Iodine nutritional status of women in their first trimester of pregnancy in Catalonia.

BACKGROUND: Sufficient iodine intake is needed during pregnancy to ensure proper fetal development. The iodine levels of women in their first trimester of pregnancy in Catalonia are currently unknown. This data would help to determine whether our public health services should establish recommendations or interventions in this line. The aim of this study was to investigate the iodine nutritional status, prevalence of urinary iodine <150 µg/L, and tobacco use in the first trimester of pregnancy in our setting. METHODS: Cross-sectional study. Data were collected during 2008-2009 from women in their first trimester at the primary care centers of the province of Barcelona (Spain). Pregnant women included in the study completed a questionnaire on eating habits and underwent urinary iodine concentration (UIC) assessment. RESULTS: Nine hundred forty five women completed the dietary questionnaire and urinary iodine testing. Median UIC was 172 µg/L, with 407 participants (43.1%) showing levels <150 µg/L. On multivariate logistic regression analysis, intake of 1-2 glasses of milk per day, OR = 0.636 95% CI (0.45-0.90) or >2 glasses, OR = 0.593 95% CI (0.37-0.95); iodized salt consumption, OR = 0.678 95% CI (0.51-0. 90); and use of iodine supplementation, OR = 0.410 95% CI (0.31-0.54), protected against the risk of UIC <150 µg/L. Simultaneous consumption of iodized salt and milk (≥1 glass/day) showed a larger protective effect: OR = 0.427, 95% CI (0.31-0.54). CONCLUSION: The median UIC of the pregnant women surveyed indicated an acceptable iodine nutritional status according to the criteria established by the WHO and ICCIDD. The risk of urinary iodine <150 µg/L decreased with simultaneous consumption of milk and iodized salt, similar to the decrease seen with iodine supplementation.

Exploring the presence of narcolepsy in patients with schizophrenia.

BACKGROUND: There are several case reports of patients with narcolepsy and schizophrenia, but a systematic examination of the association of both disorders has not been done. The aim of this work is to assess the frequency of narcolepsy with cataplexy in a large consecutive series of adult patients with schizophrenia and schizoaffective disorder. METHODS: We screened 366 consecutive patients with schizophrenia or schizoaffective disorder with a sleep questionnaire and the Epworth Sleepines scale (ESS) exploring narcoleptiform symptoms. Those who screened positive were assessed by a sleep specialist, and offered an HLA determination. CSF hypocretin-1 determination was proposed to those who were HLA DQB1*06:02 positive. RESULTS: On the screening questionnaire, 17 patients had an ESS score ≥11 without cataplexy, 15 had cataplexy-like symptoms with an ESS score < 11, and four had an ESS score ≥11 plus cataplexy-like symptoms. Of those, 24 patients were evaluated by a sleep specialist. Five of these 24 were HLA DQB1*06:02 positive, and three of these five subjects underwent lumbar puncture showing normal hypocretin-1 levels. CONCLUSIONS: Our results suggest that narcolepsy with cataplexy is not an unrecognized disease in adult patients with schizophrenia or schizoaffective disorder.

Remission of type 2 diabetes after Roux-en-Y gastric bypass or sleeve gastrectomy is associated with a distinct glycemic profile.

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) and sleeve gastrectomy (SG) have been associated with a high remission rate of type 2 diabetes mellitus (T2DM). However, whether such remission is associated with full restoration of postprandial glucose profile and/or the potentially nonrestored glycemic profile is associated with altered beta cell function, and relapse of T2DM over time is unknown. METHODS: Cross-sectional studies comparing (1) glucose and proinsulin/insulin response to a standardized liquid mixed meal (SLMM) challenge (n = 31), (2) glucose response in normal living conditions assessed using continuous glucose monitoring (CGM) (n = 16), and prospective observational study comparing (3) rates of relapse of T2DM after surgery (n = 232) in subjects with remission of T2DM ensuing RYGBP or SG. RESULTS: In RYGB individuals, SLMM elicited faster and sharper rise in plasma glucose compared with SG, with 88.2% and 42.9% of the study subjects presenting respectively a peak glucose more than 180 mg/dL (all, P < 0.05). During CGM, average percent time in hyperglycemic and hypoglycemic range was larger in RYGBP (respectively, 4.6% and 12.7%) compared with SG subjects (respectively, 0.4% and 3.2%; both P < 0.05). However, (1) no differences were found in fasting or stimulated proinsulin/insulin ratio, and (2) higher rates of T2DM relapse were observed after SG (hazard ratio: 2.339; P = 0.034). CONCLUSIONS: Remission of T2DM after RYGBP and SG is associated with distinct glycemic profiles. However, longer time spent in hyperglycemia and in hypoglycemia after RYGBP compared with SG is not associated with persistence of altered beta cell function or higher rates of relapse of T2DM over time.

