A E Meinders

Leiden University Medical Centre, Leyden, South Holland, Netherlands

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Publications (283)1232.25 Total impact

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    ABSTRACT: South Asians have a higher risk of developing type 2 diabetes than Europeans. The underlying cause of this excess risk is still poorly understood but might be related to differences in the regulation of energy/nutrient-sensing pathways in metabolic tissues and subsequent changes in whole-body substrate metabolism. In this study, we investigated the whole-body and skeletal muscle metabolic adaptations to short-term energy restriction in South Asian and European volunteers.
    Diabetologia 10/2014; · 6.49 Impact Factor
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    ABSTRACT: Macrophage markers in skeletal muscle of obese subjects are elevated and inversely relate to insulin sensitivity. The present study aimed to investigate whether short-term high-fat high-calorie (HFHC) diet already increases macophage markers and affects glucose metabolism in skeletal muscle of healthy lean subjects. Muscle biopsies were obtained from 24 healthy lean young men before and after a 5-day HFHC-diet. mRNA expression levels of relevant genes in muscle and glucose, insulin, C-peptide and cholesteryl ester transfer protein (CETP) levels in plasma were measured. In addition, we assessed hepatic triglyceride content (HTG) by MR-spectroscopy and subcutaneous white adipose tissue (sWAT) biopsies were analyzed histologically from a subset of subjects (n=8). A 5-day HFHC-diet markedly increased skeletal muscle mRNA expression of the general macrophage markers CD68 (3.7-fold, P<0.01) and CD14 (3.2-fold, P<0.01), as well as the M1 macrophage markers MARCO (11.2-fold, P<0.05), CD11c (1.8-fold, P<0.05) and MRC1 (1.7-fold, P<0.05). This was accompanied by downregulation of SLC2A4 and GYS1 mRNA expression, and elevated plasma glucose (+4%, P<0.001) and insulin (+55%, P<0.001) levels together with HOMA-IR (+48%, P<0.001), suggesting development of insulin resistance. Furthermore, the HFHC-diet markedly increased HTG (+118%, P<0.001) and plasma CETP levels (+21%, P<0.001), a marker of liver macrohpage content, while sWAT macrophage content remained unchanged. In conclusion, short-term HFHC-diet increases expression of macrophage markers in skeletal muscle of healthy men accompanied by reduced markers of insulin signaling and development of IR. Therefore, recruitment of macrophages into muscle may be an early event in development of insulin resistance in response to short-term HFHC-feeding.
    Clinical science (London, England : 1979). 08/2014;
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    ABSTRACT: South Asians (SAs) develop type 2 diabetes at a younger age and lower BMI compared with Caucasians (Cs). The underlying cause is still poorly understood but might result from an innate inability to adapt to the Westernized diet. This study aimed to compare the metabolic adaptation to a high-fat, high-calorie (HFHC) diet between both ethnicities. Twelve healthy, young lean male SAs and 12 matched Cs underwent a two-step hyperinsulinemic-euglycemic clamp with skeletal muscle biopsies and indirect calorimetry before and after a 5-day HFHC diet. Hepatic triglyceride content (HTG) and abdominal fat distribution were assessed using magnetic resonance imaging and spectroscopy. At baseline, SAs had higher insulin clamp levels than Cs, indicating reduced insulin clearance rate. Despite the higher insulin levels, endogenous glucose production was comparable between groups, suggesting lower hepatic insulin sensitivity in SAs. Furthermore, a 5-day HFHC diet decreased the insulin-stimulated (nonoxidative) glucose disposal rate only in SA. In skeletal muscle, no significant differences were found between groups in insulin/mammalian target of rapamycin signaling, metabolic gene expression, and mitochondrial respiratory chain content. Furthermore, no differences in (mobilization of) HTG and abdominal fat were detected. We conclude that HFHC feeding rapidly induces insulin resistance only in SAs. Thus, distinct adaptation to Western food may partly explain their propensity to develop type 2 diabetes.
