Metabolic Comorbidities Research Articles

Clinical Characterisation and Comorbidities of Acquired Generalised Lipodystrophy: A 14-Year Follow-Up Study

Acquired generalised lipodystrophy (AGL) is a rare disorder characterised by the gradual loss of fat that tends to generalise over time, the origin of which is still not fully clarified. The aim of this study was to offer a detailed description of seven patients with AGL (five women, 33.8 ± 18.6 years of age), evaluated over the last 14 years, in order to augment the knowledge of this disorder. The onset of the phenotype occurred during childhood and adolescence in five cases, and in adulthood in two cases. Three patients reported infections or vaccine administration prior to the development of lipodystrophy, and two subjects reported nodular swelling. The most frequent physical features were phlebomegaly, umbilical protrusion/hernia, and acanthosis nigricans. Skinfolds and body composition analysis showed the generalised absence of fat, with the exception of one patient in whom fat loss was spared in the trunk. The loss of fat in the palms/soles was observed in five subjects. Regarding metabolic comorbidities, throughout follow-up, two patients developed type 1 diabetes and one type 2 diabetes; three also presented hypertriglyceridaemia, one of whom developed acute pancreatitis, and no macrovascular complications were observed. Only one patient showed decreased complement C4. Autoimmunity was present in all cases, and six patients manifested Hashimoto’s thyroiditis, type 1 diabetes, autoimmune hepatitis, and/or celiac disease. Thus, there are certain clinical characteristics of AGL that may be considered important diagnostic criteria to differentiate this disorder from other lipodystrophy subtypes.

International evidence-based guideline on assessment and management of PCOS-A Nordic perspective.

Polycystic ovary syndrome (PCOS) affects about 12% of women of reproductive age. In 2018, the first evidence-based guideline on assessment and management of PCOS was published, and an updated extended guideline was released in August 2023. These guidelines followed best practice and are endorsed by 39 organizations worldwide, making them the most robust source of evidence to guide clinical practice. In the 2023 guideline, diagnostic criteria have been further refined as polycystic ovary morphology can now be assessed with gynecological ultrasound or elevated anti-Müllerian hormone levels. A healthy lifestyle should be at the focus of care for all women with PCOS; however, with no specific diet or physical exercise recommended. The latest evidence on medical treatments and fertility management are reviewed, including special considerations regarding long-term follow-up of metabolic and psychiatric comorbidities and pregnancy in women with PCOS. Here we summarize the recommendations from a Nordic perspective.

Urinary metabolite signatures reflect the altered host metabolism in severe obstructive sleep apnea

Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder. The onset and progression of OSA are often linked with severe cardiovascular and metabolic comorbidities. At the same time, given the increasing prevalence of OSA, novel methods to screen OSA and its follow-up are needed. Untargeted metabolic profiling of OSA patients and healthy controls was planned to capture a snapshot of urinary metabolites and potential biomarkers using the gas chromatography-mass spectrometry (GC–MS) method.Polysomnography (PSG) confirmed severe OSA patients with AHI index ≥ 30 were considered for urine sample collection. The sample size was constituted of OSA (n = 36) and healthy controls (n = 36). Metabolite extraction and derivatization were performed and metabolomic analysis was performed by using GC–MS.The obtained data set was statistically analyzed using univariate and multivariate analysis. The Orthogonal partial least-squares discriminant analysis (OPLS-DA) was performed to screen differential metabolites between OSA patients and healthy controls.The metabolomic analysis revealed a total of 142 significantly altered metabolites of interest.Biomarker analysis allows for the creation of a list of putative urinary biomarkers including GABA, malic acid, glutamic acid, epichoric acid etc., with an accuracy of 99.8 % to 100 % for OSA screening. Subsequently, pathway analysis revealed that related biochemical pathways like the tricarboxylic acid cycle (TCA), glutamate/glutamine, amino acid and fatty acid metabolism, that are significantly interlinked with these metabolic biomarkers can play a crucial role in the pathogenesis of OSA. This study paves the way to undertake mass screening in a larger population to identify specific and reliable biomarkers.

From Non-Alcoholic Steatohepatitis (NASH) to Hepatocellular Carcinoma (HCC): Epidemiology, Incidence, Predictions, Risk Factors, and Prevention.

