Association between exposure to air pollution and blood lipids in the general population of Spain.

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 (PM10 ), <2.5 µm (PM2.5 ) and nitrogen dioxide (NO2 ), 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 PM10 , PM2.5 and NO2 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 PM10 , PM2.5 and NO2 concentrations and the odds of presenting low HDL-c (<40 mg/dL), low HDL-p (

Cross-sectional association between severe periodontitis and diabetes mellitus: A nation-wide cohort study.

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.

Serum vascular endothelial growth factor b and metabolic syndrome incidence in the population based cohort Di@bet.es study.

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.

Ambient air pollution and thyroid function in Spanish adults. A nationwide population-based study (Di@bet.es study).

BACKGROUND: Recent reports have suggested that air pollution may impact thyroid function, although the evidence is still scarce and inconclusive. In this study we evaluated the association of exposure to air pollutants to thyroid function parameters in a nationwide sample representative of the adult population of Spain. METHODS: The Di@bet.es study is a national, cross-sectional, population-based survey which was conducted in 2008-2010 using a random cluster sampling of the Spanish population. The present analyses included 3859 individuals, without a previous thyroid disease diagnosis, and with negative thyroid peroxidase antibodies (TPO Abs) and thyroid-stimulating hormone (TSH) levels of 0.1-20 mIU/L. Participants were assigned air pollution concentrations for particulate matter <2.5µm (PM2.5) and Nitrogen Dioxide (NO2), corresponding to the health examination year, obtained by means of modeling combined with measurements taken at air quality stations (CHIMERE chemistry-transport model). TSH, free thyroxine (FT4), free triiodothyronine (FT3) and TPO Abs concentrations were analyzed using an electrochemiluminescence immunoassay (Modular Analytics E170 Roche). RESULTS: In multivariate linear regression models, there was a highly significant negative correlation between PM2.5 concentrations and both FT4 (p<0.001), and FT3 levels (p<0.001). In multivariate logistic regression, there was a significant association between PM2.5 concentrations and the odds of presenting high TSH [OR 1.24 (1.01-1.52) p=0.043], lower FT4 [OR 1.25 (1.02-1.54) p=0.032] and low FT3 levels [1.48 (1.19-1.84) p=<0.001] per each IQR increase in PM2.5 (4.86 µg/m3). There was no association between NO2 concentrations and thyroid hormone levels. No significant heterogeneity was seen in the results between groups of men, pre-menopausal and post-menopausal women. CONCLUSIONS: Exposures to PM2.5 in the general population were associated with mild alterations in thyroid function.

Changes in Serum Creatinine Levels Can Help Distinguish Hypovolemic from Euvolemic Hyponatremia.

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.

Validation of self-reported measures of periodontitis in a Spanish Population.

BACKGROUND AND OBJECTIVE: Use of self-reported questionnaires in Dentistry may be useful to estimate the prevalence of periodontitis in epidemiological studies. This study aims to assess the accuracy of self-reporting for predicting the prevalence of periodontitis in a Spanish population participating in a diabetes incidence study. MATERIALS AND METHODS: Data were collected from 231 patients participating in the Di@bet.es study. Eight questions about periodontal health were included in a health patient-reported questionnaire. The outcomes from self-reporting were validated against a full-mouth periodontal examination. Multivariable logistic regression predictive modeling was used to determine the sensitivity, specificity, and area under the receiver operator characteristic curve (AUROCC). RESULTS: Self-reported gum health, loose teeth, tooth appearance, and use of dental floss were associated with different definitions of severe periodontitis. Correlations between responses to the questions were weak. The question "Do you think you might have gum disease?" combined with demographic and well-established risk factors resulted in an AUC value of 0.75, sensitivity of 75.2%, and specificity of 60.6% for severe periodontitis. The answer to 4 questions combined with age, educational level, smoking status, and tooth loss was 76.4% sensitive and 63.5% specific, with an AUC of 0.75 in predicting prevalence of ≥25% of teeth with probing pocket depth (PPD) ≥6 mm. CONCLUSION: Predictive models, combining self-reporting on oral health status with demographic and risk factors, were useful for estimating the prevalence of severe periodontitis in the Spanish population.

