Expert Review of Endocrinology & Metabolism最新文献

Introduction: Obesity and metabolic-associated fatty liver disease (MAFLD) during pregnancy constitute significant problems for routine antenatal care, with increasing prevalence globally. Similar to obesity, MAFLD is associated with a higher risk for maternal complications (e.g. pre-eclampsia and gestational diabetes) and long-term adverse health outcomes for the offspring. However, MAFLD during pregnancy is often under-recognized, with limited management/treatment options.

Areas covered: PubMed/MEDLINE, EMBASE, and Scopus were searched based on a search strategy for obesity and/or MAFLD in pregnancy to identify relevant papers up to 2024. This review summarizes the pertinent evidence on the relationship between maternal obesity and MAFLD during pregnancy. Key mechanisms implicated in the underlying pathophysiology linking obesity and MAFLD during pregnancy (e.g. insulin resistance and dysregulated adipokine secretion) are highlighted. Moreover, a diagnostic approach for MAFLD diagnosis during pregnancy and its complications are presented. Finally, promising relevant areas for future research are covered.

Expert opinion: Research progress regarding maternal obesity, MAFLD, and their impact on maternal and fetal/offspring health is expected to improve the relevant diagnostic methods and lead to novel treatments. Thus, routine practice could apply more personalized management strategies, incorporating individualized algorithms with genetic and/or multi-biomarker profiling to guide prevention, early diagnosis, and treatment.

Introduction: Familial chylomicronemia syndrome (FCS) is a rare autosomal recessive condition. Effective treatment is important as patients are at risk for severe and potentially fatal acute pancreatitis. We review recent developments in pharmacologic treatment for FCS, namely biological inhibitors of apolipoprotein (apo) C-III and angiopoietin-like protein 3 (ANGPTL3).

Areas covered: FCS follows a biallelic inheritance pattern in which an individual inherits two pathogenic loss-of-function alleles of one of the five causal genes - LPL (in 60-80% of patients), GPIHBP1, APOA5, APOC2, and LMF1 - leading to the absence of lipolytic activity. Patients present from childhood with severely elevated triglyceride (TG) levels >10 mmol/L. Most patients with severe hypertriglyceridemia do not have FCS. A strict low-fat diet is the current first-line treatment, and existing lipid-lowering therapies are minimally effective in FCS. Apo C-III inhibitors are emerging TG-lowering therapies shown to be efficacious and safe in clinical trials. ANGPTL3 inhibitors, another class of emerging TG-lowering therapies, have been found to require at least partial lipoprotein lipase activity to lower plasma TG in clinical trials. ANGPTL3 inhibitors reduce plasma TG in patients with multifactorial chylomicronemia but not in patients with FCS who completely lack lipoprotein lipase activity.

Expert opinion: Apo C-III inhibitors currently in development are promising treatments for FCS.

Background: The severity of diabetic ketoacidosis (DKA) at diagnosis increased during the global COVID-19 pandemic. This study aimed to analyze the impact of the pandemic on the clinical and biological severity of DKA in patients with new-onset diabetes mellitus (DM) in Tunisia.

Research design and methods: The study included patients hospitalized for new-onset DKA 2 years prior and 2 years during the COVID-19 pandemic. Data was collected retrospectively, and DKA severity was classified based on biological parameters like potential of hydrogen (pH) and HCO3-.

Results: The results showed that DKA was more severe during COVID-19, as evidenced by lower potential of hydrogen (pH) (p = 0.006), and serum bicarbonate (HCO3-) levels (p = 0,005). Despite the higher severity of DKA was higher during COVID-19, intensive care unit hospitalizations remained equivalent (p = 0.359). The prevalence of hyponatremia was also higher during COVID-19 (p = 0.024).

Conclusion: The findings suggest that delayed diagnosis and COVID-19 May contribute to the increased severity of DKA and electrolyte imbalance during the pandemic. Further research is needed to better understand the underlying mechanisms and develop appropriate strategies to address this issue.

Background: The effects of pomegranate juice (PJ) and its components on uterine smooth muscle are unknown. Hence, this study unequivocally demonstrates that pomegranate juice (PJ) significantly impacts myometrial function, providing crucial insights into its relaxant properties and their potential therapeutic applications for uterine-related disorders.

Research design and methods: Rat uterine smooth muscle horn strips were suspended in Krebs solution organ baths. Contractions were measured isometrically using a transducer (AD instrument Australia). The effects of PJ were evaluated on contractile activity elicited by potassium chloride (KCl 60 Mm) depolarization. Inhibitors of nitric oxide (L-NAME 3 X 10^-4), guanylate cyclase (methylene blue 1 X 10^-5), and Prostaglandin I₂ (indomethacin 3 X 10^-5), as well as Potassium Channels blockers, were determined.

Results: The juice at concentrations from 1.5-5 mg/ml significantly decreased the rat uterine horn contraction induced by KCl. The NO, cGMP, and PGI₂ inhibitors did not block the relaxation response. Furthermore, the PGI₂ inhibitor significantly enhanced the relaxation effects; K⁺ channel blockers had no inhibitory effects on the relaxation responses. Contrarily, GLIB improved considerably relaxation.

