Differential Behavior of 25(OH)D and f25(OH)D3 in Patients with Morbid Obesity After Bariatric Surgery.

BACKGROUND: Total 25-OH-vitamin D (25(OH)D) levels are decreased in patients with obesity, but few data exist regarding free-vitamin D3 (f25(OH)D3) concentrations. We aimed to evaluate the effect of bariatric surgery on 25(OH)D and f25(OH)D3 in a cohort of patients with morbid obesity. METHODS: Twenty-four patients submitted to sleeve gastrectomy (SG) (mean age 48 years, body mass index (BMI) 48.16±10.73k/m2) were evaluated before and 1 year after surgery. Anthropometric data, parathormone (PTH), calcium, alkaline phosphatase, 25(OH)D, and f25(OH)D3 were recorded. RESULTS: 25(OH)D and f25(OH)D3 correlated well before and after SG. Baseline determinations did not correlate with BMI, but they inversely correlated with BMI 1 year after surgery (rs=-0.46, p=0.02 and rs=-0.60, p=0.002, respectively). Post-surgery % total body weight loss (%TBWL) was 27.4±13.8 %; f25(OH)D3 concentrations increased significantly (5.28±2.29 pg/mL vs 6.64±2.25 pg/mL; p=0.03), whereas 25(OH)D did not change. Patients who achieved a BMI <35 kg/m2 1 year after surgery had significantly higher concentrations of f25(OH)D3 (7.9±1 pg/mL vs 4.8±1.1, p<0.001) and 25(OH)D (30.9±9.4 ng/mL vs 22.3±13.4; p=0.03) compared to those who remained with BMI >35 kg/m2. CONCLUSION: There is a significant inverse relationship between BMI and both f25(OH)D3 and 25(OH)D 1 year after surgery. Only f25(OH)D3 concentrations increased 1 year after surgery, which could be explained by a greater f25(OH)D3 sequestration before SG in the adipose tissue, potentially due to the more liposoluble nature of f25(OH)D3 than the protein-bound form 25(OH)D.

Intermittent Cooling During Judo Training in a Warm/Humid Environment Reduces Autonomic and Hormonal Impact.

Carballeira, E, Morales, J, Fukuda, DH, Granada, ML, Carratalá-Deval, V, López Díaz de Durana, A, and Stout, JR. Intermittent cooling during Judo training in a warm/humid environment reduces autonomic and hormonal impact. J Strength Cond Res 33(8): 2241-2250, 2019-The purpose of this study was to identify the effects of superficial cooling on physiological responses while training in a warm, humid environment during an international Judo training camp. Sixteen judokas (8 women and 8 men) participated in the experiment. Four high-level women and 4 men were randomly assigned to wear a cooling vest (vest group [VG]) during the recovery periods within a training session (i.e., 8 bouts of 5-minute fighting with 5-minute rest) and up to 10 minutes after the session, whereas the remaining athletes in the control group (CG) trained without the use of any cooling aids. No differences between groups were reported in well-being before the session or in perceived fatigue after the session. The temperature was increased after the training session (p = 0.02) without significant differences between groups; however, CG demonstrated a moderate effect size (ES = 0.95, 90% confidence interval [CI] = 0.09-1.82; probability of superiority [PS] = 74.9%) in contrast to the small effect for VG (ES = 0.28, 90% CI = -0.55 to 1.11; PS = 57.9%). There were time × group interactions for heart rate variability (lnRMSSD) (p = 0.006; VG vs. CG, PS = 79.0%) and the dehydroepiandrosterone-cortisol ratio (DHEA/C ratio) (p = 0.04; VG vs. CG, PS = 99.9%). Vest group preserved the cardiac autonomic control (p > = 0.05; ES = -0.06, 90% CI = -0.88 to 0.76; PS = 51.7%) compared with the large decrement of CG (p < 0.05; ES = -1.18, 90% CI = -2.07 to -0.29; PS = 74.9%). Furthermore, VG showed an increase of DHEA/C (p = 0.002) from presession to postsession based on a moderate decrease of cortisol (p > = 0.05; ES = -0.67, 90% CI = -1.52 to 0.17; PS = 68.2%) with a concomitant small increase of DHEA (p > = 0.05; ES = 0.46, 90% CI = -0.38 to 1.29; PS = 62.7%). Conversely, the CG showed a moderate effect for increased DHEA and a small effect for increased cortisol after training. No significant interactions or main effects were shown for isometric handgrip values. Cooling vests diminished the cardiovascular strain and hormonal impact of the Judo training session in high-level athletes and may be considered for recovery purposes during exercise in warm/humid environments.