Non-alcoholic fatty liver disease (NAFLD) affects up to a quarter of the adult population in many developed and developing countries. This spectrum of liver disease ranges from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. The incidence of NASH is projected to increase by up to 56% over the next 10 years. There is growing epidemiological evidence that NAFLD has become the fastest-growing cause of hepatocellular carcinoma (HCC) in industrialized countries. The annual incidence of HCC varies between patients with NASH cirrhosis and patients with noncirrhotic NAFLD. In this review, NAFLD/NASH-associated HCC will be described, including its epidemiology, risk factors promoting hepatocarcinogenesis, and management of HCC in patients with obesity and associated metabolic comorbidities, including preventive strategies and therapeutic approaches to address this growing problem.

PREVALENCE OF AMPUTATIONS IN DIABETIC INDIVIDUALS TREATED AT A REFERRAL CENTER

Diabetes Mellitus (DM) has high rates of morbidity and mortality due to its complications. Objective: To analyze the prevalence of amputations in individuals with DM treated at a referral center in Salvador, Bahia. Method: Cross-sectional study, with data from 160 medical records adult people with diabetes who suffered or not amputation, attended at the specialized outpatient service. Data analysis was performed using the Statistical Package for the Social Sciences®. The results are presented in absolute and relative frequencies, χ2 test and Fisher’s exact test, when appropriate, considering significance of 5%. Results: The prevalence of amputation was 53.75%. It was associated with male gender (p=0;00), time since diagnosis of DM greater than 10 years (p=0.046) and metabolic comorbidities (p=0.047). Conclusion: The high rates of amputations in males of productive and working age reveal the need to control DM and its comorbidities, as well as prevention of skin lesions that lead to amputation.

Abstract 14175: Risk of Cardiovascular Disease in Women Who Underwent Salpingo-Oophorectomy to Prevent Hereditary Breast Ovarian Cancer: A Systematic Review and Meta-Analysis

Introduction: Hereditary breast and ovarian cancer (HBOC) syndrome is defined by family history and identification of germline pathogenic variants (PVs). In particular, the mutations in BRCA1/2 (BRCAm) increased approximately 44% and 17% risk of ovarian cancer or fallopian tube cancer and 72% and 69% risk of breast cancer. Risk-reducing salpingo-oophorectomy (RRSO), the physiologic removal of the ovaries and fallopian tubes, effectively reduces the risk of ovarian cancer by 80-95% in women with HBOC. Hypothesis: Is performing a RRSO in women with HBOC or BRCAm associated with the development of cardiac and metabolic diseases? Aims: To assess the risk of myocardial infarction (MI)/coronary artery disease (CAD), hypertension, diabetes mellitus (DM), and hypercholesterolemia/dyslipidemia among women with HBOC or BRCA1/2 mutation after performing RRSO. Methods: We searched in PubMed, Scopus, and Web of Science databases for studies that assessed cardiovascular and metabolic events following RRSO in women with HBOC or BRCAm. Statistical analysis was performed using RStudio v4.4.2 using the DerSimonian and Laird random-effects model. Heterogeneity was examined using the Cochran Q test and I 2 statistics. Significance for heterogeneity was set at a p-value<0.01. Results: Five studies were included with a total of 1320 patients. Among them, 956/1320 (72.4%) had BRCAm: 469 (35.5%) had BRCA1 and 400 (30.3%) had BRCA2. The majority of patients (928;69.3%) had RRSO<50 years, and the mean age of the study sample was 54.3 years (41.45-57, 2.35). The incidence of MI events was reported in 18/1126 patients (1.4%, 95% Cl, 5-2.3%; I 2 =40.15%). Most common metabolic comorbidities were hypercholesterolemia. Observed in 170/994 women (19.6%, 95% Cl, 4.6-34.6%; I 2 =97.88%), hypertension, in 125/994 women (12.9%, 95% Cl, 4-21.8%; I 2 =96.93%), and DM, reported in 46/1320 patients (3%, 95% Cl, 1.2-4.7%; I 2 =75.41%). Conclusions: This meta-analysis provides evidence to support that patients with HBOC or BRCAm who undergo RRSO have an increased risk of developing heart and metabolic diseases. Larger studies with longer follow-up are required to further explore these associations.

