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OBJECTIVE The use of the new International Association of the Diabetes and Pregnancy Study Groups criteria (IADPSGC) for the diagnosis of gestational diabetes mellitus (GDM) results in an increased prevalence of GDM. Whether their introduction improves pregnancy outcomes has yet to be established. We sought to evaluate the cost-effectiveness of one-step IADPSGC for screening and diagnosis of GDM compared with traditional two-step Carpenter-Coustan (CC) criteria. RESEARCH DESIGN AND METHODS GDM risk factors and pregnancy and newborn outcomes were prospectively assessed in 1,750 pregnant women from April 2011 to March 2012 using CC and in 1,526 pregnant women from April 2012 to March 2013 using IADPSGC between 24 and 28 weeks of gestation. Both groups received the same treatment and follow-up regimes. RESULTS The use of IADPSGC resulted in an important increase in GDM rate (35.5% vs. 10.6%) and an improvement in pregnancy outcomes, with a decrease in the rate of gestational hypertension (4.1 to 3.5%: -14.6%, P < 0.021), prematurity (6.4 to 5.7%: -10.9%, P < 0.039), cesarean section (25.4 to 19.7%: -23.9%, P < 0.002), small for gestational age (7.7 to 7.1%: -6.5%, P < 0.042), large for gestational age (4.6 to 3.7%: -20%, P < 0.004), Apgar 1-min score <7 (3.8 to 3.5%: -9%, P < 0.015), and admission to neonatal intensive care unit (8.2 to 6.2%: -24.4%, P < 0.001). Estimated cost savings was of €14,358.06 per 100 women evaluated using IADPSGC versus the group diagnosed using CC. CONCLUSIONS The application of the new IADPSGC was associated with a 3.5-fold increase in GDM prevalence in our study population, as well as significant improvements in pregnancy outcomes, and was cost-effective. Our results support their adoption. [ABSTRACT FROM AUTHOR]

The aims are to define the regression rate in newly diagnosed type 2 diabetes after lifestyle intervention and pharmacological therapy based on a SMBG (self-monitoring of blood glucose) strategy in routine practice as compared to standard HbA1c-based treatment and to assess whether a supervised exercise program has additional effects. St Carlos study is a 3-year, prospective, randomized, clinic-based, interventional study with three parallel groups. Hundred and ninety-five patients were randomized to the SMBG intervention group [I group; n = 130; Ia: SMBG ( n = 65) and Ib: SMBG + supervised exercise ( n = 65)] and to the HbA1c control group (C group) ( n = 65). The primary outcome was to estimate the regression rate of type 2 diabetes (HbA1c <6 % on metformin treatment). After 3 years of follow-up, diabetes regression was achieved by 56 patients, 6 (9.2 %) from the C group, 21 (32.3 %) from the Ia group and 29 (44.6 %) from the Ib group. RR (95 % CI) for diabetes regression in the intervention group (Ia + Ib) was 4.5 (2.1-9); p < 0.001 and remained after stratification by gender, age and BMI. This difference was associated with healthier changes in lifestyle and greater weight loss. RR for a weight loss >4 kg was 3.6 (1.8-7); p < 0.001. This study shows that the use of SMBG in an educational program effectively increases the regression rate in newly diagnosed type 2 diabetic patients after 3 years of follow-up. These data suggest that SMBG-based programs should be extended to primary care settings where diabetic patients are usually attended. [ABSTRACT FROM AUTHOR]

Background: Data about the immigrant population living in Spain, their lifestyle habits, and risk factors for gestational diabetes mellitus (GDM) are limited. Thus, the aim of the present study was to describe risk factors for the onset of GDM, the evolution of gestation and delivery, and newborns of Hispanic women living in Spain compared with those of Spanish women. Methods: A semiquantitative questionnaire regarding lifestyle habits was administered to 459 pregnant women (115 Hispanic) with a positive O'Sullivan test (24-28 weeks gestation) between 1 April 2007 and 31 March 2008. Information was collected regarding gestation, delivery, and the newborn. Results: The prevalence of GDM increased with mother's age, pregestational overweight/obesity, and multiparity. In addition, GDM was associated with lower pregestational fiber and a lower intake of low glycaemic index foods in Hispanic women. The odds ratios (OR) for the total population were 2.53 (95% confidence interval [CI] 1.28-5.01) for overweight, 3.68 (95% CI 1.72-7.90) for obesity, 3.83 (95% 2.03-7.23) for age ≥35 years, and 1.64 (95% CI 1.02-3.01) for multiparity. Newborns from the Hispanic population were significantly heavier than newborns from Spanish women and the rate of Caesarean delivery was significantly higher in the Hispanic population with GDM compared with those without GDM. Conclusions: The immigrant Hispanic population living in Spain trends to acquire the same risk factors associated with lifestyle to the indigenous population. Preventive strategies must stress increased physical activity and fiber intake, decreased intake of sweetened beverages, and an effective reduction in body weight before pregnancy. [ABSTRACT FROM AUTHOR]

Abstract: Objective: We have measured circulating plasma sCD40L as well as the platelet-surface of CD40L and its receptor in a sample of non-diabetic dyslipidemic patients and then evaluated its relationship with the insulin resistance (IR) and insulin secretion (IS) status. Design and methods: Anthropometric measurements, fasting glucose, insulin, lipids, and IR and IS [estimated by the homeostasis model assessment (HOMA)] were assessed in 86 dyslipidemic subjects. Circulating sCD40L were determined by ELISA. By flow cytometry, CD40L, CD40 and P-selectin were evaluated in the platelet-surface. Results: Non-diabetic dyslipidemic IR patients (HOMA-IR≥3.8) showed higher plasma sCD40L concentrations and a more unfavorable cardiovascular risk profile (higher BMI, waist, fasting insulin and mean triglyceride levels) than dyslipidemic patients with low IS (HOMA β-cell<98). In a multivariable model, only measures of insulin sensitivity and higher waist remained significantly associated with increased plasma levels of sCD40L. Surface expression of CD40L on platelets decreased significantly and CD40 increased in IR patients, compared with patients with low IS. Conclusions: IR dyslipidemic patients show increased plasma sCD40L and decreased platelet-membrane CD40L expression compared to dyslipidemic patients with low IS. [Copyright &y& Elsevier]

Background: Overcorrection of serum sodium (SNa) during therapy of hyponatremia can result in osmotic demyelination syndrome. Our aim was to determine the relationship between the isotonic saline solution dose (ISSD) administered and the 24-h SNa increase (24SNa) in patients with hypovolemic hyponatremia (HH). Methods: Retrospective study of HH patients treated with ISS in a tertiary hospital of Madrid, Spain, between 1 January–30 May 2019. The 24-h ISSD received and corresponding 24SNa were calculated. The latter was classified as 3 groups: ≥8 mmol/L, ≥6 mmol/L, or <4 mmol/L. Multivariate regression analyses were performed and ROC curves calculated to study the relationship between ISSD and 24SNa. Results: Thirty patients were included, age 72 years (60–80), 50% were women. 24SNa was ≥8 mmol/L/24 h in 33%, ≥6 mmol/L/24 h in 50%, and <4 mmol/L/24 h in 30%. Median ISSD in each group was: 32 mL/kg/24 h (29–37), 31 mL/kg/24 h (25–33), and 20 mL/kg/24 h (14–22), respectively. An ISSD ≥ 30 mL/kg/24 h had an odds ratio (OR) of 16 (95% CI: 2.5–95.1; p = 0.004) for a 24SNa ≥8 mmol/L, with a sensitivity and specificity of 80%. Conclusions: The 24SNa depends on ISSD. An ISSD between 23–30 mL/kg/24 h seems to be safe and effective. [ABSTRACT FROM AUTHOR]

The intrauterine environment may be related to the future development of chronic diseases in the offspring. The St. Carlos gestational diabetes mellitus (GDM) prevention study, is a randomized controlled trial that evaluated the influence of the early (before 12th gestational week) Mediterranean diet (MedDiet) on the onset of GDM and adverse gestational outcomes. Out of 874 women assessed after delivery (440 control group (CG)/434 intervention group (IG)), 703 children were followed (365/338; CG/IG), with the aim to assess whether the adherence to a MedDiet during pregnancy induces health benefits for the offspring during the first two years of life. Logistic regression analysis showed that the IG in children of mothers with pre-gestational body mass index (BMI) < 25 kg/m2 and normal glucose tolerance (NGT), was associated with a lower risk (RR(95% CI)) of suffering from severe events requiring hospitalization due to bronchiolitis/asthma (0.75(0.58–0.98) and 0.77(0.59–0.99), respectively) or other diseases that required either antibiotic (0.80(0.65–0.98) and 0.80(0.65–0.99), respectively), corticosteroid treatment (0.73(0.59–0.90) and 0.79(0.62–1.00) respectively) or both (all p < 0.05). A nutritional intervention based on the MedDiet during pregnancy is associated with a reduction in offspring's hospital admissions, especially in women with pre-gestational BMI < 25 kg/m2 and NGT. [ABSTRACT FROM AUTHOR]

