Therapeutic Advances in Endocrinology and Metabolism最新文献

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that was previously considered a lifelong disease and requires long-term reliance on hypoglycemic medications. However, recent studies have shown that certain patients may achieve remission through various intervention strategies, which may alter the ultimate therapeutic targets for clinicians. This review aims to summarize and update the latest clinical evidence and research advancements regarding remission strategies for T2DM, primarily including intensive lifestyle interventions, metabolic surgery, short-term intensive insulin therapy, and non-insulin hypoglycemic drugs (e.g., glucagon-like peptide-1 receptor agonists and dorzagliatin) treatments, to guide the selection of appropriate treatment modalities for diverse patient populations. Additionally, the durability of sustained diabetes remission is briefly discussed.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become essential medications in the management of type 2 diabetes mellitus and obesity due to their ability to improve glucose control and facilitate weight loss by enhancing insulin secretion, reducing glucagon release, and slowing gastric emptying. These mechanisms make GLP-1RAs highly effective for metabolic disorders, benefiting patients who require both glycemic control and weight reduction. However, despite their clinical efficacy, GLP-1RAs have been associated with an increased risk of gallbladder disease, including gallstone formation known as cholelithiasis and inflammation of the gallbladder called cholecystitis, especially with prolonged use and higher doses. This review explores the potential mechanisms by which GLP-1RAs may contribute to biliary disease, focusing on the roles of cholecystokinin suppression, bile acid receptor signaling, and alterations in gut-brain pathways. In addition, we present a novel algorithm designed to outline strategies to address the risks of biliary disease in patients treated with GLP-1RAs.

SHORT syndrome is a rare genetic multisystemic disorder caused by a loss-of-function mutation in the phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) gene. The disease's acronym represents its key features: short stature, hyperextensibility, ocular depression, Rieger anomaly, and teeth delay. Insulin resistance, hyperglycemia, and diabetes mellitus are common endocrinological manifestations of this condition. Currently, there are no established guidelines for the treatment of diabetes in SHORT syndrome patients. In this report, we describe a young adult male patient of Chinese descent with atypical diabetes mellitus associated with SHORT syndrome. This case was challenging due to the patient's young-onset diabetes and poor diabetes control, complicated by insulin resistance from lipodystrophy, and a strong aversion to insulin injections. By utilizing a combination of oral anti-glycemic agents with complementary mechanisms of action (metformin, sodium-glucose co-transporter 2 (SGLT-2) inhibitors, sulfonylureas, thiazolidinediones, and GLP-1 agonists), insulin therapy was delayed. The patient's blood glucose levels improved significantly, with HbA1c decreased from 14% to 8.8% within 6 months of starting the multi-agent regimen, and further improved to 7.4% with a fasting plasma glucose of 4.8 mmol/L. With an oral medication regimen that the patient found acceptable, both his quality of life and adherence to treatment improved. These findings provide useful insights into tailoring an individualized diabetes treatment plan.

Background: Metabolic disorders significantly contribute to global morbidity and mortality. However, data on these trends in the Arab region remain limited despite rising obesity rates and declining metabolic health.

Objectives: This study aims to investigate the trends and burdens of metabolic diseases, including diabetes mellitus, cardiovascular disease (CVD), chronic kidney disease (CKD), metabolic dysfunction-associated fatty liver disease (MAFLD), and ischemic stroke and related risk factors in the Arab region.

Design: A retrospective analysis of metabolic diseases based on the Global Burden of Disease 2021 database.

Methods: We analyzed age-standardized rates of disease prevalence, incidence, mortality, and disability-adjusted life years (DALYs) from 1990 to 2021, using data from the Global Burden of Disease Study 2021.

Results: In 2021, the Arab region faced a substantial burden: 34.6 million with diabetes, 30.8 million with CVD, 32 million with CKD, 109.4 million with MAFLD, and 3 million with stroke. Mortality and DALYs for these diseases often exceeded global averages.

Conclusion: The Arab region faces a significant public health challenge due to increasing metabolic disease burdens and inconsistent mortality reduction. A comprehensive approach addressing lifestyle factors and improving healthcare access is crucial to improving health outcomes and managing this growing burden.

Background: Studies have suggested that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may modulate asthma-related immune pathways, but evidence directly linking the use of GLP-1 RAs to asthma onset remains limited.

Objectives: We aimed to evaluate whether the use of GLP-1 RAs in patients with type 2 diabetes mellitus (T2DM) is associated with a reduced risk and severity of asthma development.

Design: This retrospective cohort study was designed to evaluate asthma onset and severity in patients with T2DM treated with GLP-1 RAs, using data from the National Health Insurance Database (2011-2015).

Methods: Asthma onset and severity were evaluated in 1345 patients with T2DM treated with GLP-1 RAs from a cohort of 1,936,512 individuals, excluding those with pre-existing asthma. Asthma risk was assessed across four severity levels.