Development of Laboratory Investigations in Disorders of Sex Development.

Scientific knowledge to understand the biological basis of sex development was prompted by the observation of variants different from the 2 most frequent body types, and this became one of the fields first studied by modern pediatric endocrinology. The clinical observation was supported by professionals working in different areas of laboratory sciences which led to the description of adrenal and gonadal steroidogenesis, the enzymes involved, and the different deficiencies. Steroid hormone measurements evolved from colorimetry to radioimmunoassay (RIA) and automated immunoassays, although gas and liquid chromatography coupled to mass spectrometry are now the gold standard techniques for steroid measurements. Peptide hormones and growth factors were purified, and their measurement evolved from RIA to automated immunoassays. Hormone action mechanisms were described, and their specific receptors were characterized and assayed in experimental materials and in patient tissues and cell cultures. The discovery of the genetic basis for variant sex developments began with the description of the sex chromosomes. Molecular technology allowed cloning of genes coding for the different proteins involved in sex determination and development. Experimental animal models aided in verifying the roles of proteins and also suggested new genes to be investigated. New candidate genes continue to be described based on experimental models and on next-generation sequencing of patient DNAs.

A Probabilistic Model for Cushing's Syndrome Screening in At-Risk Populations: A Prospective Multicenter Study.

CONTEXT: Cushing's syndrome (CS) is challenging to diagnose. Increased prevalence of CS in specific patient populations has been reported, but routine screening for CS remains questionable. To decrease the diagnostic delay and improve disease outcomes, simple new screening methods for CS in at-risk populations are needed. OBJECTIVE: To develop and validate a simple scoring system to predict CS based on clinical signs and an easy-to-use biochemical test. DESIGN: Observational, prospective, multicenter. SETTING: Referral hospital. PATIENTS: A cohort of 353 patients attending endocrinology units for outpatient visits. INTERVENTIONS: All patients were evaluated with late-night salivary cortisol (LNSC) and a low-dose dexamethasone suppression test for CS. MAIN OUTCOME MEASURES: Diagnosis or exclusion of CS. RESULTS: Twenty-six cases of CS were diagnosed in the cohort. A risk scoring system was developed by logistic regression analysis, and cutoff values were derived from a receiver operating characteristic curve. This risk score included clinical signs and symptoms (muscular atrophy, osteoporosis, and dorsocervical fat pad) and LNSC levels. The estimated area under the receiver operating characteristic curve was 0.93, with a sensitivity of 96.2% and specificity of 82.9%. CONCLUSIONS: We developed a risk score to predict CS in an at-risk population. This score may help to identify at-risk patients in non-endocrinological settings such as primary care, but external validation is warranted.

Baseline circulating ghrelin does not predict weight regain neither maintenance of weight loss after gastric bypass at long term.

BACKGROUND: Predictors of weight loss (WL) or weight regain (WR) after Roux-en-Y gastric bypass (RYGBP) are not established. The aim of this study was to analyze the usefulness of some baseline peptides (leptin, insulin, and ghrelin) as biomarkers of WL and WR in morbid obese patients after RYGBP at long term. METHODS: Seventy-six morbid obese (47 women, age 41.6 ± 9.6 years, body mass index [BMI] 52.1 ± 8 kg/m(2)) patients were evaluated at baseline and at 1, 2, and 6 years after surgery. RESULTS: Excess body weight loss after 6 years was of 63.9%. Age, BMI, and studied hormones at baseline or their changes over time did not predict long-term excess body weight loss. WR greater than 10% was observed in 36.8% of patients between 2 and 6 years of follow-up, but it was not correlated with BMI, age, or baseline peptide concentrations. CONCLUSION: Measurement of ghrelin, insulin, and leptin before surgery is not useful as predictors of WL or WR at long term after RYGBP.

Regulatory T cells and other lymphocyte subpopulations in patients with melanoma developing interferon-induced thyroiditis during high-dose interferon-α2b treatment.

