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A Edo Meinders

Publications and source records attributed to A Edo Meinders.

35 records · Page 2Linked to original sources

Enhanced circadian ACTH release in obese premenopausal women: reversal by short-term acipimox treatment.

Several studies suggest that the hypothalamo-pituitary-adrenal (HPA) axis is exceedingly active in obese individuals. Experimental studies show that circulating free fatty acids (FFAs) promote the secretory activity of the HPA axis and that human obesity is associated with high circulating FFAs. We hypothesized that HPA axis activity is enhanced and that lowering of circulating FFAs by acipimox would reduce spontaneous secretion of the HPA hormonal ensemble in obese humans. To evaluate these hypotheses, diurnal ACTH and cortisol secretion was studied in 11 obese and 9 lean premenopausal women (body mass index: obese 33.5 +/- 0.9 vs. lean 21.2 +/- 0.6 kg/m(2), P < 0.001) in the early follicular stage of their menstrual cycle. Obese women were randomly assigned to treatment with either acipimox (inhibitor of lipolysis, 250 mg orally four times daily) or placebo in a double-blind crossover design, starting one day before admission until the end of the blood-sampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of plasma ACTH and cortisol concentrations. ACTH and cortisol secretion rates were estimated by multiparameter deconvolution analysis. Daily ACTH secretion was substantially higher in obese than in lean women (7,950 +/- 1,212 vs. 2,808 +/- 329 ng/24 h, P = 0.002), whereas cortisol was not altered (obese 36,362 +/- 5,639 vs. lean 37,187 +/- 4,239 nmol/24 h, P = 0.912). Acipimox significantly reduced ACTH secretion in the obese subjects (acipimox 5,850 +/- 769 ng/24 h, P = 0.039 vs. placebo), whereas cortisol release did not change (acipimox 33,542 +/- 3,436 nmol/24 h, P = 0.484 vs. placebo). In conclusion, spontaneous ACTH secretion is enhanced in obese premenopausal women, whereas cortisol production is normal. Reduction of circulating FFA concentrations by acipimox blunts ACTH release in obese women, which suggests that FFAs are involved in the pathophysiology of this neuroendocrine anomaly.

Adrenocorticotropic Hormone↗

Incidence and risk factors of early venous thrombosis associated with permanent pacemaker leads.

INTRODUCTION: Pacemaker lead implantation can cause thrombosis, which can be associated with serious local morbidity and complicated by pulmonary embolism. Few reliable estimates of the incidence of thrombosis have been reported. The contribution of established risk factors to venous thrombosis in patients with implanted pacemaker leads is unknown. METHODS AND RESULTS: One hundred forty-five consecutive patients n = 145) underwent routine clinical and Doppler ultrasound evaluation for thrombosis before and 3, 6, and 12 months after lead implantation. Established risk factors for venous thrombosis were assessed in detail for all patients. Clinical outcome, including clinically manifest thrombosis, pulmonary embolism, associated pacemaker lead infection, complicated reinterventions, and death, was evaluated. Thrombosis was observed in 34 (23%) of 145 patients. Thrombosis did not cause any signs or symptoms in 31 patients but resulted in overt clinical symptoms in 3 patients. The absence of anticoagulant therapy, use of hormone therapy, and a personal history of venous thrombosis were associated with an increased risk of thrombosis. The risk of thrombosis increased in the presence of multiple pacemaker leads compared to a single lead. CONCLUSION: Established risk factors for venous thrombosis and the presence of multiple pacemaker leads contribute substantially to the occurrence of thrombosis associated with permanent pacemaker leads. Risk factor assessment prior to implantation may be useful for identifying patients at risk for thrombotic complications. Preventive management in these patients is warranted.

Adult↗

Prolactin release is enhanced in proportion to excess visceral fat in obese women.

