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J M Elbers

Publications and source records attributed to J M Elbers.

12 recordsLinked to original sources

Arterial compliance and distensibility are modulated by body composition in both men and women but by insulin sensitivity only in women.

Large artery stiffening could contribute to the development of cardiovascular disease. The aim of this study was to investigate associations between arterial stiffness and diameter with insulin sensitivity and body composition in healthy men and women. In healthy, young (< 41 years old), non-obese (BMI < 27 kg/m2) men (n = 17) and women (n = 17), we measured the arterial diameter, the distension, the distensibility coefficient and the compliance coefficient of the elastic common carotid and muscular femoral arteries with a non-invasive ultrasonographic method. We also assessed glucose uptake (by a euglycaemic hyperinsulinaemic clamp technique), total body fat and lean body mass (by bioelectrical impedance analysis) and abdominal subcutaneous and visceral fat area (by magnetic resonance imaging). In women, but not in men, the distension and distensibility and compliance coefficients of the femoral artery were negatively associated with insulin concentrations (beta = -0.62, p = 0.008; beta = -0.65, p = 0.005 and beta = -0.59, p = 0.01), and positively with glucose uptake (beta = 0.59, p = 0.02; beta = 0.68, p = 0.005 and beta = 0.54, p = 0.04). Associations with glucose uptake were independent of the mean arterial pressure and body composition. In men and women, arterial compliance was positively associated with fat mass variables, which were mediated by a strong association between the femoral artery diameter and lean body mass (beta = 0.80, p < 0.001) and between the common carotid artery diameter and visceral fat area (beta = 0.56, p = 0.001). We found an independent association between insulin resistance and arterial stiffness, which was more pronounced in women than in men.

Abdomen↗

Changes in fat cell size and in vitro lipolytic activity of abdominal and gluteal adipocytes after a one-year cross-sex hormone administration in transsexuals.

We prospectively studied the effects of cross-sex hormone administration on fat cell size and in vitro lipolytic activity in subcutaneous abdominal and gluteal fat biopsies obtained from 19 male-to-female (M-F) transsexuals and 17 female-to-male (F-M) transsexuals. The amount of subcutaneous fat at the abdominal and gluteal levels was quantified with the use of magnetic resonance imaging (MRI). Before cross-sex hormone administration, M-F transsexuals had less subcutaneous fat with smaller fat cells compared with F-M transsexuals, with a higher baseline in vitro lipolytic activity expressed as glycerol release per milligram of triglyceride (TG) in the abdominal region (P < .05). Before cross-sex hormone treatment, no differences in lipolytic activity stimulated with arterenol (ART), isoproterenol (ISO), or ISO + insulin (INS) were observed between groups or regions. After a 1-year treatment with estrogens and antiandrogens in M-F transsexuals, subcutaneous fat areas on MRI and fat cell size were increased (P < .001) and reductions were observed in the basal lipolytic activity of gluteal and abdominal fat biopsies (P < .05). Following administration of testosterone to F-M transsexuals, subcutaneous fat and fat cell size at the gluteal and abdominal depots were decreased (P < .01) and basal lipolysis was increased significantly at the abdominal level (P < .05) but not at the gluteal level. In both M-F and F-M transsexuals, no effect of sex hormone administration was observed on stimulated lipolytic activities. In conclusion, regional sex differences in the amount of subcutaneous fat, adipocyte size, and in vitro basal lipolytic activity were demonstrated that could be largely reversed by cross-sex hormone treatment in adult subjects, providing evidence for their dependence on the sex steroid milieu.

Abdomen↗

Effects of administration of 17beta-oestradiol on serum leptin levels in healthy postmenopausal women.

OBJECTIVE: Women have higher leptin levels than men at a certain degree of adiposity. The role of oestrogens in the regulation of serum leptin levels remains inconclusive. The aim of the present study was to investigate the effect of unopposed oestrogen replacement therapy, during two months, on serum leptin levels in postmenopausal women. DESIGN: A double-blind, placebo-controlled, randomized study. SUBJECTS: Twenty-five healthy postmenopausal women were studied (mean (+/- SD) age: 52.9 +/- 2.7 years, range of age: 48.7-57.4 years; mean body mass index (BMI): 26.4 +/- 4.2 kg/m2, range of BMI: 21.0-39.0 kg/m2). Twelve of these women were treated with 2 mg 17beta-oestradiol daily, and 13 postmenopausal women received placebo. MEASUREMENTS: Before and at the end of a 2-month study period, anthropometric and bio-electrical impedance measurements were performed, and fasting blood samples were taken, to determine serum levels of sex hormones and leptin. RESULTS: During the 2-month study period, body weight had increased significantly in the placebo group compared with the treatment group, but no significant changes were observed in percentage of body fat or the amount of body fat in kg between the groups. Following administration of 17beta-estradiol, the median leptin level increased from 17.6 microg/l to 24.1 microg/l after 2 months (P = 0. 008 compared with baseline). This increase was significantly different from the placebo group (P = 0.019), which showed no change in circulating leptin levels. CONCLUSION: This study demonstrates that unopposed oestrogen replacement therapy during 2 months in postmenopausal women slightly, but significantly, increases total serum leptin levels. This observation suggests a role for oestrogens in the regulation of leptin.

