J Soler

Hospital Universitari de Bellvitge, l'Hospitalet de Llobregat, Catalonia, Spain

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Publications (114)296.19 Total impact

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    ABSTRACT: To evaluate whether treatment with insulin analogues is associated with a lower risk of hypoglycaemia (HYPO score) and less glycaemic variability (Lability Index) than treatment with human insulin in patients with type 1 diabetes. In a 6-month prospective, open-labelled trial, we randomized 47 patients treated with human insulin to receive treatment with human insulin (n = 21) or insulin analogues (n = 26). HYPO score, Lability Index (LI), and hypoglycaemic episode characteristics were assessed at baseline and at the end of follow-up. A 72-h, continuous glucose monitoring was performed at the end in a subgroup of patients. Groups were compared with nonparametric tests. Significance was defined as P < 0.05. HYPO score (71.5 [36.0-162] vs. 260 [52.0-676], P < 0.05), nocturnal hypoglycaemia (0.4 vs. 1.4 events/patient/4-week, P < 0.05), and <2.5 mmol/l hypoglycaemic events were lower in insulin analogue group after 6 months. There was a trend towards a lower LI in insulin analogue group (74.3 [51.3-133] vs. 123 [76.4-171] mmol/l(2)/h week(-1), P = 0.064). HbA(1c) and insulin dose were comparable between groups. In type 1 diabetes, insulin analogues were associated with a lower hypoglycaemic risk and a trend towards reduced glycaemic variability compared with human insulin. These effects occurred despite comparable metabolic control.
    Acta Diabetologica 08/2011; 50(4). DOI:10.1007/s00592-011-0320-y · 3.68 Impact Factor
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    ABSTRACT: To analyse in a cohort of healthy subjects and in a group of morbidly obese patients, we studied the association amongst 25(OH) D and plasma concentrations of adipocytokines, inflammatory cytokines and insulin resistance. We also aimed to determine whether vitamin D-deficient patients showed a greater inflammatory profile. In the observational study that the authors conducted, plasma concentrations of 25(OH) D, leptin, resistin, adiponectin and interleukine-18 were determined in 134 healthy men and 127 women. In the population consisting of 44 patients with morbid obesity, plasma concentrations of 25(OH) D, leptin, resistin, adiponectin, interleukine-18, soluble tumor necrosis factor receptors 1 and 2 and C-reactive protein were analysed. In the healthy population, plasma 25(OH) D showed a negative correlation with body mass index, body fat, waist, hip circumference and with leptin. However, no significant associations were found amongst 25(OH) D and plasma concentrations of resistin, adiponectin or interleukine-18. Patients with vitamin D deficiency showed higher body mass index, fat mass percentage and higher leptin concentrations compared with subjects with normal 25(OH) D concentrations. In the morbidly obese subjects, 25(OH) D did not correlate with leptin, resistin, adiponectin, interleukine-18, soluble tumor necrosis factor receptors 1 and 2 or with C-reactive protein. In patients with morbid obesity, no differences were found in adipokines and inflammatory cytokines concentrations regarding 25(OH) D status. No associations were found either between 25(OH) D and plasma glucose and insulin resistance or with lipid profile. Plasma 25(OH) D concentrations are associated with adiposity markers but not with adipocytokines implicated in inflammation. This lack of association does not support a major role of 25(OH) D in the pro-inflammatory environment observed in morbidly obese subjects. In addition, subjects with vitamin D deficiency are not characterized by a greater inflammatory state.
    Endocrine 10/2010; 38(2):235-42. DOI:10.1007/s12020-010-9379-4 · 3.53 Impact Factor
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    ABSTRACT: Objective Analysis of the relationship between adiponectin, interleukin-18 (IL-18) and ghrelin and bone mineral density (BMD), in a group of women that had undergone a gastric- bypass for morbid obesity a year before. Methods Forty-one morbidly obese patients aged 46 ± 9 years and with an initial body mass index of 49.5 ± 7.6 were included in the study and a gastric by-pass operation was performed in all of them. Anthropometric variables, body composition measured with dual energy X-ray absorptiometry (DEXA) and plasma concentrations of parathormone (PTH), 25(OH) vitamin D, insulin growth factor (IGF-I), adiponectin, IL-18 and ghrelin were determined before and a year after surgery. BMD was evaluated with DEXA 12 months after bariatric surgery. Results A year after surgery 36.2% of inicial body weight was lost and this was associated with an improvement of the inflammatory profile reflected by a significant reduction of IL-18 and a increase of adiponectin plasma concentrations. In the univariate analysis BMD inversely correlated with age (r = −0.287, p = 0.008) and with lean mass (r = 0.318, p = 0.043) but not with adiponectin, IL-18 and ghrelin concentrations. PTH showed a positive correlation with weight (r = 0.362, p = 0.03), lean mass (r = 0.372, p = 0.039), and a negative association with plasma concentrations of calcium (r = −0.48, p = 0.003) and 25(OH) vitamin D (r = −0.44, p = 0.014). Plasma 25(OH) vitamin D correlated negatively with the sum of fat mass and lean mass measured with DEXA (r = -0.210, p = 0.043). In the multiple regression analysis BMD remained associated only with lean mass (β = 0.193, p = 0.016). Conclusions Our study does not support the existance of a direct effect of adipose tissue on bone metabolism through the secretion of adiponectin. The absence of association between inflammatory cytokine IL-18 and ghrelin with BMD also argues against their implication in bone regulation.
