bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of acute reduction of free fatty acids by acipimox on growth hormone‐releasing hormone‐induced GH secretion in type 1 diabetic patients
Authors: Alvarez Paula , Isidro Luisa , Peinó Roberto , Leal‐Cerro Alfonso , Casanueva Felipe F. , Dieguez Carlos , Cordido Fernando 
Published: September 2003

Summarybackground  In type 1 diabetes mellitus (DM1), high GH basal levels and exaggerated responses to several stimuli have been described. Acipimox is an antilipolytic drug that produces an acute reduction of free fatty acids (FFA). The aim of this study was to evaluate the effect of the reduction of plasma FFA with acipimox, alone or in combination with GHRH, on GH secretion in DM1.methods  Six type 1 diabetic patients were studied (three women, three men), mean age of 30 ± 2·1 years, body mass index (BMI) 23·1 ± 1·5 kg/m2. As a control group, six normal healthy subjects of similar age, sex and weight were studied. Each patient and control received GHRH [1 µg/kg intravenously (i.v.) at min 180], acipimox (250 mg orally at min 0 and 120) and GHRH plus acipimox on three separated days. Subjects served as their own control. Blood samples were taken at appropriate intervals for determination of GH, FFA and glucose.result  In control subjects, the GH area under the curve (AUC; µg/l × 120 min) was for acipimox‐treated 1339 ± 292 and 1528 ± 330 for GHRH‐induced secretion. The GH AUC after the administration of GHRH plus acipimox was 3031 ± 669, significantly greater than the response after acipimox alone (P < 0·05) or GHRH alone (P < 0·05). In diabetic patients, the GH AUC was for acipimox‐treated 2516 ± 606 and 1821 ± 311 for GHRH‐induced secretion. The GH AUC after the administration of GHRH plus acipimox was 7311 ± 1154, significantly greater than the response after acipimox alone (P < 0·05) or GHRH alone (P < 0·05). The GH response after acipimox was increased in diabetic when compared with normal (P < 0·05), with a GH AUC of 1339 ± 292 and 2515 ± 606 for normal subjects and diabetic patients, respectively. The GH response after acipimox plus GHRH was increased in diabetic when compared with normal (P < 0·05), with a GH AUC of 3031 ± 669 and 7311 ± 1154 for normal subjects and diabetic patients, respectively. The administration of acipimox induced a FFA reduction during the entire test.conclusions  Reduction of free fatty acids with acipimox is a stimulus for GH secretion in DM1. The combined administration of GHRH plus acipimox induces a markedly increased GH secretion in type 1 diabetic patients when compared with normal subjects. These data suggest that patients with DM1 exhibit a greater GH secretory capacity than control subjects, despite the fact that endogenous FFA levels seems to exert a greater inhibitory effect on GH secretion in these patients.
A functional site on the human TSH receptor: a potential therapeutic target in Graves’ disease
Authors: Johnstone Alan P. , Cridland Jeremy C. , Da Costa Clive R. , Nussey Stephen S. , Shepherd Philip S. 
Published: September 2003

Summaryobjective  Identifying sites on the TSH‐receptor that are involved in the pathological stimulation of the thyroid by autoantibodies in Graves’ disease would aid the development of new therapies. We tested a series of monoclonal antibodies that recognize the native receptor for their ability to inhibit stimulation of the receptor in vitro.patients and methods  Heterologous cells expressing the recombinant human TSH‐receptor were stimulated with TSH or serum samples from 13 Graves’ disease patients or the MRC Long‐Acting Thyroid Stimulator standard B (LATS‐B) and their cAMP responses measured. The effect on this stimulation of various doses of purified monoclonal antibodies with defined epitopes was determined.results  Antibodies against one epitope (residues 381–384) inhibited TSH‐stimulated cyclic adenosine monophosphate (cAMP) production (1 µg/ml causing 50% inhibition of the response to 100 µU/ml TSH) and also inhibited cAMP production induced by sera from approximately 40% (6/14) of Graves’ disease patients, including the MRC LATS‐B standard.conclusions  Residues 381–384 of the human TSH‐receptor are important in the physiological and pathological stimulation of the thyroid. This opens the possibility of more specific therapy of some Graves’ disease patients by agents directed against this epitope.
Association of two apolipoprotein A‐I gene MspI polymorphisms with high density lipoprotein (HDL)‐cholesterol levels and indices of obesity in selected healthy Chinese subjects and in patients with early‐onset type 2 diabetes
Authors: Ma Yan Qing , Thomas G Neil , Ng Maggie C. Y. , Critchley Julian A. J. H. , Cockram Clive S. , Chan Juliana C. N. , Tomlinson Brian 
Published: September 2003

