UNASSIGNED: Progression of alcohol-associated liver disease (ALD) is driven by genetic predisposition. The rs13702 variant in the lipoprotein lipase (LPL) gene is linked to non-alcoholic fatty liver disease. We aimed at clarifying its role in ALD.
UNASSIGNED: Patients with alcohol-associated cirrhosis, with (n = 385) and without hepatocellular carcinoma (HCC) (n = 656), with HCC attributable to viral hepatitis C (n = 280), controls with alcohol abuse without liver damage (n = 366), and healthy controls (n = 277) were genotyped regarding the LPL rs13702 polymorphism. Furthermore, the UK Biobank cohort was analysed. LPL expression was investigated in human liver specimens and in liver cell lines.
UNASSIGNED: Frequency of the LPL rs13702 CC genotype was lower in ALD with HCC in comparison to ALD without HCC both in the initial (3.9% vs. 9.3%) and the validation cohort (4.7% vs. 9.5%; p <0.05 each) and compared with patients with viral HCC (11.4%), alcohol misuse without cirrhosis (8.7%), or healthy controls (9.0%). This protective effect (odds ratio [OR] = 0.5) was confirmed in multivariate analysis including age (OR = 1.1/year), male sex (OR = 3.0), diabetes (OR = 1.8), and carriage of the PNPLA3 I148M risk variant (OR = 2.0). In the UK Biobank cohort, the LPL rs13702 C allele was replicated as a risk factor for HCC. Liver expression of LPL mRNA was dependent on LPL rs13702 genotype and significantly higher in patients with ALD cirrhosis compared with controls and alcohol-associated HCC. Although hepatocyte cell lines showed negligible LPL protein expression, hepatic stellate cells and liver sinusoidal endothelial cells expressed LPL.
UNASSIGNED: LPL is upregulated in the liver of patients with alcohol-associated cirrhosis. The LPL rs13702 high producer variant confers protection against HCC in ALD, which might help to stratify people for HCC risk.
UNASSIGNED: Hepatocellular carcinoma is a severe complication of liver cirrhosis influenced by genetic predisposition. We found that a genetic variant in the gene encoding lipoprotein lipase reduces the risk for hepatocellular carcinoma in alcohol-associated cirrhosis. This genetic variation may directly affect the liver, because, unlike in healthy adult liver, lipoprotein lipase is produced from liver cells in alcohol-associated cirrhosis.

UNASSIGNED: Cardiovascular diseases (CVD) are leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). Increased soluble sP-selectin and 715Thr > Pro polymorphism were studied in CVD and T2DM, but association between them hasn\'t been explored in Saudi Arabia. We aimed to assess sP-selectin levels in T2DM and T2DM-associated CVD patients in comparison to healthy control cohort. Also, we sought to investigate relationship between Thr715Pro polymorphism and sP-selectin levels and disease state.
UNASSIGNED: This is a cross-sectional case-control study. sP-selectin level (measured by Enzyme-linked immunosorbent assay) and prevalence of Thr715Pro polymorphism (assessed by Sanger sequencing) were investigated in 136 Saudi participants. The study comprised 3 groups: group1 included 41 T2DM patients; group 2 (48 T2DM patients with CVD), and group 3 (47 healthy controls).
UNASSIGNED: sP-selectin levels were significantly higher in diabetics and diabetics + CVD groups as compared to the corresponding control. In addition, results showed that the prevalence of 715Thr > Pro polymorphism is 11.75 % in the study population amongst the three study groups (9.55 % Thr/Pro, and 2.2 % Pro/Pro). No statistical difference was found between sP-selectin levels in subject carrying the wildtype genotype of this polymorphism and these who carry the mutant gene. There could be an association between this polymorphism and T2DM, whilst the polymorphism may protect diabetic patients from having CVD. However, odds ratio is not statistically significant in both cases.
UNASSIGNED: Our study supports the previous researches\' results that Thr715Pro is neither influencing the sP-selectin level nor the risk of CVD in T2DM patients.