The activation of endoplasmic reticulum (ER) stress and a reduction of AMP-dependent protein kinase (AMPK) phosphorylation have been described in obesity. We hypothesize that a moderate caloric restriction (CR) might contribute to reducing ER stress and increasing AMPK phosphorylation in peripheral tissues from genetically obese Zucker fa/fa rats and in peripheral blood mononuclear cells (PBMCs). Zucker Lean and Zucker fa/fa rats were fed with chow diet either ad libitum (AL) (C, as controls) or 80% of AL (CR) for 2 weeks, giving rise to four experimental groups: Lean C, Lean CR, fa/fa C and fa/fa CR. CR significantly increased AMPK phosphorylation in the liver, perirenal adipose tissue (PRAT) and PBMCs from fa/fa rats but not in the subcutaneous AT (SCAT), suggesting a reduced response of SCAT to CR. Liver samples of fa/fa rats exhibited an increased mRNA expression of PERK, EIF-2α, XBP-1(s), Chop and caspase 3, which was significantly reduced by CR. PRAT exhibited an overexpression of Edem and PDIA-4 in fa/fa rats, but only PDIA-4 expression was reduced by CR. eIF-2α phosphorylation was significantly increased in all studied tissues from fa/fa rats and reduced by CR. A negative correlation was detected between p-AMPK and p-eIF-2α in the liver, PRAT and PBMCs from fa/fa rats but not in SCAT. This study shows that a moderate CR reduces ER stress and improves AMPK phosphorylation in several peripheral tissues and in circulating PBMCs, suggesting that alterations observed in PBMCs could reflect metabolic alterations associated with obesity. [ABSTRACT FROM AUTHOR]

Obesity is a risk factor for the development of gestational diabetes mellitus (GDM). However, the most optimal type of nutritional intervention to prevent GDM in high-risk women is not clearly defined. This study investigates if nutritional treatment based on the Mediterranean diet (MedDiet) before the 12th gestational week (GW) in women at high risk due to a body mass index (BMI) ≥ 25 kg/m 2 reduces the rate of GDM and metabolic syndrome (MetS) at 3 years postpartum. We performed a post-hoc analysis of the San Carlos Gestational Prevention Study. A total of 735 women with BMI ≥ 25 kg/m 2 were evaluated between 2015 and 2018, with 246 in the standard diet control group (CG) and 489 in the MedDiet intervention group (IG). The rate of GDM was significantly lower in IG compared to CG (25.1% vs. 31.7%), relative risk (95% confidence interval), and 0.89 (0.78-0.99); p = 0.037. Postnatal follow-up was completed by 141 women in CG (57%) and 312 women in IG (64%). At 3 years postpartum, we observed a reduction in the rates of impaired fasting glucose (IFG) (0.51 (0.28-0.92); p = 0.019), obesity (0.51 (0.28-0.92); p = 0.041), waist circumference (WC) ≥ 89.5 cm (0.54 (0.31-0.94); p = 0.022), and MetS (0.56 (0.33-0.94); p = 0.003). MedDiet reduces the rate of GDM and postpartum MetS in women with BMI) ≥ 25 kg/m 2 , suggesting that its implementation should be routinely recommended from the first GWs.

The pathophysiology of gestational diabetes mellitus (GDM) comprises clinical and genetic factors. In fact, GDM is associated with several single nucleotide polymorphisms (SNPs). This study aimed to build a prediction model of GDM combining clinical and genetic risk factors. A total of 1588 pregnant women from the San Carlos Cohort participated in the present study, including 1069 (67.3%) Caucasian (CAU) and 519 (32.7%) Latin American (LAT) individuals, and 255 (16.1%) had GDM. The incidence of GDM was similar in both groups (16.1% CAU and 16.0% LAT). Genotyping was performed via IPLEX Mass ARRAY PCR, selecting 110 SNPs based on literature references. SNPs showing the strongest likelihood of developing GDM were rs10830963, rs7651090, and rs1371614 in CAU and rs1387153 and rs9368222 in LAT. Clinical variables, including age, pre-pregnancy body mass index, and fasting plasma glucose (FPG) at 12 gestational weeks, predicted the risk of GDM (AUC 0.648, 95% CI 0.601-0.695 in CAU; AUC 0.688, 95% CI 0.628-9.748 in LAT), and adding SNPs modestly improved prediction (AUC 0.722, 95%CI 0.680-0.764 in CAU; AUC 0.769, 95% CI 0.711-0.826 in LAT). In conclusion, adding genetic variants enhanced the prediction model of GDM risk in CAU and LAT pregnant women.

Aim: To evaluate the cross-sectional association between severe periodontitis and diabetes mellitus (DM), in a representative sample of Spanish population., Materials and Methods: The di@bet.es epidemiological study is a population-based cohort study aimed to determine the prevalence and incidence of DM in the adult population of Spain. The at-risk sample at the final examination (2016-2017) included 1751 subjects who completed an oral health questionnaire. This questionnaire, together with demographic and risk factors, had been previously validated to build an algorithm to predict severe periodontitis in the Spanish population. Logistic regression models were used to evaluate the association between severe periodontitis and DM with adjustment for confounding factors., Results: In total, 144 subjects developed DM, which yielded 8.2% cumulative incidence. Severe periodontitis was detected in 59.0%, 54.7% or 68.8% of the subjects depending on three different selected criteria at the 2016-2017 exam. All criteria used to define severe periodontitis were associated with DM in unadjusted analysis, but the magnitude of the association decreased after adjusting for significant confounders. The criteria '≥50% of teeth with clinical attachment loss ≥5 mm' presented an odds ratio of 4.9 (95% confidence interval: 2.2-10.7; p ≤ .001) for DM., Conclusions: Severe periodontitis is associated with DM in the Spanish population., (© 2023 The Authors. Journal of Clinical Periodontology published by John Wiley & Sons Ltd.)

Introduction: Hypoaldosteronism is characterized by hyperkalemia, and/or hypovolemic hyponatremia (HH), often accompanied by metabolic acidosis. HH is typical of hypoaldosteronism, whereas euvolemic hyponatremia (EH) is not. The purpose of the current study is to describe the characteristics of hyponatremia in hypoaldosteronism and elucidate whether EH can be considered part of the disease's spectrum., Methods: In a hypoaldosteronism cohort, we analyzed the factors associated with hyponatremia, comparing the characteristics of EH and HH and their associated factors. Correlation analyses of mineralocorticoid biomarkers, such as the transtubular potassium gradient (TTKG), the urinary Na+/K+ ratio (UNa+/UK+) with serum, and urinary electrolytes were performed in both types of hyponatremia., Results: Of 112 hypoaldosteronism episodes, 77.7% were ≥65 years old, 44.6% were women, and 80 (71.4%) had hyponatremia. Hyponatremia was negatively associated with the presence of chronic kidney disease, and positively with a hypovolemic state, malnutrition, a prior history of hyponatremia, and glucocorticoid therapy. HH: 61/80 and EH: 19/80 episodes. HH was associated with an age ≥65 years and the use of diuretics, as well as factors related to an aldosterone deficit and/or mineralocorticoid resistance. In HH but not in EH, urinary potassium was correlated with the TTKG, and urinary sodium with both the TTKG and the UNa+/UK+., Conclusion: Both HH and EH can be observed in hypoaldosteronism. However, only the former would be related to insufficient mineralocorticoid activity., Significance Statement: Isolated hypoaldosteronism is a poorly understood and underdiagnosed endocrinological disorder, classically recognized only when hyperkalemia is present. The development of hypovolemic hyponatremia, however, is also easily explained by the physiopathology of the disorder. The current study addresses the features of hyponatremia when found in the context of mineralocorticoid insufficiency, and confirms an association between hypovolemic hyponatremia and isolated hypoaldosteronism. Thus, the clinical spectrum of hypoaldosteronism is extended to include hypovolemic hyponatremia as a frequent manifestation of the disorder.

Background and Aims: We aimed to assess the associations of exposure to air pollutants and standard and advanced lipoprotein measures, in a nationwide sample representative of the adult population of Spain., Methods: We included 4647 adults (>18 years), participants in the national, cross-sectional, population-based di@bet.es study, conducted in 2008-2010. Standard lipid measurements were analysed on an Architect C8000 Analyzer (Abbott Laboratories SA). Lipoprotein analysis was made by an advanced 1 H-NMR lipoprotein test (Liposcale®). Participants were assigned air pollution concentrations for particulate matter <10 μm (PM 10 ), <2.5 μm (PM 2.5 ) and nitrogen dioxide (NO 2 ), corresponding to the health examination year, obtained by modelling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model)., Results: In multivariate linear regression models, each IQR increase in PM 10 , PM 2.5 and NO 2 was associated with 3.3%, 3.3% and 3% lower levels of HDL-c and 1.3%, 1.4% and 1.1% lower HDL particle (HDL-p) concentrations (p < .001 for all associations). In multivariate logistic regression, there was a significant association between PM 10 , PM 2.5 and NO 2 concentrations and the odds of presenting low HDL-c (<40 mg/dL), low HDL-p (10 and NO 2 and low HDL-p in men (p for interaction .008 and .034), and between NO 2 and low HDL-p in individuals with obesity (p for interaction .015)., Conclusions: Our study shows an association between the exposure to air pollutants and blood lipids in the general population of Spain, suggesting a link to atherosclerosis., (© 2023 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.)

