Selective effects of PPARgamma agonists and antagonists on human pre-adipocyte differentiation.

AIM: The insulin sensitizer rosiglitazone (RTZ) acts by activating peroxisome proliferator and activated receptor gamma (PPAR gamma), an effect accompanied in vivo in humans by an increase in fat storage. We hypothesized that this effect concerns PPARgamma(1) and PPARgamma(2) differently and is dependant on the origin of the adipose cells (subcutaneous or visceral). To this aim, the effect of RTZ, the PPARgamma antagonist GW9662 and lentiviral vectors expressing interfering RNA were evaluated on human pre-adipocyte models. METHODS: Two models were investigated: the human pre-adipose cell line Chub-S7 and primary pre-adipocytes derived from subcutaneous and visceral biopsies of adipose tissue (AT) obtained from obese patients. Cells were used to perform oil-red O staining, gene expression measurements and lentiviral infections. RESULTS: In both models, RTZ was found to stimulate the differentiation of pre-adipocytes into mature cells. This was accompanied by significant increases in both the PPARgamma(1) and PPARgamma(2) gene expression, with a relatively stronger stimulation of PPARgamma(2). In contrast, RTZ failed to stimulate differentiation processes when cells were incubated in the presence of GW9662. This effect was similar to the effect observed using interfering RNA against PPARgamma(2). It was accompanied by an abrogation of the RTZ-induced PPARgamma(2) gene expression, whereas the level of PPARgamma(1) was not affected. CONCLUSIONS: Both the GW9662 treatment and interfering RNA against PPARgamma(2) are able to abrogate RTZ-induced differentiation without a significant change of PPARgamma(1) gene expression. These results are consistent with previous results obtained in animal models and suggest that in humans PPARgamma(2) may also be the key isoform involved in fat storage.

Nocturnal hypoglycaemias in type 1 diabetic patients: what can we learn with continuous glucose monitoring?

AIM: In type 1 diabetic patients (T1DM), nocturnal hypoglycaemias (NH) are a serious complication of T1DM treatment; self-monitoring of blood glucose (SMBG) is recommended to detect them. However, the majority of NH remains undetected on an occasional SMBG done during the night. An alternative strategy is the Continuous glucose monitoring (CGMS), which retrospectively shows the glycaemic profile. The aims of this retrospective study were to evaluate the true incidence of NH in T1DM, the best SMBG time to predict NH, the relationship between morning hyperglycaemia and NH (Somogyi phenomenon) and the utility of CGMS to reduce NH. METHODS: Eighty-eight T1DM who underwent a CGMS exam were included. Indications for CGMS evaluation, hypoglycaemias and correlation with morning hyperglycaemias were recorded. The efficiency of CGMS to reduce the suspected NH was evaluated after 6-9 months. RESULTS: The prevalence of NH was 67% (32% of them unsuspected). A measured hypoglycaemia at bedtime (22-24 h) had a sensitivity of 37% to detect NH (OR=2.37, P=0.001), while a single measure < or =4 mmol/l at 3-hour had a sensitivity of 43% (OR=4.60, P<0.001). NH were not associated with morning hyperglycaemias but with morning hypoglycaemias (OR=3.95, P<0.001). After 6-9 months, suspicions of NH decreased from 60 to 14% (P<0.001). CONCLUSION: NH were highly prevalent and often undetected. SMBG at bedtime, which detected hypoglycaemia had sensitivity almost equal to that of 3-hour and should be preferred because it is easier to perform. Somogyi phenomenon was not observed. CGMS is useful to reduce the risk of NH in 75% of patients.

SPECT myocardial perfusion imaging: long-term prognostic value in diabetic patients with and without coronary artery disease.

