A standardized approach to measuring gender transparency in languages.

Languages can express grammatical gender through different ortho-phonological regularities present in nouns (e.g., the cues "-o" and "-a" for the masculine and the feminine respectively in Italian, Portuguese, or Spanish). The term "gender transparency" was coined to describe these regularities (Bates et al., 1995). In gendered languages, we can hence distinguish between transparent nouns, i.e., those displaying form regularities; opaque nouns, i.e., those with ambiguous endings; and irregular nouns, i.e., those that display the typical form regularities but are associated with the opposite gender. Following a descriptive analysis of such regularities, languages have been recently classified according to their degree of gender transparency, which seems relevant in regard to gender acquisition and processing. Yet, there are certain inconsistencies in determining which languages are overall transparent and which are opaque. In particular, it is not clear whether some other complex regularities such as derivational suffixes are also "transparent" cues for gender, what really constitutes an "opaque" noun, or which role orthography and morphology have in transparency. Given the existing inconsistencies in classifying languages as transparent or opaque, this work introduces a proposal to assess gender transparency systematically. Our methodology adapts the standardized factors proposed by Audring (2019) to analyse the relative complexity of gender systems. Such factors are adapted to gender transparency on the basis of the literature on gender acquisition and processing. To support the feasibility of such a proposal, the concepts have been instantiated in a quantitative model to obtain for the first time an objective measure of gender transparency using European Portuguese and Dutch as instances of target languages. Our results coincide with the theoretically expected outcome: European Portuguese obtains a high value of gender transparency while Dutch obtains a moderately low one. Future adaptations of this model to the gender systems of other languages could allow the continuum of gender transparency to sustain robust predictions in studies on gender processing and acquisition.

Serum prolactin levels and mortality in adults without prolactinoma: A meta-analysis.

PURPOSE: Prolactin is a highly versatile, multifunctional hormone synthesized and secreted by lactotroph cells of the anterior pituitary. Its metabolic role has been extensively studied even in normoprolactinemic populations. Recently, a wealth of observational data outlines the potential prognostic value of prolactin in various clinical settings. This systematic review aims to systematically evaluate and quantitatively synthesize the association between serum prolactin levels and risk of mortality in adults without prolactinoma. METHODS: A systematic literature search was conducted up to June 10, 2023 to identify studies reporting the association of serum prolactin levels with clinical outcomes of adults without prolactinoma. A random-effects meta-analysis was conducted to quantify the adjusted hazard ratios [(a)HRs] for all-cause and cardiovascular death during follow-up. RESULTS: Twenty-eight studies were deemed eligible reporting the outcomes of adults without prolactinoma, in whom serum prolactin levels were measured for risk-stratification. Fourteen studies reported appropriate data for meta-analysis encompassing a total of 23,596 individuals. Each unit of prolactin increase was independently associated with increased risk of all-cause (pooled aHR=1.17 [1.08-1.27]; I2=48%) and cardiovascular mortality (pooled aHR=1.54 [1.14-2.09]; I2=89%). Individuals belonging to the highest prolactin category had significantly higher risk for all-cause (pooled aHR=1.81 [1.43-2.30]; I2=65%) and cardiovascular (pooled aHR=1.59 [1.04-2.42]; I2=82%) mortality compared to their lowest prolactin category counterparts. The association between prolactin levels and in-hospital death did not reach statistical significance. CONCLUSIONS: Prolactin levels seem to be an independent predictor for mortality. Further validation is warranted before its role as a risk stratification tool can be delineated in clinical practice.

Association of metabolic syndrome components and NAFLD with quality of life: Insights from a cross-sectional study.

