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ABSTRACT: : To evaluate the association between glucagon-like peptide 1 (GLP-1) secretion and the long-term (>2 years) outcome of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGBP).
: Cross-sectional study in 18 T2DM morbidly obese subjects who underwent RYGBP but differed in the long-term outcome of T2DM (remission: G1, n = 6; relapse: G2, n = 6; lack of remission: G3: n = 6). Groups were matched for their sex, age, and body mass index. The GLP-1, glucose, C-peptide, and glucagon responses to a standardized test meal (STM) were evaluated. Insulin secretion and insulin sensitivity were estimated from the STM and by frequently sampling intravenous glucose tolerance test (FSIVGTT). Dual-energy X-ray absorptiometry was used to assess body composition.
: Patients in G1 presented a lower area under the curve (AUC0-120) of glucose in response to the STM as compared with G2, and G3 (P < 0.01). In contrast, the AUC0-120 of GLP-1 (P = 0.884) and glucagon (P = 0.630) did not differ significantly among the 3 groups. Indices of insulin secretion adjusted by the prevailing insulin sensitivity derived from STM and FSIVGTT, demonstrated larger β-cell function in subjects in G1 as compared with G2 or G3 (Disposition Index-STM, P = 0.005; DI-FSIVGTT, P = 0.006). Body composition and inflammatory markers did not differ significantly among the 3 study groups.
: Our data show that in subjects with T2DM an enhanced GLP-1 response to meal intake is not sufficient to maintain normal glucose tolerance in the long term after RYGBP. Our data suggest that β-cell function is a key determinant of the long-term remission of T2DM after this bariatric surgery technique.
Annals of surgery 05/2013; 257(5):894-9. · 7.90 Impact Factor
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ABSTRACT: OBJECTIVE
Glucagon like peptide-1 (GLP-1) has been suggested as a major factor for the improved glucose tolerance ensuing after Roux-en-Y Gastric Bypass (RYGBP) surgery. We examined the effect of blocking endogenous GLP-1 action on glucose tolerance in subjects with sustained remission of type 2 diabetes (T2DM) present before RYGBP.RESEARCH DESIGN AND METHODS
Blood glucose, insulin, C-peptide, glucagon, GLP-1, and glucose-dependent insulinotropic peptide levels were measured after a meal challenge with either exendin-(9-39) (a GLP-1r antagonist) or saline infusion in eight subjects with sustained remission of T2DM after RYGBP and seven healthy controls.RESULTSInfusion of exendin-(9-39) resulted in marginal deterioration of the 2-h plasma glucose after meal intake in RYGBP subjects (saline 78.4 ± 15.1 mg/dL compared with exendin-(9-39) 116.5 ± 22.3 mg/dL; P < 0.001). Furthermore, glucose response to meal intake was similarly enlarged in the two study groups (percent change in the area under the curve of glucose exendin-(9-39)-infusion versus saline-infusion: controls 10.84 ± 8.8% versus RYGBP 9.94 ± 8.4%; P = 0.884). In the RYGBP group, the blockade of the enlarged GLP-1 response to meal intake resulted in reduced insulin (P = 0.001) and C-peptide (P < 0.001), but no change in glucagon (P = 0.258) responses.CONCLUSION
The limited deterioration of glucose tolerance on blockade of GLP-1 action in our study suggests the resolution of T2DM after RYGBP may be explained by mechanisms beyond enhancement of GLP-1 action.
