Current Opinion in Endocrinology & Diabetes and Obesity最新文献

Purpose of review: Given the global rise of MASLD, which impacts approximately one-third of the population, there is a need for earlier diagnosis and effective treatment strategies to avoid long-term hepatic cardiovascular and renal complications. This review summarizes the recent advances in noninvasive diagnosis and new pharmacological agents approved for MASLD.

Recent findings: The main step forward in diagnostics is a step away from invasive biopsy and emphasis on noninvasive methods including serum biomarkers (e.g. CK-18 and FGF21), imaging (e.g. MRI-PDFF and US-FLI), combination of the two and use of artificial intelligence and machine learning models, for early detection and risk stratification of MASLD and MASH. Multiomics approaches, such as metabolomics and lipidomics, reveal disease-specific signatures, and may help with phenotypic classification of MASLD. Personalized management for MASLD include gut microbiota modulation and point-of-care devices for rapid diagnosis. Novel therapies include THR β agonists, GLP-1/dual GLP-1/GIP agonists, FXR agonists and FGF analogues, which show promise in reducing hepatic fat and fibrosis.

Summary: These findings enable earlier MASLD diagnosis and tailored interventions, improving clinical outcomes in primary care and resource-limited settings. Future research should focus on validating cost-effective tools, and developing combination therapies to address the multifaceted nature of MASLD.

Purpose of review: Obesity is a global health concern and is intricately linked to cardiovascular disease and metabolic disorders. While its causal association with chronic kidney disease (CKD) has also been recognized, this entity has not been discussed extensively. Obesity-related glomerulopathy (ORG) is pathologically a secondary form of focal segmental glomerulosclerosis (FSGS), which typically presents clinically with subnephrotic proteinuria, and histopathologically as glomerulomegaly, and the perihilar variant of FSGS.

Recent findings: This review discusses the latest update on pathophysiology, risk factors, clinical features, diagnosis, prevention, staging, and management of ORG. Special emphasis is placed on diagnostic criteria distinguishing ORG from other FSGS variants and CKD aetiologies.

Summary: While obesity can impact renal health, renal status influences choice of antiobesity medication as well. Early recognition and intervention are critical to preventing progression to end-stage kidney disease.

Purpose of review: Early gestational diabetes mellitus (eGDM) is being increasingly detected on the background of rising obesity rates and widespread early pregnancy screening. However, diagnostic criteria and management strategies remain uncertain. This review summarizes current evidence on diagnostic thresholds, maternal and fetal outcomes, and the impact of early treatment, with an emphasis on balancing benefits and risks.

Recent findings: While observational studies link eGDM to adverse maternal and fetal outcomes, evidence from intervention studies remains limited. The Treatment of Booking Gestational Diabetes Mellitus (TOBOGM) is the only large multicenter randomized controlled trial (RCT) published till date. The early intervention arm in the study received education on dietary counseling and capillary blood glucose monitoring, with pharmacotherapy using insulin or metformin introduced when indicated. The trial reported that treatment before 14 weeks reduced neonatal respiratory distress in higher glycemic bands but increased the risk of small-for-gestational-age state at lower glycemic bands. Notably, one-third of the untreated control group reverted to normoglycemia at 24-28 weeks. Given the uncertainties in diagnostic thresholds used in TOBOGM, a composite risk score-based approach integrating clinical and biochemical parameters may provide an alternative for identifying pregnancies in need of intervention.

Summary: Current diagnostic criteria may not identify eGDM pregnancies that would benefit from intervention. Redefining diagnostic thresholds and integrating them with clinical risk factors could categorize pregnancies in need of intervention. Appropriately designed RCTs are required to generate evidence for accurate identification and optimal treatment of eGDM.

Purpose of review: Premenopausal osteoporosis, characterized by low bone mass and fractures, is rare but poses long-term skeletal risks. Unlike postmenopausal osteoporosis, it often stems from inadequate peak bone mass accrual or secondary causes such as systemic diseases, medications, or lifestyle factors. This review explores contemporary approaches to defining, diagnosing, and treating low bone mass and osteoporosis in premenopausal women.