UNASSIGNED: Adverse muscle composition (MC) (i.e., low muscle volume and high muscle fat) has previously been linked to poor functional performance and comorbidities in non-alcoholic fatty liver disease (NAFLD). In this study we aimed to investigate associations of all-cause mortality with liver fat, NAFLD, and MC in the UK Biobank imaging study.
UNASSIGNED: Magnetic resonance images of 40,174 participants were analyzed for liver proton density fat fraction (PDFF), thigh fat-free muscle volume (FFMV) z-score, and muscle fat infiltration (MFI) using the AMRA® Researcher. Participants with NAFLD were sex-, age-, and BMI-matched to participants without NAFLD with low alcohol consumption. Adverse MC was identified using previously published cut-offs. All-cause mortality was investigated using Cox regression. Models within NAFLD were crude and subsequently adjusted for sex, age, BMI (M1), hand grip strength, physical activity, smoking, alcohol (M2), and previous cancer, coronary heart disease, type 2 diabetes (M3).
UNASSIGNED: A total of 5,069 participants had NAFLD. During a mean (±SD) follow-up of 3.9 (±1.4) years, 150 out of the 10,138 participants (53% men, age 64.4 [±7.6] years, BMI 29.7 [±4.4] kg/m2) died. In the matched dataset, neither NAFLD nor liver PDFF were associated with all-cause mortality, while all MC variables achieved significance. Within NAFLD, adverse MC, MFI and FFMV z-score were significantly associated with all-cause mortality and remained so in M1 and M2 (crude hazard ratios [HRs] 2.84, 95% CI 1.70-4.75, p <0.001; 1.15, 95% CI 1.07-1.24, p <0.001; 0.70, 95% CI 0.55-0.88, p <0.001). In M3, the relationship was attenuated for adverse MC and FFMV z-score (adjusted HRs 1.72, 95% CI 1.00-2.98, p = 0.051; 0.77, 95% CI 0.58-1.02, p = 0.069) but remained significant for MFI (adjusted HR 1.13, 95% CI 1.01-1.26, p = 0.026).
UNASSIGNED: Neither NAFLD nor liver PDFF was predictive of all-cause mortality. Adverse MC was a strong predictor of all-cause mortality in individuals with NAFLD.
UNASSIGNED: Individuals with fatty liver disease and poor muscle health more often suffer from poor functional performance and comorbidities. This study shows that they are also at a higher risk of dying. The study results indicate that measuring muscle health (the patient\'s muscle volume and how much fat they have in their muscles) could help in the early detection of high-risk patients and enable targeted preventative care.

Elevated concentration of lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease, including coronary artery disease, stroke, peripheral artery disease, and so on. Emerging data suggest that Lp(a) contributes to the increased risk for cardiovascular events even in the setting of effective reduction of plasma low-density lipoprotein cholesterol. Nevertheless, puzzling issues exist covering potential genetic factors, Lp(a) assay, possible individuals for analysis, a cutoff point of increased risk, and clinical interventions. In the Chinese population, Lp(a) exhibited a distinctive prevalence and regulated various cardiovascular diseases in specific ways. Hence, it is valuable to clarify the role of Lp(a) in cardiovascular diseases and explore prevention and control measures for the increase in Lp(a) prevalence in the Chinese population. This Beijing Heart Society experts\' scientific statement will present the detailed knowledge concerning Lp(a)-related studies combined with Chinese population observations to provide the key points of reference.

Remarkable transformations in science and healthcare have resulted in declines in mortality from cardiovascular disease over the past several decades, largely driven by progress in prevention and treatment of persons at risk. However, these trends are now beginning to stall, as our county faces increases in cardiovascular risk factors including overweight and obesity, type 2 diabetes mellitus, and metabolic syndrome. Furthermore, poor long-term adherence to a healthy lifestyle and lifesaving pharmacotherapy have exacerbated these trends, with recent data suggesting unprecedented increases in cardiovascular morbidity and mortality. A paradigm shift is needed to improve the cardiovascular health of our nation. Preventive cardiology, a growing subspecialty of cardiovascular medicine, is the practice of primordial, primary, and secondary prevention of all cardiovascular diseases. Preventive cardiologists and preventive cardiology specialists are well equipped with the knowledge and skill-set necessary to reduce deaths related to the growing burden of heart disease and its risk factors. Despite dedicated efforts, cardiovascular disease remains the leading killer of men and women in the United States. Although there is little debate regarding the importance of prevention, many healthcare professionals question the need for preventive cardiology as a distinct subspecialty. Additionally, the field\'s growth has been hampered by a lack of organization and standardization, and variability of training within programs across the country. The purpose of this document is to delineate the key attributes that define the field of preventive cardiology according to the American Society for Preventive Cardiology.

