Expert Review of Endocrinology & Metabolism最新文献

Background: DPP-4 inhibitors have anti-diabetic effects in T2DM, but their impact on pancreatic function and underlying mechanisms remain unclear. This study aimed to evaluate the effects of sitagliptin on pancreatic function and glucose regulation, focusing on the roles of IL-18, IL-1, and IL-6 in T2DM patients.

Research design and methods: A 12-week clinical trial included 60 T2DM patients, randomly assigned to receive either metformin (2000 mg/day) or sitagliptin + metformin (100 mg and 2000 mg/day, respectively). Metabolic indices (fasting blood sugar [FBS], hemoglobin A1c [HbA1c], triglycerides [TG], cholesterol [Chol]), biochemical parameters, and vitamin D3 levels were measured at baseline and after 12 weeks. IL-1, IL-6, IL-18, and insulin levels were also evaluated.

Results: Sitagliptin + metformin group showed a greater reduction in FBS (p = 0.005), blood sugar (p = 0.011), and improvements in cholesterol (p = 0.001), TG-G index (p = 0.017), and pancreatic efficiency (p = 0.003) compared to metformin alone. Reductions in IL-1, IL-6, and IL-18 levels were observed (p = 0.00). Sitagliptin significantly reduced IL-1 levels (p = 0.034) compared to metformin alone. No significant changes were seen in HbA1c or vitamin D3.

Conclusion: Sitagliptin plus metformin improved pancreatic function, glucose homeostasis, and reduced IL-1, IL-6, and IL-18 levels in T2DM patients with inadequate glycemic control on metformin alone, offering cardiovascular benefits (Clinical Trial Registration: https://www.irct.ir/trial/44061).

Introduction: Endogenous Cushing's syndrome (CS) is associated with substantial morbidity and mortality. Patients in remission may experience many comorbidities, including growth hormone deficiency (GHD).

Areas covered: Electronic searches (PubMed) were conducted through July 2025. The published data largely pertain to patients with Cushing's disease (CS caused by a pituitary tumor). This article reviews the epidemiology of GHD in patients with CS in remission, underlying mechanisms, and clinical manifestations. The diagnosis of GHD is discussed along with data on the effectiveness and safety of growth hormone replacement.

Expert opinion: GHD is common in patients with active CS and may persist among patients in remission. In children, decreased linear growth is prevalent. In adults in remission, GHD has been associated with a higher prevalence of cardiometabolic burden (hypertension, diabetes mellitus, cardiovascular and cerebrovascular disease), decreased muscle strength, lower bone mineral density and increased prevalence of fractures. The diagnosis of GHD generally requires stimulation testing and should only be undertaken in patients in remission. In children with CS in remission, growth hormone replacement improves adult height. In adults, growth hormone replacement may improve quality of life, bone mineral density, muscle strength and dyslipidemia but requires careful monitoring for the possible development of hyperglycemia.

Introduction: Prader-Willi syndrome (PWS) is a rare disorder caused by the lack of expression of paternal genes on chromosome 15q11.2-q13. The clinical picture of PWS is characterized by neonatal hypotonia, hyperphagia, obesity, altered body composition, cognitive impairment, behavioral disturbances, short stature, and multiple endocrinopathies, including growth hormone (GH)/IGF-I axis dysfunction.

Areas covered: This narrative review addresses the current state-of-the-art of recombinant human GH therapy (rhGHT) in adults with PWS, focusing on its effects on body composition, muscle strength and exercise capacity, cardiovascular and respiratory function, endocrine and metabolic parameters, bone health, and psychological aspects.

Expert opinion: Available data demonstrated the positive effects of rhGHT on the body composition of GH-treated subjects. This observation is significant, as improving body composition has been shown to increase muscle strength and exercise tolerance. Overall, rhGHT appears to improve both cardiorespiratory function and psychological outcomes. However, most of the studies are uncontrolled and short-term. Therefore, longitudinal trials evaluating the long-term effects of rhGHT are recommended to confirm these findings. Since the beneficial effects of rhGHT appear to be independent of the presence of GH deficiency, we believe that its approval should be considered in adults with genetically confirmed PWS without testing for GH secretion.

Objectives: Raised asprosin may be related to the development of postmenopausal osteoporosis. This study aimed to determine the role of asprosin in oxidative stress in postmenopausal osteoporosis and its relation with estrogen, osteoprotegerin (OPG), and bone mineral density (BMD).

Methods: A case-control study included 80 women, aged 42-65, presenting at Shalamar Hospital, Lahore, Pakistan. Informed consent was taken, and single blinding was done. Demographic details and a bone mineral density scan were done. Three ml of venous blood sample was taken to measure asprosin, glutathione (GSH), osteoprotegerin, and estrogen levels.

Results: Women with osteoporosis had significantly higher levels of serum asprosin and lower levels of OPG than those without osteoporosis. (p < 0.05) Asprosin was negatively correlated with BMD, OPG, and GSH, and positively with body mass index (p < 0.05). The cutoff value of serum asprosin for screening postmenopausal osteoporosis by area under the curve was > 27.4 ng/ml with a sensitivity of 75% and a 1-specificity of 14%.