AIM: Metabolic syndrome (MetS) is associated with higher cardiovascular and metabolic risks, as well as with psychosocial disorders. Data regarding quality of life (QoL) in patients with MetS, point towards a significative association between MetS and a worse QoL. It remains unclear whether MetS components and non-alcoholic fatty liver disease (NAFLD) are associated with QoL in these individuals. We aimed to evaluate the association between QoL of patients with MetS and prespecified metabolic parameters (anthropometric, lipidic and glucose profiles), the risk of hepatic steatosis and fibrosis, and hepatic elastography parameters. METHODS: Cross-sectional study including patients from microDHNA cohort. This cohort includes patients diagnosed with MetS, 18 to 75 years old, followed in our tertiary center. The evaluation included anamnesis, physical examination, a QoL questionnaire (Short-Form Health Survey, SF-36), blood sampling and hepatic elastography. We used ordered logistic regression models adjusted to sex, age and body mass index to evaluate the associations between the QoL domains evaluated by SF-36 and the prespecified parameters. RESULTS: We included a total of 65 participants with MetS, with 54% being female and the mean age 61.9 ± 9.6 years old. A worse metabolic profile, specifically higher waist circumference, lower HDL, higher triglycerides, and more severe hepatic steatosis, were associated with worse QoL scores in several domains. We found no significant association of hepatic fibrosis with QoL. CONCLUSION: Our data suggests that there is a link between a worse metabolic profile (specifically poorer lipidic profile and presence of hepatic steatosis) and a worse QoL in patients with MetS.

Relation between weight gain during pregnancy and postpartum reclassification in gestational diabetes.

PURPOSE: Gestational diabetes mellitus (GDM) is the most common metabolic disease in pregnancy. It is known that GDM is a precursor to type 2 diabetes (T2D). There is evidence that excessive gestational weight variation (GWV) increases the risk of GDM. So, in this study, we aimed to evaluate the association between GWV and the persistence of diabetes in postpartum reclassification. METHODS: A retrospective observational study including pregnant women based on data from the Portuguese National Registry of Gestational Diabetes. Six-to-eight weeks after delivery, all women included underwent a reclassification test. We performed unadjusted and adjusted logistic regression models to evaluate the associations between GWV and diabetes diagnosis at the reclassification test. A subgroup analysis according to the pre-gestational BMI was also performed. RESULTS: We included 10,389 pregnant women, of which 19.6% had GDM in a previous pregnancy. The median of GWV was 10.0 [6.4, 14.0] kg and was found to be higher for those with a normal BMI. At the DM reclassification test, 1% of the women were diagnosed with T2D. We found a negative association between GWV and postpartum diabetes mellitus (DM). We also present a subgroup analysis, and these associations were only significant for the group with a normal pre-gestational BMI. CONCLUSION: Our results showed that women with normal pre-gestational BMI and lower GWV were more likely to have a diagnosis of DM in the postpartum reclassification test. This study helps to fill the gap in the effect of GWG on the persistence of diabetes in postpartum reclassification.

The impact of integrase inhibitors on steatosis and fibrosis biomarkers in persons with HIV naïve to antiretroviral therapy.

BACKGROUND: Non-alcoholic Fatty Liver Disease (NAFLD) has a high prevalence among persons with HIV infection. Since Integrase Strand Transfer Inhibitors (INSTIs) are used worldwide and have been associated with weight gain, we must determine their effect in the development of NAFLD and Non-alcoholic Steatohepatitis (NASH) in these patients. The aim of this study was to explore the impact of INSTIs on variation of liver steatosis and fibrosis in the ART-naïve person with HIV, using Hepatic Steatosis Index (HSI), Fibrosis-4 Index (FIB-4), BARD score and NAFLD Fibrosis Score (NFS). METHODS: We performed a monocentric, retrospective cohort study in ART-naïve persons with HIV that initiated INSTI based regimens between December 2019 and January 2022. Data was collected at baseline, 6 and 12 months after initiation. Demographic, clinical and laboratory characteristics, hepatic steatosis, and fibrosis scores were compared between baseline and last visit at 12 months. Linear regression models were performed to analyse the associations between analytical data at baseline and hepatic scores variation during the 12 months of treatment. Models were performed unadjusted and adjusted for age and sex. RESULTS: 99 patients were included in our study. 82% were male and median age was 36 years. We observed a significant increase in body mass index (BMI), HDL, platelet count, albumin, and creatinine and a significant decrease in AST levels. HSI showed no statistically significant differences during follow-up (p = 0.114). We observed a significant decrease in FIB-4 (p = 0.007) and NFS (p = 0.002). BARD score showed a significant increase (p = 0.006). The linear regression model demonstrated a significant negative association between baseline HIV RNA and FIB-4 change (ß= -0.08, 95% CI [-0.16 to -0.00], p = 0.045), suggesting that higher HIV RNA loads at baseline were associated with a greater decrease in FIB-4. CONCLUSION: INSTIs seem to have no impact on hepatic steatosis, even though they were associated with a significant increase in BMI. This might be explained by the direct effect of a dolutegravir-containing regimen and/or by the "return-to-health effect" observed with ART initiation. Furthermore, INSTIs were associated with a reduction in risk of liver fibrosis in ART-naïve persons with HIV, possibly due to their effect on viral suppression.