AIM: To determine the long-term prognostic value of SPECT myocardial perfusion imaging (MPI) for the occurrence of cardiovascular events in diabetic patients. PATIENTS, METHODS: SPECT MPI of 210 consecutive Caucasian diabetic patients were analysed using Kaplan-Meier event-free survival curves and independent predictors were determined by Cox multivariate analyses. RESULTS: Follow-up was complete in 200 (95%) patients with a median period of 3.0 years (0.8-5.0). The population was composed of 114 (57%) men, age 65 +/- 10 years, 181 (90.5%) type 2 diabetes mellitus, 50 (25%) with a history of coronary artery disease (CAD) and 98 (49%) presenting chest pain prior to MPI. The prevalence of abnormal MPI was 58%. Patients with a normal MPI had neither cardiac death, nor myocardial infarction, independently of a history of coronary artery disease or chest pain. Among the independent predictors of cardiac death and myocardial infarction, the strongest was abnormal MPI (p < 0.0001), followed by history of CAD (Hazard Ratio (HR) = 15.9; p = 0.0001), diabetic retinopathy (HR = 10.0; p = 0.001) and inability to exercise (HR = 7.7; p = 0.02). Patients with normal MPI had a low revascularisation rate of 2.4% during the follow-up period. Compared to normal MPI, cardiovascular events increased 5.2 fold for reversible defects, 8.5 fold for fixed defects and 20.1 fold for the association of both defects. CONCLUSION: Diabetic patients with normal MPI had an excellent prognosis independently of history of CAD. On the opposite, an abnormal MPI led to a >5-fold increase in cardiovascular events. This emphasizes the value of SPECT MPI in predicting and risk-stratifying cardiovascular events in diabetic patients.

Changes in body composition, metabolic profile and nutritional status 24 months after gastric banding.

BACKGROUND: Laparoscopic adjustable gastric banding (LAGB) causes significant weight loss in morbidly obese adults. However, its consequences on nutritional status still remain unclear. This study aimed to investigate the effects of LAGB on body composition, metabolic profile and nutritional status in obese, premenopausal women. METHODS: 36 obese, premenopausal women (age 24-52 years; mean BMI 43.8 kg/m2) who underwent LAGB were included. Body composition was measured using dual-X-ray absorptiometry at baseline, 6, 12 and 24 months after surgery. Blood pressure, total cholesterol, HDL-cholesterol, triglycerides, glucose, uric acid, total proteins, iron, ferritin, vitamin B12, folic acid, hemoglobin and mean corpuscular volume were measured at baseline, 6, 12, 18 and 24 months after surgery. RESULTS: All patients lost weight over 24 months (range 16.0-71.9 kg): there was a significant loss of fat mass (-51.4%; P<0.0001) as well as of fat-free mass (-13.1%; P<0.0001). There was a significant improvement in blood pressure, glucose, total cholesterol, HDL-cholesterol, triglycerides and urates during the first year; during the second year, a further significant decline was noted only in glucose and urates. According to ATP III criteria, 21 of our patients (58%) had a metabolic syndrome before surgery, but only 9 of them (25%) after 12 months and 1 of them (3%) after 24 months. No nutritional deficiency was noted, except for a significant decrease in serum folate (44.1%; P<0.0001 between baseline and month 24). CONCLUSION: LAGB allows significant improvements in metabolic profile, especially during the first postoperative year, without causing major nutritional deficiencies, except for folates.

Impact of transient correction of increased adrenocortical activity in hypothalamo-damaged, hyperadipose female rats.

