Current Opinion in Endocrinology & Diabetes and Obesity最新文献

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.

Purpose of review: Early health economic evaluations of new medications are useful, as they consider the implications for health services.We reviewed recent literature on expected clinical outcomes of lowering of elevated plasma lipoprotein(a) [Lp(a)] in secondary prevention, which is essential information on effectiveness for economic evaluations.We reviewed a recent early economic evaluation of RNA therapies targeted at Lp(a).

Recent findings: RNA-based therapies, if approved, would likely be used initially in adults with established atherosclerotic cardiovascular disease (ASCVD) and very high Lp(a). Adults with ASCVD have high absolute risk of recurrent events and elevated Lp(a) serves as a risk-enhancing factor.Potent lowering of Lp(a) in secondary prevention may be associated with significant relative risk reductions of coronary heart disease or ASCVD events; this needs confirmation in currently ongoing and future clinical trials.One economic evaluation has estimated the value of olpasiran and pelacarsen, at various willingness-to-pay thresholds, compared with standard-of-care secondary prevention.

Summary: Early economic evaluations estimate longer-term clinical benefits and cost consequences associated with new medications.Existing casual evidence of Lp(a) and cardiovascular disease can be used in early economic evaluations as best available evidence, while awaiting results from major cardiovascular outcomes trials.

Purpose of review: The aim of this review was to discuss cardiometabolic risk factors that affect women.

Recent findings: Recent calls to action to address cardiometabolic risk factors specific to women relate to increasing evidence of sex-specific differences in patient-related, drug-related, and socio-demographic factors leading to sub-optimal care of women.

Summary: Certain aspects of common modifiable cardiovascular risk factors (e.g. smoking, hypertension, dyslipidaemia and diabetes) affect female individuals more adversely. Additionally, there are risk factors or enhancers that particularly affect cardiometabolic health in women [e.g. premature menopause, polycystic ovarian syndrome (PCOS), familial partial lipodystrophy, socio-cultural factors]. Understanding these risk factors may provide insight on how to improve cardiometabolic outcomes in women.

Purpose of review: The causal role of high-density lipoprotein (HDL) in atherosclerotic cardiovascular disease (CVD) remains debated. Considering recent evidence, the purpose of this review is to a provide a focused update and new perspectives on HDL and CVD.

Recent findings: A Mendelian randomization study demonstrated an increased risk of CVD when HDL-cholesterol was predominantly transported in larger HDL particles and a decreased risk of CVD when HDL-cholesterol was predominantly transported in smaller HDL particles. Moreover, another Mendelian randomization study demonstrated that concentration and content of medium HDL particles is associated with CVD. A Mendelian randomization study that utilized stratified analyses demonstrated that individuals with HDL-cholesterol 50 mg/dl or less were at increased risk of CVD. Lastly, the AEGIS-II trial demonstrated that CSL112, a human apolipoprotein A-I that increases cholesterol efflux, did not significantly reduce cardiovascular events in patients at very high risk. Exploratory analyses showed that patients treated with CSL112 had numerically lower rates of cardiovascular events.

Summary: Qualitative markers of HDL may be causally related to CVD. There is a need for ongoing research into HDL therapeutics that promote the biological properties of HDL. The optimal cohort or disease state that will benefit from these therapies needs to be identified.