Body Composition↗

Effects of sex steroid hormones on regional fat depots as assessed by magnetic resonance imaging in transsexuals.

We investigated prospectively the effect of sex steroids on regional fat depots and thigh muscle mass in adult transsexuals. Ethinyl estradiol in combination with cyproterone acetate, a progestational antiandrogen, was given to 20 male-to-female (M-F) transsexuals, and parenteral testosterone esters were given to 17 female-to-male (F-M) transsexuals. Before and after 12 mo of cross-sex hormone administration, several anthropometric measurements (weight, skinfolds, body circumferences, and bioimpedance) were performed, and transverse magnetic resonance images were obtained at the level of the abdomen, hip, and thigh to quantify fat depots (subcutaneous and visceral) and muscle areas. We observed that treatment with ethinyl estradiol in M-F transsexuals induced a significant increase in all subcutaneous fat depots, with a lesser but proportional and significant increase in the visceral fat depot and a decrease in thigh muscle area. Testosterone administration in F-M transsexuals markedly increased thigh muscle area, reduced subcutaneous fat deposition at all levels measured, but slightly increased the visceral fat area. We conclude that sex steroid hormones are important determinants of the sex-specific localization of body fat.

Adipose Tissue↗

Sex steroids, insulin, and arterial stiffness in women and Men.

Arterial stiffness may be influenced by sex steroids and insulin; the association with fasting insulin level may be stronger in women than in men. Therefore, we analyzed the effects of sex steroid administration on (1) arterial stiffness and (2) the relationship between fasting insulin level and arterial stiffness. Twelve male-to-female transsexuals were treated with ethinyl estradiol and cyproterone acetate, and 18 female-to-male transsexuals were treated with testosterone esters, with assessments made at baseline and after 4 and 12 months. Changes in distensibility and compliance coefficients (DC and CC, respectively) of the common carotid artery, femoral artery (FA), and brachial artery (BA) were analyzed in relation to changes in fasting plasma levels of glucose, insulin, HDL-cholesterol, and triglycerides. After 4 months of estrogens and antiandrogens in men, significant reductions in the CC and DC of the FA (P=0.006 and P=0.04, respectively) and BA (P=0.04 and P=0.04, respectively) were observed. In women, testosterone, on average, did not affect DC or CC, but the changes in fasting insulin level were strongly negatively associated with changes in the CC and DC, especially in the FA and BA. These associations were significantly less strong in genetic men and were independent of age, mean arterial pressure, and glucose and lipid levels. This experimental study shows (1) that short-term administration of estrogens and antiandrogens increases FA and BA stiffness in men and (2) that the fasting insulin level is a stronger determinant of arterial stiffness in women than in men.

Adolescent↗

Visceral fat accumulation is an important determinant of PAI-1 levels in young, nonobese men and women: modulation by cross-sex hormone administration.

Increased plasminogen activator inhibitor type-1 (PAI-1) levels, leading to impaired fibrinolysis, are associated with increased visceral fat in middle-aged and obese subjects. It is unknown, however, whether this association is independent of other disturbances clustered in the insulin resistance syndrome. We analyzed this association in young, nonobese transsexual men and women before and after administration of cross-sex steroids, which potentially influence many elements of the insulin resistance syndrome, including PAI-1 levels and visceral fat accumulation. We assessed the visceral fat area (by MRI); total body fat; insulin sensitivity (with a glucose clamp technique); and plasma levels of PAI-1, insulin, and triglycerides in young (<37 years old), nonobese (body mass index <28 kg/m2), healthy men (n=18) and women (n=15) before and after 12 months of cross-sex hormone administration. Men were treated with ethinyl estradiol 100 microgram/d plus cyproterone acetate 100 mg/d, and women were treated with testosterone esters 250 mg IM every 2 weeks. At baseline, only visceral fat area was significantly correlated with plasma PAI-1 levels in both men (r=0.57, P=0.03) and women (r=0.59, P=0.03). In multivariate linear regression analysis, this association was independent of total body fat, insulin sensitivity, and plasma levels of triglycerides and insulin. After 12 months of cross-sex hormone administration, the plasma PAI-1 levels were no longer correlated with visceral fat (which had increased). We conclude that in young, nonobese men and women, visceral fat area is an important determinant of plasma PAI-1 levels. After cross-sex hormone administration, this association was no longer demonstrable.