    Diabetes 01/2014; 63(1):248-58. · 7.90 Impact Factor
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    ABSTRACT: Higher insulin levels during an oral glucose test (OGTT) have been shown in South Asians. We aimed to investigate if this increased insulin response causes reactive hypoglycemia later on, and if an increased glucagon-like-peptide-1 (GLP-1) response, which could contribute to the hyperinsulinemia, is present in this ethnic group. A prolonged, 6-h, 75-g OGTT was performed in healthy, young Caucasian (n=10) and South Asian (n=8) men. The glucose, insulin and GLP-1 response was measured and indices of insulin sensitivity and beta-cell activity were calculated. Age (Caucasians (CAU) 21.5±0.7years vs South Asians (SA) 21.4±0.7years (mean±SEM)) and body mass index (CAU 22.7±0.7kg/m(2) vs SA 22.1±0.8kg/m(2)) were comparable between the two groups. South Asian men were more insulin resistant, as indicated by a comparable glucose but significantly higher insulin response, and a significantly lower Matsuda index (CAU 8.7(8.6) vs SA 3.2(19.2), median(IQR)). South Asians showed a higher GLP-1 response, as reflected by a higher area under the curve for GLP-1 (CAU 851±99.8mmol/l vs SA 1235±155.0mmol/L). During the whole 6-h period, no reactive hypoglycemia was observed. Healthy, young South Asian men have higher insulin levels during an OGTT as compared to Caucasians. This does not, however, lead to reactive hypoglycemia. The hyperinsulinemia is accompanied by increased levels of GLP-1. Whether this is an adaptive response to facilitate hyperinsulinemia to overcome insulin resistance or reflects a GLP-1 resistant state has yet to be elucidated.
    Metabolism: clinical and experimental 10/2013; · 3.10 Impact Factor
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    ABSTRACT: 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-dependent T2DM patients (mean ± SEM: age 53 ± 2 years; BMI 35 ± 1 kg/m(2)) were treated by a VLCD (450 kcal/day) during 16 weeks. Cardiac function and myocardial triglyceride (TG) content were measured by magnetic resonance imaging and spectroscopy at baseline, after a 16-week VLCD and after 14 months of follow-up on a regular diet. BMI decreased from 35 ± 1 to 28 ± 1 kg/m(2) after VLCD and increased again to 32 ± 1 kg/m(2) at 18 months (both P < 0.05 vs. baseline). Left ventricular (LV) end-diastolic volume index increased after the 16-week VLCD (80 ± 3 to 89 ± 4 ml/m(2), P < 0.05) and remained increased after follow-up (90 ± 3 ml/m(2); P < 0.05 vs. baseline) at comparable filling pressures. The improvement in LV diastolic function after the 16-week VLCD, was sustained at 18 months [early (E)/atrial (A) diastolic filling phase ratio: 0.96 ± 0.07 (baseline); 1.12 ± 0.06 (after VLCD); 1.06 ± 0.07 (18 months, P < 0.05 vs. baseline)]. Myocardial TG content decreased after the 16-week VLCD [0.74 (0.41-1.10) to 0.45 (0.31-0.54) %, P < 0.05], but returned to baseline levels at 18 months [0.76 (0.65-1.32) %]. Weight reduction by a 16-week VLCD in T2DM patients results in sustained cardiac remodeling and improved diastolic function after 14 months of follow-up, despite weight regain on a regular diet.
    The international journal of cardiovascular imaging 10/2013; · 2.15 Impact Factor
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    Diabetes care 10/2013; 36(10):e178-9. · 7.74 Impact Factor
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    ABSTRACT: The risk of developing T2DM is exceptionally high among both native and migrant South Asians. T2DM occurs more often and at a younger age and lower BMI, and the risk of coronary artery and cerebrovascular disease and renal complications is higher for this ethnicity compared to people of Caucasian descent. The high prevalence of T2DM and its related complications in South Asians, which comprise one fifth of the total world's population, poses a major health and socioeconomic burden. The underlying cause of this excess risk, however, is still not completely understood. Therefore, gaining insight in the pathogenesis of T2DM in South Asians is of great importance. The predominant mechanism in this ethnicity seems to be insulin resistance rather than an impairment in β-cell function. In this systematic review we describe several possible mechanisms that may underlie or contribute to the increased insulin resistance observed in South Asians.