Exploring the nature of the gender-congruency effect: implicit gender activation and social bias.

The aim of the study was to explore the nature of the gender-congruency effect, characterized by a facilitation on the processing of congruent words in grammatical gender. Moreover, we explored whether resemblances between gender identities and gender attitudes with grammatical gender modulated lexical processing. We designed a gender-priming paradigm in Spanish, in which participants decided the gender of a masculine or feminine pronoun preceded by three different primes: biological gender nouns (mapping biological sex), stereotypical nouns (mapping biological and stereotypical information), and epicene nouns (arbitrary gender assignment). We found faster processing of gender congruent pronouns independently of the type of prime, showing that the grammatical gender feature is active even when processing bare nouns that are not conceptually related to gender. This indicates that the gender-congruency effect is driven by the activation of the gender information at the lexical level, which is transferred to the semantic level. Interestingly, the results showed an asymmetry for epicene primes: the gender-congruency effect was smaller for epicene primes when preceding the feminine pronoun, probably driven by the grammatical rule of the masculine being the generic gender. Furthermore, we found that masculine oriented attitudes can bias language processing diminishing the activation of feminine gender, which ultimately could overshadow the female figure.

Clinical and Pathophysiologic Insights of Free triiodothyronine/Free thyroxine Ratio in Patients with Heart Failure with Preserved Ejection Fraction: Data from the NETDiamond Cohort.

BACKGROUND: Thyroid dysfunction is common in patients with heart failure (HF). Impaired conversion of free T4 (FT4) into free T3 (FT3) is thought to occur in these patients, decreasing the availability of FT3 and contributing to HF progression. In HF with preserved ejection fraction (HFpEF), it is not known whether changes in conversion of thyroid hormones (THs) are associated with clinical status and outcomes. OBJECTIVES: The objective of this study was to evaluate the association of FT3/FT4 ratio and TH with clinical, analytical, and echocardiographic parameters, as well as their prognostic impact in individuals with stable HFpEF. METHODS: We evaluated 74 HFpEF participants of the NETDiamond cohort without known thyroid disease. We performed regression modeling to study the associations of TH and FT3/FT4 ratio with clinical, anthropometric, analytical, and echocardiographic parameters, and survival analysis to evaluate associations with the composite of diuretic intensification, urgent HF visit, HF hospitalization, or cardiovascular death over a median follow-up of 2.8 years. RESULTS: The mean age was 73.7 years and 62% were men. The mean FT3/FT4 ratio was 2.63 (standard deviation: 0.43). Subjects with lower FT3/FT4 ratio were more likely to be obese and have atrial fibrillation. Lower FT3/FT4 ratio was associated with higher body fat (ß = -5.60 kg per FT3/FT4 unit, p = 0.034), higher pulmonary arterial systolic pressure (PASP) (ß = -10.26 mm Hg per FT3/FT4 unit, p = 0.002), and lower left ventricular ejection fraction (LVEF) (ß = 3.60% per FT3/FT4 unit, p = 0.008). Lower FT3/FT4 ratio was associated with higher risk for the composite HF outcome (HR = 2.50, 95% CI: 1.04-5.88, per 1-unit decrease in FT3/FT4, p = 0.041). CONCLUSIONS: In patients with HFpEF, lower FT3/FT4 ratio was associated with higher body fat, higher PASP, and lower LVEF. Lower FT3/FT4 predicted a higher risk of diuretic intensification, urgent HF visits, HF hospitalization, or cardiovascular death. These findings suggest that decreased FT4 to FT3 conversion might be a mechanism associated with HFpEF progression.

Effects of Triiodothyronine Treatment in an Animal Model of Heart Failure with Preserved Ejection Fraction.