Prolactin (PRL) promotes (visceral) fat accrual in a variety of animal models. The release of PRL by the pituitary is tonically inhibited by dopamine through activation of the dopamine D2 receptor (D2R) of lactotroph cells, and obese humans appear to have reduced D2R-binding sites in their brain. Therefore, we hypothesized that spontaneous PRL release is enhanced in obese humans. To evaluate this hypothesis, we measured 24-h plasma PRL concentrations at 10-min intervals in 11 obese premenopausal women [body mass index (BMI), 33.3 +/- 0.7 kg/m(2)] and 10 lean premenopausal women of similar age (BMI, 21.2 +/- 0.6 kg/m(2)). Total body fat was determined using dual energy x-ray absorptiometry, and sc and visceral fat area was measured by magnetic resonance imaging in 10 obese subjects. PRL secretion rate was estimated by deconvolution analysis. All subjects were studied in the early follicular stage of their menstrual cycle. PRL secretion was significantly enhanced in obese women (total daily release, 137 +/- 8; lean controls, 92 +/- 8 microg/liter.24 h; P = 0.001) in proportion to their BMI (r(2) = 0.55; P < 0.001). Interestingly, PRL release was particularly associated with the size of the visceral fat mass (total PRL secretion vs. visceral fat area, r(2) = 0.64; P = 0.006). These data show that spontaneous PRL release is considerably enhanced in obese women in proportion to the size of their visceral fat mass. Because PRL is inhibited by D2R activation we speculate that elevated PRL secretion may be due to reduced D2R availability in the brain.

Adipose Tissue↗

Two-year statin therapy does not alter the progression of intima-media thickness in patients with type 2 diabetes without manifest cardiovascular disease.

OBJECTIVE: Cardiovascular disease (CVD) is the most important cause of mortality in patients with type 2 diabetes. We aimed to determine the effect of statin therapy versus placebo on the progression of carotid intima-media thickness (IMT) in type 2 diabetic patients without manifest CVD. RESEARCH DESIGN AND METHODS: A randomized, placebo-controlled, double-blind clinical trial was performed in 250 patients with type 2 diabetes. Patients were given either 0.4 mg cerivastatin or placebo daily. In August 2001, when cerivastatin was withdrawn from the market, 0.4 mg cerivastatin was replaced by 20 mg simvastatin without deblinding the study. The primary end point was the change of mean common carotid IMT, as measured by B-mode ultrasound, over 2 years. RESULTS: Common carotid IMT at baseline was 0.780 mm in the placebo group and 0.763 mm in the statin group and did not change significantly after 2 years. There was no significant difference in IMT change in any carotid segment between the groups. LDL cholesterol was reduced by 25% in the statin group and increased by 8% in the placebo group (P <0.001). Cardiovascular events occurred in 12 patients in the placebo group and two patients in the statin group (P=0.006). CONCLUSIONS: There was no effect of 2 years' statin therapy on carotid IMT in type 2 diabetic subjects. The natural history of IMT in our patients was milder than anticipated. In contrast, we observed a significantly lower cardiovascular event rate on statin therapy. Prognostic tools other than IMT should be explored in this patient group.

Body Mass Index↗

The contribution of factor V Leiden and prothrombin G20210A mutation to the risk of central venous catheter-related thrombosis.

BACKGROUND AND OBJECTIVES: The purpose of this study was to assess the incidence of central venous catheter (CVC)-related thrombosis and the contribution of two common inherited coagulation disorders (factor V Leiden, prothrombin G20210A mutation) to this complication in a large hospital population. DESIGN AND METHODS: In a prospective setting, patients were assessed daily for signs and symptoms suggestive of thrombosis. Routine Doppler-ultrasound was performed weekly in all patients until CVC removal. Doppler-ultrasound examinations were stored on videotape and assessed by two blinded observers. In the case of clinically suspected thrombosis the physicians followed routine diagnostic and therapeutic procedures. The presence of factor V Leiden and prothrombin G20210A mutation and other potential risk factors were assessed in all patients. RESULTS: In 252 consecutive patients the cumulative incidence of-CVC related thrombosis was 30% (clinically manifested thrombosis: 7%). The relative risk of factor V Leiden or prothrombin G20210A mutation for thrombosis was 2.7 (CI95% 1.9 to 3.8). In addition, a personal history of venous thrombosis was associated with CVC-related thrombosis, whereas the severity of thrombosis was affected by the absence of anticoagulants and the presence of cancer. INTERPRETATION AND CONCLUSIONS: Thrombosis is frequently observed after central venous catheterization. Common inherited abnormalities in blood coagulation contribute substantially to CVC-related thrombosis. In view of physicians' reluctance to prescribe prophylactic anticoagulant treatment in vulnerable patients, a priori determination of common inherited and acquired risk factors may form a basis to guide these treatment decisions.

5' Untranslated Regions↗

Retention of estradiol negative feedback relationship to LH predicts ovulation in response to caloric restriction and weight loss in obese patients with polycystic ovary syndrome.