    European Journal of Endocrinology 08/2013; · 3.14 Impact Factor
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    ABSTRACT: - Brown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP1.- It has recently been discovered that BAT is present and active in adults. BAT is situated predominantly around the aorta and in the supraclavicular area.- BAT volume and activity are lower in individuals who are obese. This suggests that BAT significantly contributes to total energy expenditure. .- Several pathological conditions that are accompanied by activation of BAT, such as hyperthyroidism and phaeochromocytoma, result in the increased expenditure of energy and in weight loss.- Various ways in which BAT can be manipulated to increase the expenditure of energy have been identified, e.g. exposure to cold, the use of so-called uncoupling agents or the administration of the hormone irisin.- The activation of BAT could potentially be used to induce weight loss.
    Nederlands tijdschrift voor geneeskunde 01/2013; 157(20):A5502.
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    ABSTRACT: Reduction of 50% excess body weight, using a very low-calorie diet (VLCD; 450 kcal/d) improves insulin sensitivity in obese type 2 diabetes mellitus patients. The objective of the study was to evaluate whether adding exercise to the VLCD has additional benefits. This was a randomized intervention study. The study was conducted at a clinical research center in an academic medical center. Twenty-seven obese [body mass index 37.2 ± 0.9 kg/m(2) (mean ± sem)] insulin-treated type 2 diabetes mellitus patients. Patients followed a 16-wk VLCD. Thirteen of them simultaneously participated in an exercise program (E) consisting of 1-h, in-hospital training and four 30-min training sessions on a cycloergometer weekly. Insulin resistance was measured by a hyperinsulinemic euglycemic clamp. Insulin signaling, mitochondrial DNA (mtDNA) content, and intramyocellular lipid content was measured in skeletal muscle biopsies. Baseline characteristics were identical in both groups. Substantial weight loss occurred (-23.7 ± 1.7 kg VLCD-only vs. -27.2 ± 1.9 kg VLCD+E, P = NS within groups). The exercise group lost more fat mass. Insulin-stimulated glucose disposal increased similarly in both study groups [15.0 ± 0.9 to 39.2 ± 4.7 μmol/min(-1) · kg lean body mass (LBM(-1)) VLCD-only vs. 17.0 ± 1.0 to 37.5 ± 3.5 μmol/min(-1) · kg LBM(-1) in VLCD+E], as did phosphorylation of the phosphatidylinositol 3-kinase-protein kinase B/AKT insulin signaling pathway. In contrast, skeletal muscle mtDNA content increased only in the VLCD+E group (1211 ± 185 to 2288 ± 358, arbitrary units, P = 0.016 vs. 1397 ± 240 to 1196 ± 179, P = NS, VLCD-only group). Maximum aerobic capacity also only increased significantly in the VLCD+E group (+6.6 ± 1.7 ml/min(-1) · kg LBM(-1) vs. +0.7 ± 1.5 ml/min(-1) · kg LBM(-1) VLCD-only, P = 0.017). Addition of exercise to a 16-wk VLCD induces more fat loss. Exercise augments maximum aerobic capacity and skeletal muscle mtDNA content. These changes are, however, not reflected in a higher insulin-stimulated glucose disposal rate.