    Endocrinología y Nutrición 08/2009; 56(7):355-360. DOI:10.1016/S1575-0922(09)72454-4
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    ABSTRACT: BackgroundThe mechanisms by which increased body weight influence bone mass density (BMD) are still unknown. The aim of our study was to analyze the relationship between anthropometric and body composition variables, insulin growth factor-I (IGF-I), adiponectin and soluble tumor necrosis factor-α receptors (sTNFR) 1 and 2 with BMD in two cohorts of morbid obese patients, before and after bypass surgery. MethodsThe first cohort included 25 women aged 48 ± 7.6years studied before bypass surgery. The second included 41 women aged 46 ± 9.2years, 12months after surgery. We studied anthropometric variables obtained from whole body DEXA composition analysis. Serum IGF-I, intact serum parathyroid hormone, 25-hydroxivitamin D3, plasma adiponectin concentrations, sTNFR1, sTNFR2 concentrations were measured. ResultsIn the first cohort, the BMI was 44.5 ± 3.6kg/m2, parathyroid hormone, IGF-I, and adiponectin concentrations were lower, and sTNFR1 concentrations were higher than in the second cohort. In the multiple regression analysis, BMD remained significantly associated with body fat percentage (β −0.154, p = 0.01), lean mass (β 0.057, p = 0.016) and phosphate concentration (β 0.225, p = 0.05). In the second cohort, BMI was 31 ± 5.1kg/m2. In the multiple regression analysis, BMD remained significantly associated with lean mass (β 0.006, p = 0.03). ConclusionThe inverse correlation found between body fat and BMD in the first cohort indicates morbid obesity increases the risk of osteoporosis and we found a positive correlation with lean and fat mass before bariatric surgery and with lean mass after bypass surgery.
    Obesity Surgery 03/2009; 19(3):345-350. DOI:10.1007/s11695-008-9529-4 · 3.74 Impact Factor
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    ABSTRACT: The aim of this study is to test several biomarkers of inflammation, of endothelial dysfunction, glycated haemoglobin, and their reflection in arterial dilatation, in patients with type 2 diabetes mellitus and in their relatives, in order to demonstrate if relatives present markers as a form of precocious indicators of diabetes mellitus. Individuals between 30 and 55 years of age and without clinical arterial disease were divided in three groups: type 2 diabetes mellitus patients without complications (12 men and 18 women); first degree relatives of type 2 diabetes mellitus (14 men and 20 women); and control individuals (9 men and 16 women). Body composition was measured with a bioelectrical impedance analyzer and endothelial function with an eco-Doppler device. We determined glucose, insulin, C-peptide, glycated haemoglobin, fibrinogen, E-selectin, P-selectin, soluble intercellular cell adhesion molecule-1 (ICAM-1), soluble vascular cell adhesion molecule-1 (VCAM-1), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), C-reactive protein (CRP) in plasma. We also studied endothelium independent dilatation and endothelium dependent dilatation. The results: ICAM-1 and VCAM-1 were significantly higher in the diabetic group (237.5+/-43.4 and 692.5+/-168.6 ng/l) than in controls (197.4+/-51.2 and 573.5+/-121.1 ng/l, p=0.011 and 0.013, respectively), but were not higher in the family group (224.5+/-45.2 and 599.8+/-150.4 ng/l). CRP was higher in the diabetic group (3.35+/-3.27 mg/l) than in the other groups (1.28+/-1.29 and 1.61+/-1.54 mg/l, p=0.002) and correlated with glycated haemoglobin. The non-endothelium mediated dilatation was lesser in the diabetic group than in the family group (17.3+/-6.1 vs. 24+/-8, p=0.029) and controls. In conclusion patients with uncomplicated type 2 diabetes, but not their relatives, have biochemical markers of sub-clinical inflammation in relationship with glycated haemoglobin and dysfunction of the endothelial cells markers. In these patients endothelium independent dilatation is more affected than endothelium dependent dilatation.
