Minerva endocrinology最新文献

Background: There are cost-effective, non-invasive, and predictive tools used to predict the CVD risk in patients with diabetes such as the "atherogenic index of plasma (AIP)" which is defined as the logarithm to the base 10 of the ratio of fasting plasma TG (mg/dL) to HDL-C [log (TG/HDL-C)], triglyceride to high density lipoprotein (TG-to-HDL-C) ratio and the triglyceride glucose (TyG) index which is calculated as Ln (fasting TG [mg/dL] × fasting blood glucose (mg/dL)/2). These tools are indirect markers of atherosclerosis. Dapagliflozin and empagliflozin have exhibited cardiovascular beneficial effects and this study evaluated the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on AIP, TyG index and TG-to-HDL-C ratio in patients with type 2 diabetes.

Methods: This single center, retrospective, observational study involved patients with type 2 diabetic patients who were prescribed SGLT2i in the endocrinology outpatient clinic between January 2017 and June 2019. Demographic and clinical data were collected from patient files. AIP, TyG index and TG-to-HDL-C ratio were calculated obtained at the first visit and the sixth month visit.

Results: Overall, 143 patients with T2DM (75 women, 68 men) were recruited in this study. Sixty-six patients were prescribed dapagliflozin (46.2%), and 77 were prescribed empagliflozin (53.8%). SGLT2i treatment did not alter the lipid profile except the serum triglyceride (TG) levels. Serum TG levels were significantly reduced after 6 months of SGLT2i therapy (P=0.045). All patients had significant reductions in AIP at 6-month follow-up (P<0.001), accompanied by a significant reduction in TyG index (P<0.001). Both empagliflozin and dapagliflozin caused significant decrease in AIP (P=0.043 and P<0.001, respectively) and TyG index (P=0.010 and P<0.001, respectively).

Conclusions: Both dapagliflozin and empagliflozin were noted to significantly affect AIP and TyG indexes, which indicate atherosclerotic cardiovascular risk, with or without statin treatment regardless of lipid parameters.

Nonalcoholic fatty liver disease (NAFLD) was recently renamed to metabolic (dysfunction)-associated fatty liver disease (MAFLD) to better characterize its pathogenic origin. NAFLD represents, at least in western societies, a potential epidemic with raising prevalence. Its multifactorial pathogenesis is partially unraveled and till now there is no approved pharmacotherapy for NAFLD. A plethora of various choices are investigated in clinical trials, targeting an arsenal of different pathways and molecules. Since the mineralocorticoid receptor (MR) and renin-angiotensin-aldosterone system (RAAS) appear to be implicated in NAFLD, within this concise review, we focus on a rather classical and inexpensive pharmacological agent, spironolactone. We present the current lines of evidence of MR and RAAS-related preclinical models and human trials reporting an association with NAFLD. In conclusion, evidence about spironolactone of RAAS is commented, as potential future pharmacological management of NAFLD.

Background: The aim of this study is to investigate the use of once-weekly semaglutide in a real population of patients with type 2 diabetes mellitus (T2DM) over 70 years in two Spanish hospitals.

Methods: An observational, retrospective, and multicenter clinical study was designed. It included 60 patients with T2DM, with a mean age of 76.5 years, 63.3% women, and a mean of 15.5 years of evolution of T2DM, all managed in the outpatient clinical setting. The primary endpoint was the change in HbA1c from baseline to the end of the study. The secondary endpoints included changes in body weight and the proportion of patients achieving HbA1c <7.0% and body weight loss >5%.

Results: After 12 months of follow-up, the reductions in HbA1c were -0.61±0.9% (P<0.0001) in the total cohort. Body weight reductions were -8.2±5.3 kg (P<0.0001). Overall, 67% reached the objective of an HbA1c level of <7%, and 73% achieved a weight loss of ≥5%.

Conclusions: In routine clinical practice in Spain, the use of semaglutide once a week was associated with statistically significant and clinically relevant improvements in HbA1c and body weight in adults aged over 70 years with T2DM, without notable adverse effects, which supports real-world use.