Objective: Evaluation of the influence of potential risk factors (RFs) on glycemic changes at 3 years postpartum., Methods: The glycemic status of 1400 women, in absence of a new pregnancy, was evaluated at 3 months (3 m) and 3 years (3 y) postpartum, after participation in the St. Carlos Gestational Study (2228 normoglycemic pregnant women followed from before gestational week 12 to delivery, from 2015-2017). Abnormal glucose regulation (AGR) was defined as fasting serum glucose ≥ 100 mg/dL and/or HbA1c ≥ 5.7% and/or 2 h 75 g OGTT glucose ≥ 140 mg/dL. In total, 12 modifiable and 3 unmodifiable RFs were analyzed., Results: 3 m postpartum, 110/1400 (7.9%) women had AGR; 3 y postpartum, 137 (9.8%) women exhibited AGR (110 with 3 m normal glucose tolerance [NGT]); 1263 (90.2%) had NGT (83 with 3 m AGR). More women with gestational diabetes mellitus (GDM) progressed to AGR at 3 y (OR: 1.60 [1.33-1.92]) than women without GDM. Yet, most women with 3 m and/or 3 y AGR had no GDM history. Having ≥2 unmodifiable RFs was associated with increased risk for progression to AGR (OR: 1.90 [1.28-2.83]) at 3 y postpartum. Having >5/12 modifiable RFs was associated with increased progression from NGT to AGR (OR: 1.40 [1.00-2.09]) and AGR persistence (OR: 2.57 [1.05-6.31]). Pregestational BMI ≥ 25 kg/m 2 (OR: 0.59 [0.41-0.85]), postdelivery weight gain (OR: 0.53 [0.29-0.94]), and waist circumference > 89.5 cm (OR: 0.54 [0.36-0.79]) reduced the likelihood of NGT persisting at 3 y., Conclusions: 3-month and/or 3-year postpartum AGR can be detected if sought in women with no prior GDM. Modifiable and unmodifiable RF predictors of AGR at 3 y postpartum were identified. Universal screening for glycemic alterations should be considered in all women following delivery, regardless of prior GDM. These findings could be useful to design personalized strategies in women with risk factors for 3 y AGR.

Bariatric surgery is increasingly used in women of childbearing age due to the rising prevalence of obesity and the effectiveness and availability of this treatment. Pregnancy in women with previous bariatric surgery deserves special attention. Weight loss induced by surgery reduces the risks that obesity poses to pregnancy. But on the other hand, decreased intake and malabsorption may increase the risk of malnutrition and micronutrient deficiency and negatively affect maternal and foetal health. The aim of this narrative review is to provide an updated analysis of the impact of different bariatric surgery techniques on mineral and micronutrient nutritional status during pregnancy and the possible effect on maternal-foetal health.

Introduction: Admission hyponatremia, frequent in patients hospitalized for COVID-19, has been associated with increased mortality. However, although euvolemic hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis (SIAD) is the single most common cause of hyponatremia in community-acquired pneumonia (CAP), a thorough and rigorous assessment of the volemia of hyponatremic COVID-19 subjects has yet to be described. We sought to identify factors contributing to mortality and hospital length-of-stay (LOS) in hospitalized COVID-19 patients admitted with hyponatremia, taking volemia into account., Method: Retrospective study of 247 patients admitted with COVID-19 to a tertiary hospital in Madrid, Spain from March 1st through March 30th, 2020, with a glycemia-corrected serum sodium level (SNa) < 135 mmol/L. Variables were collected at admission, at 2nd-3rd day of hospitalization, and ensuing days when hyponatremia persisted. Admission volemia (based on both physical and analytical parameters), therapy, and its adequacy as a function of volemia, were determined., Results: Age: 68 years [56-81]; 39.9% were female. Median admission SNa was 133 mmol/L [131- 134]. Hyponatremia was mild (SNa 131-134 mmol/L) in 188/247 (76%). Volemia was available in 208/247 patients; 57.2% were euvolemic and the rest (42.8%) hypovolemic. Hyponatremia was left untreated in 154/247 (62.3%) patients. Admission therapy was not concordant with volemia in 43/84 (51.2%). In fact, the majority of treated euvolemic patients received incorrect therapy with isotonic saline (37/41, 90.2%), whereas hypovolemics did not (p=0.001). The latter showed higher mortality rates than those receiving adequate or no therapy (36.7% vs. 19% respectively, p=0.023). The administration of isotonic saline to euvolemic hyponatremic subjects was independently associated with an elevation of in-hospital mortality (Odds Ratio: 3.877, 95%; Confidence Interval: 1.25-12.03)., Conclusion: Hyponatremia in COVID-19 is predominantly euvolemic. Isotonic saline infusion therapy in euvolemic hyponatremic COVID-19 patients can lead to an increased mortality rate. Thus, an exhaustive and precise volemic assessment of the hyponatremic patient with CAP, particularly when due to COVID-19, is mandatory before instauration of therapy, even when hyponatremia is mild., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Pazos-Guerra, Ruiz-Sánchez, Pérez-Candel, López-Nevado, Hernández-Olmeda, Cuesta-Hernández, Martín-Sánchez, Calle-Pascual and Runkle-de la Vega.)

A Mediterranean diet (MedDiet)-based intervention reduces the rate of immediate postpartum maternal metabolic disorders. Whether these effects persist long-term remains to be determined. A total of 2526 normoglycemic women were randomized before the 12th gestational week (GW). IG women followed a MedDiet with extra virgin olive oil (EVOO) (>40 mL/day) and a handful of nuts daily, whereas CG women had to restrict all kinds of dietary fat. At 3 months postpartum, a motivational lifestyle interview was held. The endpoint of the study evaluated the rate of abnormal glucose regulation (AGR) and metabolic syndrome (MetS) at 3 years postpartum in women of the San Carlos cohort. A total of 369/625 (59%) CG women and 1031/1603 (64.3%) IG women were finally analyzed. At 3 months and 3 years postdelivery, the IG women showed higher adherence to the MedDiet, which was associated with lower values of body mass index (BMI) and lipid and glycemic profiles. Body weight change and waist circumference were lower in the IG women. After applying multiple regression analysis, the ORs (95%CI) resulted in AGR (3.18 (2.48-4.08); p < 0.001)/MetS (3.79 (1.81-7.95); p = 0.001) for women with GDM and higher OR for development of MetS in CG women (3.73 (1.77-7.87); p = 0.001). A MedDiet-based intervention early in pregnancy demonstrated persistent beneficial effects on AGR and MetS rates at 3 years postpartum.

The San Carlos Gestational Diabetes Mellitus (GDM) prevention study, a nutritional intervention RCT based on a Mediterranean Diet (MedDiet), has been shown to reduce the incidence of GDM. The objective of this study is to investigate the relationship of leptin, adiponectin, interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), insulin and HOMA-IRand circulating miRNAs (miR-29a-3p, miR-103a-3p, miR-132-3p, miR-222-3p) with the appearance of GDM and with MedDiet-based nutritional intervention, at 24−28 gestational weeks (GW), and in glucose regulation 2−3 years post-delivery (PD). A total of 313 pregnant women, 77 with GDM vs. 236 with normal glucose tolerance (NGT), 141 from the control group (CG, MedDiet restricting the consumption of dietary fat including EVOO and nuts during pregnancy) vs. 172 from the intervention group (IG, MedDiet supplemented with extra virgin olive oil (EVOO) and pistachios during pregnancy) were compared at Visit 1 (8−12 GW), Visit 2 (24−28 GW) and Visit 3 (2−3 years PD). Expression of miRNAs was determined by the Exiqon miRCURY LNA RT-PCR system. Leptin, adiponectin, IL-6 and TNF-α, were measured by Milliplex® immunoassays on Luminex 200 and insulin by RIA. Women with GDM vs. NTG had significantly higher leptin median (Q1−Q3) levels (14.6 (9.2−19.4) vs. 9.6 (6.0−15.1) ng/mL; p < 0.05) and insulin levels (11.4 (8.6−16.5) vs. 9.4 (7.0−12.8) µUI/mL; p < 0.001) and lower adiponectin (12.9 (9.8−17.2) vs. 17.0 (13.3−22.4) µg/mL; p < 0.001) at Visit 2. These findings persisted in Visit 3, with overexpression of miR-222-3p (1.45 (0.76−2.21) vs. 0.99 (0.21−1.70); p < 0.05)) and higher levels of Il-6 and TNF-α. When the IG is compared with the CG lower levels of insulin, HOMA-IR-IR, IL-6 levels at Visit 2 and 3 and leptin levels only at Visit 2 were observed. An overexpression of miR-222-3p and miR-103a-3p were also observed in IG at Visit 2 and 3. The miR-222-3p and miR103a-3p expression correlated with insulin levels, HOMA-IR, IL-6 and TNF-α at Visit 2 (all p < 0.05). These data support the association of leptin, adiponectin and insulin/HOMA-IR with GDM, as well as the association of insulin/HOMA-IR and IL-6 and miR-222-3p and miR-103a-3p expression with a MedDiet-based nutritional intervention.