Summaryobjective  Previous studies have reported associations between two apolipoprotein A‐I (apoA‐I) gene MspI polymorphisms (G‐75A and C83T) and high density lipoprotein (HDL)‐cholesterol and/or apoA‐I levels, but have not investigated the relationship with obesity.methods  We determined the distribution of these polymorphisms in 482 early‐onset (≤ 40 years) Type 2 Chinese diabetics and 167 Chinese selected healthy controls.results  The −75A and 83T allele frequencies were similar in the diabetic and healthy subjects. In the healthy control subjects, HDL‐cholesterol levels were significantly higher in the AA homozygotes than in the GG/GA carriers (1·74 ± 0·58 vs. 1·45 ± 0·58 mmol/l, P < 0·001). Furthermore, analyses showed a significant relationship between increasing HDL‐cholesterol tertiles and the AA genotype frequency in the selected healthy subjects (3·6, 8·9 and 16·1%, P = 0·026). For the C83T polymorphism, healthy male CT carriers had higher HDL‐cholesterol levels than CC homozygotes (1·71 ± 0·57 vs. 1·25 ± 0·30 mmol/l, P = 0·001), but this was not found in females. No relationship between these polymorphisms and lipid levels was found in the diabetics, who had a more adverse lipid profile than the selected controls. In the diabetics, but not the controls, in CT carriers compared to CC homozygotes there were lower levels of body mass index (BMI; 23·8 ± 3·9 vs. 25·4 ± 4·7 kg/m2, P = 0·048) and waist‐to‐height ratio (0·49 ± 0·06 vs. 0·52 ± 0·07, P = 0·023), and this relationship was supported by tertile analysis.conclusions  The −75AA genotype was associated with higher HDL‐cholesterol levels in the selected healthy, but not diabetic, subjects. The 83T allele was associated with greater indices of obesity in the diabetic patients, and with higher HDL‐cholesterol in heterozygous healthy male subjects.
Neuromuscular dysfunction in adult growth hormone deficiency
Authors: Webb Susan M. , De Andrés‐Aguayo Irene , Rojas‐García Ricard , Ortega Emilio , Gallardo Eduard , Mestrón Antonio , Serrano‐Munuera Carmen , Casamitjana Roser , Illa Isabel 
Published: September 2003

Summarybackground  Adult growth hormone deficiency (AGHD) is associated with fatigue, tiredness and myalgias, which improve after initiating recombinant human GH (rhGH) therapy.aim  To conduct an extensive neuromuscular investigation of patients with AGHD in an attempt to explain their neuromuscular symptoms.patients and methods  Twenty adult patients (11 males) with untreated GHD of whom 10 were childhood‐onset (CO) underwent a prospective neurological protocol, including physical examination and a neurophysiological study that comprised sensory and motor neurography, repetitive stimulation, electromyogram (EMG) and interference pattern analysis (IPA). In the first seven patients (four CO), a biceps muscle biopsy was also performed for histochemical analysis and Western blot, and investigation of signal transducers and activators of transcription (STATs)‐1 and ‐3 and the two isoforms STAT‐5a and ‐5b.results  Neuromuscular examination, sensory and motor neurography and repetitive stimulation were normal in 20/20 patients. Fourteen [seven CO and seven adult‐onset (AO)] of the 20 patients had abnormal EMG and/or IPA suggestive of a neurogenic involvement. In those seven patients with initially abnormal results, who also remained on regular rhGH for at least 1 year, repeated IPA was normal in six and improved in the remaining patient (P = 0·004). The biceps muscle biopsy disclosed abnormal groupings in the seven cases tested, indicative of a neurogenic pattern. No changes in skeletal muscle STAT‐1 and ‐3 were seen compared to controls, but a marked increase in both STAT‐5 isoforms was observed in all seven patients.conclusion  Skeletal muscle of patients with both adult‐onset and childhood‐onset adult GH deficiency shows a neuromuscular dysfunction, indicated by the muscle biopsy and the neurophysiological study, which in the subgroup of treated patients responds positively to rhGH therapy. The results obtained suggest that the STAT‐5 signal transduction pathway in muscle is abnormal in adult GH deficiency.
Effect of dehydroepiandrosterone supplementation on fatty acid and hormone levels in patients with X‐linked adrenoleucodystrophy
Authors: Assies J. , Haverkort E. B. , Lieverse R. , Vreken P. 
Published: September 2003