Abstract 13673: Effects of Bariatric Surgery on Blood Pressure Management in Type 2 Diabetes: Analysis From a Thirteen-Year Cohort Study

Introduction: Bariatric surgery (BS) is an effective intervention for both weight loss and improved metabolic health in those with Type 2 diabetes (T2D), yet there is limited data on its long-term effect on blood pressure (BP) control. Aim: This prospective cohort study aims to evaluate the long-term effect of BS on BP and metabolic health in T2D patients in a tertiary centre in North-West England. Methods: Patients who underwent BS (gastric bypass/sleeve gastrectomy) between 2009 - 2012 at a single tertiary surgical centre in North-West England were followed for up to 13 years. Preoperative and follow-up data including BP readings, HbA1c, BMI and antihypertensive medication use was obtained from electronic patient records at regular intervals to ascertain longitudinal outcomes in BP, BMI and HbA1c. Results: 119 patients were included in the study. Optimal metabolic health state was achieved at 12 months post-surgery for BMI (-14.78kg/m 2 (95%CI: 13.37-16.20, p<0.001)), systolic BP (sBP) (-15.02mmHg 95%CI: 8.23-21.81mmHg, p<0.001)), diastolic BP (dBP) (-8.1mmHg, 95%CI: 4.26-11.91, p<0.001)) and HbA1c (-24.41mmol/mol, 95%CI: 18.25-30.58, p<0.001). A sustained reduction in both sBP and dBP was maintained for up to 5 years, mirroring a reduction in concurrent use of antihypertensive medications (164 prescriptions v 66 at 5 years). However, at latest follow-up, there was an observed increase in antihypertensive prescription (95 v 66) yet there was no statistically significant change in mean BP. Furthermore, the number of patients with clinically diagnosed hypertension (BP 140/90 or more was lowest at 5 years (n=53 v 86 pre-op) before rising at the latest follow-up (n=57). Conclusions: Our study demonstrates that BS has a sustained benefit on BP as reflected by both absolute measurements and reduction in antihypertensive medication use. It remains an effective strategy not only for weight loss but also for the comprehensive management of metabolic comorbidities in T2D patients as evidenced by reductions in antihypertensive use, HbA1c, BMI and BP. However, more research is needed to explore the longer-term effects of these benefits at ≥ 10 years given the increases in antihypertensive use, BMI and HbA1c after this period.

Nutritional Intervention in Cushing's Disease: The Ketogenic Diet's Effects on Metabolic Comorbidities and Adrenal Steroids.

a very low-calorie ketogenic diet (VLCKD) is associated with improvement of metabolic and cardiovascular disorders. We aimed to evaluate the effects of a VLCKD in patients with Cushing's disease (CD) as adjunctive therapy to treatment for the primary disease. we evaluated clinical, hormonal and metabolic parameters in 15 patients with CD and 15 controls at baseline after 1 week and 3 weeks of VLCKD and, further, after 2 weeks of a low-carbohydrate ketogenic diet (LCKD). after 5 weeks of diet, a significant decrease in BMI (p = 0.002), waist circumference (WC) (p = 0.024), systolic blood pressure (p = 0.015), diastolic blood pressure (p = 0.005), ACTH (p = 0.026), cortisone (p = 0.025), total cholesterol (p = 0.006), LDL cholesterol (p = 0.017), triglycerides (p = 0.016) and alkaline phosphatase (p = 0.008) and a significant increase in HDL cholesterol (p = 0.017), vitamin D (p = 0.015) and oral disposition index (oDI) (p = 0.004) was observed in the CD patients. A significant decrease in BMI (p = 0.003), WC (p = 0.002), systolic blood pressure (p = 0.025), diastolic (p = 0.007) blood pressure and total cholesterol (p = 0.026) and an increase in HDL cholesterol (p = 0.001) and oDI (p < 0.001) was observed in controls. the current study confirms that a ketogenic diet is effective in improving metabolic disorders in CD and shows that a nutritional approach may be combined with conventional CD therapy in order to improve metabolic and cardiovascular comorbidities.