    The Journal of Clinical Endocrinology and Metabolism 05/2012; 97(7):2512-20. · 6.31 Impact Factor
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    ABSTRACT: To evaluate whether the addition of exercise to a very low calorie diet (VLCD) has beneficial short- and long-term effects on health-related quality of life (QoL) in obese patients with type 2 diabetes mellitus (T2DM). We included 27 obese, insulin-dependent T2DM patients in a 16-week VLCD study, of whom 13 participated simultaneously in an exercise program (VLCD+E). Before, immediately after and 18 months after the intervention anthropometric measurements, glucoregulation and QoL (SF-36, HADS, NHP and MFI-20) were assessed. Patients were compared to healthy lean and obese (matched for body mass index) controls matched for gender and age. At baseline, T2DM patients had significantly worse QoL scores in 18 and 14 of the 22 subscales of the QoL questionnaires, compared to lean and obese controls, resp. The 16-week VLCD (n=27) decreased bodyweight (-25.4±1.3 kg, p<0.0001, p=0.179 between groups), and improved glucoregulation (HbA1c -1.3±0.3%, p<0.0001, p=0.488 between groups) and 9 (VLCD-only) and 11 (VLCD+E) of the 22 subscales of QoL. After 18 months, in the VLCD+E group the QoL subscales did not differ from those in obese controls and only 4 of the 22 subscales were significantly worse compared to lean controls. However, in the VLCD-only group 17 and 13 of the 22 QoL subscales were significantly worse compared to the lean and obese controls, resp. A 16-week VLCD induces considerable weight loss, metabolic amelioration, and major improvements in QoL in obese T2DM patients. The addition of exercise is of paramount importance for the maintenance of better QoL.
    European Journal of Internal Medicine 03/2012; 23(2):143-9. · 2.30 Impact Factor
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    ABSTRACT: Pericardial fat accumulation has been associated with an increased cardiovascular risk. A very low calorie diet (VLCD) improves the cardiovascular risk profile in patients with type 2 diabetes mellitus (T2DM), by improving the metabolic profile, heart function, and triglyceride (TG) stores in (non)adipose tissues. However, long-term effects of a VLCD on pericardial fat volume and tissue-specific TG accumulation have not been documented. The aim of this study was therefore to assess the effects of a 16-week VLCD and of subsequent 14 months follow-up on a regular diet on pericardial fat in relation to other TG stores in obese T2DM patients. We included 14 obese patients with insulin-treated T2DM (mean ± s.e.m.: age 53 ± 2 years; BMI 35 ± 1 kg/m(2)). Pericardial fat and other (non)adipose TG stores were measured using magnetic resonance (MR) imaging and proton spectroscopy before and after a 16-week VLCD and after a 14-month follow-up without dietary interventions. A 16-week VLCD reduced body weight, pericardial fat, hepatic TG content, visceral and subcutaneous abdominal fat volumes to 78, 83, 16, 40, and 53% of baseline values respectively, (all P < 0.05). After an additional 14 months of follow-up on a regular diet, the reduction in pericardial fat volume sustained, despite a substantial regain in body weight, visceral abdominal fat, and hepatic TG content (respectively 90, 83 and 73% of baseline values). In conclusion, VLCD-induced weight loss in obese T2DM patients is accompanied by a substantial decrease in pericardial fat volume, which is sustained even after subsequent weight regain.
    Obesity 01/2012; 20(8):1572-6. · 3.92 Impact Factor
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    ABSTRACT: The storage of triglyceride (TG) droplets in nonadipose tissues is called ectopic fat storage. Ectopic fat is associated with insulin resistance and type 2 diabetes mellitus (T2DM). Not the triglycerides per se but the accumulation of intermediates of lipid metabolism in organs, such as the liver, skeletal muscle, and heart seem to disrupt metabolic processes and impair organ function. We describe the mechanisms of ectopic fat depositions in the liver, skeletal muscle, and in and around the heart and the consequences for each organs function. In addition, we systematically reviewed the literature for the effects of diet-induced weight loss and exercise on ectopic fat depositions.