Recent findings: Prevalence varies according to ethnicity and is further influenced by the diagnostic criteria, with higher risks in Caucasian and Asian women. Key determinants of peak bone mass achieved by the late 20 s include genetics (60-80% of variability), nutrition (calcium, vitamin D, and protein), lifestyle (exercise, smoking, and alcohol), and occupational exposures (e.g., heavy metals and sedentary work). Pregnancy and lactation-associated osteoporosis also cause transient bone loss, particularly in high-risk individuals. Bone mineral density by dual-energy X-ray absorptiometry is the gold standard for diagnosis despite of certain limitations. Additionally, emerging technologies like radiofrequency echographic multi spectrometry show promise. Management focuses on optimizing bone health through adequate nutrition, weight-bearing exercises, and addressing secondary causes, when present like rheumatoid arthritis, long-term glucocorticoid use, hypogonadism, etc. Pharmacological options such as bisphosphonates and teriparatide can be considered in high-risk cases, but evidence on their safety and efficacy in premenopausal women is limited, and concerns about teratogenicity remain.

Summary: Early identification and intervention are critical to reduce fracture risk, emphasizing the need for better diagnostic tools and individualized treatment strategies.

Purpose of review: Obesity during pregnancy is a growing global health concern with implications for maternal, fetal, and intergenerational outcomes. This review highlights pathophysiological mechanisms, clinical risks, and evidence-based management strategies across the preconception, antenatal, and postpartum periods.

Recent findings: Maternal obesity amplifies pregnancy-associated insulin resistance, disrupts adipokine balance, and promotes inflammation, placental hormone dysregulation, and aberrant mTOR signaling. These mechanisms increase risks of gestational diabetes, hypertensive disorders, cesarean delivery, and macrosomia. Epigenetic modifications contribute to fetal metabolic programming, raising offspring risk of obesity, type 2 diabetes, and cardiovascular disease. Recent advances emphasize early risk stratification using continuous glucose monitoring, lipid and inflammatory biomarkers, and integration of telehealth-based lifestyle interventions. Precision medicine and microbiome-targeted therapies represent emerging frontiers.

Summary: Management of obesity in pregnancy requires a continuum of care. Preconception optimization through lifestyle interventions and, in select cases, bariatric surgery improves outcomes. Antenatal care demands individualized metabolic monitoring, adherence to gestational weight gain targets, and pharmacologic interventions such as metformin when indicated. Postpartum priorities include structured weight management, diabetes prevention, and lactation support. Multidisciplinary, culturally tailored strategies are essential to mitigate the global burden of maternal obesity and its intergenerational consequences.

Purpose of review: Obesity is present in up to 85% of individuals with type 2 diabetes mellitus (T2DM) and poses a major therapeutic challenge. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), initially developed for T2DM, are now widely used for obesity management and increasingly recognized for their impact on body composition beyond weight reduction. This review summarizes evidence on the effects of GLP-1RAs, particularly semaglutide and liraglutide, on fat mass, lean body mass (LBM), visceral adipose tissue (VAT), and resting energy expenditure (REE).

Recent findings: Clinical trials and meta-analyses show GLP-1RAs achieve marked fat mass loss, preferentially reducing VAT, with modest proportional declines in LBM. Despite reductions in absolute LBM, relative preservation or improvement is observed, and REE is largely maintained, with some reports of increases during prolonged therapy. In both diabetic and nondiabetic populations, GLP-1RAs improve metabolic health without accelerating sarcopenia. Rodent data support protective muscle effects through anti-inflammatory and myogenic mechanisms. Withdrawal, however, predictably results in weight regain, primarily as fat mass, highlighting the importance of continued therapy or supportive lifestyle strategies.

Summary: GLP-1RAs confer favourable body composition outcomes, with clinical implications for obesity, sarcopenic obesity, and broader metabolic disease management.

Purpose of review: The aim of radioactive iodine (RAI) in differentiated thyroid cancer (DTC) is ablation of thyroid remnant and/or treatment of residual disease. This review compares guidelines recommending the use of RAI (or not) in DTC, with a focus on randomized trials in low-risk DTC. Molecular genotyping offers therapeutic options in advanced RAI-refractory DTC.

Recent findings: The ESTIMABL2 and IoN trials suggest that thyroidectomy (with or without central compartment lymph node dissection) followed by surveillance is sufficient in low-risk DTC, despite key differences in inclusion criteria, recurrence-definition, and monitoring protocols. RAI practice is tailored in many aspects: selection of intermediate-risk DTC for RAI and activity based on individual factors, including early dynamic risk assessment; lesional dosimetry in advanced DTC; restrictions following RAI; and choice of systemic therapy in the RAI-refractory setting.