    Glycoconjugate Journal 09/2008; 25(6):573-9. DOI:10.1007/s10719-008-9118-8 · 1.95 Impact Factor
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    ABSTRACT: Interleukin-18 (IL-18) is a potent proinflammatory cytokine whose role in human obesity has recently been suggested. The aim of our study was to analyse in morbidly obese patients undergoing gastric bypass, the relationship of IL-18 with insulin resistance and with proinflammatory cytokines (tumour necrosis factor-alpha receptors, sTNFR), C-reactive protein (CRP) and with adiponectin. Observational and prospective study. Sixty-five morbidly obese patients, aged 45 +/- 8.9 years, were studied before and 12 months after gastric bypass. We analysed plasma concentrations of IL-18, sTNFR, CRP and adiponectin. Plasma concentrations of sTNFR2, IL-18 and CRP were decreased and adiponectin significantly increased after bypass surgery. In the multiple regression analysis, preoperative values of IL-18 remained significantly associated with preoperative triglycerides (beta = 0.47, P = 0.005) and TNFR2 (beta = 0.47, P = 0.004). R(2) for the model = 0.38. Postoperative IL-18 concentrations in the multiple regression analysis were significantly associated with postoperative homeostasis model assessment of insulin resistance (HOMA-IR) (beta = 0.092, P = 0.019) and triglycerides (beta = 0.40, P = 0.036). R(2) for the model = 0.46. IL-18 did not correlate with body mass index, fat mass, fat-free mass or body fat. No relationship was either found between adiponectin and IL-18, TNFR1 and -2 and CRP. Massive weight loss induced by gastric bypass reduces IL-18, TNFR2 and CRP. IL-18 might be a marker of the chronic inflammatory process underlying insulin resistance but its lack of association with anthropometric and body composition parameters does not support a major secretion by human adipocytes. IL-18 and sTNFR1 and -2 do not play a main role in the inhibition of the secretion of adiponectin.
    Clinical Endocrinology 12/2007; 67(5):679-86. DOI:10.1111/j.1365-2265.2007.02945.x · 3.35 Impact Factor
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    ABSTRACT: Obesity is associated with low concentrations of 25-hydroxyvitamin D [25(OH) D]. However, conflicting results have been found regarding the relationship of 25(OH) D with anthropometric and adiposity parameters. The aim of our study was to analyze the association between 25(OH) D and body fat (BF) in a homogeneous cohort of non-obese, obese, and morbidly obese Caucasian women. The study was performed in L'Hospitalet de Llobregat, a city adjacent to Barcelona with a latitude of 41 degrees, 22 minutes, and 5 seconds north. Plasma concentrations of 25(OH) D were determined and body composition was evaluated by bioelectrical impedance in a group of 43 women with morbid obesity, 28 non-morbidly obese, and 50 non-obese women matched for age. Morbidly obese women showed lower 25(OH) D concentrations compared to non-morbidly and non-obese women (37.9+/-16 vs 40.2+/-13 vs 56.7+/-21 nmol/l, p=0.001). Fifty-one percent of morbidly obese women had vitamin D deficiency [25(OH) D<38 nmol/l] compared to 22% of non-obese patients, (p=0.004). In the bivariate correlation analysis 25(OH) D was inversely associated with weight (r=-0.41, p=0.001), body mass index (BMI) (r=-0.432, p=0.001), waist to hip ratio (WHR)(r=-0.40, p=0.001), BF (r=-0.53, p=0001), fat mass (r=-0.44, p=0.0001), fat-free mass (r=-0.35, p=0.001). In the multivariate general linear model analysis, 25(OH) D was associated with season of examination (p=0.001) and was negatively associated with BF (beta=-0.75, p=0.001), after adjusting for age, BMI, and WHR. 25(OH) D concentrations are associated with body composition variables especially by BF, independently of seasonal variability. Therefore, body adiposity should be considered when assessing vitamin D requirements in obese patients.
    Journal of endocrinological investigation 09/2007; 30(8):653-8. DOI:10.1007/BF03347445 · 1.55 Impact Factor
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    ABSTRACT: To study the value of early (24 h) post-operative ACTH and serum cortisol as predictors of remission after transsphenoidal surgery in Cushing's disease. We prospectively studied 44 patients who underwent transsphenoidal surgery for Cushing's disease between 1997 and 2005. The mean follow-up period of patients after surgery was 49 months (19-102 months). The predictive value of clinical characteristics, pre-operative hormonal studies, radiological, surgical and histological findings, and post-operative hormonal studies were analysed. For the post-operative hormonal study plasma ACTH and serum cortisol were determined at 8.00 a.m. the day after surgery. After surgery, Cushing's disease remitted in 39 patients (89%) and persisted in 5 patients (11%). Three patients relapsed during the follow-up period. Only three study variables were predictive of persistence of Cushing's disease after surgery: the non identification of the adenoma in histology (an adenoma was found in 87% of the patients in remission, and in 20% of treatment failures, p = 0.01), the early post-operative plasma ACTH (patients in remission: 2 pmol/L (1.1-10.8 pmol/L), treatment failures: 8.2 pmol/L (1.1-12 pmol/L), p = 0.019), and the early post-operative serum cortisol (patients in remission: 128.4 nmol/L (27.6-4644 nmol/L), treatment failures: 797 nmol/L (606-1037 nmol/L), p = 0.003). ROC curves indicated that plasma ACTH < or = 7.55 pmol/L distinguished patients in remission from treatment failures with 80% sensitivity and 97.4% specificity, and serum cortisol < or = 585 nmol/L with 100% sensitivity and 90% specificity. Twenty-four hours after transsesphenoidal surgery for Cushing's disease, and without glucocorticoids replacement, patients with serum cortisol concentrations higher than 585 nmol/L, and/or plasma ACTH higher than 7.55 pmol/L, and/or those in which an adenoma is not identified in the histological study, have a high risk of treatment failure.