Conclusion: Higher serum asprosin and oxidative stress biomarkers are related to decreased bone mineral density in postmenopausal women. Asprosin may be used as a potential biomarker for early screening of postmenopausal osteoporosis. Small sample size and observational study design were the key limitations of this study.

Background: Thyroid hormone (TH) variations, even within the normal range, influence cardiometabolic health. In type 1 diabetes (T1D), optimizing glycemic control and cardiovascular risk is crucial to prevent complications. We aim to explore the association of TH within normal range with cardiometabolic profile in T1D.

Research design and methods: Cross-sectional analysis including adult patients with T1D followed at our Endocrinology Department between 2022-2024. We excluded patients with TSH or fT4 outside the reference range. Associations between TH (TSH, fT4, fT3 and fT3/fT4 ratio) and glycemic, anthropometric, and cardiometabolic parameters, were evaluated using linear regression models unadjusted and adjusted for relevant variables. Restricted cubic splines between TH and glycemic control parameters were performed to assess non-linear associations.

Results: We included 296 patients (median age 35 years, 42.6% female). Patients with mid-range TSH had better glycemic control, with higher time in range and a lower time above range. Waist circumference and body mass index were negatively associated with fT4, and positively with fT3 and fT3/fT4 ratio. Estimated glomerular filtration rate was negatively associated with TSH and fT4, and positively with fT3 and fT3/fT4.

Conclusions: Variations in TH within the normal range were associated with glycemic control and cardiovascular risk factors in T1D.

Introduction: Type 2 diabetes (T2D) continues to worsen globally alongside rise in obesity. Asymptomatic dysglycaemia, which precedes T2D, provides opportunities to identify those at risk and target prevention but prediabetes is highly variable. Not all with overweight develop dysglycaemia and not all with dysglycaemia are overweight. Important is the deposition of ectopic lipids in the pancreas, liver, and muscle. With no international definition, several prediabetes phenotypes exist, each based on one or more components of fasting glucose, postprandial glucose and/or HbA_1c.

Areas covered: We address variability in prediabetes phenotype and absence of a universal definition. With four main phenotypes based on the various glycemic definitions, it is likely they have different etiologies, risk profiles, timelines to T2D, and response to lifestyle intervention. Who do we treat, and when? Do we treat early or late? What is the optimum diet for T2D prevention? Do different phenotypes require different prevention approaches?

Expert opinion: Personalized lifestyle, or phenotype-specific treatments, are likely to be more successful for T2D prevention than a 'one-size-fits-all' approach. Artificial intelligence (AI) methods, currently in their infancy, are expected to revolutionize personalized nutrition with integration of 'big data' better characterizing and predicting prediabetes phenotype, and phenotype-specific response to diet and lifestyle interventions.

Introduction: Very-low calorie-diets (VLCD) are becoming increasingly popular for managing overweight, obesity and type 2 diabetes (T2D). Beta-cell dysfunction and insulin resistance (IR) is present in individuals living with overweight and obesity, with or without T2D. Results from metabolic studies investigating the effect of VLCD on beta cell function (BCF) and IR are inconsistent, despite the well-documented effects on weight and glycaemic control.

Areas covered: We undertook a narrative review of studies identified from PubMed and their associated reference lists, examining apparent discrepancies in the literature on this topic. Evidence broadly suggests a positive impact of VLCD, although the outcome being measured, and method of assessment could influence the observed effect. The VLCD duration is a critical factor, as longer-term interventions are required to consistently demonstrate improvements in BCF and peripheral IR. Hepatic IR appears to be particularly responsive to short-term caloric restriction.

Expert opinion: When interpreting metabolic results of VLCD intervention studies, particular attention must be paid to the selected method of assessing BCF and IR. Improvement in BCF exhibits significant heterogeneity, possibly related to individual participant's clinical characteristics. Beneficial effects on hepatic IR occur in the early stage of VCLD intervention, preceding changes in peripheral IR and BCF.

Introduction: Treatment targets can be considered the threshold where treatments generate optimal health outcomes while causing minimal complications. Treatment targets often uses a surrogate measure for the disease process, but are linked with an important outcome of disease management. Unlike chronic diseases such as type 1 diabetes, type 2 diabetes, hypertension, and dyslipidemia, which have clear treatment targets, obesity management lacks defined therapeutic targets. Insights from other chronic diseases may improve patient outcomes. They guide care, assess therapy response, and reduce complications.

Areas covered: This article explores how treatment targets for diabetes, hypertension, and dyslipidemia were developed, drawing on a narrative review of literature from 1950 to 2025 using PubMed and Embase. It examines how similar principles could inform obesity treatment, proposing early hypotheses like BMI ≤ 27 kg/m² and WHtR < 0.53 that warrant future validation.

Expert opinion: Targets in chronic disease care reduce complications. While not yet validated, BMI ≤ 27 kg/m² and WHtR < 0.53 May serve as early anchors for structured obesity treatment strategies.