Background/objectives: Although vascular endothelial growth factor b (VEGFb) might have an impact on the development of obesity, diabetes and related disorders, the possible relationship between VEGFb serum levels and the incidence of these metabolic complications in humans is still unknown. The aim of our study was to evaluate the association between VEGFb serum levels and the new-onset of metabolic syndrome (MS) and its components in the Spanish adult population after 7.5 years of follow-up., Subjects/methods: A total of 908 subjects from the Di@bet.es cohort study without MS at cross-sectional stage according to International Diabetes Federation (IDF) or Adult Treatment Panel III (ATP-III) criteria were included. Additionally, five sub-populations were grouped according to the absence of each MS component at baseline. Socio-demographic, anthropometric and clinical data were recorded. The Short Form of International Physical Activity Questionnaire (SF-IPAQ) was used to estimate physical activity. A fasting blood extraction and an oral glucose tolerance test were performed. Serum determinations of glucose, lipids, hsCRP and insulin were made. VEGFb levels were determined and categorized according to the 75th percentile of the variable. New cases of MS and its components were defined according to ATPIII and IDF criteria., Results: A total of 181 or 146 people developed MS defined by IDF or ATP-III criteria respectively. Serum triglyceride levels, hs-CRP and systolic blood pressure at the baseline study were significantly different according to the VEGFb categories. Adjusted logistic regression analysis showed that the likelihood of developing MS and abdominal obesity was statistically reduced in subjects included in the higher VEGFb category., Conclusion: Low serum levels of VEGFb may be considered as early indicators of incident MS and abdominal obesity in the Spanish adult population free of MS, independently of other important predictor variables., (© 2022. The Author(s).)

Hypothesis: Gestational diabetes mellitus (GDM) entails a complex underlying pathogenesis, with a specific genetic background and the effect of environmental factors. This study examines the link between a set of single nucleotide polymorphisms (SNPs) associated with diabetes and the development of GDM in pregnant women with different ethnicities, and evaluates its potential modulation with a clinical intervention based on a Mediterranean diet., Methods: 2418 women from our hospital-based cohort of pregnant women screened for GDM from January 2015 to November 2017 (the San Carlos Cohort, randomized controlled trial for the prevention of GDM ISRCTN84389045 and real-world study ISRCTN13389832) were assessed for evaluation. Diagnosis of GDM was made according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria. Genotyping was performed by IPLEX MassARRAY PCR using the Agena platform (Agena Bioscience, SanDiego, CA). 110 SNPs were selected for analysis based on selected literature references. Statistical analyses regarding patients' characteristics were performed in SPSS (Chicago, IL, USA) version 24.0. Genetic association tests were performed using PLINK v.1.9 and 2.0 software. Bioinformatics analysis, with mapping of SNPs was performed using STRING, version 11.5., Results: Quality controls retrieved a total 98 SNPs and 1573 samples, 272 (17.3%) with GDM and 1301 (82.7%) without GDM. 1104 (70.2%) were Caucasian (CAU) and 469 (29.8%) Hispanic (HIS). 415 (26.4%) were from the control group (CG), 418 (26.6%) from the nutritional intervention group (IG) and 740 (47.0%) from the real-world group (RW). 40 SNPs (40.8%) presented some kind of significant association with GDM in at least one of the genetic tests considered. The nutritional intervention presented a significant association with GDM, regardless of the variant considered. In CAU, variants rs4402960, rs7651090, IGF2BP2; rs1387153, rs10830963, MTNR1B; rs17676067, GLP2R; rs1371614, DPYSL5; rs5215, KCNJ1; and rs2293941, PDX1 were significantly associated with an increased risk of GDM, whilst rs780094, GCKR; rs7607980, COBLL1; rs3746750, SLC17A9; rs6048205, FOXA2; rs7041847, rs7034200, rs10814916, GLIS3; rs3783347, WARS; and rs1805087, MTR, were significantly associated with a decreased risk of GDM, In HIS, variants significantly associated with increased risk of GDM were rs9368222, CDKAL1; rs2302593, GIPR; rs10885122, ADRA2A; rs1387153, MTNR1B; rs737288, BACE2; rs1371614, DPYSL5; and rs2293941, PDX1, whilst rs340874, PROX1; rs2943634, IRS1; rs7041847, GLIS3; rs780094, GCKR; rs563694, G6PC2; and rs11605924, CRY2 were significantly associated with decreased risk for GDM., Conclusions: We identify a core set of SNPs in their association with diabetes and GDM in a large cohort of patients from two main ethnicities from a single center. Identification of these genetic variants, even in the setting of a nutritional intervention, deems useful to design preventive and therapeutic strategies., Competing Interests: LM, MZ, LS, MA are employees of Patia Europe. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ramos-Levi, Barabash, Valerio, García de la Torre, Mendizabal, Zulueta, de Miguel, Diaz, Duran, Familiar, Jimenez, del Valle, Melero, Moraga, Herraiz, Torrejon, Arregi, Simón, Rubio and Calle-Pascual.)

Introduction: Hypoaldosteronism can be congenital or acquired, isolated or part of primary adrenal insufficiency, and caused by an aldosterone deficit, resistance, or a combination of both. Reduced mineralocorticoid action can induce a decrease in urine K+ and H+ excretion and an increase in urine Na+ excretion, leading to hyperkalemia, and/or hyponatremia, often combined with metabolic acidosis. We aimed to characterize the clinical manifestations of hypoaldosteronism, and their associated factors., Methods: Retrospective analysis of 112 episodes of hypoaldosteronism diagnosed in 86 adult patients from 2012-2019 by the Endocrinology and Nutrition Department of a tertiary hospital. The frequency of hyperkalemia, hypovolemic hyponatremia (HH) and metabolic acidosis (MA), and their associated factors were evaluated., Results: Patients had a median age of 77 [65 - 84], 55.4% were male. 94.6% cases showed hyperkalemia, 54.5% HH, and 60.3% MA. The mean serum K+ of all cases was 5.4 ± 0.5 mmol/L, Na+: 132.1 ± 6.3 mmol/L, HCO3: 22.6 ± 3.3 mmol/L. Hypoaldosteronism was isolated in the majority of cases: only 6/112 (5%) had primary adrenal insufficiency. Hypovolemia was associated with hyponatremia and a more florid clinical presentation. HH was associated with a combined presence of aldosterone-lowering and mineralocorticoid resistance factors. MA was associated with the presence of mineralocorticoid resistance factors., Conclusions: Hypoaldosteronism in adult endocrinological clinical practice is primarily isolated, and acquired. It predisposes not only to the development of hyperkalemia and MA, but also to that of HH. Hypoaldosteronism must be considered in the differential diagnosis of HH with urinary sodium wasting., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ruiz-Sánchez, Calle-Pascual, Rubio-Herrera, De Miguel Novoa, Gómez-Hoyos and Runkle.)

The Circadian Locomotor Output Cycles Kaput (CLOCK) gene has been linked to metabolic dysfunction and obesity. The purpose of this study was to analyze the association between single nucleotide polymorphisms (SNPs) of CLOCK gene with obesity and with long-term weight response after different bariatric surgery (BS) techniques. The cohort includes 375 patients with morbid obesity (MO) and 230 controls. In the association study of SNPs with weight response we combined several variables as phenotype at 6 years after surgery. The study protocol was registered in ISRCTN (ID80961259). The analysis of the selected SNPs was performed by allelic discrimination using Taqman ® probes. The genotype association study was performed using the SNPStats program, with comparisons adjusted for sex, age, initial Body Mass Index, type 2 diabetes and hypertension diagnosis, and type of surgery. In the case-control study two of three SNPs were significantly associated with MO. The variant rs1801260 had a protective effect for MO whereas the TT genotype of rs3749474 variant had the strongest association with MO (OR = 2.25 (1.39-3.66); p = 0.0006). In the linear regression analysis both variants showed significant association with long-term weight loss and weight regain after BS, independently of the pre-surgery patient profile.

Background and Objectives: Differentiating between hypovolemic (HH) and euvolemic hyponatremia (EH) is crucial for correct diagnosis and therapy, but can be a challenge. We aim to ascertain whether changes in serum creatinine (SC) can be helpful in distinguishing HH from EH. Materials and Methods: Retrospective analysis of patients followed in a monographic hyponatremia outpatient clinic of a tertiary hospital during 1 January 2014−30 November 2019. SC changes during HH and EH from eunatremia were studied. The diagnostic accuracy of the SC change from eunatremia to hyponatremia (∆SC) was analyzed. Results: A total of 122 hyponatremic patients, median age 79 years (70−85), 46.7% women. In total, 70/122 patients had EH, 52/122 HH. During hyponatremia, median SC levels increased in the HH group: +0.18 mg/dL [0.09−0.39, p < 0.001], but decreased in the EH group: −0.07 mg/dL (−0.15−0.02, p < 0.001), as compared to SC in eunatremia. HH subjects presented a higher rate of a positive ∆SC than EH (90.4% vs. 25.7%, p < 0.001). EH subjects presented a higher rate of a negative/null ∆SC than HH (74.3% vs. 9.6%, p < 0.001). ROC curve analysis found an AUC of 0.908 (95%CI: 0.853 to 0.962, p < 0.001) for ∆SC%. A ∆SC% ≥ 10% had an OR of 29.0 (95%CI: 10.3 to 81.7, p < 0.001) for HH. A ∆SC% ≤ 3% had an OR of 68.3 (95%CI: 13.0 to 262.2, p < 0.001) for EH. Conclusions: The assessment of SC changes from eunatremia to hyponatremia can be useful in distinguishing between HH and EH.