OBJECTIVE: To explore the effects of transient correction of enhanced corticoadrenal activity in monosodium L-glutamate (MSG)-damaged female rats on peripheral insulin sensitivity and in vitro retroperitoneal (RP) adipocyte function. DESIGNS: A dose of 4 mg/g body weight (BW) of MSG or vehicle (CTR) was i.p. injected, once every 2 days, between days 2 and 10 of age, in female rats. Intact and 21 day-operated (sham or adrenal enucleation (AE)) rats from both (CTR and MSG) groups were used for experimentation on day 120 of age. Circulating levels of several hormones, in basal and after i.v. high-glucose load conditions, and RP adiposity morphology and function were then evaluated. RESULTS: MSG rats developed increased adrenocortical function, hyperadiposity, hyperleptinemia, hyperinsulinemia and decreased peripheral insulin sensitivity. These characteristics were fully reversed after transient correction of corticoadrenal hyperactivity induced by AE. In addition, in vitro experimentation with isolated RP adipocytes indicated that cells from intact MSG animals displayed decreased sensitivity to insulin and dexamethasone stimulation of leptin secretion. Interestingly, adipocyte dysfunction in MSG rats was fully abrogated after AE-induced transient correction of insulinemia, leptinemia and adrenocortical activity. Importantly, the reversion of these metabolic abnormalities, induced by AE for 21 days, in MSG animals did occur, despite no significant changes in BW values. CONCLUSION: Our results support that the changes in adipocyte characteristics and peripheral insulin resistance, developed in this pseudo-obese female rat model, are mainly due to increased glucocorticoid production. Importantly, appropriate correction of the enhanced adrenocortical activity fully reversed these abnormal functions.

Gestational diabetes mellitus and the risk of metabolic syndrome: a population-based study in Lausanne, Switzerland.

AIMS: To investigate the relationships between gestational diabetes mellitus (GDM) and the metabolic syndrome (MS), as it was suggested that insulin resistance was the hallmark of both conditions. To analyse post-partum screening in order to identify risk factors for the subsequent development of type 2 diabetes mellitus (DM). METHODS: A retrospective analysis of all singleton pregnancies diagnosed with GDM at the Lausanne University Hospital for 3 consecutive years. Pre-pregnancy obesity, hypertension and dyslipidaemia were recorded as constituents of the MS. RESULTS: For 5788 deliveries, 159 women (2.7%) with GDM were identified. Constituents of the MS were present before GDM pregnancy in 26% (n = 37/144): 84% (n = 31/37) were obese, 38% (n = 14/37) had hypertension and 22% (n = 8/37) had dyslipidaemia. Gestational hypertension was associated with obesity (OR = 3.2, P = 0.02) and dyslipidaemia (OR = 5.4, P=0.002). Seventy-four women (47%) returned for post-partum OGTT, which was abnormal in 20 women (27%): 11% (n = 8) had type 2 diabetes and 16% (n = 12) had impaired glucose tolerance. Independent predictors of abnormal glucose tolerance in the post-partum were: having > 2 abnormal values on the diagnostic OGTT during pregnancy and presenting MS constituents (OR = 5.2, CI 1.8-23.2 and OR = 5.3, CI 1.3-22.2). CONCLUSIONS: In one fourth of GDM pregnancies, metabolic abnormalities precede the appearance of glucose intolerance. These women have a high risk of developing the MS and type 2 diabetes in later years. Where GDM screening is not universal, practitioners should be aware of those metabolic risks in every pregnant woman presenting with obesity, hypertension or dyslipidaemia, in order to achieve better diagnosis and especially better post-partum follow-up and treatment.

Increased plasma levels of N-terminal brain natriuretic peptide (NT-proBNP) in type 2 diabetic patients with vascular complications.

AIMS: The plasma levels of either brain natriuretic peptide (BNP) or the N-terminal fragment of the prohormone (NT-proBNP) have recently gained extreme importance as markers of myocardial dysfunction. Patients with type 2 diabetes are at high risk of developing cardiovascular complications. This study was aimed to assess whether plasma NT-proBNP levels are at similar levels in type 2 diabetics with or without overt cardiovascular diseases. METHODS: We assayed plasma NT-proBNP in 54 type 2 diabetics, 27 of whom had no overt macro- and/or microvascular complications, while the remaining ones had either or both. The same assay was carried out in 38 healthy control subjects age and sex matched as a group with the diabetics. RESULTS: Plasma NT-proBNP was higher in diabetics (median 121 pg/ml, interquartile range 50-240 pg/ml, ) than in those without complications (37 pg/ml, 21-54 pg/ml, P<0.01). Compared with the controls (55 pg/ml, 40-79 pg/ml), only diabetics with vascular complications had significantly increased plasma NT-proBNP levels (P<0.001). In the diabetics, coronary heart disease and nephropathy (defined according to urinary excretion of albumin) were each independently associated with elevated values of plasma NT-proBNP. CONCLUSIONS: In type 2 diabetes mellitus, patients with macro- and/or micro-vascular complications exhibit an elevation of plasma NT-proBNP levels compared to corresponding patients with no evidence of vascular disease. The excessive secretion of this peptide is independently associated with coronary artery disease and overt nephropathy. The measurement of circulating NT-proBNP concentration may therefore be useful to screen for the presence of macro- and/or microvascular disease.