Summary: RAI in DTC is evolving towards a risk-adapted model. Escalating evidence indicates that RAI may be safely withheld in a large proportion of low-risk DTC. Optimal management of intermediate-risk DTC remains controversial, due to heterogeneity in clinical and pathological characteristics and conflicting data over survival advantage. Well designed studies incorporating molecular genotype may be key in identifying those most likely to benefit from RAI and in elucidating mechanisms of RAI-resistance.

Purpose of review: Familial chylomicronemia (FCS) and multifactorial or persistent chylomicronemia syndromes (MCS, pCS) are rare, severe disorders characterized by extreme hypertriglyceridemia and a high risk of recurrent, potentially life-threatening acute pancreatitis. Most patients do not achieve adequate triglyceride control with lifestyle interventions or conventional lipid-lowering therapies, leaving them exposed to persistent complications. This review critically examines emerging therapeutic strategies aimed at improving triglyceride control and reducing acute pancreatitis risk.

Recent findings: Advances targeting key molecular regulators of triglyceride metabolism have shown substantial promise. APOC3 inhibitors, including volanesorsen, olezarsen, and plozasiran, achieve up to 80% reductions in triglycerides and markedly lower AP incidence, with favorable safety profiles. ANGPTL3 inhibition via evinacumab may benefit patients with residual lipoprotein lipase activity, including polygenic or mixed chylomicronemia, and could be used during acute sHTG episodes. Lomitapide, acting independently of LPL, is effective in selected FCS patients but requires careful hepatic monitoring. FGF21 analogs, such as pegozafermin, are in early development and show potential for metabolic dysfunction-associated steatotic liver disease, though their impact on acute pancreatitis prevention remains to be established.

Summary: These emerging mechanism-based therapies are reshaping the management of severe hypertriglyceridemia, offering targeted approaches to reduce triglycerides and acute pancreatitis risk. Ongoing studies will clarify long-term safety, durability of response, and optimal patient selection, providing a framework for improved clinical outcomes.

Purpose of review: Endogenous Cushing's syndrome is one of the most difficult diagnoses in endocrinology. It is mainly based on biochemical tests that assess qualitative and quantitative alterations in cortisol production. Whether performed on blood, saliva, urine, or hair, the biochemical tests currently available have limited diagnostic specificity and sensitivity. Their performance varies depending on the individual characteristics of the patient, the stage of the disease, and the laboratory techniques used to determine cortisol levels. Knowledge of these factors will help physicians choose the most appropriate diagnostic test for each individual.

Recent findings: Relevant studies and meta-analyses have clarified the actual performance of various biochemical tests in a real-world setting. In addition, the diagnostic arsenal for Cushing's syndrome has been expanded with new tools, such as hair cortisol and cortisone assays, new methods for measuring cortisol in urine or saliva, and new approaches such as steroid metabolomics or multiomics techniques.

Summary: This review is a critical reappraisal of the merits and drawbacks of the various "old" and new biochemical tools. Its purpose is to provide the physician with practical advice on the use of biochemical tests at various stages of Cushing's syndrome in order to improve diagnostic accuracy.

Purpose of review: This review examines the critical role of the high-density lipoprotein (HDL)/scavenger receptor class B type 1 (SCARB1) pathway in adrenal glucocorticoid production during stress, emphasizing recent mechanistic evidence and its clinical implications.

Recent findings: SCARB1 mediates the selective uptake of HDL-derived cholesteryl esters by adrenocortical cells, providing the cholesterol substrate needed for rapid glucocorticoid synthesis under stress. Experimental models show that loss of SCARB1 function abolishes stress-induced glucocorticoid production even when low-density lipoprotein (LDL) is abundant, confirming that LDL cannot substitute for HDL/SCARB1-mediated cholesterol delivery. ACTH rapidly upregulates SCARB1 expression and function, driving microvillar channel formation and enhancing cholesterol flux to mitochondria. Disruption of this pathway impairs the physiologic stress response and increases vulnerability to inflammatory complications. Human genetic data and clinical observations reinforce these findings and highlight the impact of hypoalphalipoproteinemia and SCARB1 defects on adrenal reserve.

Summary: The HDL/SCARB1 axis is essential for acute glucocorticoid synthesis and integrates lipid metabolism with endocrine and immune resilience. This shifts the focus from HDL-C from a passive biomarker to HDL to an active endocrine cofactor. Preserving HDL functionality and SCARB1 integrity should guide the design of HDL-targeted interventions, especially in patients at risk for sepsis, systemic inflammation, or adrenal insufficiency.