Diabetes care 01/2013; · 8.09 Impact Factor
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José Manuel Fernández-Real,
Josep Puig,
Marta Serrano,
Mónica Sabater,
Antoni Rubió,
José María Moreno-Navarrete,
Marina Fontan, Roser Casamitjana,
Gemma Xifra,
Francisco José Ortega,
Javier Salvador,
Gema Frühbeck,
Wifredo Ricart
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ABSTRACT: Fibroblast growth factor 23 (FGF-23) is known to be produced by the bone and linked to metabolic risk. We aimed to explore circulating FGF-23 in association with fatness and insulin sensitivity, atherosclerosis and bone mineral density (BMD). Circulating intact FGF-23 (iFGF-23) and C-terminal (CtFGF-23) concentrations (ELISA) were measured in 133 middle aged men from the general population in association with insulin sensitivity (Cohort 1); and in association with fat mass and bone mineral density (DEXA) and atherosclerosis (intima media thickness, IMT) in 78 subjects (52 women) with a wide range of adiposity (Cohort 2). Circulating iFGF-23 was also measured before and after weight loss. In all subjects as a whole, serum intact and C-terminal concentrations were linearly and positively associated with BMI. In cohort 1, both serum iFGF-23 and CtFGF-23 concentrations increased with insulin resistance. Serum creatinine contributed to iFGF-23 variance, while serum ferritin and insulin sensitivity (but not BMI, age or serum creatinine) contributed to 17% of CtFGF-23 variance. In cohort 2, CtFGF-23 levels were higher in women vs. men, and increased with BMI, fat mass, fasting and post-load serum glucose, insulin, HOMA-IR and PTH, being negatively associated with circulating vitamin D and ferritin levels. The associations of CtFGF-23 with bone density in the radius, lumbar spine and carotid IMT were no longer significant after controlling for BMI. Weight loss led to decreased iFGF-23 concentrations. In summary, the associations of circulating FGF-23 concentration with parameters of glucose metabolism, bone density and atherosclerosis are dependent on iron and obesity status-associated insulin resistance.
PLoS ONE 01/2013; 8(3):e58961. · 4.09 Impact Factor
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ABSTRACT: OBJECTIVE:: To identify the rates and the predictors of long-term remission and the recurrence of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGBP) or sleeve gastrectomy (SG). BACKGROUND:: The durability of the improvement of T2DM after bariatric surgery is not well characterized. METHODS:: One hundred fifty-three subjects with T2DM (RYGBP: n = 98; SG: n = 55) were evaluated for remission and recurrence of the disease throughout 35.4 ± 13.5 months' follow-up. The type of surgery, demographic, anthropometric, and biochemical parameters were ascertained as predictors of T2DM outcomes. Glucagon-like peptide 1 (GLP-1) responses after a standard mixed liquid meal were compared between patients presenting with T2DM remission after RYGBP or SG. RESULTS:: 75.2% of subjects presented with remission of T2DM lasting at least 12 months. However, in 12.1% of subjects, T2DM recurred. Regression analysis showed a longer duration of T2DM (P = 0.006), a higher presurgical glycated hemoglobin level (P = 0.019), insulin treatment at baseline (P = 0.001), and a lower excess weight loss at last follow-up visit (P < 0.001) as independent predictors for the lack of T2DM remission. Insulin use before surgery (P = 0.005), an older age (P = 0.05), and weight regain after remission (P = 0.021) predicted recurrence of the disease. Long-term remission of T2DM after SG or RYGBP was associated with a comparably enlarged GLP-1 response to a standard mixed liquid meal challenge. CONCLUSIONS:: Roux-en-Y gastric bypass and SG are associated with comparable remission rates of T2DM. However, insufficient weight loss or weight regain in those with a more advanced disease may hamper the benefits of these surgical techniques on T2DM.
Annals of surgery 09/2012; · 7.90 Impact Factor
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ABSTRACT: Recent evidence supports a specific and broad role of androgen produced by theca cells in reproductive physiology. This pilot study evaluated the usefulness of hCG theca stimulation test in predicting ovarian response and pregnancy.
Prospective cohort study including 80 infertile women treated with IVF/ICSI. On Day 3 of the menstrual cycle preceding, the first IVF/ICSI cycle a blood sample was drawn to evaluate baseline FSH, estradiol (E(2)), 17-hydroxy-progesterone, androstenedione and testosterone levels. All women then received 250 µg recombinant hCG s.c. and underwent a second blood sampling 24 h after hCG injection to measurement steroid serum levels.
Percentage increment of E(2) but not its precursors was significantly higher in normo-responders and pregnancy cycles than in poor responders and non-pregnancy cycles (P = 0.03 and P = 0.02, respectively) diagnostic accuracy being 67 and 75%, respectively. The percentage increase in E(2) thus still fails in as many as 33 and 25% of patients in predicting ovarian response and pregnancy, respectively. In addition, E(2) concentrations are poorly reproducible and a wide range of variation in all serum steroids investigated-including E(2)-after hCG injection was observed.
The predictive power of the hCG test is based on E(2) but not androgen response to hCG injection. This test cannot be recommended in routine clinical practice because it is too laborious for screening purposes, shows great variability in the response obtained and its overall accuracy is not better than that reported for other available markers of ovarian reserve. The use of the currently available markers, antral follicle count and anti-Müllerian hormone, is therefore recommended.