Gastric banding induces negative bone remodelling in the absence of secondary hyperparathyroidism: potential role of serum C telopeptides for follow-up.

OBJECTIVE: Data about the consequences of laparoscopic adjustable gastric banding (LAGB) on phospho-calcic and bone metabolism remain scarce. SUBJECTS: We studied a group of 37 obese premenopausal women (age: 24-52 y; mean BMI = 43.7 kg/m2) who underwent LAGB. METHODS: Serum calcium, phosphate, alkaline phosphatase, parathormone (PTH), vitamin D3, serum C-telopeptides, IGFBP-3 and IGF-1 were measured at baseline, 6, 12, 18 and 24 months after surgery. Body composition, bone mineral content (BMC) and density (BMD) were measured using dual-X-ray absorptiometry (DXA) at baseline, 6, 12 and 24 months after surgery. RESULTS: There was no clinically significant decrease of calcemia; PTH remained stable. Serum telopeptides increased by 100% (P < 0.001) and serum IGFBP-3 decreased by 16% (P < 0.001) during the first 6 months, and then stabilized, whereas IGF-1 remained stable over the 2 y. BMC and BMD decreased, especially at the femoral neck; this decrease was significantly correlated with the decrease of waist and hip circumference. CONCLUSIONS: We concluded that there was no evidence of secondary hyperparathyroidism 24 months after LAGB. The observed bone resorption could be linked to the decrease of IGFBP-3, although this decrease could be attributable to other confounding factors. Serum telopeptides seem to be a reliable marker of bone metabolism after gastric banding. DXA must be interpreted cautiously during major weight loss, because of the artefacts caused by the important variation of fat tissue after LAGB.

[Genetics of multiple endocrine neoplasies: clinical implications]. / Génétique des néoplasies endocriniennes multiples: implications cliniques.

The multiple endocrine neoplasia (MEN) syndromes are hereditary monogenic diseases that are transmitted as autosomal dominant traits, and are characterized by the development of tumors and hyperplasias in several endocrine organs. The causative genes of the 2 principal forms of MEN have been recently identified; a protooncogene for MEN2 (the RET gene) and a tumor suppressor gene for MEN1 (the MEN1 gene). Correlations between phenotype and genotype were described in the case of RET mutations that could help in defining the screening methods and the preferable age of prophylactic thyroidectomy. No correlations were established between the mutations of the MEN1 gene and the phenotype of patients suffering from MEN1. We present here a synopsis of the recent results of the genetics of MEN syndromes underlining their clinical implications.

Impact of preoperative teaching on surgical option of patients qualifying for bariatric surgery.

BACKGROUND: During the last 5 years, the performance of bariatric operations has doubled via our outpatient obesity clinic. Currently, 52% of the patients presenting for weight loss are interested in bariatric surgery. Gastric banding and Roux-en-Y gastric bypass are the two laparoscopic procedures proposed. The aim of this study was to evaluate the impact of preoperative teaching on the patients' surgical option. METHODS: All the candidates for bariatric surgery were submitted to preoperative teaching and those between February 2001 and December 2002 are the subject of this study. The teaching consisted of 3 weekly interactive 2-hour sessions. During the first session, the patients were asked about the type of operation that they had in mind: gastric banding, gastric bypass, or not yet decided. The same questions were repeated at the end of the third session, with an additional possible answer: no surgery. RESULTS: 297 consecutive patients with a BMI >35 kg/m(2) with at least one severe co-morbidity, were submitted to preoperative teaching. 80% of the patients were women. Median age was 41 years. Before teaching, 68 patients (23%) were uncertain, 100 (34%) favored gastric banding, and 129 (43%) wanted a gastric bypass. After education, only 3 patients (1%) remained uncertain, 45 (15%) changed their surgical option, and 27 (9%) declined surgery. The proportion of patients opting for gastric banding decreased from 34% to 20%, whereas those electing bypass increased from 43% to 70%. CONCLUSIONS: Preoperative training provides an informed and better patient selection for bariatric surgery. It helps the patients understand the various surgical options, and makes their decision easier.