    Acta Neurochirurgica 05/2007; 149(5):471-7; discussion 477-9. DOI:10.1007/s00701-007-1133-1 · 1.79 Impact Factor
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    ABSTRACT: Increased mortality due to cardiovascular disease has been described in adult patients with untreated growth hormone (GH) deficiency. GH replacement therapy has been demonstrate to improve vascular reactivity and reverses early atherosclerotic changes in GH deficient adults. The objective of this study was the assessment of fibrinolytic markers, soluble adhesion molecules, inflammatory cytokines and endothelial function in hypopituitary adults with GH deficiency and with GH replacement therapy. We studied 20 GH deficient patients, 10 men and 10 women (aged, 43.4 +/- 8.4 years) under GH replacement therapy compared with a control group matched for age and body mass index, 9 men and 16 women. All subjects, patients and controls, were life-long non-smokers, normotensive and non-diabetic. The following variables were recorded: anthropometrical and body composition variables, serum concentrations of glucose, insulin and C-peptide; thrombin anti-thrombin fragments and fibrin degradation product D-dimer that were determined by an enzyme-linked-immunosorbent assay (ELISA); IGF-I by radioimmunoassay; C-reactive protein by highly sensitive immunonephelometry; E-selectine, P-selectine, soluble intercellular cell adhesion molecule-1, soluble vascular cell adhesion molecule-1, interleukin-6 and monocyte chemoattractant protein-1 by ELISA. The assessment of endothelial function in vivo was measured by Doppler. Patients with GH deficiency had higher hip/waist ratio and C-peptide and triglycerides concentrations than controls. Our results demonstrated no difference in fibrinolytic markers among patients and controls. E-selectin concentrations were higher in patients than in controls, 22.5+/-11.4 vs. 10.7+/-6.2 microg/L, p = 0.0001. P-selectin, soluble intercellular cell adhesion molecule-1, soluble vascular cell adhesion molecule-1, interleukin-6, monocyte chemoattractant protein-1 and C-reactive protein were similar in the 2 groups. Vascular reactivity and carotid intima-media thickness were also similar in patients and controls. In this study we have demonstrated in adults with GH deficiency under GH substitution elevation of E-selectin concentrations that may correlate with potential endothelial dysfunction suggesting that the protective effect of GH in these patients may be enhancing other mechanisms.
    Current Neurovascular Research 03/2007; 4(1):55-62. DOI:10.2174/156720207779940662 · 2.74 Impact Factor
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    ABSTRACT: Aims/hypothesisInterleukin-1 receptor antagonist (IL1RN, also known as IL1RA) is a naturally occurring inhibitor of IL-1 action and its overproduction protects pancreatic islets from the deleterious effects of IL-1β on beta cell replication, apoptosis and function. The aim of this study was to determine whether viral gene transfer of the Il1rn gene into rat islets ex vivo had a beneficial effect on the outcome of the graft. Materials and methodsStreptozotocin-diabetic Lewis rats were syngeneically transplanted with 500 or 800 Ad-Il1rn-infected or uninfected islets. Islet grafts were collected on day 3, 10 or 28 after transplantation and beta cell apoptosis, replication, size and mass were determined. ResultsAnimals transplanted with 500 islets remained hyperglycaemic throughout the follow-up, as expected. Beta cell replication increased in the Ad-Il1rn group on days 3, 10 and 28 after transplantation compared with normal pancreas. In uninfected islets, by contrast, beta cell replication was increased only on day 10. Beta cell apoptosis was increased in all transplanted groups; it was 25% lower in the Ad-Il1rn than in uninfected groups, but differences were not statistically significant. The initially transplanted beta cell mass was reduced on day 3, increasing subsequently in Ad-Il1rn grafts, but not in uninfected grafts. When 800 islets were transplanted, all animals grafted with Ad-Il1rn-infected islets, but only 40% of those transplanted with uninfected islets, achieved normoglycaemia 14days after transplantation. Conclusions/interpretationOverproduction of IL1RN increased beta cell replication and mass of islet grafts and reduced the beta cell number required to achieve normoglycaemia.