Summaryobjective  In X‐linked adrenoleucodystrophy (X‐ALD) the peroxisomal β‐oxidation of saturated very long‐chain fatty acids (VLCFAs; carbon length > 22 atoms) is impaired. These fatty acids accumulate in blood and tissues, in particular in the nervous system, adrenal cortex and testis. Most patients have a primary adrenocortical insufficiency with low levels of cortisol and dehydroepiandrosterone (DHEA) and its sulphate ester (DHEA‐S), collectively called DHEA(S). Surprisingly, very low plasma levels of DHEA(S) may be found when plasma cortisol and ACTH levels are normal. In animal studies DHEA administration had a peroxisome proliferating effect and induced the expression of peroxisomal enzymes involved in the β‐oxidation of fatty acids.patients and design  To study the effect of DHEA on fatty acids in X‐ALD patients, we conducted a randomized double‐blind study in which 14 men (age range 21–63 years) and one boy (12 years) received 50 mg of DHEA or placebo for 3 months, followed by a 1‐month wash‐out period, then 3 months of placebo or vice versa.results  A significant rise was seen in the plasma levels of DHEA‐S, Δ4‐androstenedione and IGF‐I. The elevated saturated VLCFAs in plasma and erythrocytes did not change. However, in erythrocytes significant decreases were found in the total amount of fatty acids, in C16:0, C18:0 and in C20:4ω‐6, C22:5ω‐6, C18:1ω‐9, C20:1ω‐9 and C20:3ω‐9. In plasma, decreases were found for C18:1ω‐9 and increases for C20:1ω‐9.conclusions  Dehydroepiandrosterone supplementation for 3 months did not lower the elevated plasma levels of saturated very long‐chain fatty acids in patients with X‐linked adrenoleucodystrophy. Instead, a decrease in saturated and mono‐ and polyunsaturated fatty acids in erythrocytes and plasma was found. An increase of C20:1ω‐9 was found in plasma only.
Psychological effects of withdrawal of growth hormone therapy from adults with growth hormone deficiency
Authors: McMillan C. V. , Bradley C. , Gibney J. , Healy M. L. , Russell‐Jones D. L. , Sönksen P. H. 
Published: September 2003

Summaryobjective  Growth hormone (GH) is known to be required for physical well‐being. Although it is also widely believed to be important for quality of life (QoL) and psychological health, there is less supportive evidence. The objective of this study was to investigate the psychological effects of discontinuation of GH replacement from adults with severe GH deficiency (GHD).design  A double‐blind, placebo‐controlled trial in which GH replacement therapy was discontinued for 3 months from 12 of 21 GH‐deficient adults, where nine continued with GH replacement.patients  GH‐treated adults (10 men, 11 women), all with severe GHD (peak GH < 7·7 mU/l on provocative testing), mean age 44·9 years (range 25–68 years).measurements  Semi‐structured interviews were given at baseline and end‐point plus questionnaires that included a new hormone‐deficiency specific, individualized, QoL questionnaire (HDQoL), the General Well‐being Index (GWBI), the Well‐being Questionnaire (W‐BQ12), the Short‐Form 36 health status questionnaire (SF‐36), the Nottingham Health Profile (NHP) and the General Health Questionnaire (GHQ).results  Three months after baseline the serum total IGF‐I of placebo‐treated patients fell from normal, age‐related levels (mean 26·6 ± 13·2 nmol/l) to levels indicative of severe GHD (11·6 ± 6·6 nmol/l) (P < 0·001). Psychological symptoms of GH withdrawal, reported in interviews at end‐point by placebo‐treated patients, included decreased energy, and increased tiredness, pain, irritability and depression. Patients who believed they knew which treatment they had received correctly identified the treatment (GH or placebo) at end‐point (χ2 = 11·25, P < 0·01). Significant between‐treatment‐group differences in change scores were found for SF‐36 General Health (P < 0·01), W‐BQ12 Energy (P < 0·01) and HDQoL do physically (P < 0·05), indicating reduced general health, reduced energy and greater perceived impact of hormone deficiency on physical capabilities in the placebo‐treated group at end‐point relative to GH‐treated patients.conclusion  Withdrawal of GH treatment from adults with severe GH deficiency has detrimental psychological effects.
The glutamine 27 glutamic acid polymorphism of the β2‐adrenoceptor gene is associated with abdominal obesity and greater risk of impaired glucose tolerance in men but not in women: a population‐based study in Spain
Authors: González Sánchez J. L. , Proenza A. M. , Martínez Larrad M. T. , Ramis J. M. , Fernández Pérez C. , Palou A. , Serrano Ríos M. 
Published: September 2003