The identification of nutritional patterns associated with the development of type 2 diabetes (T2D) might help lead the way to a more efficient and personalized nutritional intervention. Our study is aimed at evaluating the association between fatty acids (FA) in red blood cell (RBC) membranes, as a quantitative biomarker of regular dietary fat intake, and incident type 2 diabetes in a Spanish population. We included 1032 adult Spaniards (57% women, age 49 ± 15 years, 18% prediabetes), without diabetes at study entry, from the Di@bet.es cohort. Incident diabetes was diagnosed at the end of the study follow-up. The FA percentage in RBC was determined at baseline by gas chromatography. Participants were followed on average 7.5 ± 0.6 years. Lower percentages of linoleic acid (LA), α-linolenic (ALA), and eicosapentaenoic acid (EPA), and higher percentages of docosahexaenoic acid (DHA) in RBC membranes were associated, independently of classical risk factors, with worse glucose metabolism at the end of the study follow-up. In addition, higher percentages of ALA and EPA, and moderate percentages of DHA, were associated with lower risk of diabetes. No significant associations were found for LA and diabetes risk. Dietary patterns rich in vegetables are independently associated with lower risk of both deterioration of glucose regulation and incident diabetes, and should be reinforced for the prevention of diabetes.

Introduction: Hyponatremia often occurs during the practice of endurance sports. We evaluated the impact on hyponatremia of the hydration recommendations of the Third International Exercise-Associated Hyponatremia Consensus Development Conference 2015 (3IE-AHCD) during the 2017 Gran Trail de Peñalara marathon (GTP) and the Vitoria Gasteiz Ironman triathlon (VGI)., Methods: Prospective study of GTP and VGI athletes participating in four information sessions in the months prior to the events, to explain that hydration should only be according to their level of thirst, per the recommendations of the 3IE-AHCD. Consenting event finishers were included in final analysis. Pre- and post-race anthropometric and biochemical parameters were compared., Results: Thirty-six GTP (33 male) and 94 VGI (88 male) finishers were evaluated. GTP race median fluid intake was 800 ml/h, with 900 ml/h in the VGI race. 83.3% GTPfin and 77.6% VGIfin remained eunatremic (blood sodium 135-145 mmol/L). Only 1/36 GTP and 1/94 VGI participant finished in hyponatremia, both with a sodium level of 134 mmol/L. Fourteen percent of GTP, and 21.2% of VGI participants finished in hypernatremia, with no increase in race completion times. No participating athlete required medical attention, except for musculoskeletal complaints. Pro-BNP and Copeptin levels rose significantly. Changes in copeptin levels did not correlate with changes in plasma osmolality, nor total body water content in impedance analysis., Conclusions: Recommending that athletes' fluid intake in endurance events be a function of their thirst almost entirely prevented development of hyponatremia, without induction of clinically significant hypernatremia, or a negative repercussion on race completion times., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 López de Lara, Ruiz-Sánchez, Cuesta, Seara, Calle-Pascual, Rubio Herrera, Runkle and Verbalis.)

A pre-gestational thyroid reserve of iodine is crucial to guarantee the increased demand for thyroid hormone production of early pregnancy. An iodine intake ≥150 µg/day is currently recommended. The objective of this study was to assess average pre-gestational food-based iodine consumption in pregnant women at their first prenatal visit (<12 gestational weeks), and its association with adverse materno-fetal events (history of miscarriages, early fetal losses, Gestational Diabetes, prematurity, caesarean sections, and new-borns large/small for gestational age). Between 2015-2017, 2523 normoglycemic women out of 3026 eligible had data in the modified Diabetes Nutrition and Complication Trial (DNCT) questionnaire permitting assessment of pre-gestational food-based iodine consumption, and were included in this study. Daily food-based iodine intake was 123 ± 48 µg, with 1922 (76.1%) not reaching 150 µg/day. Attaining this amount was associated with consuming 8 weekly servings of vegetables (3.84; 3.16-4.65), 1 of shellfish (8.72; 6.96-10.93) and/or 2 daily dairy products (6.43; 5.27-7.86). Women who reached a pre-gestational intake ≥150 µg had lower rates of hypothyroxinemia (104 (17.3%)/384 (21.4%); p = 0.026), a lower miscarriage rate, and a decrease in the composite of materno-fetal adverse events (0.81; 0.67-0.98). Reaching the recommended iodine pre-pregnancy intake with foods could benefit the progression of pregnancy.

The optimal maternal levels of thyroid hormones (TH) during the first trimester of gestation have not been established, nor has the ideal moment to initiate levothyroxine treatment (LT) to improve the evolution of gestation and fetal development. Cut-off points for Thyroid-stimulating hormone (TSH) <2.5 µIU/mL and free thyroxine (FT4)>7.5 pg/mL have been recommended. There are no data on whether initiation of LT <9th Gestational Week (GW) can have a favourable impact., Objective: To define the TSH/FT4 percentiles corresponding with 2.5 µIU/mL and 7.5 pg/mL levels, respectively, at GW8 (Study 1), and evaluate the effects of protocol-based LT before GW9 on gestation evolution, in women with TSH ≥2.5 µIU/mL and/or FT4≤ 7.5 pg/mL (study 2)., Subjects: 2768 consecutive pregnant women attending the first gestational visit from 2013-2014 and 3026 from 2015-2016 were eligible for Study I and 2 respectively. A final 2043 (study 1) and 2069 (study 2) women were assessed in these studies., Results: Study 1: The FT4 level of 7.5 pg/mL corresponds with the 17.9th percentile, a TSH level of 2.5 µIU/mL with the 75.8 th . Women with TSH ≥2.5 µIU/mL had a history of fetal losses more frequently than those <2.5 (OR 2.33 (95%CI): 1.58-3.12), as did those with FT4 ≤7.5 pg/ml compared to those >7.5 (OR 4.81; 3.25-8.89). Study 2: A total of 1259 women had optimal TSH/FT4 levels (Group 1), 672 (32.4%, Group 2) had suboptimal TSH or T4l, and 138 (6.7%, Group 3) had suboptimal values of both. 393 (58.5%) in Group 2 and 88 (63.8%) in Group 3 started LT before GW9. Mean (SD) GW24 levels were TSH: 1.96 ± 1.22 µIU/mL and FT4: 7.07 ± 1.25 pg/mL. The highest FT4 value was 12.84 pg/mL. The adjusted risk for an adverse event if LT was started early was 0.71 (0.43-0.91) for Group 2 and 0.80 (0.66-0.94) for Group 3., Conclusions: Early LT in women with suboptimum levels of TSH/FT4 (≥2.5µIU/mL/≤7.5 pg/ml) at or before GW9 is safe and improves gestation progression. These data support the recommendation to adopt these cut-off points for LT initiation, which should be started as early as possible., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Runkle, de Miguel, Barabash, Cuesta, Diaz, Duran, Familiar, de la Torre, Herraiz, Izquierdo, Diaz, Marcuello, Matia, Melero, Montañez, Moraga, Perez-Ferre, Perez, Assaf-Balut, Rubio, Ruiz-Sanchez, Sanabria, Torrejon, Valerio, del Valle and Calle-Pascual.)

