Expert Review of Endocrinology & Metabolism最新文献

Introduction: In 2023, metabolic dysfunction-associated steatotic liver disease (MASLD) was introduced following metabolic dysfunction-associated fatty liver disease (MAFLD). Both aim to address the limitations of nonalcoholic fatty liver disease (NAFLD). This review analyzes the similarities and differences between MAFLD and MASLD, focusing on their impacts on epidemiology, diagnosis, stigma, and related liver diseases.

Areas covered: Current evidence suggests that MAFLD criteria effectively identify individuals at higher risk through a good balance of sensitivity and specificity. Moreover, MAFLD is a more generalizable term that is easily understood globally.

Expert opinion: The transition from NAFLD to MAFLD and MASLD marks a significant advance in understanding fatty liver disease within hepatology. MAFLD identifies a homogeneous cohort of patients with fatty liver due to metabolic dysfunction and provides a valuable framework for holistic, patient-centered management strategies that consider various contributing factors to improve health outcomes.

Introduction: Hypothyroidism is a relatively common condition, which generally cannot be reversed. Hypothyroid individuals are dependent on provision of exogenous thyroid hormone as a lifetime therapy. Levothyroxine therapy provides satisfactory treatment for most. However, a subset of patients are not restored to their baseline quality of life.

Areas covered: As discussed here, a number of solutions have been tried, including addressing accompanying conditions, rigorous titration of therapy, and combination therapy with levothyroxine and liothyronine. The latter has limited success with improving quality of life, but does appear to be associated with patient preference. The discrepancy between quality of life and patient preference may be important to understanding the nuances of successful hypothyroidism treatment.

Expert opinion: Future efforts to improve hypothyroidism therapy could tease out which are the specific subset of patients who benefit from combination therapy, such as those who have unresolved symptoms attributable to hypothyroidism at baseline and those with genetic polymorphisms that might impair thyroid hormone delivery to tissues. Better understanding of the drivers of patient preference for combination therapy should also be revealing. A future goal is to prevent autoimmune hypothyroidism from developing and to treat hypothyroidism completely by generating fully functioning thyroid follicles from stem cells.

Background: Epithelial-to-mesenchymal transition (EMT) may be involved in the pathogenesis of diabetic nephropathy (DN) among adults with type 2 diabetes. The current study aimed to evaluate the role of E-cadherin as a surrogate marker of EMT among children and adolescent with type 1 diabetes (T1D) and DN and its possible relation to carotid intima media thickness (CIMT).

Research design and methods: Sixty participants with T1D were divided equally into two groups based on urinary albumin creatinine ratio (UACR) and compared with 30 healthy controls. Hemoglobin A1c (HbA1c), kidney function tests, serum E-cadherin and CIMT were assessed.

Results: E-cadherin levels were significantly lower in patients with microalbuminuria (56.5 ± 15.8 ng/mL) compared with patients with normoalbuminuria (179.8 ± 45.1 ng/mL) and healthy controls (222.5 ± 39.9 ng/mL) (p < 0.001). E-cadherin correlated negatively with HbA1c (r = -0.42, p = 0.001), UACR (r = -0.89, p < 0.001) and CIMT (r = -0.716, p < 0.001). ROC curve analysis showed that the E-cadherin cutoff value 135 ng/mL could detect nephropathy with 96.67% sensitivity and 86.67% specificity. Logistic regression showed that E-cadherin was a significant independent factor for nephropathy.

Conclusions: E-cadherin is a potential biomarker reflecting EMT activity in both pathogenesis and progression of DN and subclinical atherosclerosis in pediatric patients with T1D.

Background: Considering the important role of obesity and related factors in different societies on increasing the burden of non-communicable diseases, in this review we will investigate the possible effects of Beinaglutide on these risk factors.

Research design and methods: In order to identify all randomized controlled trials that investigated the effects of Beinaglutide on cardiometabolic factors, a systematic search was conducted in the original databases using predefined keywords until July 2024. The pooled weighted mean difference (WMD) and 95% confidence intervals were computed using the random-effects model.