Predictive factors of binge eating disorder in women searching to lose weight.

METHODS: The aim of this study was to detect predictive factors of binge eating disorder (BED) in an out-patient obesity clinic. Eating behaviour, weight history and body composition were assessed in 138 consecutive patients. BED was diagnosed according to the criteria of appendix B of the Diagnostic and Statistical Manual of Mental Disorders. RESULTS: The body mass index (BMI; p < 0.005) and the waist circumference (p < 0.05) were significantly higher in binge patients than in patients without eating disorders. Similar differences were observed between patients who regularly went through weight loss programmes and patients who consulted for the first time. The prevalence of BED increases with the degree of obesity and especially with the number of previous intentional weight loss programmes. A positive and significant correlation was found between the weight cycling syndrome and BMI (p < 0.0001), waist circumference (p < 0.0001) and body fat (p < 0.001). DISCUSSION: The patients with BED present a specific anthropometric profile and a typical behavioural pattern characterized by a higher degree of central obesity and a weight history with a higher number of attempts of weight loss.

Effects of laparoscopic gastric banding on body composition, metabolic profile and nutritional status of obese women: 12-months follow-up.

BACKGROUND: Obesity is frequently associated with metabolic and cardiovascular co-morbidities and high mortality rates. Besides, because of the increasingly recognized fact that conservative therapy for morbid obesity is associated with an almost 90-95% failure rate in the long term, and probably because of the development of laparoscopic surgery,the demand for bariatric surgery is increasing rapidly. The significant weight loss observed during the first 6-12 months after gastric banding is related to the severe food restriction, related hypercatabolism, and has a potential risk of mineral and vitamin deficiencies. The aim of this study was to evaluate the effects of gastric banding on total body composition, metabolic profile and nutritional status. METHODS: 31 women were studied with median age 36 years (range 25-52), body weight 118.6 kg (range 98-156), BMI 43.6 kg/m(2) (range 36-56 kg/m(2)), percentage of excess body weight (%EW) of 107% (range 72- 166%), waist 115 cm (range 98-132) and hip 138 cm (range 119-155). Total body composition was measured before, 6 and 12 months after laparoscopic gastric banding, using dual-energy x-ray absorptiometry. Metabolic and nutritional profile were evaluated before and 1, 3, 6, 9 and 12 months postoperatively. RESULTS: There was a 23.3% reduction of total body weight and 36.8% reduction of body fat. Unfortunately we also observed a reduction of Fat Free Mass (FFM) of 9.6%. In addition, the major determinants of weight loss were the initial body weight and abdominal distribution of fat mass. Reduction of FFM was positively correlated with the rapidity of weight loss. A significant improvement of glucidic profile was observed, with disappearance of impaired fasting glucose, and normalization of the values of triglycerides in all patients. The prevalence of the metabolic syndrome decreased from 89% in preoperative conditions to 15% 1 year after gastric banding. No major nutritional deficiencies was found following gastric banding. CONCLUSIONS: This prospective study suggests that the first 6 months postoperatively are crucial for weight loss and changes in body composition. Furthermore, the significant reduction of body weight is accompanied by an important improvement of biological abnormalities.

Molecular determinants of human adipose tissue: differences between visceral and subcutaneous compartments in obese women.