Summaryobjetive  Given the important role of the β2‐adrenoceptor (β2‐AR) in lipid mobilization and the lack of studies in Southern European countries, the aim of this study was to investigate the role of the glutamine 27 glutamic acid (Gln27Glu) β2‐AR polymorphism in the susceptibility to obesity and its metabolic complications in a population‐based nationwide multicentre study in Spain, especially focusing on the hypothetical influence of gender.design  Cross‐sectional population‐based study.patients  We studied 666 nonrelated adults (47·9% men and 52·1% women), aged 35–64 years, chosen randomly from a nationwide population‐based survey of obesity, and related conditions including insulin resistance and cardiovascular risk factors.measurements  Body mass index (BMI), waist‐to‐hip ratio (WHR), sagittal abdominal diameter (SAD), systolic and diastolic blood pressure, fasting and 2‐h post‐glucose load glycaemic levels, total cholesterol, high density lipoprotein (HDL)‐ and low density lipoprotein (LDL)‐cholesterol, triglycerides, insulin, proinsulin and leptin plasma levels were measured. β2‐AR Gln27Glu genotypes were determined by restriction fragment length polymorphism (RFLP)‐polymerase chain reaction (PCR).results  Glu27 homozygous obese men had significantly higher BMI and SAD mean values than both heterozygous and Gln27 homozygous obese men. Two‐hour post‐load plasma glucose concentration was higher in Glu27 homozygous than in Gln27 homozygous in the whole population and only in men when stratified by gender. No differences according to the genotype were found for the rest of the parameters studied, including homeostasis model assessment (HOMA), insulin, proinsulin and leptin levels, but for total and LDL‐cholesterol these increased in men. We did not find differences in the anthropometrical and biochemical parameters according to the genotype in women. Multivariate logistic regression analysis showed that Glu27 homozygosity after adjustment for SAD was associated with type 2 diabetes mellitus.conclusions  Our results suggest that the glutamic acid 27 allele of the β2‐adrenoceptor may be a risk factor in men but not in women for the accumulation of visceral fat and for its association with the development of type 2 diabetes mellitus.
The gender differences in growth hormone‐binding protein and leptin persist in 80‐year‐old men and women and is not caused by sex hormones
Authors: Bülow B. , Ahrén B. , Fisker S. , Dehlin O. , Hagberg B. , Jensen E. , Svensson T. , Samuelsson G. , Erfurth E. M. 
Published: September 2003

Summaryobjective  Leptin and growth hormone‐binding protein (GHBP) both show gender differences that might be explained by sex hormones. To study the potential relevance of oestradiol and testosterone, we have examined 80‐year‐old subjects in whom oestradiol is higher in men than in women. The interrelationships between leptin, insulin, GHBP and fat mass in this age group were also investigated.design and subjects  Ninety‐four subjects (55 females and 39 males), all 80 years old, were investigated in a community‐based study. None of the investigated subjects was being treated for diabetes mellitus and none of the women had oestrogen replacement.methods  Levels of testosterone, oestradiol, SHBG, IGF‐I, GHBP, glucose, insulin and leptin were analysed. Body composition was measured with bioimpedance analysis (BIA).results  As in younger age groups, serum leptin, the ratio leptin/kilogram fat mass and serum GHBP were higher in the women (all, P ≤ 0·007), although serum oestradiol was higher in the men (P < 0·001). There were no significant associations between sex hormones and leptin or GHBP either in women or in men (all, r < 0·13, P > 0·1). Leptin correlated to kilogram fat mass in both women (r = 0·55, P < 0·001) and men (r = 0·47, P = 0·003), but in contrast, there were no significant correlations between GHBP and fat mass and GHBP and IGF‐I, either in women or in men (all, r < 0·24, P > 0·2). Insulin and leptin were significantly associated with GHBP, both in women (r = 0·48, P < 0·001 and r = 0·43, P = 0·001, respectively) and in men (r = 0·40, P = 0·01 and r = 0·34, P = 0·03, respectively).conclusions  Although the 80‐year‐old men had higher oestradiol levels than the women, the women had higher levels of leptin and GHBP. There were no correlations between sex hormones and leptin and GHBP, which indicates that the gender differences are not caused by sex hormones in old age. In contrast to studies in younger subjects, GHBP did not correlate to fat mass in the investigated 80‐year‐old men and women. In the older subjects investigated, as in younger subjects, GHBP was significantly correlated with leptin and insulin.
Bone density and body composition in children with growth hormone insensitivity syndrome receiving recombinant IGF‐I
Authors: Shaw N. J. , Fraser N. C. , Rose S. , Crabtree N. J. , Boivin C. M. 
Published: September 2003