    International Journal of Endocrinology 01/2012; 2012:983814. · 2.52 Impact Factor
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    ABSTRACT: To assess the short- and long-term effects of addition of exercise to a very low calorie diet (VLCD) on low-grade inflammation in obese patients with type 2 diabetes mellitus (T2DM). Twenty seven obese, insulin-dependent T2DM patients followed a 4-month VLCD with (n=13) or without (n=14) exercise and were followed up to 18 months. Anthropometric measurements, metabolic and inflammatory parameters were assessed before, directly after the intervention and at 6 and 18 months follow-up. The same measurements were performed only once in 56 healthy lean and 56 healthy obese controls. At baseline hsCRP, IL10 and IL8 were significantly elevated in obese T2DM compared to lean healthy controls. After 4 months, despite substantial weight loss (-25.4 ± 1.3 kg), neither the VLCD nor VLCD+exercise had an effect on plasma cytokines. At 6 months, in the weight-stabilizing period, measures of low-grade inflammation had decreased substantially and equally in both intervention groups. Despite subsequent weight regain, beneficial effect was sustained up to 18 months in both groups, except for IL1 and hsCRP which had returned to baseline in the VLCD-only group. Our findings suggest that severe caloric restriction increases cytokine production by adipose tissue macrophages and that the beneficial effects of weight loss become apparent only in the eucaloric state.
    Food and chemical toxicology: an international journal published for the British Industrial Biological Research Association 12/2011; 49(12):3104-11. · 2.99 Impact Factor
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    ABSTRACT: Using a mouse model for human-like lipoprotein metabolism, we observed previously that reduction of the hepatic triglyceride (TG) content resulted in a decrease in plasma cholesteryl ester transfer protein (CETP) and an increase in HDL levels. The aim of the current study was to investigate the effects of prolonged caloric restriction in obese patients with type 2 diabetes mellitus, resulting in a major reduction in hepatic TG content, on plasma CETP and HDL levels. We studied 27 obese (BMI: 37.2 ± 0.9 kg/m(2)) insulin-dependent patients with type 2 diabetes mellitus (14 men and 13 women, aged 55 ± 2 years) who received a 16-week very low calorie diet (VLCD). At baseline and after a 16-week VLCD, plasma lipids, lipoproteins, and CETP were measured. Furthermore, functionality of HDL with respect to inducing cholesterol efflux from human monocyte cells (THP-1) was determined. A 16-week VLCD markedly decreased plasma CETP concentration (-18%; P < 0.01) and increased plasma apolipoprotein (apo)AI levels (+16%; P < 0.05), without significantly affecting plasma HDL-cholesterol and HDL-phospholipids. Although a VLCD results in HDL that is less lipidated, the functionality of HDL with respect to inducing cholesterol efflux in vitro was unchanged. The marked decrease in hepatic TG content induced by a 16-week VLCD is accompanied by a decrease in plasma CETP concentration and an increase in apoAI levels, without improving the cholesterol efflux properties of HDL in vitro.
    Diabetes care 12/2011; 34(12):2576-80. · 7.74 Impact Factor
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    Journal of Cardiovascular Magnetic Resonance 01/2011; 13:1-1. · 4.44 Impact Factor
  • A J Meinders, F H Bosch, A E Meinders
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    ABSTRACT: - A negative water and sodium balance develops during the first hours to days after reaching a high altitude.- The fluid and sodium balance does not alter in cases of altitude sickness, or may even become positive.- This is attributed to a decreased diuresis and natriuresis in those who develop altitude sickness, while their fluid intake is no different to that of people who do not suffer from altitude sickness.- This is a consequence of stimulation of the renin-angiotensin-aldosterone system (RAAS) and an increased secretion of antidiuretic hormone (ADH) combined with a higher than normal sympathetic activity.- Therefore there is no argument for an increased fluid intake for the prevention of altitude illness. In theory this might even be harmful.
    Nederlands tijdschrift voor geneeskunde 01/2011; 155(29):A3526.
  • Nederlands tijdschrift voor geneeskunde 06/2009; 153(19):920-5.