    Diabetologia 03/2007; 50(3):602-611. DOI:10.1007/s00125-006-0548-1 · 6.88 Impact Factor
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    ABSTRACT: Sex-hormone binding globulin (SHBG) is a glycoprotein synthesised in the liver and it is a transport protein which is primary modulator of the androgen signal. This cross-sectional study prompted us to investigate the relati-onship between SHBG and, age, anthropometric, body composition variables, the IGF-I system and leptin in a group of healthy adult men randomly selected. Included 134 men, aged 41.6 years, range 15-70 years. Body mass index (BMI) was calculated, and body composition was determined by a bioelectrical impedance analyser. Serum total IGF-I concentrations after acid-ethanol extraction, free IGF-I concentrations, IGFBP3, leptin, testosterone and SHBG were determined. Testosterone concentrations increased in the 2th decade and SHBG concentrations increased in the 4th decade. We observed an increase in leptin in the 4th decade with a decrease in IGF-I, free IGF-I and IGFBP3 throughout the decades. Total IGF-I correlated with waist/hip ratio; free IGF-I with BMI and waist/hip ratio and IGFBP3 did not correlated with any variable. As expected, there was a positive correlation between leptin and BMI, waist/hip ratio, fat free mass and fat mass. On the other hand, SHBG was negatively correlated with BMI, fat mass, total IGF-I, free IGF-I, IGFBP3 and leptin. Testosterone did not correlated with any anthropometric or body composition variable, IGF-I system components, leptin or SHBG. The multiple linear regression analysis produced a model that explained the 40.5% of SHBG variability; only fat mass and IGFBP3 brought an independent significant contribution to SHBG variability. In conclusion, in this population of healthy men randomly selected, we found that they had significant negative correlation between SHBG concentrations and anthropometric, body composition variables, the IGF-I system and leptin levels, and that fat mass and IGFBP3 may be the main determinants of SHBG changes.
    The Journal of Nutrition Health and Aging 01/2007; 11(1):60-4. · 2.66 Impact Factor
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    ABSTRACT: Interleukin-18 (IL-18) is a potent pro-inflammatory cytokine with potential atherogenic properties whose role in human obesity has been recently suggested. The aim of our study was to analyze the physiologic distribution of IL-18 among sexes and all decades of the adult life in a healthy population randomly selected and to study its relationship with anthropometric, body composition measurements and leptin concentrations. We also studied the relationship of IL-18 with smoking and arterial hypertension, known risk factors implicated in atherogenesis. One hundred and thirty four men and 127 healthy women were included in the study. Plasma concentrations of IL-18 and leptin were determined in all subjects. Body composition was evaluated by bioelectrical impedanciometry. IL-18 was distributed similarly in men and women and throughout decades. No significant differences were found in IL-18 between obese and normal-weight men and women according to their body mass index and body fat content. Higher IL-18 concentrations were found in subjects with arterial hypertension. In the bivariate correlation analysis only waist to hip ratio correlated weakly with IL-18 in the whole population (r=0.12, p=0.04). In the multiple regression analysis the relationship between IL-18 and waist to hip ratio lost significance after adjusting for age, sex and body mass index. However, IL-18 remained associated with arterial hypertension (adjusted r2=0.25, p=0.023). The lack of correlation between IL-18 with anthropometric, body composition variables and leptin in our healthy population argues against a role of this cytokine in obesity. Moreover, our findings suggest the implication of this interleukin in the atherogenic process induced by arterial hypertension.
    Hormone and Metabolic Research 09/2006; 38(8):507-12. DOI:10.1055/s-2006-949122 · 2.04 Impact Factor
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    ABSTRACT: No consensus exists until now about the suitable dose of tetracosactin in the ACTH stimulation test for detecting adrenal insufficiency. Our aim was to characterize both the ACTH(1-24) and the cortisol profiles after standard high-dose test (250 microg) (HDT) and low-dose test (1 microg) (LDT) in healthy subjects in order to provide a deeper knowledge about the relationship between stimulus and response. ACTH tests were performed in 10 healthy volunteers (five men, five women) with at least 1 week of difference. Plasma ACTH(1-24) and ACTH(1-39) and serum cortisol were measured before tetracosactin i.v. injection and at 5, 15, 30, 45, 60, 75 and 90 min after stimulus. Area under the curve (AUC) of ACTH(1-24) and cortisol, as well as mean residence time (MRT) for ACTH(1-24) were calculated in both tests. Elimination of ACTH(1-24) was faster in HDT than in LDT (MRTs of 0.14 vs 0.37, respectively, P = 0.008), but plasma concentrations were higher up to 60 min cortisol production in HDT reaching a higher maximum concentration (Cmax: 1144 vs 960 nmol/l) but delayed in time (75 vs 52.5 min). No significant relationship was observed between AUC or Cmax of ACTH(1-24) and AUC, Cmax and increment of cortisol in any of the tests. However, a negative correlation of basal cortisol values was observed with relative cortisol increment (HDT: r = 0.77 P = 0.009; LDT: r = 0.94 P < 0.0001), but not so with Cmax (HDT: r = 0.22 P = 0.55; LDT: r = 0.57 P = 0.09). The elimination rate of ACTH in healthy volunteers was significantly lower in LDT than in HDT, but cortisol production rate appears to be identical in both tests, so that a maximum adrenal stimulation seems to exist. The use of LDT may be more adequate, although data from patients need studying.
