Current Opinion in Endocrinology & Diabetes and Obesity最新文献

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.

Purpose of review: Familial hypercholesterolemia (FH) is an autosomal semi-dominant condition, characterized by excessive circulating low-density lipoprotein cholesterol (LDL-C) from birth that substantially accelerates the onset and progression of atherosclerotic cardiovascular disease (ASCVD), classically coronary artery disease (CAD). Elevated plasma LDL-C integrated over time is unequivocally the major determinant of ASCVD in heterozygous FH (HeFH); however, the wide variation in incidence and progression of ASCVD suggests a role for a wide spectrum of risk modifiers. We reviewed recent evidence describing the features of an ASCVD-free entity referred to as resilient FH among patients with HeFH.

Recent findings: Compared with nonresilient FH patients, resilient patients are more likely to be female, and have a lower prevalence of ASCVD comorbidities, higher levels of HDL-C and larger HDL particles, as well as a lower level of lipoprotein(a). A lower SAFEHEART risk score is also an independent predictor of resilient FH. Gene expression studies also demonstrate that resilient FH patients are associated with a less atherogenic gene expression profile in relation to HDL metabolism and immune responses, as reflected by higher expression of ABCA1 and ABCG1, and lower expression of STAT2 and STAT3, respectively.

Summary: A group of HeFH patients, referred as resilient FH, can survive to advance ages without experiencing any ASCVD events. Several key contributors to the event-fee CAD in HeFH patients have been identified. This could not only improve risk stratification and management for FH but also be of major importance for the general population in primary and secondary prevention. However, resilient FH remains an under-investigated area and requires further research.

Purpose of review: Patients with familial hypercholesterolemia have an elevated risk of premature atherosclerotic cardiovascular disease. Risks can be minimized through pharmacological and 'lifestyle' behavioral (low fat diet, physical activity) therapies, although therapeutic adherence is sub-optimal. Behavioral interventions to promote familial hypercholesterolemia therapy adherence should be informed by theory-based psychological determinants for maximal efficacy. The current review summarizes research on determinants of familial hypercholesterolemia therapy adherence and behavior change interventions, identifies limitations of the extant research, and sets future research agenda.

Recent findings: A recent meta-analysis identified attitudes, subjective norms, self-efficacy, and risk perceptions as key determinants of familial hypercholesterolemia therapy adherence intentions, with intentions identified as a key correlate of concurrent behavior. Studies have specified techniques targeting key theory-based determinants that may be efficacious in interventions. Research is limited by overuse of cross-sectional correlational study designs, use of self-report behavioral measures, few theory-based intervention tests, and limited consideration of nonconscious processes and effects of socio-structural variables.

Summary: Researchers should adopt study designs permitting better directional and causal inferences in determinant effects, provide tests of interventions targeting determinants and their mechanisms of action, consider determinants representing nonconscious processes (habits, implicit attitudes), and test determinants as mediators of socio-structural variables on familial hypercholesterolemia therapy adherence.

Purpose of review: The aim of this review is to provide an overview of severe hypertriglyceridemia presenting in the form of chylomicronemia that persists despite treatment of secondary causes and the use of conventional lipid-lowering treatment.

Recent findings: Persistent chylomicronemia is a rare syndromic disorder that affects carriers of bi-allelic combinations of pathogenic gene variants impairing lipoprotein lipase (LPL) activity, as well as a significant number of individuals who do not meet this genetic criterion. It is associated with a high risk of acute pancreatitis and other morbidities. Effective innovative treatments for severe hypertriglyceridemia are being developed and are becoming available. Patients with persistent chylomicronemia of any cause respond equally to next-generation therapies with LPL-independent mechanisms of action and do not generally respond to conventional LPL-dependent treatments.

Summary: Not all individuals with persistent chylomicronemia carry a proven pathogenic combination of gene variants that impair LPL activity. Documenting the clinical characteristics of people with persistent chylomicronemia and their response to emerging therapies is essential to correctly establish their risk trajectory and ensure equitable access to personalized treatment.