The adipose tissue is playing an important role in the development of human obesity and its related comorbidities, but little is known about the mechanisms governing its differentiation and proliferation. In this work, we studied the expression of transcription factors involved in fat storage and metabolic regulations in adipose tissue of 50 well-characterized obese women. In multivariate analyses, 80% of c enhancer binding protein alpha (cEBP alpha), c and a sterol regulatory element binding protein 1 (c and a SREBP1), and retinoid X receptor (RXR alpha) levels in sc adipose tissue (SAT) could be explained by other transcription factors. In addition, RXR alpha was the major determinant of peroxisome proliferator and activated receptor-gamma 1 variability in SAT, with the two factors being involved in the determination of the variability of insulin resistance. In contrast, the levels of all these transcription factors, together with various phenotypic and biological characteristics of the patients, seemed to participate only marginally in the regulation of visceral adipose tissue activity. In similar multivariate analyses, they could explain only a minor part of the variability of cEBP alpha, c and a SREBP1, or RXR alpha, suggesting the involvement of other regulators. Overall, our results demonstrate a different regulation of visceral adipose tissue and SAT and a different role of both tissues in insulin resistance and lipid storage.

Local gamma-aminobutyric acid and glutamate circuit control of hypophyseotrophic corticotropin-releasing factor neuron activity in the paraventricular nucleus of the hypothalamus.

Paraventricular corticotropin-releasing factor (CRF) neurons play a pivotal role in regulating neuroendocrine responses to stress. The mechanisms by which synaptic inputs control the activity of these neurons are not well understood. The present study was undertaken to determine the role of the intrinsic gamma-aminobutyric acid (GABA)- and glutamatergic neural circuits of the hypothalamic paraventricular nucleus (PVN) in the control of CRF neural activity. We show that in organotypic cultures of the PVN, blockade of the intrinsic GABAergic neurotransmission by the GABAA receptor antagonist bicuculline resulted in a significant increase in CRF secretion. The bicuculline-induced CRF secretory activity was abolished by the coadministration of the selective alpha-amino-3-hydroxy-5-methyl-4-isoxazoleprionic acid (AMPA)/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Electrical stimulation of the CRF cell division elicited glutamatergic extracellular field potentials that were dramatically enhanced by bicuculline and were suppressed by CNQX. These results show that the functional activity of CRF neurons in organotypic cultures of the PVN is under a tonic inhibitory influence of an intrinsic GABAergic circuit. Suppression of GABAergic transmission appears to have a permissive role for inducing an increased secretory activity of CRF neurons that is driven by an excitatory glutamatergic network via AMPA/kainate receptors.

Diagnosis and complications of Cushing's syndrome: a consensus statement.

In October 2002, a workshop was held in Ancona, Italy, to reach a Consensus on the management of Cushing's syndrome. The workshop was organized by the University of Ancona and sponsored by the Pituitary Society, the European Neuroendocrine Association, and the Italian Society of Endocrinology. Invited international participants included almost 50 leading endocrinologists with specific expertise in the management of Cushing's syndrome. The consensus statement on diagnostic criteria and the diagnosis and treatment of complications of this syndrome reached at the workshop is hereby summarized.

Circulating IGF-I levels in monitoring and predicting efficacy during long-term GH treatment of GH-deficient adults.

OBJECTIVE: To investigate the effects of long-term GH in GH-deficient adults, as predicted by IGF-I levels. METHODS: Patients received GH, 5 microg/kg per day for 1 Month and 10 microg/kg per day for another 12-30 Months. Changes in body composition, cardiac structure/function, serum lipids and quality of life were measured. RESULTS: There was a significant increase in lean body mass (LBM) (2.21 kg; P<0.0001) after 6 Months, which was sustained throughout treatment. A larger increase occurred in males than females (2.97 vs 1.19 kg; P<0.0001). Total fat mass was reduced (2.56 kg; P<0.0001 (3.26 kg males, 1.63 kg females)). Responsiveness to GH varied greatly, but LBM changes correlated with IGF-I changes (P<0.004). Furthermore, thinner patients experienced greater and progressive LBM increases. There was an increase in ejection fraction (3.85+/-9.95%; P=0.0002) after 6 Months, sustained to 18 Months. These cardiac effects were equal for males and females, and did not correlate with IGF-I levels. Serum low-density lipoprotein/high-density lipoprotein ratios decreased within 6 Months, and were sustained thereafter. Quality of life improved significantly after 6 Months, an effect that was sustained/enhanced as treatment continued. No major adverse events were identified. CONCLUSIONS: Improved body composition is both reflected by IGF-I changes and predicted inversely by baseline adiposity. Other effects of GH replacement on cardiac function, dyslipidaemia and quality of life, however, do not correlate with circulating IGF-I concentrations. Our findings validate the importance of sustained GH therapy, but caution on the interpretation of IGF-I levels in monitoring the long-term effects of GH treatment.