    Clinical Endocrinology 09/2006; 65(3):346-51. DOI:10.1111/j.1365-2265.2006.02602.x · 3.35 Impact Factor
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    ABSTRACT: Increased mortality due to cardiovascular disease has been described in adult patients with untreated GH deficiency (GHD). GH replacement has been demonstrate to improve vascular reactivity and reverse early atherosclerotic changes in adults with GHD. Assessment of fibrinolytic markers, soluble adhesion molecules, inflammatory cytokines and endothelial function in hypopituitary adults with GHD at baseline and 1 year after GH replacement therapy. We studied 10 patients with GHD (five men and five women; aged 45.6 +/- 10.4 years) at baseline and 1 year after GH replacement therapy compared with a control group (nine men and 16 women) matched for age and body mass index (BMI). All subjects, patients and controls, were life-long nonsmokers, normotensive and nondiabetic. The following variables were recorded: anthropometric and body composition variables, serum concentrations of glucose, insulin and C-peptide; thrombin anti-thrombin (TAT) fragments and fibrin degradation product D-dimer, which were determined by an enzyme-linked immunosorbent assay (ELISA); IGF-I by radioimmunoassay (RIA); C-reactive protein (CRP) by highly sensitive immunonephelometry; E-selectin, P-selectin, soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) by ELISA. The assessment of endothelial function in vivo was measured with a Doppler device. Patients with GHD without GH substitution had higher hip/waist ratio and body fat than controls. Insulin, C-peptide and triglyceride concentrations were also higher. Our results demonstrated no difference in fibrinogen and in TAT fragment concentrations among patients and controls. E-selectin concentrations were higher in patients than in controls (26.1 +/- 11 vs. 10.7 +/- 6.2 microg/l, P = 0.0001). P-selectin, sICAM-1, sVCAM-1, IL-6, MCP-1 and CRP were similar in the two groups. Vascular reactivity and carotid intima-media thickness (IMT) were also similar in patients and controls. After 1 year of GH treatment we found no changes in biochemical parameters, fibrinolytic markers, soluble adhesion molecules, inflammatory cytokines and endothelial function. Adults with GHD show some subtle changes in soluble adhesion molecules but our data suggest no beneficial effects of GH over these markers in relationship to endothelial function. Factors other than GH treatment, such as differences in age, degree of obesity, the presence of diabetes mellitus and arterial hypertension or tobacco consumption, could explain the observed increase in markers of vascular risk in GH-deficient patients.
    Clinical Endocrinology 07/2006; 64(6):632-9. DOI:10.1111/j.1365-2265.2006.02518.x · 3.35 Impact Factor
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    ABSTRACT: TWEAK, a cytokine of the TNF family, has been found to be expressed under different inflammatory conditions but no data is available concerning the expression of this cytokine and its receptor (Fn14) in human obesity. In the present work we have evaluated the expression of many pro-inflammatory TNF system cytokines (TNF-alpha, TWEAK and their respective receptors, TNFR1, TNFR2 and Fn14) in human adipose tissue of 84 subjects some with different degree of obesity and type 2 diabetes, and its relation with inflammation by also measuring the expression of macrophage marker CD68. We detected expression of TWEAK and Fn14 in isolated mature adipocytes and in the stromovascular fraction. Additionally, we found that LPS upregulates the expression of both genes on THP-1 human monocytic cell line. TWEAK was expressed in adipose tissue of all studied subjects with no differences between obesity group, and was associated with Fn14 expression in morbid obese, mainly in women with type 2 diabetes. The data obtained here also showed that TNF-alpha and TNFR2 mRNAs were significantly more expressed in subcutaneous adipose tissue of subjects with morbid obesity compared to obese and non-obese subjects. In contrast, TNFR1 gene expression was negatively associated with BMI. Our results suggest that the expression of TNF-derived pro-inflammatory cytokines are increased in severe obesity, where macrophage infiltrate could modulate the inflammatory environment through activation of its receptors.