Human Reproduction 02/2012; 27(4):1122-9. · 4.47 Impact Factor
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ABSTRACT: Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGBP) are associated with similar type 2 diabetes mellitus (T2DM) resolution rates for morbidly obese subjects. However, the mechanisms underlying the resolution of T2DM after SG have not been clarified to date. This study aimed to compare the early changes in gastrointestinal hormones involved in insulin and glucagon secretion in morbidly obese T2DM subjects undergoing SG or RYGBP.
This prospective study investigated 12 subjects with T2DM who had undergone SG (n = 6) or RYGBP (n = 6). Five body mass index (BMI)-matched obese non-diabetic subjects and five BMI-matched obese diabetic subjects served as control subjects. Glucose, insulin, glucagon, glucagon-like peptide 1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and GLP-2 were determined after a standardized mixed liquid meal before surgery and 6 weeks afterward.
After 6 weeks, five of the six subjects in each surgical group presented with T2DM remission, although the area under the curve (AUC)0–120 of glucose was greater than that of the non-diabetic control subjects (P < 0.01). Postsurgically, the indices of insulin and glucagon secretion were comparable between the two surgical groups. The AUC0–120 of GLP-1 (P < 0.05) and GLP-2 (P < 0.05) was significantly and comparably enlarged after SG and RYGB. The postsurgical GIP response was significantly associated with the glucagon response throughout the meal test (ρ = 0.747; P < 0.01).
The data show that in a cohort of morbidly obese T2DM subjects, SG and RYGBP are associated with an early improvement in glucose tolerance, similar changes in insulin and glucagon secretion, and a similar GLP-1, GIP, and GLP-2 response to a standardized mixed liquid meal.
Surgical Endoscopy 02/2012; 26(8):2231-9. · 4.01 Impact Factor
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ABSTRACT: To study endometrial receptivity in terms of osteopontin (OPN) and αvβ3 integrin expression and co-expression in infertile women with early stages of endometriosis.
We investigated the immunohistochemical expression and co-expression of OPN and αvβ3 integrin in the endometrium of 20 infertile patients with Stage I or II endometriosis as the only detectable cause of infertility, 20 infertile patients with unexplained infertility and 20 fertile women undergoing tubal sterilization. Two endometrial biopsies were performed during a single menstrual cycle (postovulatory Day +7 to +8 and 4 days later) in each subject.
No statistically significant differences regarding OPN and αvβ3 integrin expression were found between infertile patients with endometriosis and the two control groups. There was no significant correlation between OPN and αvβ3 integrin staining intensity in the mid-luteal phase biopsies in any of the groups studied.
Endometrial OPN and αvβ3 integrin expression or co-expression is not impaired during the window of implantation in patients with Stage I-II endometriosis. Further studies are needed to determine whether these results imply normal endometrial receptivity in such patients or add to the increasing uncertainty about the clinical value of assessing the endometrium with these markers of implantation.
Human Reproduction 01/2012; 27(3):805-13. · 4.47 Impact Factor
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Lluis Vila,
Mateu Serra-Prat,
Alfonso de Castro,
Elisabet Palomera, Roser Casamitjana,
Gustavo Legaz,
Celia Barrionuevo,
José A Muñoz,
Ana J García,
Sanjay Lal-Trehan,
Amparo García,
Josep Durán,
Manel Puig-Domingo
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ABSTRACT: Catalonia (Spain) has a historically worse situation of mild iodine deficiency in the Pyrenees Mountains compared with the coastal region. The aim of this study was to evaluate the current iodine status in pregnant women living in these two areas.
An epidemiologic prospective survey included 267 consecutive pregnancies in the Catalan mountains (n = 139) and coast (n = 128) studied during the first trimester; an additional subset of 135 women from the initial cohort was available for evaluation in the third trimester. Urinary iodine (UI) was measured, and questionnaires to determine iodized salt and sea fish consumption and potassium iodide supplementation were administered.
The median UI in the first trimester was 163 μg/L for the entire cohort, with differences between mountain and coastal regions (209 versus 142 μg/L, P = 0.007). The highest prevalence of iodized salt consumption was in the mountain area (58% versus 36.4%, P < 0.001). For the entire group, a higher median UI was found in iodized salt consumers compared with non-consumers (193 versus 134 μg/L, P < 0.001). In the third trimester, an increase of median UI was seen in those to whom iodine supplements were given during pregnancy (190 versus 154 μg/L, P = 0.015).
