Minerva endocrinology最新文献

The gut microbiota plays a crucial role in the human body and has an impact on the physiological function of the host. In particular, changes in the gut microbiota are especially pronounced in patients with type 2 diabetes. There is ample evidence that glucose-lowering drugs exert their therapeutic effects precisely through their interactions with the gut microbiota, but there is a lack of summarization. An overall comparison of the effects of each hypoglycemic agent on the gut flora can provide new inspiration for combinations. In this paper, we selected several representative glucose-lowering drugs, such as metformin, sodium-dependent glucose transporters 2 inhibitors (dapagliflozin), glucagon-like peptide-1 receptor agonists (semaglutide, liraglutide), and the traditional Chinese medicine (berberine), and illustrated how they can affect the disease process by regulating metabolic homeostasis, immune response, and gut barrier. We found that each of these four hypoglycemic agents can have conflicting effects on the gut flora depending on the timing and mode of administration. Meanwhile, the potential impact of gut microbiota on drug safety is explored, and an outlook for the optimization of future type 2 diabetes treatment regimens is presented.

Despite the widespread use of murine models in in-vivo experiments, the zebrafish (Danio rerio) offers unique advantages that make it a versatile and faster preclinical model for drug screening, particularly for adrenocortical carcinoma (ACC), a rare malignancy with limited preclinical models that reflect patient heterogeneities. Over the past decade, significant progress has been made with models like cell lines, organoids, and murine models, which are crucial for advancing disease understanding and treatment development. However, recent reviews have overlooked zebrafish model for ACC. This mini review aims to fill this gap by detailing the advancements of the zebrafish model in ACC research. Recent studies have utilized zebrafish embryos xenografted with ACC cells as a novel approach to studying drug effects on tumor growth and metastasis, consistent with studies regarding other tumors. Specifically, it was demonstrated the ability of abiraterone acetate, trabectedin and progesterone to significantly reduce the tumor area at non-toxic-concentrations. Interestingly, this model allowed to confirm in vivo that metastasis-derived cells were able to metastasize and that trabectedin and progesterone reduced the rate of embryos with metastasis. One more study showed that metastasis formation was significantly reduced in H295R/TR-SF-1-xenografted embryos after fascin1 knock-out or inhibition with G2-044. Even with some limitations, the zebrafish xenografts offer a suitable and expeditious animal model for the screening of potentially effective drugs, identification of dose toxicity, and determination of the most promising compounds for more advanced preclinical phases, especially in rare diseases with limited therapeutic options such as ACC.

Background: Telemedicine was largely employed during COVID-19 pandemic to guarantee continuity of care in a period of dramatic reduction of face-to-face visits. The aim of this study was to describe the clinical characteristics of a cohort of patients with type 2 diabetes followed by tele-visits and to evaluate the changes in the glyco-metabolic control during a 12-month follow-up.

Methods: This retrospective observational study included 136 adults aged >18 years with at least three tele-visits over a 12-month follow-up period, in a Diabetes Center of the Southern Italy, from April 2020 to March 2022. Data related to glycemic and lipid profile, therapy, presence of micro or macrovascular complications, and other clinical features were extracted at three time points, at first visit (T0), after 6 months (T1) and after 12 months (T2).

Results: Mean diabetes duration and median HbA1c values were 11.6 years and 7.0%, respectively. Thirty-eight participants (27.9%) presented macro- or microvascular complications. Glycemic control remained stable over time, without clinically significant changes of HbA1c (T0 vs. T1 vs. T2, median [IQR], 7.0 [6.2-7.3], 6.6 [6.0-7.5], 6.9 [6.2-7.5], P=0.095) and fasting glucose. Lipid profile slightly improved, although without significant clinical change. Glucose lowering therapy was modified in 84 patients (61.8%) and remained unchanged in 52 patients (38.2%) during the follow-up. No participant in the study developed any complications during the 12-month follow-up.

Conclusions: People with type 2 diabetes followed by telemedicine were adults with fair glucose control generally free from chronic complications, whose diabetes control did not worsen during a 12-month follow-up.