Summaryobjective  There are few reports of the metabolic action of insulin‐like growth factor 1 (IGF‐I) in vivo. Growth hormone insensitivity syndrome is a good model to examine the effects of IGF‐I deficiency. This study was designed to assess body composition and bone density in children with growth hormone insensitivity syndrome before and after receiving treatment with recombinant IGF‐I.design  A prospective longitudinal study.patients  Four prepubertal boys age 6·1–9·8 years with short stature due to growth hormone insensitivity syndrome.measurements  Assessment of body fat by skinfold thickness measurements and dual energy X‐ray absorptiometry (DXA) was made during the first 6 months of recombinant IGF‐I treatment. Assessment of lumbar spine bone density by DXA was performed prior to IGF‐I treatment and during the subsequent five years.results  Each child showed a significant reduction in fat mass (0·26–1·22 kg) after 6 weeks of IGF‐I treatment. Bone density prior to treatment was reduced in comparison to age‐matched controls but calculated volumetric bone density was within the normal range. Volumetric bone density progressively improved over the 5‐year treatment period.conclusions  Children with growth hormone insensitivity syndrome exhibit a metabolic response to IGF‐I within 6 weeks analogous to that seen in GH‐deficient children receiving GH. Bone density when corrected for body size is within normal limits and demonstrates a response to IGF‐I, confirming the anabolic action on bone.
Glucose homeostasis in acromegaly: effects of long‐acting somatostatin analogues treatment
Authors: Baldelli Roberto , Battista Claudia , Leonetti Frida , Ghiggi Maria‐Rosaria , Ribaudo Maria‐Cristina , Paoloni Antonella , D’Amico Eugenio , Ferretti Elisabetta , Baratta Roberto , Liuzzi Antonio , Trischitta Vincenzo , Tamburrano Guido 
Published: September 2003

Summaryobjective  Acromegaly is a syndrome with a high risk of impaired glucose tolerance (IGT) and diabetes mellitus (DM). Somatostatin analogues, which are used for medical treatment of acromegaly, may exert different hormonal effects on glucose homeostasis. Twenty‐four active acromegalic patients were studied in order to determine the long‐term effects of octreotide‐LAR and SR‐lanreotide on insulin sensitivity and carbohydrate metabolism.design  Prospective study.patients  We studied 24 patients with active acromegaly, 11 males and 13 females, aged 50·7 ± 12·7 years, body mass index (BMI) 30·1 ± 4·8 (kg/m2).measurements  All patients underwent an oral glucose tolerance test (OGTT) and 12 also had an euglycaemic hyperinsulinaemic clamp. All patients were evaluated at baseline and after 6 months of somatostatin analogues therapy.results  Acromegalic patients showed low M‐values in respect to the control group at baseline (P < 0·05), followed by a significant improvement after 6 months of therapy (P < 0·005 vs. baseline). Serum glucose levels at 120 min during OGTT worsened (P < 0·05) during somatostatin analogs therapy in patients with normal glucose tolerance, but not in those with impaired glucose tolerance or diabetes mellitus. This was associated with a reduced (P < 0·05) and 30 min delayed insulin secretion during OGTT. Also, HbA1c significantly deteriorated in all subjects after treatment (4·7 ± 0·6% and 5·1 ± 0·5%, basal and after six months, respectively, P < 0·005).conclusion  In acromegalic patients, somatostatin analogues treatment reduces insulin resistance, and also impairs insulin secretion. This may suggest that the use of oral secretagogue hypoglycaemic agents and/or insulin therapy should be considered rather than insulin sensitizers, as the treatment of choice in acromegalic patients who develop frank hyperglycaemia during somatostatin analogues therapy.