The present study tests the hypothesis that specific endocrine, metabolic, and anthropometric features distinguish obese women with polycystic ovary syndrome (PCOS) who resume ovulation in response to calorie restriction and weight loss from those who do not. Fifteen obese (body mass index 39 +/- 7 kg/m(2)) hyperandrogenemic oligoovulatory patients undertook a very low calorie diet (VLCD), wherein each lost > or =10% of body weight over a mean of 6.25 mo. Body fat distribution was quantitated by magnetic resonance imaging. Hormones were measured in the morning at baseline, after 1 wk of VLCD, and after 10% weight loss. To monitor LH release, blood was sampled for 24 h at 10-min intervals before intervention and after 7 days of VLCD. Responders were defined a priori as individuals exhibiting two or more ovulatory cycles in the course of intervention, as corroborated by serum progesterone concentrations > or =18 nmol/l followed by vaginal bleeding. At baseline, responders had a higher sex hormone-binding globulin (SHBG) concentration but were otherwise indistinguishable from nonresponders. Body weight, the size of body fat depots, and plasma insulin levels declined to a similar extent in responders and nonresponders. Also, SHBG increased, and the free testosterone index decreased comparably. However, responders exhibited a significant decline of circulating estradiol concentrations (from 191 +/- 82 to 158 +/- 77 pmol/l, means +/- SD, P = 0.037) and a concurrent increase in LH secretion (from 104 +/- 42 to 140 +/- 5 U.l(-1).day(-1), P = 0.006) in response to 7 days of VLCD, whereas neither parameter changed significantly in nonresponders. We infer that evidence of retention of estradiol-dependent negative feedback on LH secretion may forecast follicle maturation and ovulation in obese patients with PCOS under dietary restriction.

Adult↗

Acipimox enhances spontaneous growth hormone secretion in obese women.

We hypothesized that a high circulating free fatty acid (FFA) concentration is involved in the pathogenesis of hyposomatotropism associated with obesity. To evaluate this hypothesis, 10 healthy premenopausal women (body mass index 33.8 +/- 1.0 kg/m(2)) were studied in the follicular phase of their menstrual cycle at two occasions with a time interval of at least 8 wk, where body weight remained stable. Subjects were randomly assigned to treatment with either acipimox (an inhibitor of lipolysis, 250 mg orally 4 times daily) or placebo in a double-blind crossover design, starting 1 day before admission until the end of the blood sampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of growth hormone (GH) concentrations, and GH secretion was estimated by deconvolution analysis. Identical methodology was used to study GH secretion in a historical control group of age-matched normal weight women. GH secretion was clearly blunted in obese women (total daily release 66 +/- 10 vs. lean controls: 201 +/- 23 mU x l(Vd)(-1) x 24 h(-1), P = 0.005, where l(Vd) is lite of distribution volume). Acipimox considerably enhanced total (113 +/- 50 vs. 66 +/- 10 mU x l(Vd)(-1) x 24 h(-1), P = 0.02) and pulsatile GH secretion (109 +/- 49 vs. 62 +/- 30 mU x l(Vd)(-1) x 24 h(-1), P = 0.02), but GH output remained lower compared with lean controls. Further analysis did not show any relationship between the effects of acipimox on GH secretion and regional body fat distribution. In conclusion, acipimox unleashes spontaneous GH secretion in obese women. It specifically enhances GH secretory burst mass. This might mean that lowering of systemic FFA concentrations by acipimox modulates neuroendocrine mechanisms that orchestrate the activity of the somatotropic ensemble.

Adipose Tissue↗

Central venous catheter related thrombosis in haematology patients and prediction of risk by screening with Doppler-ultrasound.

Patients with a central venous catheter (CVC) who receive intensive chemotherapy or a stem cell transplantation for haematological disease are at risk for developing CVC-related thrombosis. To study the incidence of thrombosis, 105 consecutive patients underwent serial Doppler-ultrasound and we evaluated whether clinically manifest thrombosis could be predicted by screening with Doppler-ultrasound. Patients with subclavian or jugular inserted CVCs were clinically assessed each day for signs and symptoms of thrombosis. Additional Doppler-ultrasound screens were performed weekly by an independent physician in all patients until CVC removal. Doppler-ultrasound recordings were assessed by two blinded observers. In cases of clinically suspected thrombosis, the attending physicians followed routine diagnostic and therapeutic procedures. The overall cumulative incidence of CVC-related thrombosis was 28.6% (30 of 105 patients). Of the 30 patients with thrombosis, 26 had subclinical thrombosis by Doppler-ultrasound, nine of whom developed clinically manifest thrombosis later. Four patients had clinically manifest thrombosis without prior abnormal Doppler-ultrasound. In cases of subclinical thrombosis the risk of developing symptomatic disease increased sevenfold (34.6% vs. 5.1%). Doppler-ultrasound screening may be useful to identify those patients that are at high and low risk for clinically manifest CVC-related thrombosis.

