Current Opinion in Endocrinology & Diabetes and Obesity最新文献

Purpose of review: Type 2 diabetes (T2D) is increasing to epidemic proportions and frequently associated with obesity and a low serum testosterone concentration in men. This review valuates recent randomized controlled trials (RCTs) investigating the effect of testosterone treatment on glycemic control and T2D prevention.

Recent findings: The 2-year Testosterone for the Prevention of Type 2 diabetes Trial (T4DM) study showed that in men aged 50 years and over with visceral obesity and impaired glucose tolerance, testosterone treatment on the background of a lifestyle intervention reduced T2D risk by 40%. The Testosterone Effects on Atherosclerosis Progression in Aging Men and Testosterone Trials demonstrated modest improvements in insulin sensitivity and body composition. However, the Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men trial found no significant glycemic benefits over 2 years. Recent data from the Diabetes Prevention Program Outcome Study support the cost efficacy and durability of metformin.

Summary: In men at high risk of T2D, treatment with testosterone prevents the disease; however, there are caveats to its use and other approaches may be more applicable. Differences in trial designs, age groups, and outcome measures contribute to varying results. HbA1C is a suboptimal outcome measure. Future research should explore potential synergies between testosterone and GLP-1 receptor agonists in T2D management, while considering cost-effectiveness.

Purpose of review: Due to technical requirements and high cost, equilibrium dialysis-free testosterone (T) measurements are not commonly available in clinical practice. Clinicians rely on calculated free T (cFT) as a proxy. This review discusses using free T as a second-line assessment, highlighting its relevance in preventing misdiagnosis and overtreatment of male hypogonadism.

Recent findings: While there is consensus on measuring total T - comprising sex hormone-binding globulin (SHBG)-bound, albumin-bound, and free T - as a first step in diagnosing male hypogonadism, evidence confirms that aging and conditions like obesity influence both total T and SHBG levels. Furthermore, low free T has been associated with symptoms of androgen deficiency, even in men with normal total T. Clinicians should, however, be aware of limitations of free T calculations, particularly the lack of standardization. Recent developments include establishing age-stratified free T reference ranges measured by equilibrium dialysis.

Summary: Free T remains a subject of longstanding controversy. Factors such as age and obesity can alter total T and SHBG levels. Free T serves as a second-line indicator of androgen exposure, taking SHBG fluctuations into account. Given that commonly used free T calculators only provide approximations of free T, there is a need to further standardize free T calculators.

Purpose of review: Physical activity (PA) is acknowledged as an important component of lifestyle therapy in the management of polycystic ovary syndrome (PCOS). The purpose of this current systematic review is to analyze recent literature assessing the role of PA and exercise interventions as potential treatment for PCOS.

Recent findings: The recent literature published since 2022 has focused on understanding the specific benefits of different PA modalities on PCOS pathophysiology, suggesting that high intensity exercise may relay greater metabolic improvements, although results are still inconclusive; expanding our understanding of the impact PA has on a wider range of outcomes, including sleep, quality of life, inflammation, and DNA methylation; and recognizing barriers and limitations of implementing efficacious PA interventions for individuals with PCOS.

Summary: Current literature supports a role for PA in improving PCOS-related cardiometabolic and reproductive outcomes; however, there is still a significant evidence gap of high-quality studies assessing optimal exercise regimens as well as strategies for implementing PA interventions in real-world settings for individuals with PCOS.

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: Evolving understanding of thyroid eye disease (TED) has led to rapidly advancing therapeutic options. Most new treatments under development or recently available to patients are predicated on insights into disease mechanism.

Recent findings: TED, a disfiguring process, involves inflammation and remodeling of the connective tissues around the eye. TED most frequently presents as a component of Graves' disease. Advances in our understanding of cells involved in TED and their molecular interactions have led to novel therapeutic targets. Among these cell types are orbital fibroblasts and a subset comprising monocyte progenitor cells, known as CD34 + CXCR4 + fibrocytes. Among the attributes of fibrocytes is their expression of several autoantigens associated with Graves' disease, including TSHR, thyroglobulin and thyroperoxidase. Fibrocytes also express high levels of the insulin-like growth factor-I (IGF-I) receptor, thought to mediate fibroblast activation. Therapeutically targeting the TSHR/IGF-IR receptor complex using an IGF-I receptor antagonist, teprotumumab, has resulted in substantial clinical benefit for patients with TED. The neural axon repellent, Slit2, and its cognate receptor, ROBO1, appear to modulate the inflammatory phenotype of these orbit-infiltrating fibrocytes.

Summary: More detailed understanding of orbital fibroblasts and the distinctions between cell subsets comprising them should lead to more effective therapies with fewer side effects.

Purpose of review: To analyze the evolving epidemiologic trends in thyroid disease, focusing on risk factors, underlying drivers of these changes, and their implications on clinical practice and research priorities.

Recent findings: Thyroid disease remains one of the most prevalent groups of disorders globally, and the shift in its frequency and distribution is multifactorial. The prevalence of hypothyroidism increases with age, although normal thyrotropin ranges appear to be age-dependent, raising concern for potentially inappropriate levothyroxine use. Hyperthyroidism and Graves' disease continue to be predominant in reproductive-age women but exhibit a milder phenotype at diagnosis. Thyroid nodules are increasingly found in asymptomatic patients, likely from more widespread use of neck and chest imaging. Thyroid cancer incidence has risen exponentially over the years, mostly driven by overdiagnosis of low-risk tumors; however, a small rise in incidence of higher risk tumors has been noted. Obesity appears to be a risk factor for thyroid cancer occurrence and more aggressive forms of the disease.

Summary: Understanding epidemiologic trends in thyroid disease is crucial for guiding clinical practice and research efforts, aiming to optimize patient outcomes while preventing unnecessary and potentially harmful interventions.

Purpose of review: Familial Hypercholesterolemia is associated with an increased risk of cardiovascular disease. The current international guidelines of the main scientific societies consider that all people with familial hypercholesterolemia have a high or very high cardiovascular risk. However, the occurrence of atherosclerotic cardiovascular disease is very heterogeneous in this population. Stratifying risk within people with familial hypercholesterolemia is essential to identify individuals who require intensive cholesterol-lowering therapies.

Recent findings: In the last year, several studies have been published focusing on the contribution of diabetes to familial hypercholesterolemia, the role of stroke, as a manifestation of atherosclerotic disease, and the external validation of the SAFEHEART risk equation in the English population diagnosed with Familial Hypercholesterolemia.

Summary: It is necessary the development of a tool that allows us to identify, in a simple, reproducible, and universal way, patients who may have a high risk of suffering a cardiovascular event and who are susceptible to more intensive treatments to reduce cholesterol levels.