Background: The Pituitary Tumors Centers of Excellence (PTCOE) concept was established to provide a multimodal approach with careful management of comorbidities. Acromegaly, one of the main concerns of PTCOE per se, leads to increased mortality rates of which cardiovascular disease is an important cause. Increased skin autofluorescence (SAF) was shown to be associated with carotid intima-media thickness (CIMT), a well-established marker of atherosclerosis, and consequently cardiovascular complications. This study aimed to evaluate SAF and CIMT in association with anthropometric, clinical, and biochemical parameters in acromegaly patients and healthy controls.

Methods: The study group included 138 acromegaly patients and 127 healthy controls from the Department of Endocrinology and Metabolism Disease, Marmara University Medical School. Growth hormone, insulin-like growth factor I, lipids, glucose, insulin levels were assessed. Advanced glycation end products (AGEs) were measured by the auto-fluorescence reader. CIMT was measured from the common carotid artery wall on B-mode ultrasound.

Results: CIMT and SAF levels were significantly higher in the acromegaly group than the control group. There was a positive correlation between SAF and CIMT both in the total cohort and acromegaly patients. The presence of acromegaly, age, and SAF were the determining factors of CIMT in the whole study cohort.

Conclusions: Our study is the first to examine the relationship between SAF and CIMT in acromegaly patients. We found higher CIMT and enhanced SAF in the acromegaly group compared to the control group with a significant positive correlation in between. The presence of acromegaly was related to increased SAF levels and CIMT. SAF was associated with CIMT in acromegaly patients. Implementation of CIMT and SAF evaluation in this clinical setting may improve cardiovascular complications, particularly in the PTCOE.

Background: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder with well-established metabolic abnormalities. In the present study, untargeted metabolomics technology was applied to analyze the serum and follicular fluid samples from women with polycystic ovary syndrome and healthy controls using ¹H nuclear magnetic resonance (NMR).

Methods: Seventy samples for PCOS analysis were collected in hospital of Shandong University of Traditional Chinese Medicine (Jinan, China), NMR was used as analytical technology and multivariate analysis was applied to analyze metabolomics difference in PCOS and healthy controls.

Results: Significant metabolic differences were found in both serum and follicular fluid samples with orthogonal partial least-squares discriminant analysis (OPLS-DA). Three discriminated metabolites (1-Methylhistidine, threonine and Citrate) in both serum and follicular fluid were altered in PCOS patients. Abnormal energy metabolism, lipid metabolism and amino acid metabolism were detected in PCOS patients. Furthermore, more significantly changed amino acids were discovered in follicular fluid samples.

Conclusions: Our findings would provide a resource for further investigations on metabolic disturbance in PCOS patients.

Background: Diabetic nephropathy (DN), a microvascular complication associated with long-standing diabetes, is a major cause of the end-stage renal disease (ESRD). Our in-silico analysis indicates several enrichment analyses involved in glucose metabolism to be affected by GDF15 transcription factors.

Methods: In-silico analysis was used to identify GDF15 and Insulin related protein-protein interaction (PPI) network and a common set of GDF15 regulating transcription factors by various databases. Common targeting miRNA of GDF15 regulating transcription factors were investigated in miRNet and TargetScan. Further, healthy controls (N.=30) and patients with pre-type-2 diabetes mellitus (pre-diabetes) (N.=30), T2DM (N.=30) and DN (N.=30) were included for analysis of routine biochemical tests, serum GDF15 levels by ELISA and to evaluate the Fold change expression (FCE) of circulating hsa-miR-21 by RT-PCR.

Results: MicroRNA-21 was found to directly target GDF15 downregulating transcription factors KLF4, TP53, and CEBPB. A significant difference in the levels of serum GDF15 was observed in Pre-diabetes (708.56±76.37), T2DM (1528.87±140.75) and DN patients (10-fold higher; 5507.90±503.88) when compared to healthy controls (567.36±69.99). The FCE of circulating hsa-miR-21 was 6.19 (pre-diabetes), 8.22 (T2DM), 9.19 (DN), folds higher in cases as compared to controls, reflecting an increasing trend and several folds higher levels of hsa-miR-21 in patients.