A New Look on the Epidemiology of Slipped Capital Femoral Epiphysis: A Topic Revisited

Background: Slipped capital femoral epiphysis (SCFE) is a common hip pathology affecting adolescents mostly in the rapid growth phase. Previous studies have presented epidemiological data to inform practitioners on its etiology to improve diagnosis, treatment, and prevention. However, in recent years national databases have been redesigned, which may change previously published information on SCFEs. The purpose of this study is to evaluate SCFE epidemiology using the 2019 Kids' Inpatient Database (KID) and HCUPnet, Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality, in conjunction with U.S. Census Data.Methods: The Kids' Inpatient Database (KID) reflects data on 5.9 million pediatric discharges in 2019 and was combined with U.S. Census data to produce epidemiologic data regarding SCFEs in the pediatric population. KID regional data was then overlayed with National Oceanographic and Atmospheric Administration (NOAA) data to assess the associations between climate patterns and UV indices with SCFE incidence.Results: Overall incidence of SCFE in the U.S. was 2.66/100,000 children 9-16 years of age. The average age at presentation with SCFE was 12.3 years with males being older at presentation (12.8 vs. 11.6 years; P<.001; r=0.34). Males were significantly more likely to develop a SCFE than females (OR 1.73; 95% CI, 1.51-1.97). Black patients were significantly more likely to present with a SCFE than all other races (OR 1.66; 95% CI, 1.40-2.97). Obesity (23.2%) was the most common metabolic and endocrine comorbidity followed by severe obesity (7.5%). Geographical regions with colder temperatures and lower UV indexes had higher SCFE rates, while regions with higher temperatures and higher UV indexes had lower SCFE rates.Conclusion: This study determined a lower SCFE incidence rate than previously reported but shows similar distributions of SCFEs amongst different races. Age of onset was increased compared to previous studies. The rate of obesity also continues to increase while the incidence of SCFEs has experienced a gradual decrease over time. It is plausible that environmental factors and race (skin tone) may have a more influential effect on the development of this pathology.Level of Evidence: III - Cross-sectional study of non-consecutive patientsKey Concepts•SCFE incidence rates are lower than previously reported.•Obesity continues to increase while SCFEs have remained stable.•Cold climate regions (with lower UV-indexes) may be a risk factor for SCFEs, while areas with hot climate regions (with higher UV-indexes) could be protective.

Abstract 12 — Prevalence and Risk Factors of Non-Alcoholic Fatty Liver Disease in Patients with Rheumatoid Arthritis: A Nationwide Population-Based Study

Background Rheumatoid arthritis (RA) is a debilitating and financially burdensome disease because of frequent presence of comorbidities including metabolic and cardiovascular abnormalities. Growing evidence suggests a link between RA and nonalcoholic fatty liver disease (NAFLD). We aimed to determine the prevalence and explore the risk factors of developing NAFLD in RA population. Methods This population-based, cross-sectional study utilized data on US adults aged [Formula: see text]20 years old from the National Health and Nutrition Examination Survey (NHANES) 2017-2018, a representative sample of the general US population. Diagnosis of RA was derived from questionnaire data. NAFLD was defined by controlled attenuation parameter (CAP) scores of [Formula: see text]278 dB/m using vibration controlled transient elastography (VCTE) in the absence of other liver disease. Weighted multiple regression analysis was further performed to assess the independent risk factors. Results Of 2,848 people included in this study, 224 of them had self-reported RA. The prevalence of NAFLD in the overall sample was 41%, with a numerically higher prevalence in RA patients than those without arthritis (47% vs. 40%, p=0.30). Compared to those without NAFLD, RA patients with concomitant NAFLD had more prevalent metabolic comorbidities including obese (75% vs. 32%, p=0.006), central obesity (100% vs. 71%, p=0.008), diabetes (39% vs. 14%, p=0.003) and hyperlipidemia (88% vs. 76%, p=0.042). Regarding laboratory findings, RA patients with NAFLD exhibited higher levels of triglyceride (188 mg/dL vs. 131 mg/dL, p=0.010), fasting plasma glucose (131 mg/dL vs. 109 mg/dL, p=0.010) and HbA1c (5.77% vs. 6.41%, p=0.002). Meanwhile, elevated levels of liver enzymes (ALT: 29 U/L vs. 19 U/L, p=0.015; AST: 25 U/L vs. 19 U/L, p=0.007) and inflammatory indicator CRP (5.1 mg/dL vs. 3.4 mg/dL, p&lt;0.001]) were more frequently reported in RA patients with NAFLD as compared with those without. Further, weighted multivariate logistic regression analysis showed that the presence of central obesity (adjusted OR=1.56 [95% CI 1.16-2.11], p=0.008) and diabetes (adjusted OR=1.28 [95% CI 1.07-1.54], p=0.014) were significantly associated with prevalent NAFLD in patients with RA. Conclusion In this population-based study, about one in two patients with RA had NAFLD, which is higher than its overall prevalence among general population. Central obesity and diabetes are predisposing factors for NAFLD in RA. Our results highlight the importance of active NAFLD screening in RA population, especially for high-risk subsets.