Results:    A quantitative meta-analysis results from seven studies with 872 participants showed that Beinaglutide has a significant lowering effect on weight (WMD: -3.74 kg; 95% CI: -5.03, -2.45), body mass index (BMI) (WMD:-1.64 kg/m2; 95% CI: -2.10, -1.17), waist circumference (WC) (WMD: -3.19 cm; 95% CI: -4.65 to -1.73), triglyceride (TG) levels (WMD: -0.14 mmol/l with; 95% CI: -0.25, -0.04), and systolic blood pressure (SBP) (WMD: -1.76 mm/Hg; 95% CI: -2.61, -0.91). In addition, body weight loss was greater in doses < 0.4 mg compared to doses ≥ 0.4 mg.

Conclusions: The results of this meta-analysis show that Beinaglutide is effective in reducing parameters related to obesity, TG as well as SBP.

Introduction: Mild autonomous cortisol secretion (MACS) is the most common hormonal alteration in patients with adrenal incidentalomas (AIs). Given its prevalence and associated adverse outcomes, reviewing its impact and interventions is essential.

Areas covered: In this article, we provide a comprehensive review on the diagnosis of MACS, the cardiometabolic burden associated with MACS and on its surgical and medical treatment. The diagnosis of MACS requires three criteria: hormonal evidence of hypercortisolism, the absence of typical Cushing's syndrome signs, and the presence of an AI. The most recommended test for MACS diagnosis is the 1 mg dexamethasone suppression test. There is plenty of evidence of the detrimental effect of MACS, including an increased risk of diabetes, hypertension, dyslipidemia and all-cause mortality. Surgery should be considered for patients with significant comorbidities and has been shown to significantly improve anthropometric variables, hyperglycemia and blood pressure. Medical therapy to lower cortisol offers an effective alternative, particularly for patients with bilateral AI, when surgery is contraindicated, or the patient declines surgery.

Expert opinion: Based on our expert opinion, steroid profiling has the potential to become the gold standard for MACS diagnosis, and further studies should identify which patients benefit most from specific treatment to guiding evidence-based recommendations.

Background: Chronic kidney disease (CKD) due to Type 2Diabetes Mellitus (T2DM) is an increasing health burden in South Asia. This study evaluates the burden, trends, and future projections of CKD from 1990-2021 using Global Burden of Disease (GBD) data and ARIMA modeling.

Research design and methods: We analyzed age-standardized rates (ASR) for prevalence, incidence, mortality, and DALYs of CKD due to T2DM in South Asia(India, Pakistan, Bangladesh, Bhutan, Nepal). Join point regression and ARIMAmodels were applied for trend analysis and projections.

Results: From 1990 to 2021, prevalence decreased slightly (e.g. India: 5.4% to 5.2%), while mortality increased (e.g.Pakistan: 33.7 to 42.1 per 100,000). Incidence increased across all countries, with Nepal (1.3% increase) and Bhutan (1.7% increase) showing the highest growth. Projections indicate a continued rise in CKD burden, especially inNepal and India.

Conclusion: CKD due to T2DM is increasing, emphasizing the need for targeted interventions.

Background: Diabetes mellitus (DM) prevalence in Qatar is among the highest worldwide. DM has been shown to be associated with reduced performance on numerous domains of cognitive function in elderly population. Here, we sought to determine whether such association also exists in a middle-aged cohort.

Research design and methods: A cross-sectional study was conducted using data from 981 participants aged 40-65 years from the Qatar Biobank. We analyzed glycemic indices: HbA1c, serum glucose, insulin levels, waist circumference, and waist-hip ratio. Cognitive function was assessed using two domains of CANTAB: the paired episodic memory (visual memory) and reaction time (motor and mental speed).