Therapeutic potential of metformin in obese/diabetic patients has been associated to its ability to combat insulin resistance. However, it remains largely unknown the signaling pathways involved and whether some cell types are particularly relevant for its beneficial effects. M1-activation of macrophages by bacterial lipopolysaccharide (LPS) promotes a paracrine activation of hypoxia-inducible factor-1α (HIF1α) in brown adipocytes which reduces insulin signaling and glucose uptake, as well as β-adrenergic sensitivity. Addition of metformin to M1-polarized macrophages blunted these signs of brown adipocyte dysfunction. At the molecular level, metformin inhibits an inflammatory program executed by HIF1α in macrophages by inducing its degradation through the inhibition of mitochondrial complex I activity, thereby reducing oxygen consumption in a reactive oxygen species (ROS)-independent manner. In obese mice, metformin reduced inflammatory features in brown adipose tissue (BAT) such as macrophage infiltration, proinflammatory signaling and gene expression, and restored the response to cold exposure. In conclusion, the impact of metformin on macrophages by suppressing a HIF1α-dependent proinflammatory program is likely responsible for a secondary beneficial effect on insulin-mediated glucose uptake and β-adrenergic responses in brown adipocytes., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Weight regain (WR) compromises the effectiveness of bariatric surgery. The objective of this study was to determine differences in long-term WR prevalence using different definitions and analyze possible preoperative predictors involved., Methods: Single-center retrospective cohort study including 445 adults who underwent 3 modalities of bariatric surgery between 2009 and 2014., Exposure: age, gender, ethnicity, body mass index (BMI), type 2 diabetes (T2D), hypertension (HTN), and type of surgery., Main Outcomes: WR at year 6 assessed by 4 definitions and 6 multivariate models based on common thresholds., Results: Our cohort (71.1% female) had a mean age of 44.78 ± 11.94 years, and mean presurgery BMI of 44.94 ± 6.88 kg/m 2 , with a median follow-up of 6 years (IQR=5-8). The prevalences of T2D and HTN were 36.0% and 46.7% respectively. WR rates over thresholds ranged from 25.4 to 68.1%, with significant differences between groups in the WR measured as the percentage of maximum weight loss (MWL) and the increase in excess weight loss (EWL). Presurgery BMI was a significant predictor in 3 models; restrictive techniques were associated with WR in all the models except for those considering WR over 10 kg and WR over 15% from nadir as dependent variables., Conclusions: In this long-term study, WR defined as percentage of MWL and increase in EWL from nadir had the greatest significance in logistic regression models with preoperative BMI and type of surgery as independent variables. These findings could serve to establish a standardized outcome reporting WR in other longitudinal studies., Key Points: • Lack of standardized outcome to measure weight regain after bariatric surgery. • Lowest rates of weight regain in malabsorptive techniques in all definitions applied. • Weight regain measured as percentage of maximum weight lost., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Dysnatremia is associated with increased mortality in patients with community-acquired pneumonia. SARS-COV2 (Severe-acute-respiratory syndrome caused by Coronavirus-type 2) pneumonia can be fatal. The aim of this study was to ascertain whether admittance dysnatremia is associated with mortality, sepsis, or intensive therapy (IT) in patients hospitalized with SARS-COV2 pneumonia. This is a retrospective study of the HOPE-COVID-19 registry, with data collected from January 1 th through April 31 th , 2020. We selected all hospitalized adult patients with RT-PCR-confirmed SARS-COV2 pneumonia and a registered admission serum sodium level (SNa). Patients were classified as hyponatremic (SNa <135 mmol/L), eunatremic (SNa 135-145 mmol/L), or hypernatremic (SNa >145 mmol/L). Multivariable analyses were performed to elucidate independent relationships of admission hyponatremia and hypernatremia, with mortality, sepsis, or IT during hospitalization. Four thousand six hundred sixty-four patients were analyzed, median age 66 (52-77), 58% males. Death occurred in 988 (21.2%) patients, sepsis was diagnosed in 551 (12%) and IT in 838 (18.4%). Hyponatremia was present in 957/4,664 (20.5%) patients, and hypernatremia in 174/4,664 (3.7%). Both hyponatremia and hypernatremia were associated with mortality and sepsis. Only hyponatremia was associated with IT. In conclusion, hyponatremia and hypernatremia at admission are factors independently associated with mortality and sepsis in patients hospitalized with SARS-COV2 pneumonia., Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT04334291, NCT04334291., Competing Interests: IR and MC have given talks sponsored by Otsuka, and worked in an advisor capacity for Otsuka. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Ruiz-Sánchez, Núñez-Gil, Cuesta, Rubio, Maroun-Eid, Arroyo-Espliguero, Romero, Becerra-Muñoz, Uribarri, Feltes, Trabattoni, Molina, García Aguado, Pepe, Cerrato, Alfonso, Castro Mejía, Roubin, Buzón, Bondia, Marin, López Pais, Abumayyaleh, D’Ascenzo, Rondano, Huang, Fernandez-Perez, Macaya, de Miguel Novoa, Calle-Pascual, Estrada Perez, Runkle and HOPE COVID-19 investigators.)

Objective: There is sparse evidence for the impact of gene-diet interaction on gestational diabetes mellitus (GDM) onset. Recent findings have shown that late first-trimester high adherence to a Mediterranean diet (MedDiet) pattern is associated with a GDM risk reduction. The aim of this study was to investigate if this effect could be modulated by TCF7L2 rs7903146 polymorphism.Research design and methods: A total of 874 pregnant women participants in the St Carlos GDM prevention study, were stratified into three groups defined as "High,5-6 on targets", "Moderate, 2-4 on targets" or "Low, 0-1 on targets" adherence to Mediterranean diet according to late first-trimester compliance with six food targets: >12 servings/week of vegetables, >12 pieces/week of fruits, <2 servings/week of juice, >3 servings/week of nuts, >6 days/week and >40 mL/day consumption of extra virgin olive oil. All patients were genotyped for rs7903146 using Taqman technology., Results: Logistic regression analysis revealed that the risk of developing GDM in those with high adherence versus low adherence was significantly reduced only in carriers of the T-allele (CT + TT), with an adjusted odds ratio of 0.15 (95% CI:0.05-0.48). This effect was not observed in CC carriers. Interaction analysis yielded significant rs7903146-MedDiet interaction in GDM risk (p < 0.03)., Conclusions: Women carrying the rs7903146 T-allele who highly adhere to a MedDiet early in pregnancy have lower risk of developing GDM than CC carriers. This reinforces the importance of identifying patients at risk of GDM who would be especially sensitive to nutritional interventions based on their genetic characteristics., Competing Interests: There are not competing interests declared. The main investigator had the overall responsibility to ensure that the participants’ anonymity is protected. The trial staff ensured that the participants’ anonymity was maintained. The participants were be identified only by a participant ID number on the electronic database. All data collected in the study were entered onto a dedicated password-protected electronic database using a secure computer and internet connection. All documents were stored securely and only accessible by trial staff and authorized personnel. We will not publish any data that could lead to the identification of any study participants. The study complied with the Data Protection Legislation which requires data to be anonymized as soon as it is mandatory to do so., (© 2020 The Authors. Published by Elsevier Inc.)

Gestational diabetes mellitus (GDM) is the most frequent morbidity found in pregnancy, and it increases the risk for several maternal-fetal complications. Hispanic women are considered at high risk. The St. Carlos GDM prevention study is a randomized controlled trial (RCT) conducted from 2016-2017. Normoglycemic women were randomized at 12-14 Gestation week (WG) to an intervention group (IG) receiving recommendations based on the MedDiet (supplemented with ExtraVirgin Olive Oil/pistachios), or to a control group (CG), recommended to limit fat intake. After RCT conclusion, IG recommendations were applied to a real-world group (RW) in routine clinical practice. The primary endpoint of the current study is an assessment of the GDM rate in Hispanic participants of the aforementioned studies: 132 RCT, 128 CT, 284 RW participants. The GDM rate was lower in IG: 19/128(14.8%), p = 0.021, and RW: 38/284(13.4%), p = 0.029) than in CG: 34/132(25.8%). Adjusted RR (95%CI) for GDM: 0.72 (0.50-0.97), p = 0.037 in IG and 0.77 (0.61-0.97), p = 0.008 in RW. Rates of urinary tract infections, emergency caesarean-sections and perineal trauma were also lower in IG and RW. Other adverse outcomes were lower in IG vs. CG. In conclusion, a MedDiet-based intervention reduces the rate of GDM and several adverse maternal-fetal outcomes in Hispanic women residing in Spain.