Glomerular Hyperfiltration: A Marker of Fibrosis Severity in Metabolic Associated Steatotic Liver Disease in an Adult Population.

Glomerular hyperfiltration (GH) is an increase in the glomerular filtration rate, possibly progressing to chronic kidney disease (CKD). Metabolic-associated steatotic liver disease (MASLD) is linked to an increased risk of CKD, especially if fibrosis is present; however, the association between GH and MASLD has not been explored. To evaluate GH prevalence in MASLD and its possible correlation with liver fibrosis. 772 consecutive patients with ultrasound MASLD (mean age 47.3 ± 8.9 years, 67.1% males) were enrolled. GH was defined as estimated glomerular filtration rate (eGFR) greater than the upper quartile of values in the cohort. Liver stiffness measurement (LSM) by FibroScan ≥ 7.2 kPa suggested liver fibrosis. GH was present in 20% of patients, liver fibrosis in 30%. In total, 53.4% of the cohort was obese, 40.9% hypertensive, 36.3% diabetic and 70.8% dyslipidaemic. GH patients compared to non-GH were significantly younger (38.4 ± 8.3 vs. 49.5 ± 7.7, p < 0.001), with higher prevalence of LSM > 7.2 kPa (35.5% vs. 29%, p < 0.001), without any difference in metabolic comorbidities. In multivariate analysis, age (OR 0.85, CI 95% 0.82-0.87) and significant fibrosis (OR 1.83; CI 95%1.10-3.03) remained independently associated with GH, regardless of the presence of metabolic alterations and nephrotoxic drugs. GH, an early marker of renal damage, is highly prevalent in MASLD and is associated with hepatic fibrosis. GH may be considered an early marker of both liver and renal disease and its recognition could prompt the management of risk factors aimed at preventing the progression of both hepatic and renal disease.

Risk factors for fibrosis progression in non-alcoholic steatohepatitis: Analysis of the European cohort in the real-world GAIN study

ObjectiveTo better understand drivers of disease progression in non-alcoholic steatohepatitis (NASH), we assessed clinical and sociodemographic markers of fibrosis progression in adults with NASH. Patients and methodsPhysician-reported patient demographics and clinical characteristics were utilised from the real-world Global Assessment of the Impact of NASH (GAIN) study. Factors associated with likelihood of fibrosis progression since NASH diagnosis were identified using a logistic regression model. ResultsOverall, 2349 patients in Europe from the GAIN study were included; mean age was 54.6 years and 41% were women. Significant covariates included age, years since diagnosis, employment status, fibrosis stage at diagnosis, type 2 diabetes mellitus, hypertension, liver transplant and liver biopsy at diagnosis. Risk of progression was 1.16 (95% confidence interval 1.12–1.20; p<0.001) times higher for each additional year since NASH diagnosis and 5.43 (2.68–11.37; p<0.001) times higher when physicians proposed a liver transplant at diagnosis. Compared with full-time employed patients, risk of progression was 1.77 (1.19–2.60; p=0.004) times higher for unemployed patients and 3.16 (1.30–7.63; p=0.010) times higher for those unable to work due to NASH. ConclusionsDisease duration, NASH severity and presence of other metabolic comorbidities could help to assess risk of progression in patients with NASH.

Pegozafermin Is a Potential Master Therapeutic Regulator in Metabolic Disorders: A Review.