Catheterization, Central Venous↗

Blunted lipolytic response to fasting in abdominally obese women: evidence for involvement of hyposomatotropism.

BACKGROUND: Abdominal obesity is associated with a blunted lipolytic response to fasting that may contribute to the preservation of adipose tissue mass. OBJECTIVE: To further explore the pathophysiology of blunted lipolysis during fasting in obesity, we simultaneously measured lipolysis and distinct neuroendocrine regulatory hormones in abdominally obese and normal-weight (NW) women. DESIGN: Eight abdominally obese [x +/- SD body mass index (BMI; in kg/m(2)): 32.1 +/- 2.6] and 6 NW (BMI: 22.7 +/- 1.5) women were studied during the last 8 h of a 20-h fast. The glycerol appearance rate and the serum and plasma concentrations of insulin, leptin, cortisol, and growth hormone were measured regularly. RESULTS: At 13 h of fasting, the mean (+/-SD) glycerol appearance rate corrected for fat mass was greater in NW women than in obese women (7.2 +/- 1.0 and 5.1 +/- 0.6 micro mol.kg(-1).min(-1), respectively; P = 0.001). After a 20-h fast, lipolysis increased to 8.9 +/- 1.5 mmol.kg(-1).min(-1) in NW women (23%), whereas it did not change significantly in obese women (-2%). Fasting decreased insulin concentrations by approximately 30% in both groups, but it did not induce significant changes in leptin concentrations. Mean cortisol concentrations and urinary catecholamine excretion were comparable in both groups. However, mean plasma growth hormone concentrations were higher in NW women than in obese women (1.81 +/- 0.98 compared with 0.74 +/- 0.52 mU/L; P = 0.046). The relative change in lipolysis tended to correlate with mean plasma growth hormone concentrations (r = 0.515, P = 0.059). CONCLUSION: Abdominal obesity-associated hyposomatotropism may be involved in the blunted increase in lipolysis during fasting.

Abdomen↗

Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial.

BACKGROUND: Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals, their efficacy and safety in elderly people is not fully established. Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with, or at high risk of developing, cardiovascular disease and stroke. METHODS: We did a randomised controlled trial in which we assigned 5804 men (n=2804) and women (n=3000) aged 70-82 years with a history of, or risk factors for, vascular disease to pravastatin (40 mg per day; n=2891) or placebo (n=2913). Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke. Analysis was by intention-to-treat. FINDINGS: Pravastatin lowered LDL cholesterol concentrations by 34% and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo (hazard ratio 0.85, 95% CI 0.74-0.97, p=0.014). Coronary heart disease death and non-fatal myocardial infarction risk was also reduced (0.81, 0.69-0.94, p=0.006). Stroke risk was unaffected (1.03, 0.81-1.31, p=0.8), but the hazard ratio for transient ischaemic attack was 0.75 (0.55-1.00, p=0.051). New cancer diagnoses were more frequent on pravastatin than on placebo (1.25, 1.04-1.51, p=0.020). However, incorporation of this finding in a meta-analysis of all pravastatin and all statin trials showed no overall increase in risk. Mortality from coronary disease fell by 24% (p=0.043) in the pravastatin group. Pravastatin had no significant effect on cognitive function or disability. INTERPRETATION: Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals. PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people.

Aged↗

A Prospective Study of Pravastatin in the Elderly at Risk (PROSPER): Screening Experience and Baseline Characteristics.