Rising role of obesity surgery caused by increase of morbid obesity, failure of conventional treatments and unrealistic expectations: trends from 1997 to 2001.

BACKGROUND: The authors analyzed the trends in anthropometric and behavioral characteristics among patients seeking weight loss and the trends in choice of treatments, between 1997 and 2001 in an outpatient obesity clinic. PATIENTS AND METHODS: 138 and 128 consecutive patients attending the out-patient obesity clinic at University Hospital of Lausanne were screened in 1997 and in 2001 respectively. Eating habits, body composition and treatment used were assessed. RESULTS: Median BMI was 35 kg/m2 in 1997 and 38 kg/m2 in 2001 (P <0.001) and waist circumference was 99 cm and 111 cm respectively (P <0.001). This increase in the average body weight involved especially patients <30 years old (P <0.01). Morbid obesity increased by 16% (P <0.01), and prevalence of abdominal obesity by 13% (P < 0.05). The median desired weight loss increased significantly from 25% to 29% (P <0.05). 64% of the patients in 1997 and 83% in 2001 (P <0.01) hoped for a weight loss of 20% of their baseline weight. Motivation to lose weight for esthetic reasons was found in 81% of the women and 55% of the men in 1997 (P <0.01), while in 2001 the percentage was 89 and 43 respectively (P <0.001). CONCLUSION: In spite of the increasing access to weight loss programs, we found that the patients are more severely obese, especially those <30 years old, and have more unrealistic expectations of weight loss. This may explain the doubling of the patients treated by surgery.

Bone metabolism and risk of secondary hyperparathyroidism 12 months after gastric banding in obese pre-menopausal women.

OBJECTIVE: To evaluate, during the first postoperative year in obese pre-menopausal women, the effects of laparoscopic gastric banding on calcium and vitamin D metabolism, the potential modifications of bone mineral content and bone mineral density, and the risk of development of secondary hyperparathyroidism. SUBJECTS: Thirty-one obese pre-menopausal women aged between 25 and 52 y with a mean body mass index (BMI) of 43.6 kg/m(2), scheduled for gastric banding were included. Patients with renal, hepatic, metabolic and bone disease were excluded. METHODS: Body composition and bone mineral density (BMD) were measured at baseline, 6 and 12 months after gastric banding using dual-energy X-ray absorptiometry. Serum calcium, phosphate, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, bilirubin, urea, creatinine, uric acid, proteins, parathormone, vitamin D(3), IGF-1, IGF-BP3 and telopeptide, as well as urinary telopeptide, were measured at baseline and 1, 3, 6, 9 and 12 months after surgery. RESULTS: After 1 y vitamin D3 remained stable and PTH decreased by 12%, but the difference was not significant. Serum telopeptide C increased significantly by 100% (P<0.001). There was an initial drop of the IGF-BP3 during the first 6 months (P<0.05), but the reduction was no longer significant after 1 y. The BMD of cortical bone (femoral neck) decreased significantly and showed a trend of a positive correlation with the increase of telopeptides (P<0.06). The BMD of trabecular bone, at the lumbar spine, increased proportionally to the reduction of hip circumference and of body fat. CONCLUSION: There is no evidence of secondary hyperparathyroidism 1 y after gastric banding. Nevertheless biochemical bone markers show a negative remodelling balance, characterized by an increase of bone resorption. The serum telopeptide seems to be a reliable parameter, not affected by weight loss, to follow up bone turnover after gastroplasty.