A reversal in the historically iodine-deficient situation was observed in the Catalan Pyrenees compared with the coastal area, with a globally acceptable iodine status in pregnant women of the two geographic locations. Iodized salt consumption seems to have contributed to maintaining an acceptable iodine status in this population.
Nutrition 05/2011; 27(10):1029-33. · 3.03 Impact Factor
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ABSTRACT: To investigate the effect of oral contraceptives (OC), metformin and ovulation induction with gonadotropins on circulating anti-müllerian hormone (AMH).
Prospective clinical study.
Thirty patients with PCOS (Group 1), 15 normogonadotropic anovulatory infertile women (WHO 2) (Group 2) and 15 normoovulatory control women (Group 3). Patients in Group 1 received OC (n = 12), metformin (n = 11) or no-treatment (n = 7) for 6 months. Ovulation induction with FSH or hMG was used in Group 2.
Total follicle number (TFN) and hormonal (fasting insulin and glucose, testosterone, SHBG, LH, androstenedione and AMH) measurements at baseline and during therapy.
Basal AMH and TFN were higher in Groups 1 and 2 than in controls. Only TFN was significantly related to AMH level in Groups 1 and 2. AMH level was significantly reduced during OC treatment, and there was a trend for AMH decrease during metformin therapy. No significant changes in AMH level were observed during ovulation induction. TFN was the only parameter showing a significant positive correlation with circulating AMH over the 6-month treatment period in patients in Group 2.
AMH is an accurate marker of the antral follicle pool in WHO-2/PCOS women but the measurement of AMH is not likely to be helpful in the management of those patients.
Gynecological Endocrinology 04/2011; 27(4):216-24. · 1.58 Impact Factor
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Gemma Prieto,
Maria Teresa Torres,
Lidia Francés,
Gemma Falguera,
Lluis Vila,
Josep María Manresa, Roser Casamitjana,
Juan Ramón Barrada,
Amèlia Acera,
Dolors Guix,
Anna Torrent,
Josep Grau,
Pere Torán
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ABSTRACT: It is a priority to achieve an adequate nutritional status of iodine during pregnancy since iodine deficiency in this population may have repercussions on the mother during both gestation and post partum as well as on the foetus, the neonate and the child at different ages. According to the WHO, iodine deficiency is the most frequent cause of mental retardation and irrreversible cerebral lesions around the world. However, few studies have been published on the nutritional status of iodine in the pregnant population within the Primary Care setting, a health care level which plays an essential role in the education and control of pregnant women. Therefore, the aim of the present study is: 1.- To know the hygiene-dietetic habits related to the intake of foods rich in iodine and smoking during pregnancy. 2.- To determine the prevalence of iodine deficiency and the factors associated with its appearance during pregnancy.
We will perform a cluster randomised, controlled, multicentre trial. Randomisation unit: Primary Care Team. Study population: 898 pregnant women over the age of 17 years attending consultation to a midwife during the first trimester of pregnancy in the participating primary care centres. Outcome measures: consumption of iodine-rich foods and iodine deficiency. Points of assessment: each trimester of the gestation. Intervention: group education during the first trimester of gestation on healthy hygiene-dietetic habits and the importance of an adequate iodine nutritional status. Statistical analysis: descriptive analysis of all variables will be performed as well as multilevel logistic regression. All analyses will be done carried out on an intention to treat basis and will be fitted for potential confounding factors and variables of clinical importance.
Evidence of generalised iodine deficiency during pregnancy could lead to the promotion of interventions of prevention such as how to improve and intensify health care educational programmes for pregnant women.
ClinicalTrials.gov: NCT01301768.
BMC Pregnancy and Childbirth 03/2011; 11:17. · 2.83 Impact Factor
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ABSTRACT: To investigate the usefulness of day-5 inhibin B and antral follicle count (AFC) in predicting ovarian response and live birth in the first cycle of assisted reproduction.
Prospective cohort study.
University hospital.
Ninety-eight infertile women treated with in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) comprising 72 normal responders and 26 poor responders.
Ovarian stimulation with gonadotropin-releasing hormone agonist-gonadotropin treatment.
Basal ultrasonographic (AFC, total ovarian volume) and basal (follicle-stimulating hormone, estradiol, and inhibin B) and stimulation day-5 (estradiol, inhibin B) hormone parameters.