Adipose Tissue↗

Effects of sex steroids on plasma total homocysteine levels: a study in transsexual males and females.

Plasma total homocysteine (tHcy) levels are higher in men vs. premenopausal women, but it is not known whether this difference is related to sex steroids. The effects of cross-sex hormone administration on plasma tHcy levels were therefore investigated. Plasma tHcy levels were measured at baseline and after 4 months of treatment in 17 male-to-female (M-->F) transsexuals treated with ethinyl estradiol (100 micrograms/day), in combination with the antiandrogen, cyproterone acetate (100 mg/day), and in 17 female-to-male (F-->M) transsexuals treated with testosterone esters (250 mg/2 weeks, im). In M-->F transsexuals, the plasma tHcy level decreased from geometric mean 8.2 mumol/L to 5.7 mumol/L (P < 0.001); and in F-->M transsexuals, it increased from 7.7 mumol/L to 9.0 mumol/L (P = 0.005). In M-->F transsexuals, changes in serum sex hormone-binding globulin levels correlated negatively, and changes in plasma creatinine and albumin levels correlated positively, with changes in plasma tHcy levels. In F-->M transsexuals, changes in serum 17 beta-estradiol levels correlated negatively, and changes in plasma creatinine levels correlated positively, with changes in plasma tHcy levels. We conclude that tHcy levels decrease after estrogen + antiandrogen administration to male (transsexual) subjects, and levels increase after androgen administration to female (transsexual) subjects. These changes may be both primary and secondary to the anabolic/catabolic effects, as reflected by changes of creatinine and albumin levels after cross-sex hormone administration.

Androgen Antagonists↗

Reproducibility of fat area measurements in young, non-obese subjects by computerized analysis of magnetic resonance images.

OBJECTIVE: To assess reproducibility, expressed as both inter-observer variability and intra-observer variability, of fat area measurements on images obtained by magnetic resonance (MR); to compare variability between fat area measurements, calculated from a single image per body region and from the average fat area of three images, and to determine reproducibility of image acquisition at the abdominal level. SUBJECTS: Thirty young, non-obese subjects (reproducibility of image analysis) and nine young, non-obese subjects (reproducibility of image acquisition). METHODS: Three MR images at the level of the abdomen (in 30 subjects) and at the level of the hip and thigh (in 14 of them). Quantification of subcutaneous fat depots (abdomen, hip and thigh) and visceral fat depots using an image-analyzing computer program. Assessment of variability of image analysis for fat area measurements between two observers and within observers. Assessment of reproducibility of image acquisition at the abdominal level (in nine subjects). RESULTS: Subcutaneous fat areas in all body regions were quantified with coefficients of variation (CV) ranging from only 2.1%-4.9%. By contrast, visceral fat area measurements showed markedly higher CVs (range: 9.4%-17.6%). Moreover, relative variability was much larger in small visceral fat areas (CVs up to 25.6%). The majority of CVs, calculated for intra-observer variability and calculated from the average fat area measurements of three images, was lower than calculated for inter-observer variability and for one single image, respectively. In particular, for the visceral fat depot, this reduction in variability had practical consequences for the number of subjects required for a study. Variation of repeated image acquisition was in the same range as variation of repeated measurements on the same image. CONCLUSION: One image per body site is sufficient to obtain a reliable estimate of subcutaneous fat depots. For estimations of the visceral fat depot, the average area measurements of three images reduces variability and increases statistical power. The availability of one single experienced observer during a study adds to accuracy.

Abdomen↗

Reversal of the sex difference in serum leptin levels upon cross-sex hormone administration in transsexuals.

