic activity of P450 enzymes in vivo can be determined by using selective probe drugs. The simultaneous administration of multiple CYP-specific probe drugs is commonly referred to as the "cocktail approach." Disadvantages of a cocktail are large volumes of samples required for analysis and time-consuming analyses. The aim of...
Article
Objectives: Knowledge of factors contributing to variation in drug metabolism is of vital importance to optimize drug treatment. This study assesses the effects of a short-term hypercaloric high fat diet on metabolism of five oral drugs, which are each specific for a single P450 isoform: midazolam (CYP3A4), omeprazole (CYP2C19), metoprolol (CYP2D6...
Article
Aim Elevated basal endogenous glucose production (EGP), impaired suppression of EGP by insulin and reduced insulin-stimulated glucose disposal are cornerstones of the pathogenesis of hyperglycemia in patients with type 2 diabetes. We aimed to determine the contribution of these processes to impaired fasting glucose (IFG) levels in obese non-diabeti...
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p>The objective of this study was to derive food-based dietary guidelines for the Dutch population. The dietary guidelines are based on 29 systematic reviews of English language meta-analyses in PubMed summarizing randomized controlled trials and prospective cohort studies on nutrients, foods and food patterns and the risk of 10 major chronic disea...
Chapter
Aet. Veroorzaakt door overmatige groeihormoonproductie. Meestal door een tumor in de hypofyse en soms door een tumor elders (ectopische productie). Overmatig GRH uit de hypothalamus of elders in het lichaam geproduceerd (tumor) is een zeldzame oorzaak. Sympt. Algemene hypertrofie van bot en weke delen (vergrote handen en oren, diasteem van de tande...
Article
Type 1 diabetes mellitus wordt gekenmerkt door een absoluut tekort aan insuline. Uit eerdere onderzoeken is echter gebleken dat insulineresistentie ook voorkomt bij patiënten met type 1 diabetes mellitus. Welke mechanismen ten grondslag liggen aan het ontstaan van insulineresistentie bij type 1 diabetes mellitus is onvoldoende bekend.
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Glucose and lipid metabolism differ between men and women, and women tend to have better whole-body or muscle insulin sensitivity. This may be explained, in part, by differences in sex hormones and adipose tissue distribution. Few studies have investigated gender differences in hepatic, adipose tissue, and whole-body insulin sensitivity between sev...
Article
The adipokine omentin is highly and selectively expressed in visceral adipose tissue and its circulating levels are decreased in obesity and type 2 diabetes mellitus (T2DM). In this study, we assessed the relationships between plasma omentin levels and cardiometabolic variables in T2DM men and age-matched overweight healthy controls. Next, only in...
Article
The GLP-1 receptor agonist exendin-4 (ex-4) improves glucose intolerance and is currently being used in the treatment of type 2 diabetes mellitus.
Article
Activation of brown adipose tissue (BAT) represents a novel opportunity to increase energy expenditure and weight loss. Glucagon-like peptide-1 (GLP-1) has biological properties which are of particular interest as a tool to treat type 2 diabetes.
Article
Background: The brain is a major target organ for cortisol considering its high density of glucocorticoid receptors. Several states of hypothalamus-pituitary-adrenal dysregulation point towards impairments in cognitive functioning. However, there is a very limited body of research on the effects of hypocortisolism on cognitive functioning. Aim:...
Article
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Glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) agonism, used in the treatment of type 2 diabetes, has recently been shown to increase thermogenesis via the brain. As brown adipose tissue (BAT) produces heat by burning triacylglycerol (TG) and takes up glucose for de novo lipogenesis, the aim of this study was to evaluate the potential of chronic...
Article
Diabetes Mellitus type 2 (T2DM) is geassocieerd met een slechtere kwaliteit van leven (KvL), in vergelijking met een gezonde controlepopulatie. Het is zeer belangrijk om de KvL te verbeteren bij patiënten met T2DM, omdat dit kan leiden tot een beter sociaal functioneren, betere compliantie met de ingestelde behandeling en betere zelfcontrole. In de...
Conference Paper
Elevated basal endogenous glucose production (EGP), impaired suppression of EGP by insulin and reduced insulin-stimulated glucose disposal are cornerstones in the pathogenesis of hyperglycemia in patients with type 2 diabetes. We aimed to determine the contribution of these processes to impaired fasting glucose in obese non-diabetic adults. We ana...
Conference Paper
Non-alcoholic fatty liver disease (NAFLD) and insulin resistance are often associated, but whether intrahepatic triglyceride (IHTG) accumulation and insulin resistance are causally related has been topic of substantial debate. We aimed to evaluate the relationship between liver fat content and insulin sensitivity in obese humans using gold standard...
Article
Background: Hydrocortisone replacement for primary adrenal insufficiency (PAI) is targeted to mimic circadian endogenous cortisol secretion. Nevertheless, patients on stable treatment report impairments in quality of life. The brain is a major target area for cortisol considering it high density of glucocorticoid receptors and previous studies in p...
Article
Experimental studies indicate that short-term fasting alters drug metabolism. However, the effects of short-term fasting on drug metabolism in human need further investigation. Therefore, the aim of this study was to evaluate the effects of short-term fasting (36h) on CYP450-mediated drug metabolism. In a randomized cross-over study design, nine he...
Article
Full-text available
Context and objective: Patients with acromegaly have persistent complaints despite long-term biochemical control. Drawings can be used to assess patients' perceptions about their disease. We aimed to explore the utility of the drawing test and its relation to illness perceptions and quality of life (QoL) in patients after long-term remission of ac...