Glycolipid metabolism disorder are major threats to human health and life. Genetic, environmental, psychological, cellular, and molecular factors contribute to their pathogenesis. Several studies demonstrated that neuroendocrine axis dysfunction, insulin resistance, oxidative stress, chronic inflammatory response, and gut microbiota dysbiosis are core pathological links associated with it. However, the underlying molecular mechanisms and therapeutic targets of glycolipid metabolism disorder remain to be elucidated. Progress in high-throughput technologies has helped clarify the pathophysiology of glycolipid metabolism disorder. In the present review, we explored the ways and means by which genomics, transcriptomics, proteomics, metabolomics, and gut microbiomics could help identify novel candidate biomarkers for the clinical management of glycolipid metabolism disorder. We also discuss the limitations and recommended future research directions of multi-omics studies on these diseases.

Chronic kidney disease (CKD) is one of the most frequent complications associated with type 2 diabetes mellitus (T2DM) and is also an independent risk factor for cardiovascular disease. The mineralocorticoid receptor (MR) is a nuclear receptor expressed in many tissue types, including kidney and heart. Aberrant and long-term activation of MR by aldosterone in patients with T2DM triggers detrimental effects (eg, inflammation and fibrosis) in these tissues. The suppression of aldosterone at the early stage of T2DM has been a therapeutic strategy for patients with T2DM-associated CKD. Although patients have been treated with renin-angiotensin system (RAS) blockers for decades, RAS blockers alone are not sufficient to prevent CKD progression. Steroidal MR antagonists (MRAs) have been used in combination with RAS blockers; however, undesired adverse effects have restricted their usage, prompting the development of nonsteroidal MRAs with better target specificity and safety profiles. Recently conducted studies, Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) and Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD), have reported that finerenone, a nonsteroidal MRA, improves both renal and cardiovascular outcomes compared with placebo. In this article, we review the history of MRA development and discuss the possibility of its combination with other treatment options, such as sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and potassium binders for patients with T2DM-associated CKD.

UNASSIGNED: Prediabetes is a precursor to type 2 diabetes mellitus and routine screening of prediabetes is crucial. Visceral fat (VF) is associated with prediabetes and insulin resistance. Ethnic and racial differences resulting in different levels of VF in the Indian population necessitates an India-specific study. There is a dearth of literature on the cut-off values of VF measured using a bioelectrical impedance analyzer (BIA) to predict prediabetes in the Indian population. Hence, the main objective of this study was to determine the sex-specific cut-off value of VF on BIA to predict prediabetes in the Indian population.
UNASSIGNED: Three hundred individuals aged 18-55 years of both sexes were selected for this cross-sectional study. VF was evaluated as a part of body composition analysis using BIA. The body composition variables for the prediction of prediabetes were examined using backward logistic regression. Optimal cut-off levels of VF to predict prediabetes were identified using receiver operator characteristic curve (ROC) analysis.
UNASSIGNED: VF, total fat, and age were found to be associated with prediabetes (p ≤ 0.05). In females, the cut-off value of VF for predicting prediabetes was identified as 8 with 77.8% sensitivity and 69.3% specificity; in males, it was 11 with 84% sensitivity and 62.9% specificity.
UNASSIGNED: This study contributes to the sex-specific cut-off values of VF level on BIA that can be used for predicting prediabetes in the Indian population.
UNASSIGNED: \"مقدمات السكري\" هي طليعة لمرض السكري من النوع 2، والفحص الروتيني لمقدمات السكري أمر بالغ الأهمية. ترتبط الدهون الحشوية بمقدمات السكري ومقاومة الأنسولين. استدعت الاختلافات العرقية التي أدت إلى مستويات مختلفة من الدهون الحشوية في السكان الهنود دراسة خاصة بالهند. هناك ندرة في الأدبيات حول القيم الفاصلة للدهون الحشوية للتنبؤ بمقدمات السكري في السكان الهنود. ومن ثم، كان الهدف الرئيس من الدراسة الحالية هو معرفة القيمة الفاصلة لدى الجنسين للدهون الحشوية للتنبؤ بمقدمات السكري في السكان الهنود.
UNASSIGNED: تم اختيار 300 فرد تتراوح أعمارهم بين 18 إلى 55 سنة من كلا الجنسين لهذه الدراسة المقطعية. تم تقييم الدهون الحشوية كجزء من تحليل تكوين الجسم باستخدام محلل المعاوقة الكهربائية الحيوية. تم فحص متغيرات تكوين الجسم للتنبؤ بمقدمات السكري باستخدام الانحدار اللوجستي العكسي. تم تحديد مستويات القيم الفاصلة للدهون الحشوية للتنبؤ بمقدمات السكري باستخدام تحليل \"منحنى خصائص فعل المستقبلات\".
UNASSIGNED: وجد أن الدهون الحشوية، والدهون الكلية، والعمر مرتبطة إحصائيا بمقدمات السكري. كما تم تحديد القيمة الفاصلة للدهون الحشوية للتنبؤ بمقدمات السكري عند الإناث على أنها 8 مع حساسية 77.8٪ وخصوصية 69.3٪. بينما في الذكور، تم تحديد 11 مع حساسية 84٪ وخصوصية 62.9٪.
UNASSIGNED: ساهمت هذه الدراسة في تحديد القيم الفاصلة بين الجنسين لمستوى الدهون الحشوية، والتي يمكن استخدامها للتنبؤ بمقدمات السكري في السكان الهنود.