    Cytokine 03/2006; 33(3):129-37. DOI:10.1016/j.cyto.2005.12.005 · 2.87 Impact Factor
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    ABSTRACT: The objective was to evaluate the effect of improved metabolic control and ACE inhibition used sequentially in the treatment of type 1 diabetic patients with microalbuminuria. We studied 44 consecutive type 1 diabetic patients with microalbuminuria not previously treated with ACE inhibitors. Improved metabolic control (optimisation period) was attempted for 6-12 months and patients with persistent microalbuminuria were subsequently treated with ACE inhibitors. Stepwise logistic regression analysis included the variables age, age at diabetes onset, duration of diabetes, HbA1c, initial albumin excretion rate (AER) and mean blood pressure as predictors of final AER. Thirty per cent of patients regressed to normoalbuminuria after the optimisation period, and 58% of them maintained normal AER 4.5+/-1.3 years later (3-7 years). Patients achieving normoalbuminuria had lower baseline AER (53+/-22 vs. 94+/-63 mg/24 h, p=0.012). The initial AER level was the only factor associated with final AER (r=0.58, p=0.021). Thirty patients with persistent microalbuminuria were treated with ACE inhibitors for two years, 35.5% of whom regressed to normal AER. Patients achieving normoalbuminuria after ACE inhibitor treatment had lower baseline AER (55+/-24 vs. 132+/-75 mg/24 h, p=0.03). The initial AER was the sole predictor of final AER (r=0.51, p<0.013). Overall, the sequential use of improved metabolic control and ACE inhibitor therapy resulted in long-term normalisation of AER in 47.4% of patients. The sequential implementation of improved metabolic control and ACE inhibitor therapy had a long-term beneficial effect in type 1 diabetic patients with microalbuminuria. We propose that type 1 diabetic patients with microalbuminuria could benefit from a period of metabolic improvement before the initiation of ACE inhibitor therapy.
    Acta Diabetologica 07/2005; 42(2):87-94. DOI:10.1007/s00592-005-0184-0 · 3.68 Impact Factor
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    ABSTRACT: The objective was to evaluate the effect of improved metabolic control and ACE inhibition used sequentially in the treatment of type 1 diabetic patients with microalbuminuria. We studied 44 consecutive type 1 diabetic patients with microalbuminuria not previously treated with ACE inhibitors. Improved metabolic control (optimisation period) was attempted for 6-12 months and patients with persistent microalbuminuria were subsequently treated with ACE inhibitors. Stepwise logistic regression analysis included the variables age, age at diabetes onset, duration of diabetes, HbA1c, initial albumin excretion rate (AER) and mean blood pressure as predictors of final AER. Thirty per cent of patients regressed to normoalbuminuria after the optimisation period, and 58% of them maintained normal AER 4.5+/-1.3 years later (3-7 years). Patients achieving normoalbuminuria had lower baseline AER (53+/-22 vs. 94+/-63 mg/24 h, p=0.012). The initial AER level was the only factor associated with final AER (r=0.58, p=0.021). Thirty patients with persistent microalbuminuria were treated with ACE inhibitors for two years, 35.5% of whom regressed to normal AER. Patients achieving normoalbuminuria after ACE inhibitor treatment had lower baseline AER (55+/-24 vs. 132+/-75 mg/24 h, p=0.03). The initial AER was the sole predictor of final AER (r=0.51, p<0.013). Overall, the sequential use of improved metabolic control and ACE inhibitor therapy resulted in long-term normalisation of AER in 47.4% of patients. The sequential implementation of improved metabolic control and ACE inhibitor therapy had a long-term beneficial effect in type 1 diabetic patients with microalbuminuria. We propose that type 1 diabetic patients with microalbuminuria could benefit from a period of metabolic improvement before the initiation of ACE inhibitor therapy.
    Acta Diabetologica 07/2005; 42(2):87-94. DOI:10.1007/s00592-005-0184-0 · 3.68 Impact Factor
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    ABSTRACT: Tumor necrosis factor alpha has a key role in insulin resistance. We study the effects of metformin on glucose tolerance, insulin resistance, beta cell function, and soluble tumor necrosis factor receptor (sTNFR) levels. We performed a double-blind, randomized metformin-placebo study. Twenty-three subjects with impaired glucose tolerance or impaired fasting glucose were studied. Oral glucose tolerance, homeostasis model assessment, and continuous infusion of glucose with model assessment tests were used to evaluate glucose tolerance, insulin sensitivity, and beta cell function, respectively. Soluble tumor necrosis factor receptor levels were measured before and after therapy. Repeated measures analysis of variance was used for statistical analysis. After 12-week treatment, fasting glucose (110.1 +/- 9.9 to 98.9 +/- 15.7 mg/dl, P < .001), fasting insulin (11.6 +/- 5.4 to 8.8 +/- 3.5 mU/L, P = .05), fasting C-peptide (2.5 +/- 0.7 to 1.8 +/- 0.5 ng/mL, P < .05), and achieved C-peptide (5.2 +/- 1.2 to 4.2 +/- 1 ng/mL, P < .05) levels decreased in the metformin group. In addition, there was an improvement in insulin sensitivity (37.4% +/- 15.2% to 50.4% +/- 23.2%, P < .05) with unchanged sTNFR1 (2.0 +/- 0.8 to 2.3 +/- 1.2 microg/L, P = NS) and sTNFR2 (4.8 +/- 1.7 to 4.4 +/- 1.2 microg/L, P = NS) levels. Metformin is able to reverse insulin resistance and hyperglycemia in high-risk subjects for type 2 diabetes mellitus independently of the effects on tumor necrosis factor alpha system activity.
