Biomedical subjects

Marijke Frölich

Publications and source records attributed to Marijke Frölich.

34 records · Page 2Linked to original sources

PubMed2004

Impaired innate immunity predicts frailty in old age. The Leiden 85-plus study.

Aging is associated with an impaired capacity of the immune system to respond properly to danger signals, such as infection and cancer. Here, we provide evidence that an impaired innate immune response, as measured by a low production capacity of pro- and anti-inflammatory cytokines upon ex vivo standardized danger signalling with bacterial LPS, is predictive for frailty in elderly people: participants who at age 85-year produced low levels of LPS-induced IL-1beta, IL-6, TNF-alpha and IL-1Ra and IL-10, were found to have a more than 2-fold elevated overall mortality risk, independent of chronic illnesses (relative risk is 2.21, 95% confidence interval 1.27-3.82, P = 0.005), compared to peers with a higher production of any of the pro- and/or anti-inflammatory cytokines. A significant genetic association with the IL-10 promoter gene was found, indicating that people who are genetically predisposed low cytokine producers are at a higher risk of losing the capacity to respond properly to danger signals with aging. We conclude that a malfunctioning innate immune response predicts frailty in old age and is under specific (immuno-) genetic control.

Aged↗

PubMed2004

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↗

PubMed2003

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↗

PubMed2003

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↗

PubMed2003

Octreotide represses secretory-burst mass and nonpulsatile secretion but does not restore event frequency or orderly GH secretion in acromegaly.

Octreotide is a potent somatostatin analog that inhibits growth hormone (GH) release and restricts somatotrope cell growth. The long-acting octreotide formulation Sandostatin LAR is effective clinically in approximately 60% of patients with acromegaly. Tumoral GH secretion in this disorder is characterized by increases in pulse amplitude and frequency, nonpulsatile (basal) release, and irregularity. Whether sustained blockade by octreotide can restore physiological secretion patterns in this setting is unknown. To address this question, we studied seven patients with GH-secreting tumors during chronic receptor agonism. Responses were monitored by sampling blood at 10-min intervals for 24 h, followed by analyses of secretion and regularity by multiparameter deconvolution and approximate entropy (ApEn). The somatostatin agonist suppressed GH secretory-burst mass, nonpulsatile (basal) GH release, and pulsatile secretion, thereby decreasing total GH secretion by 86% (range 70-96%). ApEn decreased from 1.203 +/- 0.129 to 0.804 +/- 0.141 (P = 0.032), denoting greater regularity. None of GH pulse frequency, basal GH secretion rates, or ApEn normalized. In summary, chronic somatostatin agonism is able to repress amplitude-dependent measures of excessive GH secretion in acromegaly. Presumptive tumoral autonomy is inferred by continued elevations of event frequency, overall pattern disruption (irregularity), and nonsuppressible basal GH secretion.

Acromegaly↗

PubMed2003

The decline in plasma leptin in response to calorie restriction predicts the effects of adjunctive leptin treatment on body weight in humans.

BACKGROUND: Plasma leptin levels decline in response to food restriction. We hypothesized that the magnitude of this decline would predict the amount of weight lost in response to exogenous leptin administration. METHODS: Thirty obese subjects were mildly energy-restricted for 21 days. Subsequently, they were randomized to receive either recombinant human leptin [rL, 10 mg s.c. once (n=15) or twice (n=6) daily] or placebo (n=9) as an adjunct to the dietary measures for 12 weeks. RESULTS: Weight loss amounted to 2.8+/-1.1, 5.2+/-0.9, and 7.9+/-1.4 kg (mean+/-standard error) (p=0.035 vs. placebo) in placebo, rL once daily, and rL b.i.d. treated subjects, respectively. The reduction in plasma leptin concentrations during the initial 21 days was positively correlated with the loss of body weight following leptin treatment (r(2)=0.24, p=0.04). Plasma leptin concentration prior to the initiation of rL therapy was inversely associated with the amount of body weight lost in response to intervention (r(2)=0.36, p=0.003). CONCLUSION: Leptin administration counteracts the adaptations that are actuated by the drop in leptin concentrations and thereby disrupts energy balance to promote weight loss.

Journal Article↗

PubMed2003

Causes of hyponatremia in the Departments of Internal Medicine and Neurosurgery.

