Current Opinion in Endocrinology & Diabetes and Obesity最新文献

Purpose of review: This review explores the potential of circulating miRNAs as diagnostic biomarkers for osteoporosis and bone associated disease, highlighting challenges in translating miRNA findings into clinical practice, including variability in circulating miRNA levels, the need for robust assay methods, and the importance of preanalytical and postanalytical variables.

Recent finding: Recent finding in miRNA research have identified miRNAs involved in bone cells differentiation, function, and in the regulation of osteoblasts, osteocytes, and osteoclasts. Novel miRNAs associated with osteoporosis, fracture risk, and bone turnover, as well as their utility in distinguishing between primary and secondary forms of osteoporosis have been recently identified. On the other hand, clinical implementation of miRNAs is still limited due to the lack of standardized analytical procedures.

Summary: miRNAs are noncoding RNA molecules that regulate gene expression, making them key players in complex biological processes, such as bone metabolism. The altered expression of several miRNAs may contribute to bone disorders, including osteoporosis. While significant progress has been made in identifying circulating miRNAs associated with bone disorders, the clinical implementation of miRNA-based diagnostics requires further research and standardization of methods before becoming part of clinical practice.

Purpose of review: Renal bone disease has significant detrimental effects on both cardiovascular and bone health. It is important to understand that the pathophysiologic mechanisms are different from traditional causes of bone disease; and thus, the monitoring and treatment of this disease process requires special attention. Although new guidelines are overdue, progress has been made in the treatment of hyperphosphatemia as well as investigational therapies for renal osteodystrophy.

Recent findings: At a time when the treatment of hyperphosphatemia in chronic kidney disease was once diet and phosphate binders, the novel agent tenapanor, an inhibitor of NHE3, has since been demonstrated to be effective in patients on dialysis as monotherapy or in conjunction with phosphate binders, potentially improving pill burden. Furthermore, the investigational treatment of osteoporosis in chronic kidney disease has expanded since bone mineral density testing has been adopted in practice in these populations.

Summary: New pathways for phosphate control are continually being investigated, changing practice patterns and quality of life for patients. Further research is needed in the safety and efficacy of antiresorptive and stimulatory bone agents to target the variety of mechanisms of osteoporosis; however, small studies appear promising and could change the way these patient populations are treated.

Purpose of review: Obesity significantly impacts fertility in women, contributing to hormonal imbalances, ovulatory dysfunction, and poor reproductive outcomes. This is especially pronounced in polycystic ovary syndrome (PCOS), where obesity and insulin resistance exacerbate fertility challenges. Moreover, obesity is a risk factor for type 2 diabetes (T2D) and gestational diabetes (GDM), further complicating reproductive health. Effective weight loss interventions before conception are essential to improve fertility and reduce the risks of adverse perinatal outcomes, such as GDM, hypertensive disorders, and neonatal complications.

Recent findings: Lifestyle modifications, including modest calorie restriction and exercise, improve ovulatory function and pregnancy rates but have limited impact on live-birth rates during fertility treatments. Very low-calorie diets (VLCDs) achieve rapid weight loss but raise concerns about maternal nutrition. Pharmacotherapy offers modest benefits for weight loss and fertility, though teratogenic risks persist. Bariatric surgery often results in significant weight loss and enhanced fertility, yet requires careful timing and management of potential nutrient deficiencies.

Summary: Weight-loss interventions show promise in addressing obesity-related fertility issues, but long-term outcomes and optimal strategies remain unclear. Further research is needed to bridge these gaps and improve reproductive outcomes following weight reduction.

Purpose of review: Circadian biology influences the gastrointestinal system as exemplified by hormonal patterns that modulate appetite. Indeed, people tend to get hungrier towards the later parts of the day. How misalignment of our circadian biology with behavioral factors (i.e. diet, exercise, sleep, etc.) influences obesity related disease has been an area of intense recent investigation.