BACKGROUND: PROSPER was designed to investigate the benefits of treatment with pravastatin in elderly patients for whom a typical doctor might consider the prescription of statin therapy to be a realistic option. METHODS: The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomised, double blind, placebo-controlled trial to test the hypothesis that treatment with pravastatin (40 mg/day) will reduce the risk of coronary heart disease death, non-fatal myocardial infarction, and fatal or non-fatal stroke in elderly men and women with pre-existing vascular disease or with significant risk of developing this condition. RESULTS: In Scotland, Ireland, and the Netherlands, 23,770 individuals were screened, and 5,804 subjects (2,804 men and 3,000 women), aged 70 to 82 years (average 75 years) and with baseline cholesterol 4.0-9.0 mmol/l, were randomised. Randomised subjects had similar distributions with respect to age, blood pressure, and body mass index when compared to the entire group of screenees, but had a higher prevalence of smoking, diabetes, hypertension, and a history of vascular disease. The average total cholesterol level at baseline was 5.4 mmol/l (men) and 6.0 mmol/l (women). CONCLUSIONS: Compared with previous prevention trials of cholesterol-lowering drugs, the PROSPER cohort is significantly older and for the first time includes a majority of women. The study, having achieved its initial goal of recruiting more than 5,500 elderly high-risk men and women, aims to complete all final subject follow-up visits in the first half of 2002 with the main results being available in the fourth quarter of 2002.

Journal Article↗

Testing cognitive function in elderly populations: the PROSPER study. PROspective Study of Pravastatin in the Elderly at Risk.

OBJECTIVES: For large scale follow up studies with non-demented patients in which cognition is an endpoint, there is a need for short, inexpensive, sensitive, and reliable neuropsychological tests that are suitable for repeated measurements. The commonly used Mini-Mental-State-Examination fulfils only the first two requirements. METHODS: In the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), 5804 elderly subjects aged 70 to 82 years were examined using a learning test (memory), a coding test (general speed), and a short version of the Stroop test (attention). Data presented here were collected at dual baseline, before randomisation for active treatment. RESULTS: The tests proved to be reliable (with test/retest reliabilities ranging from acceptable (r=0.63) to high (r=0.88) and sensitive to detect small differences in subjects from different age categories. All tests showed significant practice effects: performance increased from the first measurement to the first follow up after two weeks. CONCLUSION: Normative data are provided that can be used for one time neuropsychological testing as well as for assessing individual and group change. Methods for analysing cognitive change are proposed.

Aged↗

Increase in daily LH secretion in response to short-term calorie restriction in obese women with PCOS.

We hypothesized that short-term calorie restriction would blunt luteinizing hormone (LH) hypersecretion in obese women with polycystic ovary syndrome (PCOS) and thereby ameliorate the anovulatory endocrine milieu. To test this hypothesis, 15 obese patients with PCOS and nine age- and body mass index-matched healthy women underwent 24-h blood sampling to quantitate plasma LH, leptin, and insulin levels. PCOS subjects were prescribed a very low caloric liquid diet (4.2 MJ/day) for 7 days and were then resampled. Basal and pulsatile LH secretion was threefold higher in PCOS subjects, but plasma insulin and leptin levels were not different in the calorie-replete state. Contrary to expectation, calorie restriction enhanced basal and pulsatile LH secretion even further. As expected, plasma glucose, insulin, and leptin concentrations decreased by 18, 75, and 50%, respectively. Serum total testosterone concentration fell by 23%, whereas serum estrone, estradiol, sex hormone-binding globulin (SHBG), and androstenedione concentrations remained unchanged. Enhanced LH secretion in the presence of normal metabolic and hormonal adaptations to calorie restriction points to anomalous feedback control of pituitary LH release in PCOS.

Adult↗

Low amplitude and disorderly spontaneous growth hormone release in obese women with or without polycystic ovary syndrome.

Obesity is associated with considerably reduced plasma GH concentrations, which may contribute to anovulation in (obese) women with polycystic ovary disease (PCOS). This clinical investigation was undertaken to establish whether the GH release process is deranged in obese women with PCOS and, if so, whether the observed anomalies are features of the syndrome or a sequel of body fat accretion. To this end we sampled 24-h plasma GH concentration profiles at 10-min intervals in 15 obese PCOS patients [mean age, 29 yr (range, 20-38); percent body fat, 47 +/- 5.2%], 15 equally obese controls with regular menstrual cycles [age, 34 yr (range, 20-44); percent body fat, 48 +/- 4.9%], and 15 healthy age-matched lean controls [age, 34 yr (range, 21-45); percent body fat, 29 +/- 9.0%]. Compared with lean controls, obese PCOS patients exhibited a greater than 60% reduction in basal and a greater than 75% reduction in pulsatile and total daily GH secretion due to a 2.7-fold attenuation of burst mass and a lesser (1.4-fold) slowing of GH pulse frequency. The mean +/- SEM number of statistically significant GH peaks was 13.9 +/- 1.2/24 h, the endogenous GH half-life was 14.1 +/- 0.4 min, basal GH secretion was 5.0 +/- 0.7 mU/liter.24 h, and total secretion was 61.4 +/- 9.6 mU/liter.24 h in obese women with PCOS. None of these parameters differed from those in the body mass index-matched controls. The approximate entropy ratio was significantly increased in obese women (both PCOS and controls), indicating greater irregularity of the GH release process. Total GH secretion in patients and the two control groups correlated strongly and negatively with percent body fat (r = -0.775; P < 10(-8)). Serum concentrations of IGF-I and IGF-binding protein-3 were higher in patients with PCOS than in obese controls (P = 0.03 and P = 0.02, respectively), but the IGF-1/IGF-binding protein-3 ratio was equivalent in all three study groups. In conclusion, the profoundly reduced and irregular GH release in obese women with PCOS appears to be a corollary of body fat accretion and not of the syndrome per se.