BACKGROUND: Hyponatremia is a common electrolyte disorder in hospitalised patients. The distribution of the various causes of hyponatremia has been studied in hospitalised patients in general, but little is known about the distribution in specific departments. We performed a prevalence study on the aetiology of hyponatremia in two departments in our hospital, namely, the Department of Internal Medicine and the Department of Neurosurgery. METHODS: Consecutive adult patients with hyponatremia (serum sodium concentration</=130 mmol/l) who had been admitted to the Departments of Internal Medicine and Neurosurgery were included in the study. The cause of hyponatremia was determined on the basis of information obtained from medical records, estimation of extracellular fluid volume status, water balance and biochemical parameters in blood serum and urine. RESULTS: Out of 41 hyponatremic patients, 12 had hyponatremia due to normovolemic disorders, 10 due to hypervolemic disorders, 11 due to hypovolemic disorders with extrarenal sodium loss and eight due to hypovolemic disorders with renal sodium loss. The most frequent causes of hyponatremia were extrarenal sodium loss due to vomiting or diarrhoea, hepatic cirrhosis, drug-induced hyponatremia and the syndrome of inappropriate ADH secretion. CONCLUSIONS: In the Departments of Internal Medicine and Neurosurgery, certain causes of hyponatremia are more prevalent than others. The use of clinical data, in combination with a few simple laboratory tests, can lead to a correct diagnosis of the principal cause of hyponatremia.

Journal Article↗

PubMed2003

Sandostatin LAR in acromegaly: a 6-week injection interval suppresses GH secretion as effectively as a 4-week interval.

INTRODUCTION: Depot preparations of long-acting somatostatin analogues are being used increasingly in the treatment of GH hypersecretion in patients with acromegaly, either as primary treatment or as secondary treatment following incomplete surgery. In 60% of these patients, Sandostatin long-acting release (LAR), the depot preparation of octreotide, achieves effective suppression of serum GH (< 5 mU/l) and IGF-I levels. The advice is to administer Sandostatin LAR at 4-week intervals. After injection, serum octreotide shows an initial peak and thereafter maximal values between 14 and 42 days. There have been suggestions that the dose interval of this preparation could be increased, resulting in reduced costs, although this concept has not been confirmed by studies. AIM OF THE STUDY: We performed a prospective, cohort study in patients with active acromegaly but with normal serum GH and IGF-I levels during Sandostatin LAR treatment to assess whether the dose interval could be safely increased from 4 to 6 weeks, without significant effect on serum GH concentrations or other biochemical and clinical markers of GH hypersecretion. PATIENTS AND METHODS: Fourteen patients (seven males) with GH concentrations below 5 mU/l during Sandostatin LAR treatment entered an 8-week withdrawal study following an injection. Subsequently, during an interval study patients received injections at 6-week intervals (t = 0, 8, 14, 20, 26, 32, 38 and 44 weeks). Study parameters (fasting GH, average GH of eight plasma samples, IGF-I, and octreotide concentrations, symptoms score and quality-of-life score) were assessed 2, 4, 6 and 8 weeks following the first injection (withdrawal) and at 26 and 44 weeks (interval study) before the next injection. RESULTS: During the withdrawal study, mean serum GH concentration increased significantly from 1.68 +/- 0.3 at 4 weeks to 2.57 +/- 0.5 mU/l at 6 weeks (P = 0.04, 4 vs. 6 weeks) and to 2.89 +/- 0.4 mU/l at 8 weeks (P < 0.001, 4 vs. 8 weeks). Mean serum GH concentration was below 5 mU/l in all patients at all time points, except for one patient at 8 weeks, and IGF-I levels remained normal in all patients. During withdrawal up to 8 weeks there was no significant change in serum IGF-I concentration, symptoms score or quality-of-life score. Mean serum octreotide decreased significantly from 1610 +/- 355 ng/l at 2 weeks to 1045 +/- 272 ng/l at 6 weeks (P = 0.002, 2 and 4 vs. 6 weeks) and to 559 +/- 147 ng/l at 8 weeks. In the interval study, one patient had mean serum GH above 5 mU/l associated with an increase in symptoms at 26 weeks and she was withdrawn from the study. The remaining 13 patients completed the 6-weekly injection study protocol and in the long term no significant changes in mean serum GH concentration, IGF-I concentration or symptom scores were observed (6 vs. 26 and 44 weeks). All patients had a mean serum GH concentration < 5 mU/l and serum IGF-I remained normal in 11 out of 14 patients at 26 weeks and nine out of 13 patients at 44 weeks. Moreover, the mean octreotide concentrations measured 6 weeks after a Sandostatin LAR injection did not decrease in the long term. CONCLUSION: On the basis of serum GH concentrations, most patients with serum GH levels < 5 mU/l during Sandostatin LAR treatment using a 4-weekly schedule can be effectively treated with 6-weekly injections. However, during long-term treatment with 6-weekly injections, discordant IGF-I and GH results were observed in 30% of the patients and careful clinical monitoring is therefore required.

Acromegaly↗

PubMed2003

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↗

PubMed2002

Somatotropic axis in hypocretin-deficient narcoleptic humans: altered circadian distribution of GH-secretory events.