Variable patterns of obesity and cardiometabolic phenotypes and their association with lifestyle factors in the Di@bet.es study.

BACKGROUND AND AIM: Prevalence rates of "metabolically healthy obese" (MHO) subjects vary depending on the criteria used. This study examined the prevalence and characteristics of MHO subjects and metabolically abnormal normal-weight subjects and compared the findings with the NHANES 1999-2004 study. The aims of the present study were, first, to determine the prevalence rates of MHO and MNHNO subjects using the same criteria as those of the National Health and Nutrition Examination Survey (NHANES) (1999-2004) study, and second to compare the prevalence and correlates of obese subjects who are resistant to the development of adiposity-associated cardiometabolic abnormalities (CA) and normal-weight individuals who display cardiometabolic risk factor clustering between the Spanish and the US populations. METHODS AND RESULTS: Di@bet.es study is a national, cross-sectional population-based survey of 5728 adults conducted in 2009-2010. Clinical, metabolic, sociodemographic, and anthropometric data and information about lifestyle habits, such as physical activity, smoking habit, alcohol intake and food consumption, were collected. Subjects were classified according to their body mass index (BMI) (normal-weight, <25 kg/m(2); overweight, 25-29.9 kg/m(2); and obese, >30 kg/m(2)). CA included elevated blood pressure; elevated levels of triglycerides, fasting glucose, and high-sensitivity C-reactive protein (hs-CRP); and elevated homeostasis model assessment of insulin resistance (HOMA-IR) value and low high-density lipoprotein cholesterol (HDL-c) level. Two phenotypes were defined: metabolically healthy phenotype (0-1 CA) and metabolically abnormal phenotype (≥2 CA). The prevalence of metabolically abnormal normal-weight phenotype was slightly lower in the Spanish population (6.5% vs. 8.1%). The prevalence of metabolically healthy overweight and MHO subjects was 20.9% and 7.0%, respectively, while in NHANES study it was 17.9% and 9.7%, respectively. Cigarette smoking was associated with CA in each phenotype, while moderate physical activity and moderate alcohol intake were associated with being metabolically healthy. Olive oil intake was negatively associated with the prevalence of CA. CONCLUSIONS: Smoking, physical activity level, and alcohol intake contribute to the explanation of the prevalence of CA in the Spanish population, as in the US population. However in Spain, olive oil intake contributes significantly to the explanation of the variance in the prevalence of CA.

GLP-1 and the long-term outcome of type 2 diabetes mellitus after Roux-en-Y gastric bypass surgery in morbidly obese subjects.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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 ß-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. CONCLUSIONS: 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 ß-cell function is a key determinant of the long-term remission of T2DM after this bariatric surgery technique.

Factors affecting levels of urinary albumin excretion in the general population of Spain: the Di@bet.es study.