Recent findings: The gastrointestinal hormones (e.g. ghrelin, glucagon-like polypeptide-1, glucose dependent insulinotrophic peptide, peptide tyrosine-tyrosine, and insulin) play unique roles across the 24-h cycle in fostering anticipatory responses that promote desires to eat while concurrently responding to environmental stimuli. A persons chronotype has emerged as a target area since it provides a metric of circadian biology interacting with environmental factors and affects all people. In fact, later chronotypes tend to be at higher risk for obesity, due to in part, alterations in gastrointestinal hormones (e.g. GIP, insulin) that align with behavioral observations of greater food intake and desires to eat fatty/sweet foods later in the day.

Summary: Changes in gastrointestinal hormones across the 24-h cycle impact obesity risk when misalignment of our circadian biology occurs with behavioral cycles. Better understanding how chronotype modulates appetite may enable personalized prescription of exercise, diet and/or medication to foster reduced chronic disease risk.

Purpose of review: The aim of this review is to examine recent advancements in RNA-targeted therapies for the management of severe hypertriglyceridemia (sHTG) and prevention of sHTG-associated acute pancreatitis.

Recent findings: Recent developments in RNA-targeted therapies, aimed at inhibiting apolipoprotein C-III (apoC-III), have demonstrated substantial and sustained reductions in triglyceride levels. Novel therapies, including antisense oligonucleotides (ASOs) and small interfering RNA (siRNA), such as volanesorsen, olezarsen, and plozasiran, have shown promising results in recent trials. These therapies not only effectively lower plasma triglyceride levels but also significantly reduce the incidence of acute pancreatitis.

Summary: SHTG is a high-burden metabolic disorder that is associated with a significantly increased incidence and severity of acute pancreatitis. Traditional lifestyle interventions and conventional therapies, including fibrates and n-3 fatty acids, often provide only modest reductions in triglycerides and fail to prevent sHTG-associated acute pancreatitis. The emergence of novel and targeted RNA-therapies represents a potential breakthrough in the management of sHTG and acute pancreatitis prevention.

Purpose of review: To provide an update of recent studies exploring the role of the gut microbiota and diet in the pathogenesis and treatment of irritable bowel syndrome (IBS).

Recent findings: The human gut microbiome has been recognized as an important, active source of signaling molecules that explain in part the disorder of the gut brain interaction (DGBI) in IBS. Subsequent changes in the metabolome such as the production of short-chain fatty acids (SCFA) and serotonin are associated with IBS symptoms. Dietary components are recognized as important triggers of IBS symptoms and a diet low in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) has been shown effective and safe, even when used long-term. Fecal microbiota transplantation (FMT) in IBS has not shown sustained and effective IBS symptom reduction in controlled clinical trials.

Summary: This update elucidates recent developments in IBS as it relates to clinical trial results targeting dietary and gut microbiota interventions. The gut microbiome is metabolically active and affects the bi-directional signaling of the gut-brain axis.

Purpose of review: Transgender individuals have a gender identity incongruent with their sex assigned at birth. Social, medical and surgical methods are often affirming. This review focuses on updates from the last 18 months mainly in testosterone use in masculinising gender-affirming hormone therapy (GAHT) in postpubertal adults, and also antiandrogens for suppression or blockade of endogenous testosterone in feminising GAHT. Mental and sexual healthcare are vital for many transgender patients, but are not the focus of this review.

Recent findings: There has been a considerable increase in publications regarding testosterone GAHT in recent years, though narrative reviews, opinion pieces and case series continue to dominate. There has also been a notable increase in prospective studies and valuable data particularly from large longitudinal cohorts and studies aiming to refine GAHT prescribing and better understand long-term effects on aspects such as fertility, cardiometabolic and bone health as well as adverse effects.

Summary: Testosterone GAHT is life changing. Increased research will help GAHT optimisation, and improve understanding of tissue-specific impacts and long-term safety. Longer-term data, prospective studies and utilisation of novel research tools and approaches are needed to enrich our understanding and prescribing of testosterone and its blockers in GAHT.