  • I M Jazet, A E Meinders
    European Journal of Internal Medicine 06/2009; 20(3):232-5. · 2.30 Impact Factor
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    ABSTRACT: Diurnal TSH secretion is enhanced in obese premenopausal women. Dopamine inhibits TSH secretion through activation of dopamine D(2) receptors (D(2)R). Dopamine D(2)R availability in the brain is reduced in obese humans in proportion to body adiposity. We hypothesized that deficient dopamine D(2)R signaling is involved in the enhanced TSH secretion associated with obesity. The effect of short-term bromocriptine treatment on spontaneous TSH secretion in obese women was studied while body weight and caloric intake remained constant. We conducted a prospective, fixed-order, crossover study in a Clinical Research Center. Seventeen obese women (body mass index, 33.2 +/- 0.6 kg/m(2)) were studied twice in the early follicular phase of their menstrual cycle. Subjects were treated for 8 d with placebo and bromocriptine. Blood was collected for 24 h at 10-min intervals, and TSH and leptin were analyzed with deconvolution and correlation techniques, approximate entropy, and cosine regression. Bromocriptine reduced 24-h TSH secretion (placebo, 29.8 +/- 4.6 mU/liter . 24 h, vs. bromocriptine, 22.4 +/- 3.7 mU/liter . 24 h; P = 0.001), whereas free T(4) and total T(3) concentrations did not change. Bromocriptine administration reduced the mesor and amplitude of the 24-h rhythm without resetting the phase. The regularity of the subordinate TSH pattern and synchrony between leptin and TSH were unaffected by bromocriptine. Activation of dopamine D(2)R by bromocriptine reverses enhanced diurnal TSH secretion in obese women. Thus, reduced dopaminergic neuronal signaling might be involved in the perturbation of the thyrotrope hormonal axis in obese premenopausal women.
    The Journal of Clinical Endocrinology and Metabolism 03/2009; 94(4):1176-81. · 6.31 Impact Factor
  • Ingrid M Jazet, A Edo Meinders
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    ABSTRACT: Several meta-analyses imply that rosiglitazone increases the risk of myocardial infarction. However, the studies included were small and not designed to study the effect on cardiovascular risk. The Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycaemia in Diabetes study (RECORD) was specifically designed to assess the effect of rosiglitazone on cardiovascular outcomes. After a mean follow-up of 5.5 years, the study showed no increase in cardiovascular hospitalisation or cardiovascular mortality with rosiglitazone and either metformin or sulphonylurea versus metformin/sulphonylurea combination therapy. There was a non-significant increase in myocardial infarction with rosiglitazone, but this did not result in increased mortality rates. Moreover, the Bypass Angioplasty revascularisation Investigation 2 Diabetes study (BARI 2D) showed no increase in myocardial infarction or cardiovascular death in type 2 diabetic patients with coronary disease who received insulin-sensitising therapy including rosiglitazone. Therefore, rosiglitazone can be prescribed as long as the indications are followed and the patients concerned do not have heart failure or an increased risk for this.
    Nederlands tijdschrift voor geneeskunde 01/2009; 153:A942.

Publication Stats

6k Citations
1,232.25 Total Impact Points

Institutions

  • 1987–2014
    • Leiden University Medical Centre
      • Department of Infectious Diseases
      Leyden, South Holland, Netherlands
  • 2011
    • Antonius Ziekenhuis
      Sneek, Friesland, Netherlands
  • 1994–2002
    • Leiden University
      • Leiden Amsterdam Center for Drug Research
      Leyden, South Holland, Netherlands
    • University of Amsterdam
      • Central Laboratory of the Netherlands Red Cross Blood Transfusion Service
      Amsterdam, North Holland, Netherlands
  • 2000
    • Franciscus Ziekenhuis
      Roosendaal, North Brabant, Netherlands
  • 1999
    • Catharina Hospital
      Eindhoven, North Brabant, Netherlands
  • 1998
    • TNO
      Delft, South Holland, Netherlands
  • 1997
    • Onze Lieve Vrouwe Gasthuis
      Amsterdamo, North Holland, Netherlands
  • 1985
    • University Medical Center Utrecht
      • Department of Endocrinology
      Utrecht, Utrecht, Netherlands