The present study was undertaken to examine the prevalence of urinary ACR (albumin/creatinine ratio) >30 mg/g and the associated clinical and environmental factors in a representative sample of the population of Spain. Di@bet.es study is a national, cross-sectional population-based survey conducted in 2009-2010. Clinical, metabolic, socio-demographic, anthropometric data and information about lifestyle habit were collected. Those subjects without KDM (known diabetes mellitus) were given an OGTT (oral glucose tolerance test). Albumin and creatinine were measured in a urinary sample and ACR was calculated. The population prevalence of ACR >30 mg/g was 7.65% (adjusted for sex and age). The prevalence of ACR >30 mg/g increased with age (P<0.001). Subjects with carbohydrate metabolism disorders had a greater prevalence of ACR >30 mg/g but after being adjusted for age, sex and hypertension, was significant only in those subjects with UKDM (unknown diabetes mellitus) {OR (odd ratio), 2.07 [95% CI (confidence interval), 1.38-3.09]; P<0.001] and KDM [OR, 3.55 (95% CI, 2.63-4.80); P<0.001]. Prevalence of ACR >30 mg/g was associated with hypertension [OR, 1.48 (95% CI, 1.12-1.95); P=0.001], HOMA-IR (homoeostasis model assessment of insulin resistance) [OR, 1.47 (95% CI, 1.13-1.92); P≤0.01], metabolic syndrome [OR, 2.17 (95% CI, 1.72-2.72); P<0.001], smoking [OR, 1.40 (95% CI, 1.06-1.83); P≤0.05], physical activity [OR, 0.68 (95% CI, 0.54-0.88); P≤0.01] and consumption of fish [OR, 0.38 (95% CI, 0.18-0.78); P≤0.01]. This is the first study that reports the prevalence of ACR >30 mg/g in the Spanish population. The association between clinical variables and other potentially modifiable environmental variables contribute jointly, and sometimes interactively, to the explanation of prevalence of ACR >30 mg/g. Many of these risk factors are susceptible to intervention.

Long-term effects of sleeve gastrectomy and Roux-en-Y gastric bypass surgery on type 2 diabetes mellitus in morbidly obese subjects.

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.

Human chorionic gonadotrophin stimulation test as a predictor of ovarian response and pregnancy in IVF cycles stimulated with GnRH agonist gonadotrophin treatment: a pilot study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Expression pattern of osteopontin and αvß3 integrin during the implantation window in infertile patients with early stages of endometriosis.

BACKGROUND: To study endometrial receptivity in terms of osteopontin (OPN) and αvß3 integrin expression and co-expression in infertile women with early stages of endometriosis. METHODS: We investigated the immunohistochemical expression and co-expression of OPN and αvß3 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. RESULTS: No statistically significant differences regarding OPN and αvß3 integrin expression were found between infertile patients with endometriosis and the two control groups. There was no significant correlation between OPN and αvß3 integrin staining intensity in the mid-luteal phase biopsies in any of the groups studied. CONCLUSIONS: Endometrial OPN and αvß3 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.

Comparable early changes in gastrointestinal hormones after sleeve gastrectomy and Roux-En-Y gastric bypass surgery for morbidly obese type 2 diabetic subjects.

BACKGROUND: 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. METHODS: 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. RESULTS: After 6 weeks, five of the six subjects in each surgical group presented with T2DM remission, although the area under the curve (AUC)0­120 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 AUC0­120 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). CONCLUSIONS: 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.

Nutritional status of iodine in pregnant women in Catalonia (Spain): study on hygiene-dietetic habits and iodine in urine.

BACKGROUND: 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. METHODS/DESIGN: 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. DISCUSSION: 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. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01301768.

The effect of different hormone therapies on anti-müllerian hormone serum levels in anovulatory women of reproductive age.

OBJECTIVE: To investigate the effect of oral contraceptives (OC), metformin and ovulation induction with gonadotropins on circulating anti-müllerian hormone (AMH). DESIGN: Prospective clinical study. PATIENTS: 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. MAIN OUTCOME MEASURES: Total follicle number (TFN) and hormonal (fasting insulin and glucose, testosterone, SHBG, LH, androstenedione and AMH) measurements at baseline and during therapy. RESULTS: 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. CONCLUSIONS: 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.

Osteopontin and alphavbeta3 integrin as markers of endometrial receptivity: the effect of different hormone therapies.

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.

Pancreas and kidney transplantation: long-term endocrine function.

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.

Cerebrospinal hypocretin, daytime sleepiness and sleep architecture in Parkinson's disease dementia.

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.

Impact of Dietary Habit, Iodine Supplementation and Smoking Habit on Urinary Iodine Concentration During Pregnancy in a Catalonia Population.

