Current Opinion in Endocrinology & Diabetes and Obesity最新文献

Purpose of review: Familial hypercholesterolemia (FH) in pregnancy poses several challenges, requiring a delicate balance between maternal atherosclerotic cardiovascular disease (ASCVD) risk and foetal safety. The review synthesizes current evidence, research gaps, evaluates emerging data on existing lipid-lowering strategies and highlights evolving guideline recommendations.

Recent findings: Pregnancy in women with FH has unique considerations for both the mother and the foetus. Data from registries and observational studies indicate that heterozygous FH (HeFH) does not significantly increase foetal adverse outcomes such as congenital malformation, prematurity, low birth weight although there may be a predisposition to early atherogenesis. Maternal risks include preeclampsia, endothelial dysfunction and prothrombotic tendency. Pregnant women with homozygous FH (HoFH) carry a substantially higher morbidity. Management strategies emphasize the need for timely, multidisciplinary care, dietary optimization, selective use of low-dose statins in high-risk HoFH and LDL apheresis for severe cases. Despite emerging evidence of lack of a major teratogenic risk, statins remain contraindicated in most guidelines, during pregnancy and lactation. Time off statins represent a critical gap in ASCVD prevention.

Summary: Pregnancy in FH requires a nuanced, stage-specific, individualized approach. Expansion of FH pregnancy registries and prospective studies is essential to guide evidence based care and refine recommendations for the future.

Purpose of review: Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in people with type 2 diabetes mellitus (T2DM). Endothelial dysfunction is a precursor of atherosclerosis. This is a silent process that occurs over years. Focus on primary prevention to identify and target endothelial dysfunction early can slow down the atherosclerotic process and prevent ASCVD.

Recent findings: Emerging blood-based methods include novel endothelial related biomarkers, such as endothelial specific extracellular vesicles, markers of endothelial regeneration and endothelial specific polygenic risk score. Physiology imaging-based method includes the flow-mediated dilation of the brachial artery, a noninvasive procedure that had gained attention for standardization in an international consensus guideline. Recognizing the role of endothelial function in ASCVD, studies are increasingly incorporating endothelial function biomarkers and FMD as surrogate markers of response. There is also emerging evidence on how nonpharmacological and pharmacological strategies improve endothelial function.

Summary: Blood and imaging-based assessment of endothelial function is a promising area that can enhance early preventive efforts. Future studies to assess the incremental value of endothelial function assessment in contemporary longitudinal cohorts across diverse populations is necessary to identify the high-risk asymptomatic individuals who will benefit from intensive primary prevention.

Purpose of review: To highlight the recent advancements in understanding the influence of psychological factors on the causation and management of obesity, which holds significance for clinical practice.

Recent findings: This review explores developments in understanding psychological risk factors, sequelae, and treatments for obesity. Despite good evidence for psychological therapies in weight management, there are no standardized protocols for assessing patients requiring metabolic and bariatric surgery. Psychological therapies are synergistic with obesity medications.

Summary: Obesity is a complex health issue with psychological dimensions. Stress, emotional dysregulation, and cognitive factors contribute to obesity. Stress's physiological impact on adipose tissue distribution and metabolic function, mediated by cortisol, demonstrates this interaction. Obesity leads to psychological consequences, including depression, low self-esteem, and reduced quality of life. The relationship between depression and obesity is modulated by demographic factors and biological mechanisms. Body composition reflects interactions between habits and cultural ideals, and medical models may increase stigma. Psychological interventions like cognitive-behavioral therapy and motivational interviewing effectively maintain weight loss. Psychological assessments before bariatric surgery are crucial for identifying mental health issues. This review highlights psychological dimensions in obesity prevention and treatment strategies.

Purpose of review: Diabetes mellitus affects one in nine adults worldwide, with timely diagnosis and accurate classification being essential for patient management. C-peptide is an important biomarker in the diagnostic workup. As diabetes sub-typing and treatment options continue to evolve, this review will highlight the important aspects of C-peptide analysis and interpretation and additionally, evaluate its current and emerging clinical role.

Recent findings: Several sample types and testing strategies such as fasting, random and stimulated C-peptide are available which are reviewed here. Random nonfasting C-peptide is convenient to perform in clinic and performs well compared to gold standard testing for classification of severe insulin deficiency and insulin dependence. C-peptide measurement may also be useful for classifying type 2 diabetes subtypes and in predicting response to treatment. Despite ongoing efforts towards standardization of C-peptide, variation still exists between analytical methods.

Summary: This review summarizes recent literature relating to preanalytical, analytical and clinical aspects of C-peptide testing. Future research in this area may build on the role of C-peptide in predicting glycaemic control, clinical complications and response to pharmacotherapy.

Purpose of review: Peroxisome proliferator-activated receptors (PPARs) are transcription factors that regulate metabolic homeostasis and play a key role in the management of a number of metabolic disorders (e.g. diabetes and liver steatosis). This review aims to provide an overview on the impact of the three isoforms, PPAR-α, PPAR-β/δ and PPAR-γ, on diabetic-driven metabolic diseases.

Recent findings: The lack of clinical benefit observed in the PROMINENT trial with pemafibrate (a selective PPAR-α agonist) has raised questions regarding the therapeutic potential of PPAR-α activation in the prevention of major cardiovascular events. Conversely, evidence suggests a possible therapeutic role in peripheral artery disease. To reduce the adverse effects occurring consequently to PPAR-γ activation, partial agonists or selective PPAR-γ modulators (SPPARγMs) have been developed. In the context of metabolic dysfunction associated steatohepatitis, pan-PPAR agonism appears necessary to achieve significant improvements in histological endpoints.