Women have higher circulating leptin levels than men. This sex difference is not simply explained by differences in the amount of body fat and is possibly influenced by their different sex steroid milieus. This prompted us to study prospectively the effects of cross-sex steroid hormones on serum leptin levels in 17 male to female transsexuals and 15 female to male transsexuals. Male to female transsexuals were treated with 100 micrograms ethinyl estradiol and 100 mg cyproterone acetate (antiandrogen) daily, and female to male transsexuals received testosterone esters (250 mg/2 weeks, im). Before and after 4 and 12 months of cross-sex hormone treatment, serum leptin levels and measures of body fatness were assessed. Before treatment, female subjects had higher serum leptin levels than male subjects independently of the amount of body fat (P < 0.01). Cross-sex hormone administration induced a reversal of the sex difference in serum leptin levels. Estrogen treatment in combination with antiandrogens in male subjects increased median serum leptin levels from 1.9 ng/mL before treatment to 4.8 ng/mL after 4 months and 5.5 ng/mL after 12 months of treatment (P < 0.0001). Testosterone administration in female subjects decreased median serum leptin levels from 5.6 to 2.6 ng/mL after 4 months and to 2.5 ng/mL after 12 months (P < 0.0001). Analysis of covariance revealed that the changes in serum leptin levels were independent of changes in body fatness in both groups (P < 0.01). In conclusion, these results indicate that sex steroid hormones, in particular testosterone, play an important role in the regulation of serum leptin levels. The prevailing sex steroid milieu, not genetic sex, is a significant determinant of the sex difference in serum leptin levels.

Adipose Tissue↗

Long-term testosterone administration increases visceral fat in female to male transsexuals.

The amount of intraabdominal (visceral) fat is an important determinant of disturbances in lipid and glucose metabolism. Cross-sectional studies in women have found associations between high androgen levels and visceral fat accumulation. The causal relation between these phenomena is unknown. We, therefore, studied prospectively the effect of testosterone administration on body fat distribution in 10 young, nonobese, female to male transsexuals undergoing sex reassignment. Before, after 1 yr, and after 3 yr of testosterone administration, magnetic resonance images were obtained at the level of the abdomen, hip, and thigh to quantify both sc and visceral fat depots. After 1 yr of testosterone administration, sc fat depots at all levels showed significant reductions compared to baseline measurements. The mean visceral fat area did not change significantly, but subjects who gained weight in the first year after testosterone administration showed an increase in visceral fat. After 3 yr of testosterone administration, sc fat depots were no longer significantly lower compared to pretreatment measurements, but the mean visceral fat depot had increased significantly by 13 cm2 (95% confidence interval, 4-22 cm2), a relative increase of 47% (95% confidence interval, 8-91%) from baseline. The increase in visceral fat was most pronounced in those subjects who had gained weight. We conclude that long term testosterone administration in young, nonobese, female subjects increases the amount of visceral fat. In addition, an increase in weight in this hyperandrogenic state leads to a preferential storage of fat in the visceral depot.

Abdomen↗

Decrease of mucosal glutamine concentration in the nutritionally depleted patient.

A diminished glutamine delivery by peripheral tissues is suggested to play an important role in the etiology of postoperative complications of nutritionally depleted patients. Decreased glutamine supply to the gut mucosa in these nutritionally depleted patients may have important consequences for the integrity of the gut mucosa barrier. To evaluate whether glutamine concentration in the gut mucosa of depleted patients is altered, patients with either a fat-free mass index below 90% or percentage ideal body weight below 90% as a result of weight loss were studied. 22 patients admitted to the University Hospital Maastricht and 14 controls were studied. After an overnight fast, venous blood was sampled and duodenal biopsies were obtained by endoscopy. Plasma and tissue amino acids were measured. Fat-free mass was determined by bioelectrical impedance measurement. In 10 depleted patients glutamine concentration in the duodenal mucosa was 2883 +/- 250 mumol/kg dry weight. Concentration of alanine was 2570 +/- 263 mumol/kg dry weight. In the non-depleted patients glutamine and alanine concentrations were respectively 3463 +/- 171 mumol/kg dry weight and 3540 +/- 315 mumol/kg dry weight. Concentrations in controls were 3296 +/- 176 mumol/kg dry weight for glutamine and 3682 +/- 372 mumol/kg dry weight for alanine. Concentrations for alanine and glutamine were significantly lower in depleted patients compared to non-depleted patients (p < 0.05). Also, alanine and glutamine concentrations were significantly correlated with percentage ideal body weight (r=0.43, p < 0.005 for glutamine and r=0.62, p < 0.001 for alanine) and fat-free mass index (r=0.42, p < 0.05 for glutamine and r=0.48, p < 0.01 for alanine) This study suggests that in patients depletion appears to be related to decreased plasma and mucosa glutamine and alanine concentrations.

Journal Article↗