Background: Low levels of triiodothyronine (T3) are common in patients with heart failure (HF). Our aim was to evaluate the effects of supplementation with low and replacement doses of T3 in an animal model of HF with preserved ejection fraction (HFpEF). Methods: We evaluated four groups: ZSF1 Lean (n = 8, Lean-Ctrl), ZSF1 Obese (rat model of metabolic-induced HFpEF, n = 13, HFpEF), ZSF1 Obese treated with a replacement dose of T3 (n = 8, HFpEF-T3high), and ZSF1 Obese treated with a low-dose of T3 (n = 8, HFpEF-T3low). T3 was administered in drinking water from weeks 13 to 24. The animals underwent anthropometric and metabolic assessments, echocardiography, and peak effort testing with maximum O2 consumption (VO2max) determination at 22 weeks, and a terminal hemodynamic evaluation at 24 weeks. Afterwhile myocardial samples were collected for single cardiomyocyte evaluation and molecular studies. Results: HFpEF animals showed lower serum and myocardial thyroid hormone levels than Lean-Ctrl. Treatment with T3 did not normalize serum T3 levels, but increased myocardial T3 levels to normal levels in the HFpEF-T3high group. Body weight was significantly decreased in both the T3-treated groups, comparing with HFpEF. An improvement in glucose metabolism was observed only in HFpEF-T3high. Both the treated groups had improved diastolic and systolic function in vivo, as well as improved Ca2+ transients and sarcomere shortening and relaxation in vitro. Comparing with HFpEF animals, HFpEF-T3high had increased heart rate and a higher rate of premature ventricular contractions. Animals treated with T3 had higher myocardial expression of calcium transporter ryanodine receptor 2 (RYR2) and α-myosin heavy chain (MHC), with a lower expression of ß-MHC. VO2max was not influenced by treatment with T3. Myocardial fibrosis was reduced in both the treated groups. Three animals died in the HFpEF-T3high group. Conclusions: Treatment with T3 was shown to improve metabolic profile, myocardial calcium handling, and cardiac function. While the low dose was well-tolerated and safe, the replacement dose was associated with increased heart rate, and increased risk of arrhythmias and sudden death. Modulation of thyroid hormones may be a potential therapeutic target in HFpEF; however, it is important to take into account the narrow therapeutic window of T3 in this condition.

A cautionary note on the studies using the picture-word interference paradigm: the unwelcome consequences of the random use of "in/animates".

The picture-word interference (PWI) paradigm allows us to delve into the process of lexical access in language production with great precision. It creates situations of interference between target pictures and superimposed distractor words that participants must consciously ignore to name the pictures. Yet, although the PWI paradigm has offered numerous insights at all levels of lexical representation, in this work we expose an extended lack of control regarding the variable animacy. Animacy has been shown to have a great impact on cognition, especially when it comes to the mechanisms of attention, which are highly biased toward animate entities to the detriment of inanimate objects. Furthermore, animate nouns have been shown to be semantically richer and prioritized during lexical access, with effects observable in multiple psycholinguistic tasks. Indeed, not only does the performance on a PWI task directly depend on the different stages of lexical access to nouns, but also attention has a fundamental role in it, as participants must focus on targets and ignore interfering distractors. We conducted a systematic review with the terms "picture-word interference paradigm" and "animacy" in the databases PsycInfo and Psychology Database. The search revealed that only 12 from a total of 193 PWI studies controlled for animacy, and only one considered it as a factor in the design. The remaining studies included animate and inanimate stimuli in their materials randomly, sometimes in a very disproportionate amount across conditions. We speculate about the possible impact of this uncontrolled variable mixing on many types of effects within the framework of multiple theories, namely the Animate Monitoring Hypothesis, the WEAVER++ model, and the Independent Network Model in an attempt to fuel the theoretical debate on this issue as well as the empirical research to turn speculations into knowledge.

Changes in health-related quality of life and treatment effects in chronic heart failure: a meta-analysis.