Results: We found significant associations between DM and cognitive impairment. Poor reaction speed was linked to DM (beta 36.80, P < 0.01), higher HbA1c levels (beta 10.73, P < 0.05), larger waist circumference (beta 1.70, P < 0.001), and higher waist-to-hip ratio (beta 252.56, P ≤ 0.01). Poor memory performance was also associated with increased waist circumference and waist-to-hip ratio.

Conclusion: The negative association between DM, its biomarkers, and cognitive impairment reported previously in elderly populations also exists in middle-aged individuals. Further research is needed to explore the causality and impact of dysglycemia on other cognitive domains.

Introduction: The introduction of long-acting formulations in recent years is changing the landscape of growth hormone (GH) therapy. Daily recombinant human GH (rhGH) has been the treatment of choice for children and adults with GH deficiency (GHD), since its approval in 1985. However, decreasing adherence to treatment over time has been identified as a cause of the decline in rhGH efficacy, leading to significant efforts to develop long-acting rhGH (LAGH) formulations.

Areas covered: A comprehensive analysis of the literature was conducted to evaluate their mechanism of action, pharmacokinetics, pharmacodynamics, efficacy, safety profile, and administration route. The review focuses on the LAGH approved from both the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for the treatment of pediatric growth hormone deficiency (PGHD): Lonapegsomatropin, Somatrogon and Somapacitan. We aim to facilitate evidence-based clinical decisions by analyzing the available data on the three LAGH formulations.

Expert opinion: Even if current evidence suggests a non-inferiority of all the three LAGH formulations when compared to daily rhGH, long-term concerns persist regarding the non-physiological GH profile associated with LAGH, characterized by weekly instead of daily peaks. Further research and real-life studies are required to better define the long-term efficacy of these formulations.

Background: Obstructive sleep apnea (OSA) is a common sleep disorder, frequently observed in obese individuals, with shared mechanisms involving leptin and its receptor, which regulate appetite and energy expenditure. SH2B1 is a key enhancer of signaling in the leptin receptor pathway. This study aimed to investigate the association between SH2B1 variants and OSA.

Research design and methods: This case-control study included 160 male patients with OSA and 76 healthy controls, stratified into subgroups based on BMI (≤25 kg/m² and ≥ 30 kg/m²). Polysomnography and anthropometric measurements were performed, and genotyping of three SH2B1 variants (rs7498665, rs4788102, and rs7359397) was conducted.

Results: Mutant genotypes of all three SH2B1 variants were significantly associated with higher BMI. Additionally, normal genotypes of rs4788102 and rs7359397 were associated with higher apnea-hypopnea index (AHI) values, indicating a potential risk for OSA.

Conclusion: The findings suggest that while SH2B1 variants are strongly associated with BMI, specific normal genotypes may independently contribute to OSA risk by increasing AHI values.

Background: The study aimed to determine the association of vitamin D3 status with biochemical, clinical, and quality of life (QoL) in diabetic foot infection (DFI) patients.

Research design and methods: A longitudinal study was conducted in a tertiary care hospital. Baseline biochemical (glycemic, renal, plasma vitamin D3), clinical, and QoL data of the DFI patients were collected. Patients were followed up with over the telephone for four months to assess clinical outcomes (healed/not healed). A subgroup analysis was performed to investigate the effect of vitamin D3 supplementation.

Results: Eighty-nine DFI patients were enrolled, with a median age of 55 years and a male predominance (89.9%). A significant association between vitamin D3 levels and clinical outcome was not observed (p = 0.66). A moderate correlation was observed with the neutrophil-lymphocyte ratio (r = 0.24, p = 0.02). Regarding QoL, emotions (domain) were significantly associated with vitamin D3 levels (p < 0.01). The subgroup analysis showed that vitamin D3 supplements did not affect the clinical outcome.

Conclusion: The plasma vitamin D3 levels and vitamin D3 supplements do not significantly affect the biochemical, clinical, and humanistic outcomes, indicating vitamin D3 did not have a positive effect on DFI patients.