CONTEXT: One of the side effects of interferon-alpha therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT melanoma patients remains to be defined. OBJECTIVE: Our objective was to assess different peripheral blood lymphocyte subpopulations, mainly regulatory T cells (Tregs), in melanoma patients who developed IIT. DESIGN, PATIENTS AND METHODS: From 30 melanoma patients receiving high-dose interferon (HDI)-alpha 2b (IFN-α2b) treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-MM) and healthy controls (Co-H). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment and at appearance of IIT (TT). RESULTS: Nine patients developed IIT (30%): four Hashimoto's thyroiditis and five destructive thyroiditis. An increase in Tregs was observed in both melanoma groups during HDI treatment. A decrease in CD3(+) , NKT lymphocyte subpopulations and Bcl2 expression on B cells was also observed in both groups. However, no changes were observed in the percentage of CD4(+) , CD8(+) , CD3(+) γδ(+) , CD19(+) , transitional B cells (CD24(high) CD38(high) CD19(+) CD27(-) ), natural killer (NK), invariant NKT (iNKT) lymphocytes and Th1/Th2 balance when BT was compared with ET. At TT, IIT patients had a higher Tregs percentage than Co-MM (P = 0·012) and Co-H (P = 0·004), a higher iNKT percentage than Co-MM (P = 0·011), a higher transitional B cells percentage than Co-H (P = 0·015), a lower CD3(+) percentage than Co-H (P = 0·001) and a lower Bcl2 expression on B cells than Co-H (P < 0·001). CONCLUSIONS: Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Tregs in melanoma patients who developed IIT.

Obestatin does not modify weight and nutritional behaviour but is associated with metabolic syndrome in old women.

OBJECTIVE: Ghrelin and obestatin have apparent opposite orexigenic and anorexigenic effects, although the latter has not been firmly demonstrated in humans. So far, little data have been reported in relation to its potential association with metabolic syndrome (MS). The objective was to study obestatin concentrations in relation to nutritional parameters and eating behaviours in old women. DESIGN, PATIENTS AND MEASUREMENTS: Prospective study; a total of 110 women (age: 76.93 ± 6.32) from the Mataró Ageing Study were included. Individuals were characterized by anthropometric variables, lipids, glucose, blood pressure, MS components (Adult Treatment Panel III criteria), anorexia and nutritional status by Mini Nutritional Assessment Short Form (MNA-SF) and re-evaluated at 2-year follow-up. Obestatin was measured by IRMA. RESULTS: 58.2% of the subjects had MS; at 2-year follow-up 24.1% had a weight loss >5%, 7.2% >10%, and 26.4% changed their MNA-SF score to risk of malnutrition category. Anorexia was present in 38.4%. Obestatin levels were not related to either change of weight, MNA-SF or anorexia, but a positive correlation was found with the absolute difference between basal and 2-year waist circumference (WC) (r = 0.429; P < 0.001) and relative difference between basal and 2-year WC (r = 0.420; P < 0.001); both remained significant after adjusting for age and body mass index. When obestatin was divided into quartiles, a significant lineal trend was observed in relation to WC (P = 0.049), absolute and relative difference between basal and 2-year WC (both P < 0.001). Obestatin was associated with glucose impairment (69.0% in 4th quartile vs 47.5% in 1st to 3rd, P = 0.047; after adjustment, P = 0.098) and MS (77.8% in 4th vs 51.3% in 1st to 3rd, P = 0.017; after adjustment, P = 0.046, OR 2.90 (1.02-8.25) 4th vs 1st to 3rd). CONCLUSIONS: Obestatin is elevated in aged women bearing MS but is otherwise not associated with other nutritional parameters, weight loss or anorexia.

Pregnancy-associated plasma protein-A is related to gender and to adipocytokine levels: results of the Health Survey of Catalonia.

OBJECTIVE: Pregnancy-associated plasma protein-A (PAPP-A) is a protease promoting IGF1 tissue availability and considered as a new biomarker of cardiovascular disease. AIM: To evaluate the relationship between PAPP-A concentrations and anthropometric variables, physical activity, smoking status, glucose homoeostasis and adipocytokines in healthy adults. DESIGN AND METHODS: One hundred and forty-nine subjects (77 women; mean age 39·7 ± 14 years; mean BMI 23·7 ± 1·9 kg/m(2) ) were randomly selected from 8000 adults of The Health Survey of Catalonia. Possible effects of gender, age, body composition, smoking status, physical activity, glucose homoeostasis and adipocytokines on PAPP-A concentrations were assessed. RESULTS: Pregnancy-associated plasma protein-A was significantly higher in men than in women [1·04 (0·61-0·44) vs 0·61 (0·41-0·90) µIU/ml; P < 0·0001]; there were no differences in relation to physical activity or smoking status. PAPP-A showed a negative correlation with leptin in men (P = 0·01) and women (P = 0·05), and a positive correlation with adiponectin (P = 0·006) in women and a trend (P = 0·073) in men. Homoeostasis model assessment of insulin resistance (HOMA-IR) showed a negative correlation with PAPP-A only in women (P = 0·019). No association was found with blood pressure, IGF1, lipids or glucose in either gender. When a multiple regression analysis was performed including gender, age, BMI, waist-hip ratio, HOMA-IR, adiponectin and leptin as confounders, PAPP-A was independently correlated with adiponectin (ß = 0·23; P = 0·02) and leptin (ß = -0·33; P = 0·04). CONCLUSIONS: Our study shows a sexual dimorphism of PAPP-A, and a possible influence of leptin and adiponectin on its concentrations in healthy subjects. The mechanisms responsible for this relationship remain to be determined.

