Minerva endocrinology最新文献

pH changes are a cardinal feature in metabolic disorders. Based on published literature, chronic metabolic acidosis is a major finding in type 2 diabetes (T2D), which is recently described as CMAD (chronic metabolic acidosis of T2D). Several disorders characterized by overt metabolic acidosis are recognized as T2D co-morbidities or are dual risk factors that pertain to their unique signs and symptoms in T2D. Over time, many terms were used for chronic metabolic acidosis (CMA) in different disorders. However, the lack of a unified term for CMA, delayed the recognition of CMAD as a prime feature of T2D, and the setting of the diagnostic criteria and management protocol for this disorder. Other than the classical diabetic complications, CMAD contributes to non-classical organ-specific local diabetic complications. Here we described the likely clinical features of CMAD in general, such as fatigue, tiredness, cramps, and aches, as well as organ/system-specific symptoms of T2D related to the liver, skeletal muscles, bones and joints, lungs, nervous system, eyes, kidneys and urinary tract, oral cavity and teeth, gastrointestinal tract, immune system, and skin. Diagnostic criteria and confirmatory tests are enlisted together with the laboratory tools used for pH estimation in different body compartments. Finally, a management protocol is proposed, which covers: 1) lifestyle (exercise, stress management); 2) nutrition (drinks, foods, and supplements); and 3) therapeutic pH correction: general proton pump inhibitor (PPI) and alkaline minerals; and organ-specific therapies with different modalities of action. In addition, the therapeutic potentials of nanomedicine and immune and gene therapies for pH correction are raised.

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.

Introduction: Increasing evidence suggests that circulating growth differentiation factor-15 (GDF-15) may serve as a predictor of unfavorable clinical outcomes, but limited information is available on its relationship to diabetes risk. This meta-analysis was designed to evaluate quantitatively circulating GDF-15 in relation to diabetes prevalence.

Evidence acquisition: Our search encompassed the PubMed, Embase, and Web of Science databases from the inception dates to April 2024. Studies that provided data on diabetes prevalence across at least three distinct GDF-15 categories were eligible for inclusion in this meta-analysis.

Evidence synthesis: There were 27 independent studies from 25 articles included in this meta-analysis, involving 56,969 participants, 12,795 of whom were diabetic patients. The two-class meta-analysis showed participants with higher GDF-15 level had a higher diabetes prevalence [odds ratios (OR) 2.53, 95% confidence interval (CI) 2.09-3.05) than those with lower GDF-15 level. The diabetes prevalence increased by 63% (OR 1.63, 95% CI 1.47-1.80) when GDF-15 concentration was increased by 1 ng/mL, according to the dose-response meta-analysis. Nevertheless, the dose-response curve showed diabetes prevalence increased nonlinearly with increasing GDF-15 concentration (P nonlinearity <0.001), with a plateau or even a slight decrease after approximately 5.7 ng/mL of GDF-15 concentration. In the pooled estimates, considerable heterogeneity was observed and meta-regression analysis facilitated the interpretation of heterogeneity, which revealed significant correlations between diabetes prevalence and sample sizes (P<0.001) and hypertension prevalence (P=0.025).

Conclusions: This meta-analysis reveals a positive and non-linear relationship between circulating GDF-15 and diabetes prevalence, which plateaus or slightly declines after reaching a certain level of GDF-15.

Background: Polycystic ovary syndrome (PCOS) is an endocrine disorder that can result in reduced health-related quality of life (HRQOL). Metabolic changes, particularly insulin resistance and obesity, play a significant role in PCOS pathogenesis. This study examined associations between metabolic factors and HRQOL in PCOS patients.

Methods: A cross-sectional study of 77 patients was conducted at University Medical Center Mainz. At the time of inclusion in the study, patients had to be over 18 and not undergoing active PCOS therapy. A desire to conceive or fertility therapy led to exclusion. Participants were over 18, not undergoing PCOS therapy, and not seeking pregnancy. HRQOL and psychological distress were measured using the Modified-PCOS-Questionnaire (MPCOSQ) and Hospital Anxiety and Depression Scale (HADS). Linear regression analyses assessed associations between metabolic markers and HRQOL, with significant variables included in a multivariate model.

Results: Worsening metabolic markers were linked to lower HRQOL, especially in body hair and menstrual symptom domains. Markers such as HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) levels (P=0.040), elevated VAI (Visceral Adiposity Index) (P=0.035), and increased FLI (Fatty Liver Index) (P=0.023) were associated with diminished HRQOL. In the multivariate regression analysis, only a BMI ≥25kg/m² (P=0.001) emerged as a statistically significant value.

Conclusions: This study showed a significant correlation between metabolic markers, including BMI, FLI, VAI, HOMA-IR, and HRQOL in PCOS patients. BMI was the most meaningful predictor for HRQOL. BMI, despite being controversial and prone to errors, may be more indicative of HRQOL than specific metabolic markers.

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.