Current Opinion in Endocrinology & Diabetes and Obesity最新文献

Purpose of review: To summarize recent studies analyzing reclassification of estimated risk of myocardial infarction (MI) and ischemic heart disease (IHD) by inclusion of remnant cholesterol (= cholesterol content in triglyceride-rich lipoproteins) in primary and secondary prevention settings.

Recent findings: For individuals in a primary prevention setting with remnant cholesterol levels at least 95th percentile (≥1.6 mmol/l, 61 mg/dl), 23% of MI and 21% of IHD events developed later were reclassified correctly from below to above 5% for 10-year occurrence when remnant cholesterol levels were added to models based on conventional risk factors, whereas no events were reclassified incorrectly. Overall improved reclassification of MI was also observed for remnant cholesterol levels as low as at least 50th percentile (≥0.6 mmol/l, 25 mg/dl); however, the addition of remnant cholesterol over the entire concentration range yielded insignificant improvements of NRI for MI but slightly improved reclassification of NRI for IHD. In a secondary prevention setting, addition of remnant cholesterol over the entire concentration range to a conventional risk model improved reclassification.

Summary: Elevated remnant cholesterol levels considerably improves reclassification of individuals who later develop MI and IHD, in primary as well as in secondary prevention settings.

Purpose of review: Fatty liver disease is increasingly common worldwide and is associated with an increased risk of cardiovascular disease (CVD).

Recent findings: This review describes the cardiovascular outcomes, clinical assessment and management as well as the impact of emerging drug treatment on CVD risk.

Summary: Patients with fatty liver require CVD risk assessment including consideration of statin therapy. Emerging therapeutic drugs for fatty liver may have both adverse and beneficial effects on CVD risk.

Purpose of review: Interest in the use of calorie restriction with low-carbohydrate diets for patients with type 1 diabetes appears to be increasing despite physicians' discomfort about its longer term outcomes. A divergence in opinion regarding the balance of benefits and safety may lead to patient disengagement from conventional medical supervision. This review describes the current evidence regarding the benefits and risks of these diets and suggests a way forward to addressing this potential misalignment between the aims of patients and their physicians.

Recent findings: Benefits on glycaemia are observed in many studies, with improved HbA1c, time within target range and reduced glycaemic variability. A characteristic lipid profile with high LDL cholesterol is observed in many patients, but association with future cardiovascular events is undefined. A negative impact on growth has been identified in the paediatric population, and impact on mental health and disordered eating is of theoretical concern, without measurement in clinical studies.

Summary: Patients will continue to trial and, with immediate glycaemic benefits, potentially remain on lower carbohydrate diets irrespective of concern by treating physicians about potential longer term risks. A supportive multidisciplinary approach with greater nutritional supervision and more research is required, to allow these patients to achieve their desired glycaemic outcomes without compromising longer term safety.

Purpose of review: Populations with greater fatty fish intake have lower risk of coronary heart disease. However, trials testing omega-3 fatty acids (FA) on cardiovascular outcomes have yielded inconsistent results. In this review, we summarize the major cardiovascular trials examining omega-3 FA supplementation, and compare differences with eicosapentaenoic acid (EPA) alone vs. docosahexaenoic acid (DHA) combined with EPA.

Recent findings: The JELIS and REDUCE-IT trials both demonstrated significant reduction in cardiovascular events with high dose EPA in the form of icosapent ethyl (IPE), with a similar trend seen in the RESPECT-EPA trial. In contrast, the ASCEND, VITAL, STRENGTH, and OMEMI trials examining EPA+DPA combinations failed to demonstrate benefit. Beyond the difference in omega-3 FA formulations (IPE vs. omega-3 carboxylic acid), other differences between REDUCE-IT and STRENGTH include the achieved EPA levels, differing properties that EPA and DHA have on membrane stabilization, and the comparator oils tested in the trials.

Summary: The totality of evidence suggests EPA alone, administered in a highly-purified, high-dose form, improves cardiovascular outcomes among patients with elevated triglycerides at high cardiovascular risk, but EPA and DHA together does not. Current guidelines endorse the use of IPE in statin-treated patients at high cardiovascular risk who have triglycerides >135 mg/dl.

Purpose of review: Examine Setmelanotide use in patients with rare genetic variants that disrupt the melanocortin pathway.

Recent findings: Between February 2017 and September 2018, 10 participants with pro-opiomelanocortin (POMC)/ proprotein convertase subtilisin/kexin type 1 (PCSK1) deficiency and 11 participants with leptin receptor (LEPR) deficiency were enrolled in open-label, phase 3 trials at 10 centers in the United States and internationally to assess the efficacy and safety of the melanocortin-4 receptor (MC4R) agonist Setmelanotide. 80% of POMC participants and 45% of LEPR participants achieved at least 10% weight loss at 1 year. Significant changes in hunger scores were seen for both cohorts as well. Setmelanotide was well tolerated with injection site reactions and hyperpigmentation being the most common adverse events reported. As a result, Setmelanotide was approved by the U.S. FDA in 2020 for chronic weight management in adult and pediatric patients ≥6 years of age with POMC, LEPR, or PCSK1 deficiency. In 2022, its approval was extended to include patients with Bardet-Biedel syndrome (BBS) after phase 3 trial data showed that, on average, Setmelanotide treatment resulted in a BMI loss of 7.9% for the 44 BBS participants.