The AFC had the best predictive value among the basal variables for outcome of ovarian stimulation. Among the dynamic hormone measurements, day-5 inhibin serum measurement emerged as the best predictive variable of poor response in IVF-ICSI cycles, but it was not statistically significantly better than basal AFC. The association of day-5 inhibin B with live-birth rate was statistically significant and stronger than the effect of any other variable investigated.
Basal AFC and day-5 inhibin B have similar predictive properties for ovarian response in assisted reproduction cycles stimulated with gonadotropin after pituitary suppression, but day-5 inhibin B is a superior predictor of live birth.
Fertility and sterility 12/2010; 94(7):2590-5. · 3.97 Impact Factor
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ABSTRACT: OBJECTIVE: To describe the characteristics of metabolic control and beta-cell function in the long-term follow-up of patients with type-1 diabetes (T1D) who have undergone pancreas and kidney transplantation (PKTx). Patients and methods: Twelve patients (eight males/four females) with normal pancreas and kidney graft function for more than 15 yr were included. Patient age at the time of transplantation was 35.8 ± 6.9, with a duration of diabetes of 19.0 ± 4.6 yr and time on dialysis of 18.7 ± 12.4 months. In all the cases, bladder derivation was performed to drain exocrine secretion, with subsequent conversion to the intestinal tract in 42% of the patients. The functional evaluation was made at one, five, 10, and 15 yr after PKTx determining: glycosylated hemoglobin (HbA1c), oral glucose tolerance test (OGTT), measuring insulinemia, and anti-GAD antibody. Results: Comparing the results between one and 15 yr after transplantation: (i) no differences were observed in either HbA1c (4.68% vs. 4.76%) or basal glycemia (71 vs. 79 mg/dL), but an increase was seen in the area under the curve (AUC) of glucose (11,983 vs. 15,875 mg/dL/120', p = 0.02); (ii) a trend to a reduction in basal insulinemia (24 vs. 15 mU/L, p = 0.11) and a trend to a reduction in the AUC of insulinemia (8446 vs. 7057 mU/L/120', p = 0.22) were observed. The OGTT was normal in six patients, intolerant in two and diabetic in four patients. No variations were seen in insulin resistance (FIRI, QUICKI). Anti-GAD antibody became positive in one case. Conclusions: The results of this study demonstrate that pancreas transplantation has long-term functional viability, being an essential strategy for the treatment of patients with T1D with end-stage renal failure. Nevertheless, lesser response to OGTT can be expected suggesting certain deterioration in the functional capability of the pancreas graft during follow-up.
Clinical Transplantation 11/2010; 24(6):E236-40. · 1.67 Impact Factor
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ABSTRACT: To evaluate through early preclinical atherosclerosis assessment whether repeated episodes of hypoglycemia represent an aggravating factor for macrovascular disease in type 1 diabetes.
After sample-size calculation, a case-control study of 25 patients with type 1 diabetes and repeated severe/nonsevere hypoglycemia (H-group) compared with 20 age- and sex-matched type 1 diabetes control subjects (C-group) was designed. Assessment of preclinical atherosclerosis consisted of flow-mediated brachial dilatation (FMD) and carotid and femoral intima-media thickness (IMT) studies. To consider hypoglycemia awareness, two different questionnaires and symptomatic response to an acute induction to hypoglycemia were used. Evaluation of the glycemic profile was obtained from continuous glucose monitoring. Endothelial function/inflammation markers were measured in euglycemia/hypoglycemia. A multivariate linear regression analysis was performed to test whether repeated hypoglycemia was independently associated with atherosclerosis.
H-group subjects displayed hypoglycemia unawareness and presented a higher percentage of continuous glucose values and area under the curve <70 mg/dl compared with the C-group (14.2 ± 8.9 vs. 6.3 ± 7.1%, P < 0.02 and 2.4 ± 1.8 vs. 0.6 ± 1.0 mg/dl/day, P < 0.01). The percentage of maximal FMD was lower in the H-group than in the C-group (6.52 ± 2.92 vs. 8.62 ± 3.13%, P < 0.05). A significantly higher IMT was observed at both carotid and femoral sites in the H-group (carotid 0.53 ± 0.09 vs. 0.47 ± 0.08 mm, P < 0.05 and femoral 0.51 ± 0.17 vs. 0.39 ± 0.09 mm, P < 0.05). Baseline inflammation and endothelial function markers were higher in the H-group (leukocytes 7.0 ± 1.8 vs. 5.6 ± 1.4 × 10³/ml, von Willebrand factor 119 ± 29 vs. 93 ± 26%, fibrinogen 2.82 ± 0.64 vs. 2.29 ± 0.44 g/l, and soluble intercellular adhesion molecule-1 408 ± 224 vs. 296 ± 95 ng/ml; P < 0.05 for all).