    Metabolism 03/2005; 54(2):235-9. DOI:10.1016/j.metabol.2004.08.018 · 3.61 Impact Factor
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    ABSTRACT: The naturally occurring inhibitor of interleukin-1 (IL-1) action, interleukin-1 receptor antagonist protein (IRAP), binds to the type 1 IL-1 receptor but does not initiate IL-1 signal transduction. In this study, we have determined the effects of IL-1beta and IRAP overexpression on adult beta-cell replication and viability. IL-1beta reduced dramatically beta-cell replication in adult rat islets both at 5.5 mM (control: 0.29+/-0.04%; IL-1beta: 0.02+/-0.02%, P<0.05) and 22.2 mM glucose (control: 0.84+/-0.2%; IL-1beta: 0.05+/-0.05%, P<0.05). This effect was completely prevented in islets overexpressing IRAP after adenoviral gene transfer at 5.5 mM (Ad-IL-1Ra+IL-1beta: 0.84+/-0.1%, P<0.05) and 22.2 mM glucose (Ad-IL-1Ra+IL-1beta: 1.22+/-0.2%, P<0.05). Moreover, overexpression of IRAP increased glucose-stimulated beta-cell replication in the absence of IL-1beta exposure (Ad-IL-1Ra: 1.59+/-0.5%, P<0.05). beta-Cell death (TUNEL technique) was increased in IL-1beta-exposed islets but not in Ad-IL-1Ra-infected islets (control: 0.82+/-0.2%; control+IL-1beta: 1.77+/-0.2; IRAP: 0.61+/-0.2%; IRAP+IL-1beta: 0.86+/-0.1%, P<0.05). Comparable results were obtained by flow cytometry. To determine the effect of IRAP overexpression on beta-cell replication in vivo, Ad-IL-1Ra-transduced islets were transplanted into streptozotocin diabetic rats. beta-Cell replication was significantly increased in IRAP-overexpressing islet grafts (0.98+/-0.3%, P<0.05) compared to normal pancreas (0.35+/-0.02%), but not in control islet grafts (0.50+/-0.1%). This study shows that in addition to the effects of IL-1beta on beta-cell viability, this cytokine exerts a deleterious action on beta-cell replication, which can be prevented by IRAP overexpression, and provides support for the potential use of IRAP as a therapeutic tool.
    Gene Therapy 02/2005; 12(2):120-8. DOI:10.1038/sj.gt.3302351 · 4.20 Impact Factor
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    ABSTRACT: Our aim was to assess reference values of thyroid volume by ultrasonography in healthy adult subjects. We conducted an epidemiological cross-sectional study where 880 subjects were randomly selected from the town census of L'Hospitalet de Llobregat after being invited to participate in our study directly by mail and phone call. We made a clinical history of each subject and determined serum thyrotropin, antiperoxidase antibodies, urinary iodine excretion and thyroid volume by ultrasonography. Subjects with thyroid disease were excluded. We finally studied 268 representative subjects. The reference thyroid volume was median 7.31 ml, mean 8.22 ml (Confidence Interval: 7.75 - 8.69 ml). In men: median 9.19 ml, mean 9.87 ml (CI: 9.09 - 10.65 ml); in women: median 6.19 ml, mean 6.57 ml (CI: 6.22 - 9.92 ml) (p < 0.0001). We grouped the subjects into decades, and found that thyroid volume was different (p = 0.0034) in males because the younger group had lower volume. We did not find any differences among age groups in women. The mean of the urinary iodine excretion was 154.23 microg/l. We have determined reference values of thyroid volume measured by ultrasonography in our iodine non-deficient population and prepared tables that distribute thyroid volume by sex and age.
    Hormone and Metabolic Research 10/2004; 36(9):645-9. DOI:10.1055/s-2004-825901 · 2.04 Impact Factor

Publication Stats

2k Citations
296.19 Total Impact Points

Institutions

  • 1990–2011
    • Hospital Universitari de Bellvitge
      • Department of Endocrinology and Nutrition
      l'Hospitalet de Llobregat, Catalonia, Spain
  • 2002–2004
    • Hospital Clínic de Barcelona
      Barcino, Catalonia, Spain
  • 1991–2000
    • University of Barcelona
      • Department of Clinical Sciences
      Barcino, Catalonia, Spain
  • 1999
    • Hospital Arnau de Vilanova
      Valenza, Valencia, Spain
    • Institut Marqués, Spain, Barcelona
      Barcino, Catalonia, Spain