Summary: Rare genetic variants such as POMC, LEPR, and PCSK1 deficiency disrupt MC4R pathway signaling, resulting in severe early-onset obesity, hyperphagia, and increased risk for metabolic co-morbidities. Patients with BBS also demonstrate severe early-onset obesity and hyperphagia, due in part to defective MC4R signaling. Setmelanotide has shown promising benefits in improving satiety scores and weight-related outcomes in patients with these early-life genetic obesity conditions, although longer-term studies are needed.

Purpose of review: Elevated Lp(a) level is an important causal risk factor for atherosclerotic cardiovascular disease (ASCVD), principally coronary artery disease. Selective testing for Lp(a) is highly recommended in patients at intermediate and high risk for ASCVD. Lp(a) levels are predominantly genetically determined, and this has implications for cascade testing.

Recent findings: Recent studies show that cascade testing is effective in identifying elevated Lp(a) in close relatives of probands with high Lp(a). Apart from selective testing and cascade testing as detection strategies, some recent guidelines recommend testing of Lp(a) in all adults at least once in their lifetime and various implementation strategies have been suggested.

Summary: Hyper-Lp(a) is an important global health problem that can be easily detected. Hyper-Lp(a) meets all the criteria for universal screening except that there is not yet supportive evidence from clinical interventional trials showing a reduction of ASCVD events. The cost-effectiveness of the various detection and implementation strategies need to be further evaluated.

Purpose of review: In this review, we will summarize some of the landmark clinical trials of triglyceride-lowering therapies and review updates in clinical guidelines with regards to treatment of elevated triglyceride levels.

Recent findings: Accumulating evidence from epidemiologic and Mendelian randomization studies has shown that triglyceride and are causally linked to atherosclerotic cardiovascular disease (ASCVD) and contribute to atherosclerosis. However, most clinical trials evaluating use of triglyceride-lowering therapies, including fibrates, niacin and fish oils [combined eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)] have not been able to demonstrate significant cardiovascular risk reduction. REDUCE-IT is the only randomized clinical trial that showed significant cardiovascular benefit with the use of icosapent ethyl esters (a purified EPA), in patients with ASCVD or diabetes with elevated risk on maximally tolerate statin.

Summary: Current guidelines and expert consensus documents from multiple societies strongly endorse therapeutic lifestyle interventions to effectively lower TG as the first-line therapy for treatment of hypertriglyceridemia. Evaluation and treatment of secondary causes of hypertriglyceridemia including optimal glycaemic control is crucial. Statins lower ASCVD risk in patients with elevated triglycerides and are first-line for treatment of elevated triglyceride. In a patient with residual mild to moderate hypertriglyceridemia on maximally tolerate statin and elevated cardiovascular risk icosapent, ethyl ester may be used for further ASCVD risk reduction.

Purpose of review: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of mortality in adults with type 1 diabetes (T1D). Although dyslipidaemia is a modifiable and prevalent risk factor in individuals with T1D, determining when to initiate lipid-lowering therapy for primary prevention of ASCVD can be challenging. In this article, recommendations for lipid-lowering therapy from updated clinical guidelines over the last 5 years, additional risk-stratification methods, hypertriglyceridaemia management and potential barriers to optimal care in adults with T1D are discussed.

Recent findings: Low-density lipoprotein cholesterol (LDL-C) is the primary target for lipid-lowering. However, international guidelines recommend differing approaches to ASCVD risk-stratification, lipid-lowering, and LDL-C goals in individuals with diabetes, predominantly reflecting evidence from studies in type 2 diabetes. Despite guideline recommendations, several studies have demonstrated that statins are underused, and LDL-C goals are not attained by many individuals with T1D. Additional risk-stratification methods including T1D-specific ASCVD risk calculators, coronary artery calcium scoring, and lipoprotein(a) may provide additional information to define when to initiate lipid-lowering therapy.

Summary: Clinical trial evidence for lipid-lowering therapies in T1D is lacking, and further studies are needed to inform best practice. Optimization and harmonization of ASCVD risk-stratification and lipid management in individuals with T1D is required.

Purpose of review: The aim of this study was to assess the potential value of the measurement of plasma xenosterols (or phytosterols) concentrations in clinical practice.

Recent findings: Recent genetic studies suggest that individuals with elevated plasma phytosterol concentrations due to monogenic and polygenic variants are at an increased risk of coronary artery disease. This supports early observations that elevated plasma phytosterol concentrations are per se atherogenic.

Summary: Measurement of plasma phytosterols can identify individuals with xenosterolemia (or phytosterolemia). This may be clinically useful in four ways: Establishing a diagnosis and informing management of patients with homozygous phytosterolemia; Providing a comprehensive differential diagnosis for familial hypercholesterolemia; Providing an index of cholesterol absorption that may inform personalized pharmacotherapy; and Informing more precise assessment of risk of cardiovascular disease.