(1) Background: The nutritional status of women during pregnancy can have a considerable effect on maternal and fetal health, and on the perinatal outcome. Aim: to assess the changes occurring in dietary iodine intake, potassium iodide supplementation, and smoking habit, and the impact of these changes on the urinary iodine concentration (UIC) during pregnancy in a population of women in Catalonia (Spain). (2) Methods: Between 2009-2011, an observational study included a cohort of women whose pregnancies were monitored in the public health system in the Central and North Metropolitan areas of Catalonia. Women received individual educational counseling, a dietary questionnaire was completed, and a urine sample was collected for iodine determination at each trimester visit. (3) Results: 633 (67.9%) women answered the questionnaire at all 3 visits. The percentage of women with a desirable UIC (≥150 µg/L) increased from the first to the second trimester and remained stable in the third (57.3%, 68.9%, 68%; p < 0.001). Analysis of the relationship between UIC≥150 µg/L and the women's dietary habits showed that the percentage with UIC ≥150 µg/L increased with greater consumption of milk in the first trimester, and the same was true for iodized salt use in all three trimesters and iodine supplementation in all three. (4) Conclusion: During pregnancy, increased intake of milk, iodized salt, and iodine supplements were associated with an increase in the UIC.

Relationship between ghrelin and the metabolic syndrome in the elderly: a longitudinal population-based study.

CONTEXT: Ghrelin regulates energy homeostasis and may contribute to the development of the metabolic syndrome (MS) in the elderly. OBJECTIVE: To study the relationship between ghrelin and the MS, IGF-I and life style factors over a 2-year follow-up. DESIGN: Longitudinal population-based study, starting from 2002; 2 years follow-up. PARTICIPANTS: Three hundred and thirteen (153 men/160 women) individuals living independently older than 70 years. RESULTS: MS was found in 54.9% of men and 61% of women. In the 229 subjects available at follow-up, ghrelin was higher in men than in women at basal (P = 0.002) and 2-year follow-up (P = 0.004). Ghrelin decreased over time in both genders (P < 0.01). Ghrelin was lower in individuals showing MS compared to non-MS (P = 0.08), but this difference was more evident at 2-year follow-up (P = 0.016), mostly due to men with MS (P = 0.002) and even after adjustment for BMI, gender and age. Individuals with MS had an OR of 1.67 (95% CI: 1.0-2.78) for low ghrelin (< first tertile); when adjusting by BMI, gender and age, only high triglycerides with OR 1.8 (1.0-3.3), remained statistically significant among the MS components. IGF-I showed a positive correlation with ghrelin only in individuals without MS (r(s) 0.403, P < 0.001) with no gender differences; this relationship was not found in MS (r(s) 0.120, P = 0.129). A positive association of ghrelin was found with academic level, alcohol consumption and smoking. CONCLUSIONS: Ghrelin is higher in old men in comparison to women and decreases over time with a steeper decline in subjects with MS; moreover, in these subjects ghrelin/IGF-I correlation is lost.

Spectrum of neurological syndromes associated with glutamic acid decarboxylase antibodies: diagnostic clues for this association.