Introduction: This meta-analysis was conducted to compare the circulating lipocalin-2 levels in polycystic ovary syndrome (PCOS).

Evidence acquisition: Relevant studies were retrieved by online database and manual searching. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis. The subgroup analysis based on the Body Mass Index (BMI) and the homeostasis model assessment-estimated insulin resistance (HOMA-IR) was conducted. Meta-analysis of correlations and meta-regression were performed for the associations of lipocalin-2 with the metabolic and hormonal covariates. The funnel plot analysis was used for publication bias.

Evidence synthesis: The combined effect size including a total of 13 studies showed no significant difference in lipocalin-2 levels between PCOS and control groups. However, the subgroup meta-analysis based on insulin resistance showed a significant difference in the circulatory lipocalin-2 levels in PCOS as compared to controls in both HOMA-IR<3 (SMD=-1.15, Z=2.42, P=0.02) and HOMA-IR>3 subgroups (SMD=0.91, Z=2.43, P=0.02).

Conclusions: There were significant associations of lipocalin-2 with age, BMI, estrogen and hyperandrogenism in PCOS. Lipocalin-2 level alterations in PCOS are associated to insulin resistance. More is the insulin resistance, higher is the lipocalin-2 level in PCOS as compared to controls.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread disorder strongly associated with metabolic conditions such as obesity, insulin resistance, and type 2 diabetes (T2D). The progression of MASLD, which can lead to severe complications like hepatic fibrosis and cirrhosis, is closely tied to cardiometabolic risks, including cardiovascular disease, and to liver-related cancers associated with metabolic dysfunction. Endocrinologists are uniquely positioned to detect MASLD early, particularly in individuals with metabolic risk factors such as T2D, polycystic ovary syndrome (PCOS), and thyroid dysfunction. While they may not routinely perform advanced diagnostic procedures, they play a critical role in identifying at-risk patients and collaborating with specialists for further evaluation, including the use of transient elastography to assess liver stiffness and fibrosis. By doing so, they help reduce the need for invasive procedures. Beyond screening and diagnosis, endocrinologists collaborate with hepatologists, cardiologists, and nutritionists to ensure a comprehensive, multidisciplinary treatment approach. Managing MASLD requires addressing both liver-specific conditions and broader metabolic dysfunctions through lifestyle interventions and pharmacological therapies. Recent studies highlight the potential benefits of medications, such as farnesoid X receptor (FXR) agonists and peroxisome proliferator-activated receptor (PPAR) agonists, when combined with lifestyle interventions such as modifying diet and engaging in more physical activity. This review highlights the pivotal role of endocrinologists in managing MASLD, focusing on their contributions to screening, diagnosis, and integrated care. It examines the complex interplay between hormonal regulation and both pharmacological and non-non-pharmacological treatment strategies, providing insights for enhancing clinical practice and improving patient outcomes through a comprehensive, multidisciplinary approach.

Introduction: The association between betatrophin level and type 2 diabetes mellitus (T2DM) is a subject of controversy, and the reasons for conflicting results have been poorly explained. To address this gap, we conducted a meta-analysis of relevant studies to obtain a more comprehensive estimate and draw a more accurate conclusion.

Evidence acquisition: This study included literature published up to June 2023. We searched for relevant studies in the Web of Science and PubMed databases. We utilized STATA 12.0 software to calculate the standard mean difference (SMD) and 95% confidence interval (CI) to compare circulating betatrophin levels between individuals with T2DM and healthy controls (HCs).

Evidence synthesis: The meta-analysis revealed a significantly higher circulating betatrophin level in individuals with T2DM compared to HC, using a random effects model [mean value of betatrophin level (T2DM vs. HC): 388,685.23 vs. 304,857.04 pg/mL; SMD=1.37; 95%CI: 1.01, 1.73]. Subgroup analysis indicated a higher circulating betatrophin level in T2DM compared to HC among Asian individuals, while no significant difference in circulating betatrophin level was observed between T2DM and HC among Caucasian individuals (Asian: SMD=1.65; 95%CI: 1.23, 2.06; Caucasian: SMD=0.50; 95%CI: -0.21, 1.20). Additionally, subgroup analysis revealed increased plasma and serum betatrophin levels in T2DM compared to HC (plasma: SMD=1.30; 95%CI: 0.72, 1.88; serum: SMD=1.47; 95%CI: 0.98, 1.96).