Introduction: Metabolic syndrome (MetS) is an important predictor of cardiovascular mortality. Identification of occurrence and regression trends of MetS could permit elaboration of preventive strategies with new targets. The objective of this study was to analyze the occurrence and regression rates of MetS and its associated factors in the representative cohort of Spain of the di@bet.es study., Research Design and Methods: The di@bet.es study is a prospective cohort where 5072 people representative of the Spanish population over 18 years of age were randomly selected between 2009 and 2010. Follow-up was a median of 7.5 (IQR 7.2-7.9) years, with 2408 (47%) participating subjects. A total of 1881 (78%) subjects had all the pertinent data available and were included in this study., Results: Of the 1146 subjects without baseline criteria for MetS, 294 (25.7%) developed MetS during follow-up, while of the 735 patients with prior MetS, 148 (20.1%) presented regression. Adjusted MetS incidence per 1000 person-years was 38 (95% CI 32 to 44), while regression incidence was 36 (95% CI 31 to 41). Regression rate was independently higher than incidence rate in the following: women, subjects aged 18-45, university-degree holders, patients without central obesity, without hypertension, as well as those with body mass index of <25 kg/m 2 . Lower progression and higher regression rates were observed with an adapted 14-point Mediterranean Diet adherence screener questionnaire score of >11 in both groups and with >500 and>2000 MET-min/week of physical activity, respectively., Conclusions: This study provides MetS incidence and regression rates, and identifies the target population for intervention strategies in Spain and possibly in other countries., Competing Interests: Competing interests: EMo has been on advisory boards, has received consulting fees, speaker honoraria or research support from Astra Zeneca, Menarini Laboratories, Merck Sharp & Dohme, Novartis, NovoNordisk and Sanofi., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Gestational diabetes mellitus (GDM) increases the risk of adverse events in pregnancy and jeopardizes long-term health of the mother and offspring. There is currently no consensus as to what screening strategies improve the efficiency of GDM diagnosis. Which criteria should be used? Is the one-step or two-step procedure better? There is no agreement as to what the best dietary approach in the treatment of GDM is. In addition, different nutritional interventions have been studied in the prevention of GDM. The Mediterranean diet seems to be effective in preventing GDM and other maternofoetal outcomes. We review herein our experience using the one-step criteria for GDM screening; the treatment and prevention strategies used; and the overall impact of nutrition on maternofoetal health., (Copyright © 2019 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The consumption of dairy products in pregnancy is widely extended. However, whether the consumption of low or high fat dairy produce is more beneficial for maternofetal health has yet to be established., Research Design and Methods: This prospective cohort study evaluated the effect of consumption of dairy products during pregnancy on the frequency of gestational diabetes mellitus (GDM) and a composite of adverse maternofetal outcomes (CMFO). Pregnant women receiving obstetric care between 2014 and 2017 were eligible. Those who consumed ≥3 servings/day of dairy products at 24-28 gestational weeks (GWs) were included and analyzed (n=2004). The population was stratified into three groups according to intake of fat-free dairy products-skimmed milk and fat-free yoghurt and cheese-(days/week): infrequent (1-2), average (3-6) and regular (7). Logistic regression analysis compared ORs (95% CI) for GDM and CMFO between the three groups (where the group of reference was the 'infrequent' intake group)., Results: After adjusting for confounding factors, no significant associations were found between the degree of consumption of fat-free dairy products and the risk of GDM and a CMFO. Moreover, when categorized by the degree of adherence to the Mediterranean diet (above or below the median score), associations were found between the 'regular' intake group and an increased risk of having a CMFO in women with a high adherence to the Mediterranean diet (OR: 1.50; 95% CI: 1.01 to 2.22; p<0.05). Weight gain during pregnancy did not differ among groups., Conclusions: The consumption of fat-free dairy products during pregnancy does not seem to be beneficial for maternofetal health., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the efficacy and safety of one single-session of radiofrequency ablation (RFA) performed in thyroid benign and predominantly solid nodules., Patients and Method: Unicentric retrospective study in usual clinical setting that included patients with solid and benign thyroid nodules treated with one single session of RFA and with folllow-up of at at least 6 months after the procedure. RFA was performed as an alternative to surgery in cases of pressure symptoms or nodular growth evidence. Patients were evaluated basally and at one, 3 and 6 months after RFA and also at 12 months if the follow-up was available. In each evaluation efficacy variables were recorded (percentual change from basal volume, percentage of nodules reaching a volume reduction above 50% from baseline, patients with disappearance of pressure symptoms and the possibility of antithyroid drug withdrawal) and safety variables were also registered including minor complications (pain needing analgesic drugs, hematoma) and major complications (voice changes, braquial plexus injury, nodule rupture and thyroid dysfunction)., Results: Twenty-four patients with a follow-up of at least 6 months after RFA were included, 16 of them with more than 12 months of follow-up. Mean nodule volume changed from 25.4±15.5ml basally to 10.7±9.9ml at month 6 (P<.05) and to 9.9±10,4ml at month 12 in 16 nodules. Six months after RFA mean volumetric reduction was 57.5±24% and 65% of the nodules reached a volume reduction above 50% from baseline. Median percentage of reduction at month 6 was 50.4±25.8% for nodules with a basal volume above 20ml (n=13) and 65.3±20.1% for nodules with a lower basal volume (n=11). Pressure symptoms reported in 12 patients disappeared in all cases. Antithyroid drugs could be stopped in 3 of 4 cases treated before RFA. A mild and transient pain responsive to conventional analgesic drugs was recorded in 9 patients during the 24h after the procedure and in 7 a small perithyroid and transient hematoma was observed in the 48 following hours. One major complication was described as a nodule rupture that recovered spontaneously. There were no changes in hormonal values in euthyroid cases., Conclusion: A single session of RFA seems to be an effective and safe procedure in patients with solid thyroid nodules with pressure symptoms or relevant growth evidence. As an outpatient and scarless procedure with no need of general anaesthesia it could become an useful alternative to lobectomy when surgery is refused or in patients at high surgical risk., (Copyright © 2019 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

We reported that a Mediterranean Diet (MedDiet), supplemented with extra-virgin olive oil (EVOO) and pistachios, reduces GDM incidence and several other adverse outcomes. In order to assess its translational effects in the real world we evaluated the effect of MedDiet from 1st gestational visit in GDM rate compared with control (CG) and intervention (IG) groups from the previously referred trial. As secondary objective we also compared adverse perinatal outcomes between normoglycemic and diabetic women. This trial is a prospective, clinic-based, interventional study with a single group. 1066 eligible normoglycaemic women before 12 gestational weeks were assessed. 932 women (32.4 ± 5.2 years old, pre-gestational BMI 22.5 ± 3.5 kg/m 2 ) received a motivational lifestyle interview with emphasis on daily consumption of EVOO and nuts, were followed-up and analysed. Binary regression analyses were used to examine the risk for each pregnancy outcome, pregnancy-induced hypertension, preeclampsia, gestational weight gain (GWG), caesarean-section, perineal trauma, preterm delivery, small (SGA) and large for gestational age (LGA), and Neonatal Intensive Care Unit admissions. GDM was diagnosed in 13.9%. This rate was significantly lower than the CG: RR 0.81 (0.73-0.93), p < 0.001 and no different from the IG: RR 0.96 (0.85-1.07), p = 0.468. GWG was lower in diabetic women (10.88 ± 6.46 vs. 12.30 ± 5.42 Kg; p = 0.013). Excessive weight gain (EWG) was also lower in GDM [RR 0.91 (0.86-0.96); p < 0.001] without a significant increase of insufficient weight gain. LGA were also lower (1 (0.8%) vs. 31 (3.9%); p < 0.05)), and SGA were similar (5 (3.8%) vs. 30 (3.7%)). LGA were associated to EWG (RR 1.61 (1.35-1.91), p < 0.001). Differences in other maternal-foetal outcomes were not found. In conclusions an early MedDiet nutritional intervention reduces GDM incidence and maternal-foetal adverse outcomes and should be universally applied as 1st line therapy. GDM might not be consider as a high risk pregnancy any longer.

Aims: The aim of the study was to evaluate the effect of a Mediterranean diet (MedDiet), enhanced with extra virgin olive oil (EVOO) and nuts, on a composite of adverse maternofoetal outcomes of women with normoglycemia during pregnancy., Methods: This was a sub-analysis of the St Carlos gestational diabetes mellitus Prevention Study. Only normoglycemic women were analysed (697). They were randomized (at 8-12th gestational weeks) to: standard-care control group (337), where fat consumption was limited to 30% of total caloric intake; or intervention group (360), where a MedDiet, enhanced with EVOO and pistachios (40-42% fats of total caloric intake) was recommended. The primary outcome was a composite of maternofoetal outcomes (CMFOs): at least having 1 event of emergency C-section, perineal trauma, pregnancy-induced hypertension and preeclampsia, prematurity, large-for-gestational-age and small-for gestational-age., Results: Crude relative risk showed that the intervention was associated with a significant reduction in the risk of CMFOs (0.48 [0.37-0.63]; p = 0.0001), with a number-needed-to-treat = 5. Risk of urinary tract infections, emergency C-sections, perineal trauma, large-for-gestational-age and small-for gestational age new-borns were also significantly reduced., Conclusion: A MedDiet, enhanced with EVOO and nuts, was associated with a risk reduction of CMFOs in over 50% in normoglycemic pregnant women. Therefore, it might be a potentially adequate diet for pregnant women., Trial Registration: Identifier ISRCTN84389045. The study was registered on September 27, 2013. Last edited on September 26, 2018., (The Author(s). Published by S. Karger AG, Basel.)

Background/objectives: Hyponatremia is the most common electrolyte disorder, and is associated with high-morbimortality rates. The true prevalence of hyponatremia in patients on parenteral nutrition (PN) is unknown, and the relationship between PN composition and development of hyponatremia has yet to be studied. Hypoproteinemia, a common finding in patients receiving PN, induces an overestimation of serum sodium (SNa) levels, when using indirect electrolyte methodology. Thus, SNa should be corrected for serum total protein levels (TP). The objective was to accurately determine the prevalence of hyponatremia (indirect SNa corrected for PT) and evaluate the relationship between the composition of PN and the development of hyponatremia., Subjects/methods: Medical records of 222 hospitalized patients receiving total PN during a 7-month period were reviewed. Composition of PN, indirect SNa-mmol/l-, and SNa corrected for TP (SNa-TP)-mmol/l-, both upon initiation and during PN administration, were analyzed., Results: Hyponatremia (SNa < 135 mmol/l) was present in 81% of subjects when SNa was corrected for TP, vs. 43% without correction (p = 0.001). In total 64% of patients that were eunatremic upon initiation of PN developed hyponatremia during PN administration, as detected by SNa-TP, vs. 28% as detected by uncorrected SNa (p < 0.001). There were no significant differences in volume, osmolarity, sodium or total osmols administered in PN between patients who developed hyponatremia and those who remained eunatremic., Conclusions: A majority of patients receiving PN present hyponatremia, when indirect SNa levels are corrected for TP. The development of hyponatremia during PN is not related to the composition of the PN.