BACKGROUND: Heart failure (HF) is associated with poor health status, and high morbi-mortality. However, it is not well established how health status changes correlate with treatment effects on clinical outcomes. Our aim was to study the association between treatment-induced changes in health-status, assessed by Kansas City Cardiomyopathy Questionnaire 23 (KCCQ-23), and clinical outcomes in chronic HF. METHODS: Systematic search of phase III-IV pharmacological RCTs in chronic HF that assessed KCCQ-23 changes and clinical outcomes throughout follow-up. We studied the association between treatment induced changes in KCCQ-23 and treatment effects on clinical outcomes (HF hospitalization or cardiovascular death, HF hospitalization, cardiovascular death, and all-cause death) using weighted random-effects meta-regression. RESULTS: Sixteen trials were included, enrolling a total of 65,608 participants. Treatment induced KCCQ-23 changes were moderately correlated with treatment effects on the combined outcome of HF hospitalization or cardiovascular mortality (regression coefficient (RC) = -0.047, 95%CI: -0.085 to -0.009; R2 = 49%), a correlation that was mainly driven by HF hospitalization (RC = -0.076, 95%CI: -0.124 to -0.029; R2 = 56%). Correlations of treatment induced KCCQ-23 changes with cardiovascular death (RC = -0.029, 95%CI: -0.073 to 0.015; R2 = 10%) and all-cause death (RC = -0.019, 95%CI: -0.057 to 0.019; R2 = 0%) were weak and non-significant. CONCLUSIONS: Treatment-induced changes in KCCQ-23 were moderately correlated with treatment-effects on HF hospitalizations but were not correlated with the effects on cardiovascular and all-cause mortality. Treatment-induced changes in patient-centered outcomes (i.e., KCCQ-23) may reflect non-fatal symptomatic changes in the clinical course of HF leading to hospitalization.

Glucagon-like peptide 1 receptor agonists in patients with type 2 diabetes with and without chronic heart failure: A meta-analysis of randomized placebo-controlled outcome trials.

AIM: Glucagon-like peptide 1 receptor agonists (GLP1-RA) reduce atherosclerotic events in patients with type 2 diabetes (T2D) and a high cardiovascular risk. The effect of GLP1-RA to reduce heart failure (HF) has been inconsistent across T2D trials, and individual trials were underpowered to assess the effect of GLP1-RA according to HF history. In this meta-analysis we aim to assess the effect of GLP1-RA in patients with and without HF history in stable ambulatory patients with T2D. METHODS: Random-effects meta-analysis of placebo-controlled trials. The hazard ratio (HR) and 95% confidence intervals (95% CI) were extracted from the treatment effect estimates of HF subgroup analyses reported in each individual study. The primary outcome was a composite of HF hospitalization or cardiovascular death. RESULTS: In total, 54 092 patients with T2D from seven randomized controlled trials were included, of whom 8460 (16%) had HF history. Compared with placebo, GLP1-RA did not reduce the composite of HF hospitalization or cardiovascular death in patients with HF history: HR 0.96, 95% CI: 0.84-1.08, but reduced this outcome in patients without HF history: HR 0.84, 95% CI: 0.76-0.92. GLP1-RA did not reduce all-cause death in patients with HF history: HR 0.98, 95% CI: 0.86-1.11, but reduced mortality in patients without HF history: HR 0.85, 95% CI: 0.79-0.92. GLP1-RA reduced atherosclerotic events regardless of HF history: HR 0.85, 95% CI: 0.75-0.97 with HF, and HR 0.88, 95% CI: 0.83-0.93 without HF. CONCLUSIONS: Treatment with GLP1-RA did not reduce HF hospitalizations and mortality in patients with concomitant T2D and HF, but may prevent new-onset HF and mortality in patients with T2D without HF. The reduction of atherosclerotic events with GLP1-RA was not influenced by HF history status.

Control of fungal spoilage in strawberries using crude plant extracts against the fungus Botrytis cinerea.

The study evaluated the conservation of strawberries treated with crude plant extracts (barbatimão, sibipiruna, guarana, and catuaba) against fungal deterioration and physicochemical characteristics. MIC of 0.125; 0.0156; 0.25 and 0.0312 g/mL were found for barbatimão, sibipiruna, guaraná and catuaba, respectively, against B. cinerea. Treated samples showed no fungal deterioration during 11 days. Analyzes of weight loss, soluble solids, titratable acidity, and pH variation were performed. Sibipiruna showed lower values ​​of mass loss, and the greatest occurred for the catuaba extract. Barbatimão did not change soluble solids and stood out with catuaba in the color parameters L and a*. Small changes in pH were observed with time. Soluble solids maintained values ​​between 6.47 oBrix and 9.90 oBrix for catuaba and sibipiruna extracts at zero and six days. Principal component analysis did not show a strong correlation between the variables. The extracts become alternatives for strawberry conservation, increasing conservation and maintaining physicochemical characteristics.