Is adiponectin a marker of preclinical atherosclerosis in kidney transplantation?

UNLABELLED: The aim of this study was to analyze the relationship between pre-transplant adiponectin (pre-ADP), abnormalities in glucose homeostasis (AGH) at three months post-transplantation, and preclinical atherosclerosis in non-diabetic patients prior to kidney transplantation (KT). METHODS: We carried out a multicenter study in 157 non-diabetic KT patients (66.5% men; age: 50±13 yr). Pre-ADP levels were analyzed using radioimmunoassay. Carotid ultrasound was performed to determine carotid intima-media thickness (c-IMT). Oral glucose tolerance test was carried out to classify patients according ADA criteria. RESULTS: Of the patients, 52.8% had AGH. Median pre-ADP was 19.5 (14-27) µg/mL. An inverse correlation was found between ADP and HOMA index (r=-0.432; p<0.001). Median c-IMT was 0.6 (0.48-0.71) mm. Significant inverse correlation existed between ADP and c-IMT on both sides (p<0.05). Patients with c-IMT >0.6 mm had more AGH (p=0.012) and lower ADP levels (p=0.02). We performed a logistic regression analysis using preclinical atherosclerosis (c-IMT ≥0.6 mm) as dependent variable and sex, age, BMI, ADP, AGH, and HOMA index as independent variables of altered c-IMT. Age, pre-ADP, and AGH were independent risk factors for elevated c-IMT. CONCLUSIONS: Patients with AGH have a greater presence of preclinical atherosclerosis. ADP has an inverse relationship with AGH and is an independent marker of preclinical atherosclerosis.

A prospective study of lymphocyte subpopulations and regulatory T cells in patients with chronic hepatitis C virus infection developing interferon-induced thyroiditis.

OBJECTIVE: One of the side effects of interferon-alpha (IFN-α) therapy is interferon-induced thyroiditis (IIT). The role of lymphocyte subpopulations in IIT remains to be defined. The aim of this study was to assess different peripheral blood lymphocyte subpopulations, mainly CD4(+) CD25(+) CD127low/-FoxP3(+) regulatory T cells (Tregs), in patients with chronic hepatitis C virus (HCV) infection who developed IIT. DESIGN, PATIENTS AND METHODS: From 120 patients with chronic HCV who started antiviral treatment, those who developed IIT (IIT patients) were selected and compared with patients who did not develop IIT (Co-HCV). Peripheral blood mononuclear cells were obtained before treatment (BT), mid-treatment (MT), end of treatment (ET), 24 weeks post-treatment (PT) and at appearance of IIT (TT). RESULTS: Eleven patients developed IIT: three Hashimoto's thyroiditis, one Graves'disease, one positive antithyroidal antibodies, one nonautoimmune hypothyroidism and five destructive thyroiditis. During antiviral treatment, an increase in CD8(+) and in Tregs was observed in both groups. A decrease in CD3(+) , CD19(+) and NKT lymphocyte subpopulations was also observed (all P < 0·05). However, no changes were observed in the percentage of CD4(+) , CD3(+) γδ(+) and iNKT lymphocytes, Th1/Th2 balance and Bcl2 expression on B cells when BT was compared with ET. At the appearance of IIT (TT), IIT patients had a higher Th1 response (CCR5(+) CCR7(-) ) (P < 0·01) and a higher Tregs percentage (P < 0·05) than Co-HCV. CONCLUSIONS: Our results point to the immunomodulatory effects of IFN-α on different lymphocyte subpopulations and a possible role of Th1 response and Tregs in patients with HCV who developed IIT.