UNASSIGNED: The prevalence of diabetic ketoacidosis (DKA) in gestational diabetes mellitus (GDM) is very low. We describe a patient with GDM in whom severe DKA with intrauterine fetal demise developed in the setting of nonadherence to therapy.
UNASSIGNED: A 33-year-old woman, G2P0010, with no preexisting diabetes mellitus (DM) presented at 30 weeks of gestation with acute-onset altered sensorium, nausea, and emesis. GDM was diagnosed at 15 weeks of gestation with a serum glucose level of 266 mg/dL (70-134 mg/dL) after 1-hour 50-gram glucose challenge test. Glycated hemoglobin (HbA1C) was 5.9% (41 mmol/mol) at the time of GMD diagnosis. Insulin was initiated at week 20 of gestation. On presentation, serum glucose level of 920 mg/dL (70-110 mg/dL), pH of 7.02 (7.32-7.43), anion gap level of 38 mmol (5-17 mmol), bicarbonate level of 5.0 mEq/L (22-29 mEq/L), and large serum ketones were found. Ultrasound showed intrauterine fetal demise. She received intravenous fluids and continuous insulin. Following the spontaneous delivery of a nonviable fetus, DKA was resolved. Negative antiglutamic acid decarboxylase, islet cell, and zinc transporter 8 antibodies, C-peptide level of 2.4 ng/dL (1.1-4.4 ng/dL), and HbA1C level of 9% (75 mmol/mol) were found. Inpatient management included basal-bolus and sliding scale insulin therapies. Metformin was added upon discharge 7 days after admission. The HbA1C levels were 5.3% (34 mmol/mol) and 5% (31 mmol/mol) at the 3- and 6-month follow-ups, respectively. Insulin was discontinued. Currently, the patient is on metformin and glucagon-like peptide 1 receptor agonist.
UNASSIGNED: The development of insulin resistance during pregnancy is driven by multiple factors. Approximately 1% to 2% of pregnant women with impaired glucose tolerance develop DKA; most cases occur in women with type 1 DM. The approximate incidence of DKA in GDM is 0.02%.
UNASSIGNED: DKA complicating GDM is extremely infrequent, but it cannot be dismissed. Early recognition along with prompt and appropriate medical and obstetrical management is critical.

UNASSIGNED: To assess clinical and immunological benefits of passive immunization using convalescent plasma therapy (CPT) we performed sub-group analyses on a completed randomised control trial (RCT) on CPT in severe COVID-19.
UNASSIGNED: A series of subclass analyses were performed on the previously published outcome data and accompanying clinical metadata from a completed RCT (Clinical Trial Registry of India, No. CTRI/2020/05/025209).
UNASSIGNED: The subclass analyses were performed on the outcome data and accompanying clinical metadata from a completed randomized control trial. Data on the plasma abundance of a large panel of cytokines from the same cohort of patients were also utilised to characterize the heterogeneity of the putative anti-inflammatory function of convalescent plasma (CP) in addition to passively providing neutralizing antibodies.
UNASSIGNED: While across all age-groups primary clinical outcomes were not significantly different in the RCT, significant immediate mitigation of hypoxia, reduction in hospital stay as well as significant survival benefit were registered in younger (<67 years in our cohort) severe COVID-19 patients with ARDS on receiving CPT. In addition to neutralizing antibody content of convalescent plasma, its anti-inflammatory proteome on attenuation of systemic cytokine deluge, significantly contributed to the clinical benefits of CPT.
UNASSIGNED: The sub-group analyses revealed that clinical benefit of CPT in severe COVID-19 is linked to the anti-inflammatory protein content of CP, apart from the anti-SARS-CoV-2 neutralizing antibody content.