Adult↗

Growth hormone blunts protein oxidation and promotes protein turnover to a similar extent in abdominally obese and normal-weight women.

Abdominally obese individuals have reduced 24-h plasma GH concentrations. Their normal plasma IGF-I levels may reflect GH hypersensitivity. Alternatively, obesity-associated hyposomatotropism may cause less biological effect in target tissues. We therefore determined whole-body responsiveness to the anabolic effects of GH in abdominally obese (OB) and normal weight (NW) premenopausal women. A 1-h iv infusion of GH or placebo was randomly administered to six NW (body mass index, 21.1 +/- 1.9 kg/m(2)) and six OB (body mass index, 35.5 +/- 1.5 kg/m(2)) women in a cross-over design. Endogenous insulin, glucagon and GH secretion was suppressed by infusion of somatostatin. Whole-body protein turnover was measured using a 10-h infusion of [(13)C]-leucine. GH administration induced a similar plasma GH peak in NW and OB women (49.8 +/- 10.4 vs. 45.1 +/- 5.6 mU/liter). GH, compared with placebo infusion, increased nonoxidative leucine disposal, P < 0.0001) and endogenous leucine appearance (R(a), P = 0.0004) but decreased leucine oxidation (P = 0.0051). All changes were similar in both groups. Accordingly, whole-body GH responsiveness, defined as the maximum response of nonoxidative leucine disposal, leucine R(a), and oxidation per unit of GH, was not different in OB and NW women (0.25 +/- 0.18 vs. 0.19 +/- 0.17 micro mol/kg.h, 0.21 +/- 0.23 vs. 0.13 +/- 0.17 micro mol/kg.h, and -0.10 +/- 0.08 vs. -0.08 +/- 0.05 micro mol/kg.h, respectively). These results indicated that whole-body tissue responsiveness to the net anabolic effect of GH is similar in OB and NW women. Hence, we inferred that hyposomatotropism may promote amino acid oxidation and blunt protein turnover in abdominal obesity. However, hyposomatotropism cannot account for all anomalous features of protein metabolism in abdominally obese humans.

Abdomen↗

Hyposomatotropism blunts lipolysis in abdominally obese women.

Abdominal obesity is associated with reduced 24-h plasma GH concentrations. It is unclear whether hyposomatotropism in abdominally obese humans is compensated by up-regulation of GH receptor sensitivity or causes less biological effect in target tissues. We, therefore, determined the responsiveness of adipose tissue to the lipolytic action of GH in abdominally obese (OB) and normal weight (NW) postmenopausal women. An iv bolus of recombinant human GH or placebo was randomly administered to eight NW [body mass index (BMI): 22.2 +/- 1.6 kg/m(2)] and eight abdominally OB (BMI: 32.1 +/- 2.6 kg/m(2)) women. Lipolysis was measured by infusion of D5-glycerol and modeled as a function of plasma GH concentrations to describe adipose tissue responsiveness. Similar plasma GH concentration peaks ( approximately 20 mU/liter) were achieved by GH injection in both groups. During placebo conditions, the average plasma GH level was significantly lower in OB compared with NW women (0.74 +/- 0.52 vs. 2.08 +/- 1.18 mU/liter, P = 0.023). Adipose tissue responsiveness, expressed as glycerol rate of appearance per kilogram of fat mass per unit plasma GH concentration was not different in both groups (NW: 1.06, OB: 0.68, P > 0.05). These results suggest that hyposomatotropism in abdominally obese individuals is not compensated by increased adipose tissue responsiveness to GH bio-action and, therefore, blunts lipolysis in these individuals.

Abdomen↗