Pegozafermin (PGZ), a novel glycopegylated version of human fibroblast growth factor 21 (FGF21), has demonstrated potential for addressing metabolic comorbidities, including severe hypertriglyceridemia, insulin resistance, nonalcoholic fatty liver disease, and obesity. FGF21 is a naturally occurring peptide hormone primarily produced by the liver, with a half-life of 0.5 to 2 hours. It can influence metabolic processes through endocrine cellular effects. FGF21 receptors are found in the liver, adipose, skeletal muscles, and pancreatic tissues. Those receptors rely on the beta klotho (KLB) coreceptors, a transmembrane protein, to activate the FGF21 signaling pathway and FGF21's associated transcription factors. PGZ, through its extended half-life of 55 to 100 hours, has evidenced significant improvements in metabolic functions. Its mechanism of action includes promoting adiponectin levels, enhancing insulin sensitivity, increasing triglyceride uptake, and reducing de novo lipogenesis. This emerging pharmaceutical compound has shown promise in treating liver fibrosis and inflammation linked to nonalcoholic steatohepatitis. The ENTRIGUE trial, a phase 2 clinical trial of PGZ, has demonstrated a 57% reduction in triglyceride level compared to placebo; a 45% reduction in liver hepatic steatosis; improved insulin sensitivity; reductions in nonhigh-density lipoprotein-cholesterol; and reductions in apolipoprotein B-100.

The Role of the Fatty Liver Index (FLI) in the Management of Non-Alcoholic Fatty Liver Disease: A Systematic Review.

Currently, non-alcoholic fatty liver disease is the most common liver disease worldwide, with a prevalence of 32%. It is much more common among men (40%) and among patients with metabolic comorbidities such as obesity, diabetes and dyslipidemia. Being an asymptomatic disease, the diagnosis is often established on the basis of imaging methods, with an important role given to abdominal ultrasonography, computed tomography and magnetic resonance imaging. In order to facilitate diagnosis, experts have introduced a series of blood biomarkers. Two biomarker panels are currently validated for the diagnosis of non-alcoholic fatty liver disease: the fatty liver index, and the hepatic steatosis index. The fatty liver index has been in use in medical practice for over 17 years and has demonstrated its accuracy in various studies that compared it with other diagnostic methods, highlighted its role in screening patients with cardiovascular risk and validated the effects of different diets and drugs that are proposed for the treatment of the disease. In the management of non-alcoholic fatty liver disease, the fatty liver index is an important algorithm in the diagnosis and prognosis of patients with metabolic risk. Taking into account the diversity of drugs to be approved in the treatment of non-alcoholic fatty liver disease, the fatty liver index will become an effective tool in monitoring the effects of these therapies.

Predictors of Cardiovascular Morbidities in Adults With 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia.

The prevalence of cardiovascular and metabolic complications among adults with 21-hydroxylase deficiency (21OHD) is unknown. We sought to determine the prevalence of cardiovascular and metabolic morbidities among adults with 21OHD and to identify clinical factors and biomarkers associated with cardiovascular outcomes. A 10-year retrospective cross-sectional analysis was conducted on adult patients with confirmed 21OHD, aged 18 to 70 years, who had at least one clinical visit for assessment at the University of Michigan. The presence of cardiovascular diseases (CVDs) and other metabolic comorbidities was extracted from medical records based on International Classification of Diseases (ICD) codes. Medical treatments, glucocorticoid (GC) and mineralocorticoid doses, as well as specific biomarkers of disease control since age 18, were collected for analysis. A total of 254 patients with 21OHD, median age of 35 years (interquartile range, 28.25-46 y), were included in the analysis. The prevalence of CVDs in the entire cohort was 7.5%. An increase in prevalence was seen from early adulthood, reaching 25% in patients older than 60 years. Increasing age (adjusted odds ratio [OR], 1.05; 95% CI, 1.01-1.09), hypertension (OR, 4.27; 95% CI, 1.41-12.92), and higher GC doses (OR, 1.51; 95% CI, 1.11-2.06) were significantly associated with prevalent CVDs. Higher plasma renin activity was significantly associated with CVDs (OR, 1.07; 95% CI, 1.01-1.15) but not other biochemical markers of disease. Cardiometabolic morbidities are prevalent among adults with 21OHD. Hypertension, age, and GC exposure are the main predictive factors of established CVDs in our cohort.