[1-deamino-4-cyclohexylalanine] arginine vasopressin: a potent and specific agonist for vasopressin V1b receptors.

To date, there are no vasopressin (VP) agonists that exhibit a high affinity and selectivity for the VP V1b receptor with respect to the V1a, V2, and oxytocin receptors. In this study, we describe the synthesis and pharmacological properties of [1-deamino-4-cyclohexylalanine] arginine vasopressin (d[Cha4]AVP). Binding experiments performed on various membrane preparations revealed that d[Cha(4)]AVP exhibits a nanomolar affinity for V1b receptors from various mammalian species (rat, bovine, human). It exhibits high V1b/V1a and V1b/oxytocin selectivity for rat, human, and bovine receptors. Furthermore, it exhibits high V1b/V2 specificity for both bovine and human vasopressin receptors. Functional studies performed on biological models that naturally express V1b receptors indicate that d[Cha4]AVP is an agonist. Like VP, it stimulated basal and corticotropin-releasing factor-stimulated ACTH secretion and basal catecholamine release from rat anterior pituitary and bovine chromaffin cells, respectively. In vivo experiments performed in rat revealed that d[Cha4]AVP was able to stimulate both ACTH and corticosterone secretion and exhibits negligible vasopressor activity. It retains about 30% of the antidiuretic activity of VP. This long-sought selective VP V1b receptor ligand with nanomolar affinity will allow a better understanding of V1b-mediated VP physiological effects and is a promising new tool for V1b receptor structure-function studies.

Gender-specific responses of lean body composition and non-gender-specific cardiac function improvement after GH replacement in GH-deficient adults.

GH deficiency (GHD) in adulthood is accompanied by physical and psychological impairments. One hundred fifteen patients (67 male, 48 female) with pronounced GHD were enrolled in a randomized, double-blind, placebo-controlled study with objectives that included effects on body composition, cardiac structure, and function and safety of replacement therapy with recombinant human GH (Saizen). Sixty patients (31 male, 29 female) received GH at a dose of 0.005-0.010 mg/kg.d, and 55 patients (36 male, 19 female) received placebo for 6 months. Assessment of body composition by dual-energy x-ray absorptiometry demonstrated a treatment difference in lean body mass increase of 2.1 kg (between-group comparison, P < 0.0001), which was significantly greater among males than females (P < 0.0001) [males: GH, +3.13 kg (2.42, 3.84); placebo, +0.11 kg (-0.60, 0.82); and females: GH, +0.64 kg (-0.15, 1.44); placebo: -0.90 kg (-2.20, 0.39)] [mean change 0-6 months (95% confidence limits)] and was associated with IGF-I changes. The decrease in fat mass of 2.8 kg (between-group comparison, P < 0.0001) noted by DEXA was also evident from bioelectric impedance and anthropometric measurements. Echocardiography showed comparable improvement in left ventricular systolic function after GH treatment in both genders. End-systolic volume decreased by 4.3 +/- 10.5 ml (from 35.8 +/- 17.6 ml; between-group comparison, P = 0.035) and ejection fraction increased by 5.1 +/- 10.0% (from 55.0 +/- 11.2%; between-group comparison, P = 0.048), approaching normalcy. Diastolic function did not change as assessed by isovolumic relaxation time, early diastolic flow, diastolic flow secondary to atrial contraction, or ratio of peak mitral early diastolic and atrial contraction velocity. GH treatment was well tolerated, with adverse events primarily related to effects on fluid balance. No apparent relationship between IGF-I levels and the occurrence or severity of adverse events was identified. In conclusion, GH replacement therapy in adults with GHD demonstrated beneficial effects on lean body mass composition that was more pronounced in males than females. In contrast, cardiac function improvement appears to benefit both genders equally.