Conclusions: This meta-analysis provides evidence of elevated levels of betatrophin in individuals with T2DM, suggesting that betatrophin may serve as a potential diagnostic biomarker for T2DM.

Background: Ovarian senescence is associated with increased cardiovascular risk. We aimed to evaluate the association between menopausal symptoms and cardiometabolic risk factors in a cohort of apparently healthy middle-aged women.

Methods: The cohort included 2793 peri- and postmenopausal women not on menopausal hormone therapy. Demographic/anthropometric and biochemical/hormonal data were assessed. The severity of menopausal symptoms was evaluated by the Greene Climacteric Scale (GCS).

Results: GCS-Total Score was associated with BMI (b=0.12, 95% CI: 0.04 to 0.20), T2DM (b=2.10, 95% CI: 0.06 to 4.15), and late-postmenopause (b=-1.24, 95% CI: -2.17 to -0.33). GCS-psychological score was associated with BMI (b=0.06, 95% CI: 0.00 to 0.11). GCS-Physical Score was associated with BMI (b=0.06, 95% CI: 0.03 to 0.09), central obesity (b=0.18, 95% CI: 0.02 to 0.34), and postmenopause (early-/late-postmenopause vs. perimenopause, b=-0.36, 95% CI: -0.59 to -0.13 and b=-0.65, 95% CI: -0.97 to -0.34, respectively). All GCS-scores were negatively associated with age. GCS-Sexual Score was associated with early-postmenopause (incidence rate ratio (IRR)=1.53, 95% CI: 1.21 to 1.94), central obesity (IRR=1.18, 95% CI: 1.00 to 1.39), smoking, diastolic blood pressure, age. Cox-regression analysis showed that incident T2DM was positively associated with increasing age, BMI, daily alcohol consumption, moderate-to-severe vasomotor symptoms (VMS, OR=1.045, 95% CI: 1.011 to 1.079), and negatively with moderate-to-strenuous physical activity. These associations persisted in lean but not in obese women.

Conclusions: The severity of menopausal symptoms is associated with T2DM, obesity, and smoking in a cohort of peri-/postmenopausal women. VMS were associated with incident T2DM, especially in lean women. These associations must be considered in implementing primary and secondary prevention strategies.

Background: Oxidative stress has been implicated in the pathogenesis of autoimmune thyroiditis, also referred to as Hashimoto's thyroiditis (HT), and several biomarkers have been measured to evaluate the impact and clinical relevance of oxidative stress in this setting. Recently, advanced glycation end products (AGEs) have been proposed as reliable markers of oxidative stress in HT. In the present study, we investigated the relationship of AGEs with antioxidant paraoxonase (PON-1) activity as potential combined markers of oxidative stress.

Methods: We measured the levels of AGEs, and advanced oxidation protein products (AOPPs) and PON-1 activity by spectrophotometric methods, in the serum of 40 HT patients (36 F; mean age 35.4±11.5 year) and 38 age-, sex- and BMI-matched healthy controls. All subjects were euthyroid at recruitment and none was on LT-4 therapy.

Results: Serum levels of AGEs were significantly higher (median 378 vs 290 AU/g protein; P<0.001), while PON1 activity was significantly lower (median 165 vs. 201 U/L; P<0.05) in HT patients compared to controls: the two parameters were inversely correlated (P<0.01), clearly indicating a pro-oxidant imbalance in HT patients. At stepwise regression analysis, TPOAb positivity was an independent predictor of both PON-1 activity (P=0.002) and AGEs levels (P=0.000).

Conclusions: Increased formation and accumulation of AGEs contribute to enhanced oxidative stress, along with a decrease in PON-1 activity in HT. As a consequence, AGEs levels and alteration in PON 1 may serve as useful markers for monitoring the levels of oxidative stress in this disorder.