Conclusion: Research suggests pomegranate juice's active ingredient may reduce uterine contractions and treat uterotonic disorders, potentially preventing preterm birth and dysmenorrhea. Further research is needed to determine its mechanism of action.

Trial registration: Code: AEC-013.

Introduction: Neuroendocrine neoplasms (NENs) represent a complex group of tumors arising from neuroendocrine cells, characterized by heterogeneous behavior and challenging diagnostics. Despite advancements in medical technology, NENs present a major challenge in early detection, often leading to delayed diagnosis and variable outcomes. This review aims to provide an in-depth analysis of current diagnostic methods as well as the evolving and future directions of diagnostic strategies for NENs.

Area covered: The review extensively covers the evolution of diagnostic tools for NENs, from traditional imaging and biochemical tests to advanced genomic profiling and next-generation sequencing. The emerging role of technologies such as artificial intelligence, machine learning, and liquid biopsies could improve diagnostic precision, as could the integration of imaging modalities such as positron emission tomography (PET)/magnetic resonance imaging (MRI) hybrids and innovative radiotracers.

Expert opinion: Despite progress, there is still a significant gap in the early diagnosis of NENs. Bridging this diagnostic gap and integrating advanced technologies and precision medicine are crucial to improving patient outcomes. However, challenges such as low clinical awareness, limited possibility of noninvasive diagnostic tools and funding limitations for rare diseases like NENs are acknowledged.

Introduction: Obesity is a growing public health concern affecting both children and adults. Since it involves both genetic and environmental components, the management of obesity requires both, an understanding of the underlying genetics and changes in lifestyle. The knowledge of obesity genetics will enable the possibility of precision medicine in anti-obesity medications.

Areas covered: Here, we explore health complications and the prevalence of obesity. We discuss disruptions in energy balance as a symptom of obesity, examining evolutionary theories, its multi-factorial origins, and heritability. Additionally, we discuss monogenic and polygenic obesity, the converging biological pathways, potential pharmacogenomics applications, and existing anti-obesity medications - specifically focussing on the leptin-melanocortin and incretin pathways. Comparisons between childhood and adult obesity genetics are made, along with insights into structural variants, epigenetic changes, and environmental influences on epigenetic signatures.

Expert opinion: With recent advancements in anti-obesity drugs, genetic studies pinpoint new targets and allow for repurposing existing drugs. This creates opportunities for genotype-informed treatment options. Also, lifestyle interventions can help in the prevention and treatment of obesity by altering the epigenetic signatures. The comparison of genetic architecture in adults and children revealed a significant overlap. However, more robust studies with diverse ethnic representation is required in childhood obesity.

Background: To assess 20-year time trends in the prevalence of diabetes mellitus (DM) among inpatients with heart failure (HF) and the influence of coexisting DM and kidney disease (KD) on outcomes.

Research design and methods: A retrospective study of patients was admitted due to HF, during the period 2000/2019. The period of follow-up was divided into three intervals according to the European Medical Agency approval of newer hypoglycemic drugs. We analyzed in-hospital mortality and outcomes during the follow-up period.

Results: A total of 4959 patients were included. Over time, prevalence of DM was significantly raising among women with HF (50 to 53.2%) and descending among men (50% to 46.8%, p = 0.02). Total mortality and readmissions were higher in patients with DM during the and second periods. However, no significant differences were found in the third-one (HR 1.14, 95% CI 0.94-1.39, p = 0.181). A protector role of oral hypoglycemic medications was observed in this last period. According to the presence of KD, the patients with both DM and KD were who presented most of the events.

Conclusions: Over the time analyzed, the prevalence of DM raised among women and decreased among men. DM influenced the prognosis of HF except in the third period when more protective hypoglycemic drugs started to be used.

Background: Determining the relationship between cardiovascular risks, carbohydrate metabolism disorders, and renal dysfunction can help in creating new tools for their management and for better interaction of specialists in a multidisciplinary team. The purpose of this study was to determine the functional state of the kidneys and carbohydrate metabolism in patients with acute coronary syndrome without a history of such disorders.

Methods: 200 patients of the cardiology department of the City Clinical Hospital No. 7 in Almaty were examined using laboratory diagnostics and subsequent statistical data processing.

Results: Acute coronary syndrome develops in 63% of cases against the background of previous disorders of carbohydrate metabolism - prediabetes (45.5%) and type 2 diabetes mellitus (17.5%). In this group of patients, in the presence of disorders of carbohydrate metabolism, in all cases, it is accompanied by acute renal damage. It was noted that diabetes mellitus in newly diagnosed patients actually had a certain duration and occurred much earlier than cardiovascular complications - this was evidenced by an increased level of glycated hemoglobin.

Conclusions: Such results indicate the need for early diagnosis of cardio-reno-metabolic syndrome in patients with cardiovascular complications, as well as timely administration of drugs that simultaneously have antidiabetic, cardio- and nephroprotective effects.