Risk of adverse events with liraglutide in heart failure with reduced ejection fraction: A post hoc analysis of the FIGHT trial.

AIM: To perform a post hoc analysis of the FIGHT trial, evaluating the effect of liraglutide (vs. placebo) on the totality of events in patients with heart failure with reduced ejection fraction (HFrEF). MATERIALS AND METHODS: FIGHT was a double-blind randomized controlled trial (RCT) that studied liraglutide versus placebo in 300 recently hospitalized patients with HFrEF followed for 180 days. The main outcome of the present analysis was total events of hospitalizations for heart failure (HF) or all-cause death. Secondary outcomes included total arrhythmic events and prespecified total events of interest (arrhythmias, sudden cardiac death, acute coronary syndrome, worsening HF, cerebrovascular event, venous thromboembolism, lightheadedness, presyncope/syncope or worsening renal function). Treatment effect was evaluated with negative binomial regression. RESULTS: Compared to placebo, there was a trend towards increased risk with liraglutide of total HF hospitalizations or all-cause deaths (96 vs. 143 events, incidence rate ratio [IRR] 1.41, 95% confidence interval [CI] 0.98-2.04; P = 0.064) and total arrhythmias (21 vs. 39, IRR 1.76, 95% CI 0.92-3.37; P = 0.088). Total prespecified events of interest were increased with liraglutide compared to placebo (196 vs. 295, IRR 1.43, 95% CI 1.06-1.92; P = 0.018). The risk of HF hospitalizations or all-cause deaths with liraglutide was higher among patients in New York Heart Association (NYHA) Class III to IV (IRR 1.86, 95% CI 1.21-2.85) than in those in NYHA Class I to II (IRR 0.62, 95% CI 0.31-1.23; interaction P = 0.008), and among patients with diabetes (interaction P = 0.051). The risk of arrhythmic events was higher among those without an implanted cardiac device (interaction P = 0.047). CONCLUSIONS: In patients with HFrEF, liraglutide might increase the risk of cardiovascular adverse effects, an effect possibly driven by excess risk of arrhythmias and worsening HF events. As this was a post hoc analysis, these results should be interpreted as exploratory and hypothesis-generating. Further RCTs must be conducted before drawing definitive conclusions.

Association of thyroid function, within the euthyroid range, with cardiovascular risk: The EPIPorto study.

Background: Thyroid hormones are important modulators of cardiovascular function. Both hypothyroidism and hyperthyroidism are known to contribute to an increased cardiovascular risk. It remains uncertain whether thyroid hormones level within the euthyroid range are associated with cardiometabolic risk. We aimed to evaluate the association between thyroid function levels within the euthyroid range and cardiovascular risk in a population-based cohort. Methods: Eight hundred thirty-five subjects aged ≥45 years from the EPIPorto population-based cohort were included. We excluded participants with TSH, free T4 (FT4), or free T3 (FT3) outside of the reference range, or with previous cardiovascular or thyroid disease. The associations between thyroid function, cardiovascular risk factors and the 10-year estimated risk of cardiovascular events (using SCORE2 and SCORE2-OP) were evaluated in linear and logistic regression models, crudely and adjusting for age, sex, BMI, diabetes, and smoking. Results: The mean age of the participants was 61.5 (SD 10.5) years and 38.9% were men. Eleven percent of the participants had diabetes, 47.8% had dyslipidemia, and 54.8% had hypertension. The mean body mass index (BMI) was 27.4 (SD 4.6) kg/m2, and the median (percentile25-75) 10-year risk of cardiovascular events was 5.46% (2.92, 10.11). Participants with higher BMI, larger waist circumference and higher hs-CRP had higher levels of FT3 and FT3/FT4 ratio. Lower FT3/FT4 ratio and higher FT4 levels were associated with higher prevalence of diabetes and more adverse lipid profile. Higher TSH, lower FT3 and lower FT3/FT4 ratio were associated with lower eGFR. Lower FT3, lower FT3/FT4 ratio and higher FT4 were associated with an increased 10-year risk of cardiovascular events. Conclusions: In a population-based study, variations of thyroid function within the euthyroid range were associated with cardiovascular risk factors. On one hand, individuals with higher BMI, larger waist circumference and higher hs-CRP had higher levels of FT3 and FT3/FT4 ratio. On the other hand, a decreased conversion of T4 to T3 (lower FT3, lower FT3/FT4 ratio and/or higher FT4) was associated with a higher prevalence of diabetes, a more adverse lipid profile, a lower eGFR and an increased 10-year risk of cardiovascular events.