In addition to the induction of hypoglycemia unawareness and an increased risk for severe hypoglycemia, repeated hypoglycemia could be related to and considered an aggravating factor for preclinical atherosclerosis in type 1 diabetes. The precise mechanisms explaining this association remain to be clarified.
Diabetes care 10/2010; 34(1):198-203. · 8.09 Impact Factor
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ABSTRACT: The osteopontin: alphavbeta3 integrin complex has been proposed as a means of distinguishing receptive from non-receptive endometrium in clinical practice, thus offering new directions for the development of contraceptive approaches targeted to the endometrium as well as a better understanding of occult causes of infertility in women. Histological dating and immunohistochemical study were performed in control and study cycles in seven groups of women including 10 subjects per group and who received clomiphene citrate, ovarian stimulation for IVF, oral contraception, dehydrogesterone for endometrial luteal phase defect, two different regimens of hormone replacement therapy, or no treatment. Ten healthy fertile women served as a general control group. Osteopontin and alphavbeta3 integrin expression in the human endometrium was closely related to endometrial maturation and this was irrespective of the endometrium being in-phase or out-of-phase and the hormonal treatment (or no treatment) received. In conclusion, immunohistochemical assessment of the endometrium indicates that the use of osteopontin and alphavbeta3 integrin or the osteopontin: alphavbeta3 integrin complex as targets for the development of contraceptive approaches or the understanding of the pathogenesis of female infertility offer little benefit compared with simple histological dating.
Reproductive biomedicine online 09/2010; 21(3):349-59. · 2.04 Impact Factor
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José Manuel Fernández-Real,
Sergio Valdés,
Melania Manco,
Berta Chico,
Patricia Botas,
Arantza Campo, Roser Casamitjana,
Elías Delgado,
Javier Salvador,
Gema Fruhbeck,
Geltrude Mingrone,
Wifredo Ricart
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ABSTRACT: Impaired lung function and innate immunity have both attracted growing interest as a potentially novel risk factor for glucose intolerance, insulin resistance, and type 2 diabetes. We aimed to evaluate whether surfactant protein D (SP-D), a lung-derived innate immune protein, was behind these associations.
Serum SP-D was evaluated in four different cohorts. The cross-sectional associations between SP-D and metabolic and inflammatory parameters were evaluated in two cohorts, the cross-sectional relationship with lung function in one cohort, and the longitudinal effects of weight loss on fasting and circadian rhythm of serum SP-D and cortisol concentrations in one prospective cohort.
In the cross-sectional studies, serum SP-D concentration was significantly decreased in subjects with obesity and type 2 diabetes (P = 0.005) and was negatively associated with fasting and postload serum glucose. SP-D was also associated with A1C, serum lipids, insulin sensitivity, inflammatory parameters, and plasma insulinase activity. Smoking subjects with normal glucose tolerance, but not smoking patients with type 2 diabetes, showed significantly higher serum SP-D concentration than nonsmokers. Serum SP-D concentration correlated positively with end-tidal carbon dioxide tension (r = 0.54, P = 0.034). In the longitudinal study, fasting serum SP-D concentration decreased significantly after weight loss (P = 0.02). Moreover, the main components of cortisol and SP-D rhythms became synchronous after weight loss.
These findings suggest that lung innate immunity, as inferred from circulating SP-D concentrations, is at the cross-roads of inflammation, obesity, and insulin resistance.
Diabetes care 04/2010; 33(4):847-53. · 8.09 Impact Factor
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Lluís Vila,
Mateu Serra-Prat,
Elisabet Palomera, Roser Casamitjana,
Alfonso de Castro,
Gustavo Legaz,
Celia Barrionuevo,
Ana-Julia Garcia,
Sanjay Lal-Trehan,
José Antonio Muñoz,
Josep Durán,
Amparo Garcia,
Manel Puig-Domingo
Thyroid: official journal of the American Thyroid Association 02/2010; 20(2):221-5. · 2.60 Impact Factor
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Esteban Martínez,
María Larrousse,
Daniel Podzamczer,
Ignacio Pérez,
Félix Gutiérrez,
Montserrat Loncá,
Patricia Barragán,
Ramón Deulofeu, Roser Casamitjana,
Josep Mallolas,
Judit Pich,
José M Gatell
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ABSTRACT: To assess the effects of initiating abacavir-containing therapy on plasma lipids and cardiovascular biomarkers.