Exploring disparities and novel insights into metabolic and cardiovascular comorbidities among COVID-19 patients in Mexico.

The COVID-19 pandemic, especially its early stages, sparked extensive discussions regarding the potential impact of metabolic and cardiovascular comorbidities on the severity and fatality of SARS-CoV-2 infection, yielding inconclusive outcomes. In this study, we delve into the prevalence of metabolic and cardiovascular comorbidities within COVID-19 patients in Mexico. Employing a retrospective observational study design, we collected data from official databases encompassing COVID-19 patients admitted to both public and private hospitals in Mexico City. Our investigation unveiled a noteworthy incongruity in the prevalence of metabolic and cardiovascular comorbidities among COVID-19 patients, with a particular emphasis on obesity, hypertension, and diabetes. This incongruity manifests as location-dependent phenomena, where the prevalence of these comorbidities among COVID-19 patients significantly deviates from the reported values for the general population in each specific location. These findings underscore the critical importance of screening for metabolic and cardiovascular comorbidities in COVID-19 patients and advocate for the necessity of tailored interventions for this specific population. Furthermore, our study offers insights into the intricate interplay between COVID-19 and metabolic and cardiovascular comorbidities, serving as a valuable foundation for future research endeavors and informing clinical practice.

The Cellular and Protein Arms of Coagulation in Diabetes: Established and Potential Targets for the Reduction of Thrombotic Risk.

Diabetes is a metabolic condition with a rising global prevalence and is characterised by abnormally high blood glucose levels. Cardiovascular disease (CVD) accounts for the majority of deaths in diabetes and, despite improvements in therapy, mortality and hospitalisations in this cohort remain disproportionally higher compared to individuals with normal glucose metabolism. One mechanism for increased CVD risk is enhanced thrombosis potential, due to altered function of the cellular and acellular arms of coagulation. Different mechanisms have been identified that mediate disordered blood clot formation and breakdown in diabetes, including dysglycaemia, insulin resistance, and metabolic co-morbidities. Collectively, these induce platelet/endothelial dysfunction and impair the fibrinolytic process, thus creating a prothrombotic milieu. Despite these abnormalities, current antithrombotic therapies are largely similar in diabetes compared to those without this condition, which explains the high proportion of patients experiencing treatment failure while also displaying an increased risk of bleeding events. In this narrative review, we aimed to summarise the physiological functioning of haemostasis followed by the pathological effects of diabetes mellitus on platelets and the fibrin network. Moreover, we carefully reviewed the literature to describe the current and future therapeutic targets to lower the thrombosis risk and improve vascular outcomes in diabetes.

The impact of diabetes and obesity on fertility and the potential role of gut hormones as treatment.

Alongside its metabolic implications, obesity and associated diabetes impair female reproductive function, causing infertility and polycystic ovarian syndrome (PCOS). Recently, gut hormones and their receptors have been identified in various reproductive organs indicating their potential regulatory effects on reproductive function. This review aims to give an overview of their potential effects. This review focuses on literature that outlines modifications during obesity, diabetes and related infertility with an emphasis on gut hormones and their therapeutic potential. Evidence suggests that bariatric surgery has positive effects on fertility and PCOS where major alterations in metabolism occurs through restoration of gut hormone levels. This is thought to be due to the indirect effect weight loss and regulation of blood glucose has on the hypothalamic-pituitary-ovarian and hypothalamic-pituitary-adrenal axis influencing reproduction. Further research is required to elucidate the cellular mechanisms involved in the direct effects of gut hormone receptor activation on reproductive tissues. Current observations suggest a therapeutic role for gut hormones in infertility/PCOS associated with metabolic pathophysiology.