A Mediterranean Diet with an Enhanced Consumption of Extra Virgin Olive Oil and Pistachios Improves Pregnancy Outcomes in Women Without Gestational Diabetes Mellitus: A Sub-Analysis of the St. Carlos Gestational Diabetes Mellitus Prevention Study.

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.

Prevalence of Hyponatremia and Its Associated Morbimortality in Hospitalized Patients Receiving Parenteral Nutrition.

BACKGROUND: The objective of the study was to determine the prevalence of hyponatremia (HN) and its associated morbimortality in hospitalized patients receiving parenteral nutrition (PN). METHODS: A retrospective study including 222 patients receiving total PN (parenteral nutrition group [PNG]) over a 7-month period in a tertiary hospital and 176 matched to 179 control subjects without PN (control subjects group [CSG]). Demographic data, Charlson Comorbidity Index (CCI), date of HN detection-(serum sodium or SNa <135 mmol/L)-intrahospital mortality, and hospital length-of-stay (LOS) were registered. In the PNG, body mass index (BMI) and SNa before, during, and after PN were recorded. RESULTS: HN was more prevalent in the PNG: 52.8 vs. 35.8% (p = 0.001), and independent of age, gender, or CCI (OR 1.8 [95% CI 1.1-2.8], p = 0.006). In patients on PN, sustained HN (75% of all intraindividual SNa <135 mmol/L) was associated with a higher mortality rate independent of age, gender, CCI, or BMI (OR 7.38 [95% CI 1.07-50.8], p = 0.042). The absence of HN in PN patients was associated with a shorter hospital LOS (<30 days) and was independent of other comorbidities (OR 3.89 [95% CI 2.11-7.18], p = 0.001). CONCLUSIONS: HN is more prevalent in patients on PN. Sustained HN is associated with a higher intrahospital mortality rate. Absence of HN is associated with a shorter hospital LOS.

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

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

Isolated hypoaldosteronism is a cause of hypovolemic but not euvolemic hyponatremia.

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.

A Simplified Screening Model to Predict the Risk of Gestational Diabetes Mellitus in Caucasian and Latin American Pregnant Women.

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.

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

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

Influence of HbA1c levels on platelet function profiles associated with tight glycemic control in patients presenting with hyperglycemia and an acute coronary syndrome. A subanalysis of the CHIPS Study ("Control de HIperglucemia y Actividad Plaquetaria en Pacientes con Síndrome Coronario Agudo").

Patients with hyperglycemia, an acute coronary syndrome and poor glycemic control have increased platelet reactivity and poor prognosis. However, it is unclear the influence of a tight glycemic control on platelet reactivity in these patients. This is a subanalysis of the CHIPS study. This trial randomized patients with hyperglycemia to undergo an intensive glucose control (target blood glucose 80-120 mg/dL), or conventional glucose control (target blood glucose <180 mg/dL). We analyzed platelet function at discharge on the subgroup of patients with poor glycemic control, defined with admission levels of HbA1c higher than 6.5%. The primary endpoint was maximal platelet aggregation following stimuli with 20 µM ADP. We also measured aggregation following collagen, epinephrine, and thrombin receptor-activated peptide, as well as P2Y12 reactivity index and surface expression of glycoprotein IIb/IIIa and P-selectin. A total of 67 patients presented HbA1c ≥ 6.5% (37 intensive, 30 conventional), while 42 had HbA1c < 6.5% (20 intensive, 22 conventional). There were no differences in baseline characteristics between groups. At discharge, patients with HbA1c ≥6.5% had significantly reduced MPA with intensive glucose control compared with conventional control (46.1 ± 22.3 vs. 60.4 ± 20.0%; p = 0.004). Similar findings were shown with other measures of platelet function. However, glucose control strategy did not affect platelet function parameters in patients with HbA1c < 6.5%. Intensive glucose control in patients presenting with an acute coronary syndrome and hyperglycemia results in a reduction of platelet reactivity only in the presence of elevated HbA1c levels.