Sub-study of the BICOMBO study in which participants were randomized to switch their nucleoside backbone to either abacavir/lamivudine or tenofovir/emtricitabine.
We assessed 48-week changes in fasting lipids and several biomarkers including serum high-sensitivity C-reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), osteoprotegerin, interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1), selectin E and P, adiponectin, insulin, and D-dimer in otherwise healthy, virologically suppressed HIV-infected patients randomly switched to abacavir/lamivudine or tenofovir/emtricitabine with no history of cardiovascular disease, no prior abacavir or tenofovir use, and no virological failure or AIDS during follow-up.
Eighty (46 abacavir/lamivudine and 34 tenofovir/emtricitabine) patients were included. Baseline characteristics were similar between groups and between patients in the sub-study vs. those not. There were no significant differences in baseline lipids and markers between groups. Although total (6.5 vs. -6.7%, P < 0.0001) and low-density lipoprotein (LDL) (8.6 vs. -9.1%, P = 0.004) cholesterol increased significantly in the abacavir/lamivudine group relative to the tenofovir/emtricitabine group, we found no significant changes in the biomarkers: CRP (-3.9 vs. 0.0%), MCP-1 (5.9 vs. 4.0%), osteoprotegerin (5.1 vs. -2.8%), IL-6 (0.0 vs. 0.0%), IL-10 (0.0 vs. 0.0%), TNF-alpha (0.0 vs. 0.0%), ICAM-1 (6.6 vs. 5.2%), VCAM-1 (0.02 vs. -0.01%), selectin E (-0.4 vs. 7.8%), selectin P (4.6 vs. 12.6%), insulin (-2.5 vs. 8.8%), adiponectin (-2.2 vs. 15.4%), and D-dimer (0.0 vs. 0.0%) (P > or = 0.12 for all comparisons).
Abacavir/lamivudine increased total and LDL cholesterol compared with tenofovir/emtricitabine, but it did not cause inflammation, endothelial dysfunction, insulin resistance, or hypercoagulability in virologically suppressed HIV-infected patients.
AIDS (London, England) 12/2009; 24(3):F1-9. · 4.91 Impact Factor
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ABSTRACT: Excessive daytime sleepiness is common in Parkinson's disease and has been associated with Parkinson's disease-related dementia. Narcoleptic features have been observed in Parkinson's disease patients with excessive daytime sleepiness and hypocretin cell loss has been found in the hypothalamus of Parkinson's disease patients, in association with advanced disease. However, studies on cerebrospinal fluid levels of hypocretin-1 (orexin A) in Parkinson's disease have been inconclusive. Reports of sleep studies in Parkinson's disease patients with and without excessive daytime sleepiness have also been disparate, pointing towards a variety of causes underlying excessive daytime sleepiness. In this study, we aimed to measure cerebrospinal fluid hypocretin-1 levels in Parkinson's disease patients with and without dementia and to study their relationship to dementia and clinical excessive daytime sleepiness, as well as to describe potentially related sleep architecture changes. Twenty-one Parkinson's disease patients without dementia and 20 Parkinson's disease patients with dementia, along with 22 control subjects without sleep complaints, were included. Both Epworth sleepiness scale, obtained with the help of the caregivers, and mini-mental state examination were recorded. Lumbar cerebrospinal fluid hypocretin-1 levels were measured in all individuals using a radio-immunoassay technique. Additionally, eight Parkinson's disease patients without dementia and seven Parkinson's disease patients with dementia underwent video-polysomnogram and multiple sleep latencies test. Epworth sleepiness scale scores were higher in Parkinson's disease patients without dementia and Parkinson's disease patients with dementia than controls (P < 0.01) and scores >10 were more frequent in Parkinson's disease patients with dementia than in Parkinson's disease patients without dementia (P = 0.04). Cerebrospinal fluid hypocretin-1 levels were similar among groups (controls = 321.15 +/- 47.15 pg/ml; without dementia = 300.99 +/- 58.68 pg/ml; with dementia = 309.94 +/- 65.95 pg/ml; P = 0.67), and unrelated to either epworth sleepiness scale or mini-mental state examination. Dominant occipital frequency awake was slower in Parkinson's disease patients with dementia than Parkinson's disease patients without dementia (P = 0.05). Presence of slow dominant occipital frequency and/or loss of normal non-rapid eye movement sleep architecture was more frequent among Parkinson's disease patients with dementia (P = 0.029). Thus, excessive daytime sleepiness is more frequent in Parkinson's disease patients with dementia than Parkinson's disease patients without dementia, but lumbar cerebrospinal fluid hypocretin-1 levels are normal and unrelated to severity of sleepiness or the cognitive status. Lumbar cerebrospinal fluid does not accurately reflect the hypocretin cell loss known to occur in the hypothalamus of advanced Parkinson's disease. Alternatively, mechanisms other than hypocretin cells dysfunction may be responsible for excessive daytime sleepiness and the sleep architecture alterations seen in these patients.