Summary: These diversified effects, albeit with a limited risk of significant side effects, make PPAR agonists an area of growing interest and with an expanding range of potential applications.

Purpose of review: This review aims to discuss the cardiometabolic-renal-glycaemic effects of adjunctive diabetes agents in the management of type 1 diabetes.

Recent findings: Recent studies have investigated the effectiveness and safety of adjunctive diabetes agents such as metformin, SGLT2 inhibitors and GLP-1 receptor agonists in individuals with type 1 diabetes. A rising trend of use of diabetes technology, notably continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII) devices, with improvement of glycaemic control, is observed. Questions arise whether these adjunctive diabetes agents and technologies confer cardiometabolic protective effects in patients with type 1 diabetes.

Summary: The most widely studied adjunctive diabetes agent for type 1 diabetes is metformin. Meta-analyses suggest that metformin modestly improves glucose control, weight, lipid profile, and carotid intima-media thickness in patients with type 1 diabetes and mild obesity. SGLT2 inhibitors have been shown to modestly improve glycaemic control, weight, and blood pressure but are associated with increased risk of diabetic ketoacidosis in individuals with type 1 diabetes. The use of GLP-1 RA in type 1 diabetes with mild obesity provided modest HbA1c and weight reduction, but gastrointestinal side effects were common. The results of the ongoing phase 3 clinical trial of finerenone study in type 1 diabetes on chronic kidney disease progression are awaited. Observational studies suggest that CSII and CGM may also reduce cardiovascular events and hospitalizations in patients with type 1 diabetes.

Purpose of review: Alongside its impact on cardio-metabolic parameters, obesity has been linked to infertility. This article aimed to provide a comprehensive review of the most current evidence linking male and female obesity and infertility.

Recent findings: The risk of infertility affects both sexes: in males, excess adiposity alters the optimal functioning of the hypothalamic-pituitary-gonadal axis, affects function of the testicles and causes disruptions in spermatogenesis and sperm maturation whereas in females, obesity upsets the normal hormonal milieu which negatively impacts ovarian and uterine function leading to anovulation, menstrual irregularities, difficulties in development of embryo and implantation and recurrent miscarriages, especially in women with polycystic ovarian syndrome (PCOS) where hyperinsulinemia, hyperandrogenemia and other metabolic disruptions are involved.

Summary: Numerous studies have established clear links between male and female obesity with infertility and to its pathophysiology and demographics. Evidence on treatment of obesity and impact on fertility outcomes is variable and needs further exploration.

Purpose of review: Diabetes foot ulcers (DFUs) affect millions globally, and are a global health challenge, contributing significantly to morbidity, mortality, and healthcare costs. This review article critically evaluates advances in artificial intelligence and new technologies and their potential to transform diabetes foot complications.

Recent findings: Artificial intelligence-based thermal and clinical image analysis offer the potential for early detection, remote diagnosis and monitoring and to mitigate disparities in specialist access. Incorporating novel pressure and temperature sensing, wearable technologies could enhance foot monitoring and enable personalized care and intervention. However, ethical challenges with artificial intelligence, including accountability, limited explainability, data security and equitable access will have to be addressed.

Summary: Artificial intelligence and wearable technologies could herald a paradigm shift in diabetes foot health and research. However, these exciting tools are not yet ready for adoption in clinical practice. Larger, well funded clinical intervention studies and greater collaboration between clinicians, artificial intelligence scientists and product engineers, working in partnership with people with diabetes, is needed if these approaches are to fulfil their potential.

Purpose of review: This review summarizes emerging evidence on the use of the dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide in improving obstructive sleep apnea (OSA) outcomes in individuals with obesity.

Recent findings: Tirzepatide has demonstrated significant reductions in apnea-hypopnea index (AHI) among patients with OSA and coexisting obesity. It has recently become the first medication approved by the U.S. Food and Drug Administration (FDA) specifically for moderate-to-severe OSA in adults with obesity. In addition to weight loss, tirzepatide has been associated with reduced cardiovascular, hepatic, and renal events, suggesting broader systemic benefits.

Summary: As a dual GIP/GLP-1 RA, tirzepatide represents a promising therapy for OSA in individuals with obesity, offering benefits of both weight reduction and symptom improvement. Given the high burden and underdiagnosis of OSA, particularly in populations with obesity, it should be considered earlier in the treatment algorithm, either in combination with or as an alternative to traditional therapies.

Purpose of review: To summarize recent advances in therapeutic strategies targeting angiopoietin-like protein 3 (ANGPTL3), a central regulator of triglyceride and remnant lipoprotein metabolism, and to discuss the potential of emerging pharmacologic approaches.

Recent findings: Several pharmacologic approaches have demonstrated robust lipid-lowering efficacy through ANGPTL3 inhibition. Monoclonal antibodies (evinacumab, SHR-1918) and RNA-based therapies (vupanorsen, zodasiran, solbinsiran) effectively reduce triglycerides, apoprotein B (apoB)-containing lipoproteins, and nonhigh-density lipoprotein cholesterol. The newest and most promising innovation is CRISPR-mediated disruption of ANGPTL3 (CTX310).

Summary: ANGPTL3 inhibition represents one of the most powerful current strategies for lowering triglyceride-rich lipoproteins and residual cardiovascular risk. While monoclonal antibodies and RNA-based drugs offer effective, repeat-dose therapies, in vivo CRISPR editing could enable a one-time, lifelong correction of hypertriglyceridemia and mixed dyslipidemia. The main challenge ahead lies in ensuring safety, scalability, and equitable access if long-term efficacy and tolerability are confirmed in phase 3 trials.