Micronutrients in Pregnancy after Bariatric Surgery: A Narrative Review.

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.

Combined Effect of Genetic Variants on Long-Term Weight Response after Bariatric Surgery.

The pathophysiology of body weight control involves complex interactions between hormonal, environmental, behavioral and genetic factors. The purpose of this study was to analyze the association between single nucleotide polymorphisms (SNPs) of 13 genes encoding gastrointestinal peptides, their receptors or the proteins involved in their expression, with long-term weight response in a cohort of 375 patients undergoing bariatric surgery (BS). To evaluate weight response, we combined several variables to define specific response phenotypes six years after surgery. The study protocol was registered in ISRCTN (ID80961259). The analysis of the selected SNPs was performed via allelic discrimination using Taqman® probes (Applied Biosystems, Foster City, CA, USA). The genotype association study was performed using the SNPstat program, with comparisons adjusted for sex, age, initial body mass index, type 2 diabetes, hypertension diagnosis and the type of surgery. We identified eight genetic variants associated with the weight response to BS, independently of the presurgery patient profile and the type of surgical technique, from which we calculated the unweighted risk score (RS) for each phenotype. The highest scoring category in each RS was significantly associated with lower weight loss (p = 0.0001) and greater weight regain (p = 0.0012) at the end of the follow-up.

Mixed Meal Tolerance Test Versus Continuous Glucose Monitoring for an Effective Diagnosis of Persistent Post-Bariatric Hypoglycemia.

Gastric bypass determines an increase in incretin secretion and glucose excursions throughout the day and may sometimes entail the development of severe post-bariatric hypoglycemia (PBH). However, there is no consensus on the gold standard method for its diagnosis. In this study, we evaluated the usefulness of a mixed meal tolerance test (MMTT) and continuous glucose monitoring (CGM) for the diagnosis of PBH, defined as glucose levels <54 mg/dL (3.0 mmol/L). We found that hypoglycemia occurred in 60% of patients after the MMTT and in 75% during CGM, and it was predominantly asymptomatic. The MMTT confirmed the diagnosis of PBH in 88.9%of patients in whom surgery had been performed more than three years ago, in comparison to 36.4% in cases with a shorter postsurgical duration. CGM diagnosed nocturnal asymptomatic hypoglycemia in 70% of patients, and daytime postprandial hypoglycemia in 25% of cases. The mean duration of asymptomatic hypoglycemia was more than 30 min a day. Patients with ≥2% of their CGM readings with hypoglycemia exhibited a higher degree of glucose variability than those with <1% of the time in hypoglycemia. Our results show that the MMTT may be a useful dynamic test to confirm the occurrence of hypoglycemia in a large number of patients with persistent and recurrent PBH during long-term follow-up after gastric bypass. CGM, on its part, helps identify hypoglycemia in the real-world setting, especially nocturnal asymptomatic hypoglycemia, bringing to light that PBH is not always postprandial.

Inappropriate therapy of euvolemic hyponatremia, the most frequent type of hyponatremia in SARS-CoV-2 infection, is associated with increased mortality in COVID-19 patients.

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.

An Early Mediterranean-Based Nutritional Intervention during Pregnancy Reduces Metabolic Syndrome and Glucose Dysregulation Rates at 3 Years Postpartum.

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.

Modifiable Risk Factors and Trends in Changes in Glucose Regulation during the First Three Years Postdelivery: The St Carlos Gestational Diabetes Mellitus Prevention Cohort.

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/m2 (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.

Influence of CLOCK Gene Variants on Weight Response after Bariatric Surgery.

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.