Narcolepsy is a sleep disorder caused by impaired hypocretin (orexin) neurotransmission. Growth hormone (GH) secretion may be altered in narcolepsy for various reasons. Slow-wave sleep episodes, which are closely associated with GH-secretory events, are more randomly dispersed over 24 h in narcoleptics. Furthermore, hypocretins may inhibit pituitary GH release. We assessed the function of the somatotropic axis in narcolepsy by deconvolving 24-h (10-min sampling interval) plasma GH concentration profiles in seven hypocretin-deficient narcoleptic patients and in seven healthy controls matched for age, sex, and body weight. Both basal and pulsatile GH secretion rate and secretagogue-induced GH release were similar in patients and controls. However, narcoleptics secreted approximately 50% of their total production during the daytime, whereas controls secreted only 25% during the day. Also, the GH output pattern of narcoleptics was significantly less regular. We propose that hypocretin deficiency disrupts the circadian distribution of hypothalamic GH-releasing hormone release in narcoleptic patients to simultaneously cause daytime GH release and promote their propensity to fall asleep during the day.

Adult↗

PubMed2002

No effect of preoperative selective gut decontamination on endotoxemia and cytokine activation during cardiopulmonary bypass: a randomized, placebo-controlled study.

BACKGROUND: Cardiopulmonary bypass predisposes the splanchnic region to inadequate perfusion and increases in gut permeability. Related to these changes, circulating endotoxin has been shown to rise during cardiac surgery, and may contribute to cytokine activation, high oxygen consumption, and fever ("postperfusion syndrome"). To a large extent, free endotoxin in the gut is a product of the proliferation of aerobic gram-negative bacteria and may be reduced by nonabsorbable antibiotics. OBJECTIVE: To evaluate the effect of preoperative selective gut decontamination (SGD) on the incidence of endotoxemia and cytokine activation in patients undergoing open heart surgery. DESIGN: Prospective, randomized, placebo-controlled double-blind trial. SETTING: Tertiary-care university teaching hospital. INTERVENTION: Preoperative administration for 5 to 7 days of oral nonabsorbable antibiotics (polymyxin B and neomycin) vs. placebo. The efficacy of SGD was assessed by culture of rectal swabs. PATIENTS: Forty-four patients (median age 65 yrs, 29 males) were included in a pilot study to establish the sampling points of perioperative measurements. Seventy-eight consecutive patients (median age 65 yrs, 55 males) were enrolled for the prospective study; of these, 51 were randomly allocated to take SGD (n = 24) or placebo (n = 27); 27 were included in a control group (no medication). MEASUREMENTS AND RESULTS: SGD but not placebo effectively reduced the number of rectal swabs that grew aerobic gram-negative bacteria (27% vs. 93%, respectively; p < .001). SGD did not affect the occurrence of perioperative endotoxemia, nor did it reduce the tumor necrosis factor-alpha, interleukin-10, or interleukin-6 concentrations (p > .20), as determined before surgery, upon aorta declamping, 30 mins into reperfusion, or 2 hrs after surgery. Also, SGD did not alter the incidence of postoperative fever or clinical outcome measures such as duration of artificial ventilation and intensive care unit and hospital stay. CONCLUSION: SGD effectively reduces the aerobic gram-negative bowel flora in cardiac surgery patients but fails to affect the incidence of perioperative endotoxemia and cytokine activation during cardiopulmonary bypass and the occurrence of a postperfusion syndrome.

Aged↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

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↗

PubMed2002

Low production capacity of interleukin-10 associates with the metabolic syndrome and type 2 diabetes : the Leiden 85-Plus Study.

It has been suggested that the metabolic syndrome and type 2 diabetes are manifestations of the inflammatory host response. This host response is orchestrated by the production of pro- and anti-inflammatory cytokines that are under genetic control. We therefore hypothesized that a low production capacity of interleukin-10 (IL-10), a centrally operating cytokine with strong anti-inflammatory properties, associates with the metabolic syndrome and type 2 diabetes in old age. In the current study, 599 inhabitants of the city of Leiden, age 85 years, were visited at their place of residence. The production capacity of the anti-inflammatory cytokine IL-10 was assessed in a whole-blood assay in which lipopolysaccharide was used as a stimulus. Serum concentrations of lipids, lipoproteins, glucose, and HbA(1c) were determined, and a history of type 2 diabetes was obtained. Serum concentrations of total cholesterol, LDL cholesterol, triglycerides, glucose, and HbA(1c) gradually decreased over strata representing higher IL-10 production capacity, whereas the concentration of HDL cholesterol gradually increased (all P < 0.01). The odds ratio for type 2 diabetes was 2.7 (95% confidence interval 1.5-4.9) when subjects with the lowest IL-10 production capacity were compared with those with the highest IL-10 production capacity. These findings showed that low IL-10 production capacity (i.e., a pro-inflammatory response) is associated with the metabolic syndrome and type 2 diabetes.

Aged↗