Weaker SARS-CoV-2 vaccine responses in nonalcoholic fatty liver disease with advanced liver fibrosis

BackgroundSARS-CoV-2 vaccine responses that could harbor potential risks to chronic liver diseased patients. AimsTo assess immune response following Pfizer's SARS-CoV-2 vaccine in patients with different liver fibrosis severities of nonalcoholic fatty liver disease (NAFLD). MethodsClinical and histological (NAS-score and fibrosis stage) characteristics of NAFLD patients before vaccine were correlated with serologic vaccine responses of two doses of the BNT162b2. Serum SARS-CoV-2 spike immunoglobulins (anti-S) were assessed on day seven following immunization (Liaison assay). ResultsThe mean-age of patients (n = 157) was 56.9 ± 13.2 years (46.5 % males). 94.8 % had a positive response (anti-S levels ≥ 19 AU/ml). The anti-S cutoff of 200 AU/ml used to separate strong vs. weak responses. A strong response (anti-S titers ≥ 200 AU/ml) was observed in 93/157 (59.2 %) patients with a mean-age of 53.1 ± 13.8 years (45.2 % males). A weak response (anti-S titers < 200 AU/ml) was observed in 64/157 (40.8 %) cases with a mean-age of 62.3 ± 10.2 years (p < 0.0001). The strong response subgroup had lower metabolic comorbidities, including glucose hemostasis, hypertension, and dyslipidemia (p < 0.04). Moreover, the strong response subgroup had fibrosis stages F0-F2 (75.3 % vs. 56.3 %) and lower rates of advanced stages F3-F4 (24.7 % vs. 43.8 %). The F0-F2 subgroups had significantly higher rates of strong responses than the F3-F4 stages. The anti-S ≥ 200 and anti-S ≥ 400 AU/ml response achieved in 66 % and 36.8 % of the F0-F2 population was significantly higher than the 45.1 % (p = 0.006) and 23.5 % (p = 0.05) in the F3-F4 population, respectively. The Fib-4 calculations and Fibroscan evaluations were consistent with histologic fibrosis assessment. ConclusionAdvanced liver fibrosis (assessed by histology, Fib-4, or Fibroscan) is a risk factor for lower response to Pfizer's BNT162b2 vaccine, and patients should be prioritized for the vaccine booster against SARS-CoV-2.

Early-Onset Ocular Motor Cranial Neuropathy Is a Strong Predictor of Dementia: A Nationwide, Population-Based Cohort Study

PurposeTo assess the risk of dementia in individuals with newly diagnosed ocular motor cranial neuropathy (OMCN). DesignA nationwide, population-based cohort study using authenticated data from the Korean National Health Insurance Service (KNHIS). SubjectsThis study included 60,781 OMCN patients diagnosed between 2010 and 2017 and followed through 2018, with an average follow-up of 3.37 (SD, 2.21) years with a one-year lag. After excluding patients with disease related to oculomotor dysfunction preceding the OMCN diagnosis (e.g., dysthyroid exophthalmos, thyrotoxicosis, or myasthenia gravis), a total of 52,076 OMCN cases were established. Of these, 23,642 patients who had participated in the National Health Screening Program (NHSP) within two years before their OMCN diagnosis were included. After applying the exclusion criteria (e.g., age < 40 years, previous dementia, and patients with missing data), the final cohort consisted of 19,243 patients and 96,215 age- and sex-matched controls without OMCN. MethodsWe identified newly diagnosed OMCN in the KNHIS database and collected participant characteristics from the health checkup records of the NHSP. The study endpoint was determined by the first claim with a dementia diagnostic code and anti-dementia medications. OMCN’s association with dementia risk was examined using Cox proportional hazards regression analysis, adjusting for age, sex, behavioral factors, and systemic comorbidities. Main Outcome MeasuresThe main outcome measures were hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause dementia (ACD), Alzheimer’s disease (AD), and vascular dementia (VaD) development in OMCN patients relative to those without OMCN. ResultsNewly diagnosed OMCN patients demonstrated higher metabolic comorbidities than non-OMCN individuals. New OMCN was associated with an elevated risk of ACD (HR = 1.203, 95% CI: 1.113 − 1.300), AD (HR = 1.137, 95% CI: 1.041 − 1.243), and VaD (HR = 1.583, 95% CI: 1.286 − 1.948), independent of potential confounding factors. The younger age groups exhibited a stronger association between OMCN and ACD (HR = 8.690 [< 50 years] versus 1.192 [≥ 50 years], P = 0.0004; HR = 2.517 [< 65 years] versus 1.099 [≥ 65 years], P < 0.0001). ConclusionsThis study represents the first nationwide population-based epidemiological study assessing the association between OMCN and dementia risk. Our results demonstrated a robust relationship between OMCN and the risk of developing dementia, particularly in the younger population.