Brain 10/2009; 132(Pt 12):3308-17. · 9.46 Impact Factor
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ABSTRACT: Patients with hypogonadotropic hypogonadism (HH), who may be totally LH deficient, remain the primary clinical model for investigating the physiology of gonadotropin actions on ovarian steroidogenesis and follicular development.
Our objective was to investigate the effects of LH pretreatment on subsequent ovarian stimulation with FSH in longstanding HH women.
A prospective, self-controlled study was conducted at a university tertiary-care center. Patients and Interventions: Eight HH women (six idiopathic, two surgical) underwent ovarian stimulation with recombinant human (rh)FSH preceded or not by rhLH administration in two separate cycles. In one additional patient with idiopathic HH, pretreatment was conducted with recombinant human chorionic gonadotropin (rhCG) instead of rhLH.
Follicular development and serum hormone concentrations throughout LH-FSH and FSH treatment cycles were assessed.
Pretreatment with rhLH significantly decreased the mean threshold (daily effective) FSH dose and tended to lower the total amount of FSH required to induce follicular maturation in association with appropriate serum estradiol levels and endometrial thickness. Unexpectedly, in HH women retaining functional pituitary tissue, pretreatment with rhLH evoked a consistent elevation of serum LH levels during FSH administration, an effect that was also induced, even at higher magnitude, by pretreatment with rhCG.
In addition to changes in FSH requirements for follicular maturation, pretreatment with rhLH/rhCG evoked unambiguous elevations in serum levels of endogenous LH during FSH treatment in HH patients with preserved pituitary function. This is suggestive of a novel regulatory loop of LH secretion involving gonadotropin-stimulated ovarian factors whose nature and physiological relevance are yet to be disclosed, ovarian-derived kisspeptins being appealing candidates.
The Journal of clinical endocrinology and metabolism 05/2009; 94(7):2367-73. · 6.50 Impact Factor
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ABSTRACT: An enlarged incretin response after Roux-en-Y gastric bypass (RYGBP) has been proposed to promote excessive beta-cell function and mass.
The objective of the study was to determine whether RYGBP is associated with a steadily increased glucagon-like peptide 1 (GLP-1) response and a disruption of the relationship between insulin sensitivity and insulin secretion required to maintain plasma glucose in the normal range.
This was a cross-sectional study. Twenty-four women divided into three groups according to time after RYGBP (9-15, 21-30, and more than 36 months). Eight normal-weight and eight morbidly obese women served as controls.
GLP-1 was determined after a standardized test meal. Insulin secretion (AIRg) and insulin sensitivity (S(I)) were derived from an iv glucose tolerance test. Postprandial glucose profile was recorded with a continuous glucose monitoring system.
Area under the curve(0-120) of GLP-1 was larger after RYGBP compared with controls (P < 0.01) but was comparable among surgical groups (P =0.314). Time after surgery was not associated with changes in S(I) (P = 0.657), AIRg (P = 0.329), or the disposition index (DI = AIRgS(I), P = 0.915). After surgery, the GLP-1 response and the DI were not significantly correlated (P = 0.304). Glucose less than 50 mg/dl was found in operated subjects, but the proportion did not increase with time after surgery (P = 0.459). Neither the GLP-1 response (P = 0.620) nor the DI (P = 0.457) differed significantly between those with or without hypoglycemic episodes.
Although the GLP-1 response to meal intake is steadily elevated after RYGBP, this does not result over time in the development of an inappropriate insulin secretion relative to the prevailing insulin sensitivity or the occurrence of hypoglycemic episodes.
The Journal of clinical endocrinology and metabolism 12/2008; 94(3):884-91. · 6.50 Impact Factor