Conclusions: We suggest the potential of serum GDF15 and circulating-hsa-miR-21 to serve as clinically important biomarkers and therapeutic targets for controlling advancement of diabetes to DN.

Introduction: To compare survival outcome among the patients with concurrent small cell lung cancer (SCLC) and diabetes mellitus (DM) using metformin or without metformin.

Evidence acquisition: A systematic literature search for relevant studies up to Oct 2020 was conducted. Outcome of the included studies included overall survival (OS) or disease-free survival (DFS). HR values were pooled to estimate the effect of metformin on survival outcomes.

Evidence synthesis: Six studies with 539 participants with both SCLC and diabetes were included in the analysis. The patients with metformin usage had significantly longer OS and DFS than those without metformin usage (OS: HR=0.72 [0.53-0.98], P=0.04; DFS: HR=0.59 [0.45-0.76], P<0.0001). The studies included were not significantly different in the two analyses by heterogeneity test. There was no obvious publication bias.

Conclusions: Metformin may improve survival among patients with concurrent SCLC and DM. Further investigations especially randomized control trials are warranted, especially among the patients who do not have diabetes.

Beside its mechanical roles in controlling posture and locomotion, skeletal muscle system, the largest insulin and steroid hormones target tissue, plays a key role in influencing thermoregulation, secondary sexual characteristics, hormones metabolism, and glucose uptake and storage, as well as energetic metabolism. Indeed, in addition to insulin, several hormones influence the skeletal muscle metabolism/function and/or are influenced by skeletal muscles activity (i.e., physical exercise). Particularly, steroid hormones play a key role in modulating many biological processes in muscles, essential for overall muscle's function and homeostasis, both at rest and during all physical activities (i.e., physical exercise, muscular work). Phosphodiesterase type 5 (PDE5) is the enzyme engaged to hydrolyze cyclic guanosine monophosphate (cGMP) in inactive 5'-GMP form. Therefore, through the inhibition of this enzyme, the intracellular level of cGMP increases, and the cGMP-related cellular responses are prolonged. Different drugs inhibiting PDE5 (PDE5i) exist, and the commercially available PDE5i are sildenafil, vardenafil, tadalafil, and avanafil. The PDE5i tadalafil may influence cellular physiology and endocrine-metabolic pathways in skeletal muscles and exerts its functions both by activating the cell signaling linked to the insulin-related metabolic pathways and modulating the endocrine responses, protein catabolism and hormone-related anabolism/catabolism during and after physical exercise-related stress. Based on recent in-vivo and in-vitro findings, in this narrative review the aim was to summarize the available evidence describing the interactions between the PDE5i tadalafil and steroid hormones in skeletal muscle tissue and physical exercise adaptation, focusing our interest on their possible synergistic or competitive action(s) on muscle metabolism and function.

Background: Sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) are considered a new class antidiabetic agent, as well as lowering blood sugar, it has many positive effects. This study aimed to investigate the effects of SLGT2i on the gastric mucosa.

Methods: We investigated the effects of empagliflozin on indomethacin-induced gastritis using 48 male Wistar Albino rats. We performed histopathological evaluations of gastric mucosa tissue. And we studied the levels of serum disulfide, native thiol, total thiol, and ischemia modified albumin, disulfide/native thiol ratio (SSSH), native thiol/total thiol percent ratio (SH total SH), and disulfide/total thiol percent ratio (SS total SH).

Results: We found that empagliflozin increased mucin production in rat gastric mucosa. Besides, we observed milder inflammation findings and lower gastritis scores in the empagliflozin receiving groups than the placebo groups. Native thiol, total thiol, and disulfide levels were lower in the indomethacin-induced gastritis groups.

Conclusions: This study is the first to investigate the effect of empagliflozin on the gastrointestinal tract in a rat model. We concluded that empagliflozin increased mucin production and revealed positive effects in an indomethacin-induced gastritis model.