Results: The study demonstrated a mean follow-up duration of 2.92 ± 1.82 years. Notably, treatment with GLP-1 RAs significantly reduced asthma risk compared with the non-GLP-1 RA group, as indicated by an adjusted hazard ratio (HR) of 0.67 (95% confidence interval (CI), 0.45-0.76), suggesting a consistent class effect. A protective trend was observed across various severity levels of asthma. The HRs for the GLP-1 RA group compared with the non-GLP-1 RA group for cases with no acute exacerbations (No-AE), acute exacerbations (AE), and status asthmaticus (Status) were 0.55 (95% CI, 0.37-0.62), 0.59 (95% CI, 0.39-0.66), and 0.83 (95% CI, 0.56-0.93), respectively. However, in cases requiring endotracheal intubation, the HR was 0.96 (95% CI, 0.65-1.09).

Conclusion: Our study highlights a consistent effect of GLP-1 RAs in reducing asthma risk and severity, except in cases requiring endotracheal intubation, suggesting that GLP-1 RAs may contribute to reducing asthma incidence and severity in patients with T2DM.

Metformin is the most widely used antihyperglycemic agent for the treatment of a wide range of diseases. Activation of AMP-activated protein kinase (AMPK) is the best-known mechanism by which metformin exerts most of its beneficial effects. In recent years, research and applications of metformin in bone metabolism have made significant progress. The molecular mechanisms of its action are being elucidated with an increasingly complex understanding, raising the question of whether metformin acts directly or indirectly on bone. This review examines the indirect role of metformin in improving the bone marrow microenvironment by regulating autophagy, oxidative stress, inflammation, and skeletal aging. Furthermore, we focus on the direct mechanisms of metformin on osteoblasts, osteocytes, bone marrow adipocytes, and osteoclasts. In summary, metformin has been shown to affect bone in multiple ways and to exert osteoprotective effects. In light of the positive benefits of metformin in preventing osteoporosis, future treatment plans for patients with osteoporosis, particularly those with diabetes who are at high risk for fractures, may consider prioritizing the use of metformin as antidiabetic drug for bone protection. While metformin has been shown to improve bone health, particular attention should be paid to renal function, vitamin B12 status, and individual patient factors.

Background: β-Thalassemia major patients are frequently vulnerable to endocrine dysfunction due to iron overload from chronic transfusions. This impairs growth, thyroid function, glucose metabolism, and bone health, ultimately compromising quality of life and long-term outcomes.

Objectives: This study investigates the prevalence and pattern of endocrine dysfunction in β-thalassemia major patients receiving iron-chelation therapy and explores associations with iron overload markers.

Methods: This case-control study involved 60 β-thalassemia major patients and 20 age- and sex-matched controls. Hormonal and biochemical parameters were measured and linked to iron status.

Results: Among β-thalassemia major patients (7-35 years), 73.3% (n = 44/60) were splenectomized; 36 received deferiprone, 19 deferasirox, and 5 deferoxamine. Concerning iron status, both splenectomized and non-splenectomized patients had significantly higher iron and ferritin and lower haptoglobin levels compared to controls. No significant differences were found in hepcidin or hemopexin levels. Regarding thyroid function, about 15% (n = 9/60) of β-thalassemia major patients had subclinical primary hypothyroidism. Ferritin negatively correlated with free thyroxine (r = -0.330, p = 0.010). As for glycemic status, 51.7% (n = 31/60) of β-thalassemia patients had glycated hemoglobin (HbA1c) ⩾6.5% and 38.3% (n = 23/60) showed impaired fasting blood sugar. With respect to metabolic markers, splenectomized patients had higher fibroblast growth factor 21 (FGF21) than the control (p = 0.042), while no significant group differences were found in galectin-1 or sortilin. Ferritin correlated significantly and positively with FGF21 levels (r = 0.353, p = 0.006). With respect to calcium-parathyroid-vitamin D axis, hypoparathyroidism and hyperparathyroidism were each found in 11.7% (n = 7/60) of β-thalassemia patients. Vitamin D levels were significantly lower in the β-thalassemia groups compared to controls (p = 0.0001) with 71.7% (n = 43/60) deficient despite 43.3% (n = 26/60) receiving supplements. Non-splenectomized patients had higher Procollagen Type I C-Peptide, a bone formation marker, compared to controls.

Conclusion: Endocrine disturbances are common in β-thalassemia major despite chelation therapy. Incorporating endocrine assessment into routine practice is essential for early detection and management.

Background: Polycystic ovary syndrome (PCOS) is a chronic, heterogeneous and prevalent endocrine-metabolic condition.

Objectives: This study aims to synthesize the available evidence on the comparison of lipid accumulation product (LAP) and visceral adiposity index (VAI) in women with and without PCOS.

Design: Systematic review and meta-analysis.

Data sources and methods: A systematic search was executed across five electronic databases. Continuous variables were assessed using the standardized mean difference (SMD) and its 95% confidence interval (CI).

Results: A total of 46 studies were included (n = 12,442). PCOS patients have higher values of LAP (n = 10,658; SMD: 0.65; 95% CI: 0.47-0.83, p < 0.05; I ² = 93.65%) and VAI (n = 7930; SMD: 0.53; 95% CI: 0.21-0.85; p < 0.05; I ² = 97.24%) compared to those without the syndrome.

Conclusion: Women with PCOS show significantly higher VAI and LAP values than those without this syndrome.