We aimed to corroborate glycemic control after bariatric surgery (BS) using continuous glucose monitoring (CGM) and analyze if data could predict long-term outcome. We evaluated 24 of our patients with type 2 diabetes who underwent BS (12 Roux-en-Y gastric bypass, RYGB, and 12 single-anastomosis duodeno-ileal bypass with sleeve gastrectomy, SADI-S) and who were in remission after 18-24 months' follow-up. At this time, a CGM device was placed for 7 days. Patients were reevaluated thereafter for at least 5 years. Glucose variability (GV) was lower in patients after SADI-S and in the 18 patients who were still in remission after 5 years, and provided more information on long-term status than classical diabetes-related characteristics.

Unlabelled: Early-pregnancy lifestyle (EPL) could influence the development of gestational diabetes mellitus(GDM), depending on the diagnostic criteria used., Objective: We studied EPL in 1750 pregnant women using Carpenter-Coustan criteria(CCc), and in 1526 with the International Association of Diabetes and Pregnancy Study Groups criteria(IADPSGc)., Methods: GDM risk factors were assessed in women between 24 and 28 weeks of gestational age during two consecutive years. A semiquantitative frequent-food-consumption questionnaire was used to evaluate lifestyle during pregnancy. Multiple logistic regression analysis was conducted to assess GDM risk with different lifestyle patterns., Results: Using IADPSGc, the GDM ORs (95%CI) for intake/week were: nuts >3 times: 0.59 (0.39-0.91; p < 0.015), refined cereals ≤1 serving: 0.72(0.58-0.89; p < 0.003), juices <4 servings: 0.77 (0.62-0.95; p < 0.017), cookies and pastries <4 servings: 0.71(0.57-0.89; p < 0.003) as compared to opposite habits. No significant nutritional patterns were found to be significant using CCc. The OR (95%CI) for GDM with none of the four risk patterns as compared to having three-four risk factors was 0.21(0.07-0.62; p < 0.005), remaining significant after stratification by BMI, age, obstetric events, parity and family history. The multiple logistic regression model including nutritional categories and pregestational BMI, age, obstetric history, parity, personal/family history, had an area under the curve(AUC) of the receiver operating curve(ROC) for the probability to predict GDM of 0.66 (CI 95%: 0.63-0.69; p < 0.001)., Conclusion: Our study is the first to identify four early-pregnancy nutritional patterns associated with the GDM when using IADPSGc. Adherence to a low-risk nutritional pattern from early pregnancy on could be an effective strategy for GDM prevention., (Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

The beneficial effects of fish consumption in both children and adults are well known. However, the intake of methylmercury, mainly from contaminated fish and shellfish, can have adverse health effects. The study group on the prevention of exposure to methylmercury (GEPREM-Hg), made up of representatives from different Spanish scientific societies, has prepared a consensus document in a question and answer format, containing the group's main conclusions, recommendations and proposals. The objective of the document is to provide broader knowledge of factors associated with methylmercury exposure, its possible effects on health amongst the Spanish population, methods of analysis, interpretation of the results and economic costs, and to then set recommendations for fish and shellfish consumption. The group sees the merit of all initiatives aimed at reducing or prohibiting the use of mercury as well as the need to be aware of the results of contaminant analyses performed on fish and shellfish marketed in Spain. In addition, the group believes that biomonitoring systems should be set up in order to follow the evolution of methylmercury exposure in children and adults and perform studies designed to learn more about the possible health effects of concentrations found in the Spanish population, taking into account the lifestyle, eating patterns and the Mediterranean diet., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Background & Aims: Women with prior gestational diabetes mellitus (GDM) have a high risk of developing type 2 diabetes mellitus (DM2) in later life. The study aim was to evaluate the efficacy of a lifestyle intervention for the prevention of glucose disorders (impaired fasting glucose, impaired glucose tolerance or DM2) in women with prior GDM., Methods: A total of 260 women with prior GDM who presented with normal fasting plasma glucose at six to twelve weeks postpartum were randomized into two groups: a Mediterranean lifestyle intervention group (n = 130) who underwent an educational program on nutrition and a monitored physical activity program and a control group (n = 130) with a conventional follow-up. A total of 237 women completed the three-year follow-up (126 in the intervention group and 111 in the control group). Their glucose disorders rates, clinical and metabolic changes and rates of adherence to the Mediterranean lifestyle were analyzed., Results: Less women in the intervention group (42.8%) developed glucose disorders at the end of the three-year follow-up period compared with the control group (56.75%), p < 0.05. The multivariate analysis indicated a reduction in the rate of glucose disorders with a BMI of less than 27 kg/m(2) (OR 0.28; 0.12-0.65; p < 0.003), low fat intake pattern (OR 0.30; 0.13-0.70; p < 0.005), low saturated fat pattern (OR 0.30; 0.13-0.69; p < 0.005) and healthy fat pattern (OR 0.34; 0.12-0.94; p < 0.04)., Conclusions: Lifestyle intervention was effective for the prevention of glucose disorders in women with prior GDM. Body weight gain and an unhealthy fat intake pattern were found to be the most predictive factors for the development of glucose disorders. Current Controlled trials: ISRCTN24165302. http://www.controlled-trials.com/isrctn/pf/24165302., (Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Introduction and Objectives: There are no nationwide, population-based studies in Spain assessing overall cardiovascular risk. We aimed to describe cardiovascular risk and achievement of treatment goals following the 2012 European Guidelines on cardiovascular disease prevention strategy. We also investigated clinical characteristics (non-classical risk factors) associated with moderate risk., Methods: Participants (n=2310, 58% women) aged 40 to 65 years from a national population-based study (Di@bet.es Study) were identified. First, a priori high/very-high risk individuals were identified. Next, total cardiovascular risk (Systematic Coronary Risk Evaluation equation including high-density lipoprotein cholesterol) was used to assess risk of a priori non-high risk individuals. Variables independently associated with moderate versus low-risk were investigated by multiple logistic regression analysis., Results: Age-and-sex standardized (direct method) percentages of high/very-high, moderate, and low-risk were 22.8%, 43.5%, and 33.7%, respectively. Most men were at moderate (56.2%), while 55.4% of women were at low risk. Low-density lipoprotein cholesterol (< 70,<100, < 115 mg/dL) and blood pressure (<140/90 mmHg) goals for very-high, high and moderate risk were met in 15%, 26% and 46%, and 77%, 68% and 85% of the individuals, respectively. Body mass index, high triglycerides concentrations, diastolic blood pressure, and low Mediterranean diet adherence (in women) were independently associated with moderate (versus low) risk., Conclusions: Cardiovascular risk in Spain is mainly moderate in men and low in women. Achievement of treatment goals in high-risk individuals should be improved. The prevalence of non-classical cardiovascular risk factors is elevated in subjects at moderate risk, an important aspect to consider in a population-based strategy to decrease cardiovascular disease in the most prevalent group., (Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To analyze the available information about continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) systems in the public health care system of the Community of Madrid., Material and Methods: A survey consisting of 31 items was sent to the 28 endocrinology department of the Madrid public hospitals. Items focused on CSII and CGM and included patients' registrations, as well as data regarding healthcare, administrative, and logistic aspects. Responses from a total of 20 hospitals where these procedures are used were received from March 2013 to May 2014. Data about pediatric patients were obtained from adult endocrinology departments, except for two hospitals which directly reported the information., Results: A total of 1256 CSII pumps were recorded in the Madrid region, of which 1089 were used by adults, and the remaining 167 by pediatric patients. During 2013, 151 new CSII systems were implanted (12% of the total), while 14 pumps were withdrawn. Availability of human resources (medical assistance) and the number of staff practitioners experienced in management of these systems widely varied between hospitals. Eighty-five percent of hospitals used retrospective CGM systems, and 40% routinely placed them before starting an insulin pump. Thirteen hospitals (65%) used long-term, real-time CGM systems in selected cases (a total of 67 patients)., Conclusions: Use of these technologies in diabetes is unequal between public health care hospitals in Madrid, and is still significantly lower as compared to other countries with similar incomes. However, there appears to be a trend to an increase in their use., (Copyright © 2014 SEEN. Published by Elsevier España, S.L.U. All rights reserved.)

The beneficial effects of fish consumption in both children and adults are well known. However, the intake of methylmercury, mainly from contaminated fish and shellfish, can have adverse health effects. The study group on the prevention of exposure to methylmercury (GEPREM-Hg), made up of representatives from different Spanish scientific societies, has prepared a consensus document in a question and answer format, containing the group's main conclusions, recommendations and proposals. The objective of the document is to provide broader knowledge of factors associated with methylmercury exposure, its possible effects on health among the Spanish population, methods of analysis, interpretation of the results and economic costs, and to then set recommendations for fish and shellfish consumption. The group sees the merit of all initiatives aimed at reducing or prohibiting the use of mercury as well as the need to be aware of the results of contaminant analyses performed on fish and shellfish marketed in Spain. In addition, the group believes that biomonitoring systems should be set up in order to follow the evolution of methylmercury exposure in children and adults and perform studies designed to learn more about the possible health effects of concentrations found in the Spanish population, ta king into account the lifestyle, eating patterns and the Mediterranean diet., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)