The association of high levels of autoantibodies to glutamic acid decarboxylase (GAD-ab) and stiff-person syndrome (SPS) is well known. However, the full spectrum of neurological syndromes associated with GAD-ab is not well established. In addition, these patients usually present type 1 diabetes mellitus (DM1) that could justify the presence of high GAD-ab levels. To clarify these issues, we reviewed the clinical and immunological features of patients in whom high GAD-ab levels were detected in a reference centre for DM1 and for the detection of antineuronal antibodies in suspected paraneoplastic neurological syndromes (PNS). High GAD-ab levels were defined as values > or =2000 U/ml by radioimmunoassay. Intrathecal synthesis (IS) of GAD-ab was calculated in paired serum/CSF samples. Values higher than the IgG index were considered indicators for positive GAD-ab-specific IS. High GAD-ab levels were identified in 61 patients, 22 (36%) had SPS, 17 (28%) cerebellar ataxia, 11 (18%) other neurological disorders (epilepsy -- four, PNS -- four; idiopathic limbic encephalitis -- two; myasthenia gravis -- one), and 11 (18%) isolated DM1. Patients with SPS and cerebellar ataxia had the same frequency of female gender (86% vs 94%), DM1 (59% vs 53%), CSF oligoclonal bands (35% vs 69%). Three of the four PNS patients, with paraneoplastic encephalomyelitis, a predominant gait cerebellar ataxia, and limbic encephalitis, had neuroendocrine carcinomas. GAD expression was confirmed in the two tumours in which the study was done. The fourth patient presented with paraneoplastic cerebellar degeneration antedating a lung adenocarcinoma. The frequency of increased IS of GAD-ab was 85% in SPS, 100% in cerebellar ataxia, and 86% in other neurological disorders. In conclusion, our study emphasizes that high GAD-ab levels associate with other neurological disorders besides SPS. Cerebellar ataxia, the second most common syndrome associated with high GAD-ab levels, shares with SPS the same demographic, clinical and immunological features. The demonstration of an increased IS of GAD-ab is important to confirm that the GAD autoimmunity is related to the neurological syndrome particularly when there is a concomitant DM1 that could justify the presence of high GAD-ab levels. Lastly, in patients who develop neurological syndromes that suggest a PNS, the finding of GAD-ab does not rule out this possibility and appropriate studies should be done to confirm an underlying cancer.

Salicylates increase insulin secretion in healthy obese subjects.

CONTEXT: Conflicting results on the effects of salicylates on glucose tolerance in subjects with normal glucose tolerance or type 2 diabetes have been reported. OBJECTIVE: The objective of the study was to investigate the effects of a salicylate derivative (triflusal) on insulin sensitivity and insulin secretion. DESIGN, SETTING, AND PARTICIPANTS: This was a double-blind, randomized, crossover study with three treatment periods corresponding to two dose levels of triflusal and placebo in healthy obese subjects. MAIN OUTCOME MEASURES: Insulin sensitivity and insulin secretion, evaluated through frequently sampled iv glucose tolerance test that was performed after each treatment period, were measured. Insulin secretion was also evaluated in vitro in mice and human islets of Langerhans. RESULTS: The administration of triflusal led to decreased fasting serum glucose concentration in the study subjects. Insulin sensitivity did not significantly change after each treatment period. Insulin secretion, however, significantly increased in a dose-dependent fashion after each triflusal treatment period. The administration of 800 mum of the main triflusal metabolite to whole mice islets of Langerhans led to a sustained increase in intracellular calcium concentration level. This was followed by a significantly increase in insulin secretion. In human islets, 200 mum of 2-hydroxy-4-trifluoromethylbenzoic acid was sufficient to increase insulin release. CONCLUSIONS: The administration of a salicylate compound led to lowering of serum glucose concentration. We suggest that this effect was mediated through increased insulin secretion induced by salicylate directly on the beta-cell.

Osteopontin and alphavbeta3 integrin expression in the endometrium of infertile and fertile women.

Osteopontin and its receptor alpha(v)beta(3) integrin have recently been proposed as a major complex to promote embryo attachment, and thus they would be useful as markers of endometrial receptivity. In the current study alpha(v)beta(3) integrin and osteopontin expression and co-expression in in-phase and out-of-phase endometrial biopsies from normal healthy women (n = 12) and infertile patients (n = 107) were investigated. Two endometrial biopsies (post-ovulatory day +6 to +8, and 4 days later) were performed during a single menstrual cycle in each subject. Oestradiol and progesterone serum concentrations were quantified on the same days as endometrial sampling. No statistically significant difference regarding alpha(v)beta(3) integrin and osteopontin expression and their coexpression was found between fertile controls and infertile patients irrespective of endometria being in-phase or out-of-phase, infertility factors detected or whether patients became spontaneously pregnant or not. Although a co-ordinate high concentration of both glycoproteins on post-ovulatory day 8 onwards was observed, there was an evident lack of temporal co-expression of these markers during the implantation window. It is concluded that the functional significance of the osteopontin:alpha(v)beta(3) integrin complex as a marker of endometrial receptivity and implantation potential in women seems to be untenable.