Albiglutide in patients with type 2 diabetes and heart failure: a post-hoc analysis from Harmony Outcomes.

AIM: Glucagon-like peptide-1 receptor agonists (GLP1-RA) improve cardiovascular outcomes in patients with type 2 diabetes (T2D). However, some studies suggest that their effects in patients with heart failure (HF) may be attenuated. We aimed to explore the effects of the GLP1-RA albiglutide on HF outcomes in patients with and without HF history enrolled in the Harmony Outcomes trial. METHODS AND RESULTS: Harmony Outcomes enrolled patients with T2D and cardiovascular disease randomized to either albiglutide or placebo over a median follow-up of 1.6 years. A total of 9462 patients were included, of whom 1922 (20%) had HF history. Patients with HF had more cardiovascular comorbidities, poorer renal function, and had a three to four-fold higher risk of HF events compared to patients without HF. Compared to placebo, the effect of albiglutide on the composite of cardiovascular death or HF hospitalization was more pronounced among patients without HF (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.56-0.95) than in patients with HF (HR 1.06, 95% CI 0.79-1.43) (interaction p = 0.062). A similar pattern was observed for HF hospitalizations (interaction p = 0.025). The effect of albiglutide on cardiovascular death, sudden death or 'pump failure' death, and all-cause mortality was also attenuated among patients with HF history, but without significant interaction (p > 0.1). The benefit of albiglutide to reduce atherosclerotic events was consistent regardless of HF history. CONCLUSIONS: In patients with T2D and cardiovascular disease, albiglutide appeared to have no effect in reducing HF-related events among patients with HF history. These findings, placed in the context of other trials, suggest that GLP1-RA may not improve HF outcomes in patients with HF.

Nonalcoholic Fatty Liver Disease and Endocrine Axes-A Scoping Review.

Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. NAFLD often occurs associated with endocrinopathies. Evidence suggests that endocrine dysfunction may play an important role in NAFLD development, progression, and severity. Our work aimed to explore and summarize the crosstalk between the liver and different endocrine organs, their hormones, and dysfunctions. For instance, our results show that hyperprolactinemia, hypercortisolemia, and polycystic ovary syndrome seem to worsen NAFLD's pathway. Hypothyroidism and low growth hormone levels also may contribute to NAFLD's progression, and a bidirectional association between hypercortisolism and hypogonadism and the NAFLD pathway looks likely, given the current evidence. Therefore, we concluded that it appears likely that there is a link between several endocrine disorders and NAFLD other than the typically known type 2 diabetes mellitus and metabolic syndrome (MS). Nevertheless, there is controversial and insufficient evidence in this area of knowledge.

Effect of glucagon-like peptide-1 receptor agonists on cardiovascular events in overweight or obese adults without diabetes: A meta-analysis of placebo-controlled randomized trials.

Our aim was to study the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) on the risk of any cardiovascular event in adults with overweight or obesity and without diabetes. We conducted a random-effects meta-analysis of placebo-controlled randomized controlled trials. Nine trials were eligible and, in total, 11 430 patients were included, of which 7702 (67%) were submitted to treatment with GLP-1 RA. During follow-up, 673 participants receiving GLP-1 RA treatment (8.7%) and 416 participants receiving placebo (11.2%) had a cardiovascular event. Treatment with GLP-1 RA versus placebo resulted in a reduction in the risk of any cardiovascular event (RR = 0.81, CI 0.70-0.92; p = .001). In overweight or obese adults without diabetes, treatment with GLP-1 RA reduced the risk of cardiovascular events. Our findings support the use of GLP-1 RA for reducing the cardiovascular risk of these patients.