Conference Paper
Background: Insulin resistance is the major contributor to cardiometabolic complications of obesity including diabetes, cardiovascular disease and mortality. We aimed to 1) determine cutoff points for normal and abnormal insulin sensitivity from euglycemic hyperinsulinemic clamps (EHCs), 2) identify obese humans with and without insulin resistance...
Article
Objective Hypoglycemia is associated with increased heat production and, despite of this, hypothermia. Heat production is likely to be mediated by sympathetic innervation. Brown adipose tissue is activated by cold exposure and stimulated by the sympathetic nervous system. We therefore examined the effect of hypoglycemia on uptake of the labeled glu...
Article
The diurnal variation of the geophysical position of the earth in relation to the sun has imposed considerable evolutionary pressure. The suprachiasmatic nucleus, which serves as the central biological clock, receives the input regarding light-dark through the optic nerves. This nucleus in turn conveys output in a diurnal fashion to other hypothala...
Article
Context: Patients with adrenal insufficiency (AI) require daily and life-long hydrocortisone substitution with risks of under- and overreplacement, the necessity to adjust the dose in stressful situations, and a lack of clinical and biochemical parameters to assess optimal dosing. The spectrum of medication beliefs in patients with AI is currently...
Article
The melanocortin system is an important regulator of energy balance and MC4R deficiency is the most common monogenic cause of obesity. We investigated whether the relationship between melanocortin system activity and energy expenditure is mediated by brown adipose tissue (BAT) activity. Therefore, female APOE*3-Leiden.CETP transgenic mice were fed...
Article
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Introduction Adrenal steroidogenesis is essential for human survival and depends on the availability of the precursor cholesterol. Male subjects with low plasma levels of high density lipoprotein (HDL) cholesterol are characterized by decreased adrenal function. Whether this is also the case in female subjects with low plasma HDL-C levels is unreso...
Article
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Objective: Patients treated for nonfunctioning pituitary macroadenomas (NFMAs) have fatigue and alterations in sleep characteristics and sleep-wake rhythmicity frequently. As NFMAs often compress the optic chiasm, these complaints might be related to dysfunction of the adjacent suprachiasmatic nucleus (SCN). We aimed to explore whether indirect in...
Article
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A high prevalence of psychological morbidity and maladaptive personality as well as impaired quality of life (QoL) is observed in patients with and without hydrocortisone dependency following (cured) Cushing's syndrome. However, it is currently unclear whether a similar pattern is present in patients with chronic glucocorticoid replacement for prim...
Article
Insulin sensitivity is determined by direct effects of circulating insulin on metabolically active tissues in combination with indirect effects of circulating insulin, i.e. via the central nervous system. The dose-response effects of insulin differ between the various physiological effects of insulin. At lower insulin concentrations, circulating in...
Article
Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to Type 2 diabetes in humans. Four potentially functional variants in the coding region of the DRD2/ANKK1 locus (rs107959...
Article
Purpose: To assess the short-term effects of a standardized oral glucose load on regional aortic pulse wave velocity (PWV) using two-directional in-plane velocity encoded MRI. Materials and methods: A randomized, controlled intervention was performed in 16 male subjects (mean ± standard deviation: age: 59±7 years, body mass index: 28±3 kg/m2) wi...
Article
The aetiology of inflammation in the liver and vessel wall, leading to non-alcoholic steatohepatitis (NASH) and atherosclerosis, respectively, shares common mechanisms including macrophage infiltration. To treat both disorders simultaneously, it is highly important to tackle the inflammatory status. Exendin-4, a glucagon-like peptide-1 (GLP-1) rece...
Article
In healthy subjects and patients with uncomplicated type 2 diabetes, short-term very-low-calorie diet (VLCD) increases myocardial triglyceride (TG) content and decreases diastolic cardiac function (1). We hypothesized that in diabetic patients with cardiac complications, the adaptive capacity of the heart to adjust myocardial TG content, depending...
Article
Obesity has been associated with changes in the composition and function of the intestinal microbiota. Modulation of the microbiota by antibiotics also alters bile acid and glucose metabolism in mice. Hence, we hypothesized that short term administration of oral antibiotics in humans would affect fecal microbiota composition and subsequently bile a...
Article
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Important players in triglyceride (TG) metabolism include the liver (production), white adipose tissue (WAT) (storage), heart and skeletal muscle (combustion to generate ATP), and brown adipose tissue (BAT) (combustion towards heat), the collective action of which determine plasma TG levels. Interestingly, recent evidence points at a prominent role...
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Activin A released from epicardial adipose tissue has been linked to contractile dysfunction and insulin resistance in cardiomyocytes. This study investigated the role of activin A in clinical diabetic cardiomyopathy by assessing whether circulating activin A levels associate with cardiometabolic parameters in men with uncomplicated type 2 diabetes...
Article
A very low calorie diet (VLCD) results in cardiac remodeling and improved diastolic function. It is unknown how long these effects sustain after reintroduction of a regular diet. We aimed to assess the long-term effects of initial weight loss by VLCD on cardiac dimensions and function in type 2 diabetes mellitus (T2DM) patients. Fourteen insulin-de...
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Glucocorticoid (GC) overexposure period as observed in Cushing's syndrome (CS) is associated with the metabolic syndrome and cardiovascular disease, which persist after long-term correction of GC excess. We performed a mouse study to identify factors that modulate metabolic recovery from a GC overexposure period. Male C57Bl/6J mice, fed a low-fat d...