ACTA ENDOCRINOLOGICA (BUC)

Obesity is a well-recognized risk factor for type 2 diabetes, cardiovascular disease, and several types of cancer. However, a proportion of the obese individuals display a significantly lower risk for metabolic complications than expected for their degree of body mass index, and this subtype of obesity was described as “metabolically healthy obesity” (MHO). No universally accepted criteria for the diagnosis of MHO exists and the prevalence of this subtype of obesity varies largely according to criteria used. Broadly, MHO is characterized by a lower amount of visceral fat, a more favorable inflammatory profile, and less insulin resistance as compared to the metabolically unhealthy obesity. Currently, controversies exist regarding the risk of cardiovascular events and all-cause mortality associated with MHO as compared to metabolically-healthy non-obese individuals. Further research is needed in order to identify the MHO phenotype and if MHO is truly healthy for a long period of time or if it is a transient state from normal metabolic/normal weight to abnormal metabolic/obese state. This review will discuss the MHO definition criteria; the differences between MHO and metabolically unhealthy obesity; the possible underlying mechanisms and clinical implications of MHO.

Objectives. We aimed to determine lipodystrophy frequency according to insulin treatment regimen and insulin injection frequency in type 2 diabetic patients. Methods. A total of 345 type 2 diabetic patients under insulin treatment for at least one year were included in this cross-sectional study. Patients were examined for presence of lipodystrophy, insulin injection frequency and dosage. Lipodystrophy was evaluated with visual inspection and palpation of all injection sites. Patients were evaluated into three categories according to daily insulin dose requirement: Group 1= Standard-dose insulin users 0.6 U/ kg/day; Group 2= Medium-dose insulin users 0.61-1.9 U/kg/ day, Group 3= High-dose insulin users ≥2 U/kg/day. Results. Lipodystrophy was seen in 28% of the patients. Lipodystrophy was significantly higher in group 3. There was no significant difference between the groups in terms of lipodystrophy size. Duration of insulin treatment, daily total insulin dose, daily insulin dose per weight and number of daily insulin injections were significantly higher in the group with lipodystrophy. Daily injection number of long-acting, rapidly-acting analog and total insulin injections were significantly higher in group 3 than group 1 and 2. Number of daily insulin injections and lipodystrophy frequency were significantly higher in basalbolus insulin user group. Multivariate analysis showed that insulin injection frequency is the independent risk factor for lipodystrophy. Conclusion. Lipodystrophy is still a clinical problem in patients with high-dose insulin requirement and frequent insulin injections. Reducing daily insulin requirement and daily number of injections should be given priority in the management of patients to prevent the development of lipodystrophy.

Objective. Exercise intensity is one of the most important factors that determines the effects of exercise; however, there is little known about the acute glycemic control of different exercise intensities on patients with Type 2 Diabetes Mellitus (T2DM). Here we aimed at exploring the influence of a single bout of exercise with different intensities on blood glucose levels in T2DM patients. Methods. Fifteen subjects (54.7 ± 5.8 years old) participated in a session of walking (WG), jogging (JG), or sedentary control (CG) in a randomized order on three different days. Distances in both WG and JG were set as 2 Km with a speed set as 4~4.5 Km/h for walking and 5~6 Km/h for jogging based on pretrial test. Blood glucose levels at fasting (~6:30am), pre-exercise (~8:30am), post-exercise (~9am), 11am and 4pm were detected. Results. Walking and jogging reached approximately moderate and high intensity based on the immediate post-exercise heart rate and RPE scores. Blood glucose levels at fasting, pre-exercise and 4pm were not substantially different among all groups (p > 0.05). JG had a significantly lower post-exercise blood glucose level (p < 0.05) when compared with CG and WG. The blood glucose level at 11am was notably lower in WG and JG than in CG (p < 0.05). Conclusions. Both a single bout of jogging and walking can lower postprandial blood glucose levels in T2DM patients. When matched for exercise distance, jogging represents a more effective strategy to immediately lower postprandial glucose levels than walking.

Objective. This research aim was to evaluates the role of the pre-ablation neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR) as predictors of distant metastases in patients with differentiated thyroid cancer (DTC). Methods. A retrospective analysis was given to 140 patients with DTC who received 131I remnant ablation after surgery. The patients were divided into two groups based on the existence of distant metastasis. Results. The two groups showed no significant difference in age, gender, WBCs, neutrophils, monocytes, eosinophils, basophils and whether the tumor was multifocal. In the univariate analysis, significant differences were found in tumor size (p=0.021), lymphocyte (p=0.012), NLR (p=0.027), and LMR (p=0.007). According to the ROC curves, NLR had an AUC of 0.612 ± 0.097 with a cut-off value of 1.845, sensitivity of 60.0%, and specificity of 66.2% (p=0.027). LMR had an AUC of 0.638 ± 0.095 with a cutoff value of 4.630, sensitivity of 84.6%, and specificity of 35.4% (p=0.007). In the multivariate analysis, larger tumor size (OR=5.246, 95% CI 1.269-10.907, p=0.009) and higher NLR (OR=2.087, 95% CI 0.977-4.459, p=0.034) were statistically significant for distant metastases. Conclusion. This research reveals that pre-ablation NLR and tumor size are significantly statistically correlated with distant metastases in patients with DTC.

Background. The aim of the present study was to systematically review the effects of Realsil (silybin– phospholipid–vitamin E complex) on liver enzymes in patients with NAFLD or NASH. Methods. We searched Web of Science, MEDLINE, Google Scholar, Cochrane Library, Science Direct, ProQuest, Scopus, and 1868 articles were found up to December 2018. Four studies that examined the effect of Realsil intake on liver enzymes among NAFLD or NASH patients were included. Exclusion criteria include: animal studies, studies with the design other than clinical trials, studies on non-adult individuals, studies that assess the effect of vitamin E, silybin, or phospholipid solely, studies that examined the effect of Realsil on other outcomes, or studies with insufficient data. Results. The analysis demonstrated that Realsil intake led to a significant decrease in Gamma-Glutamyl Transpeptidase (GGT) levels (standardized mean difference (SMD) =-0.37; 95% confidence interval (CI]): -0.68 to -0.06). Realsil intake non-significantly decrease alanine transaminase (ALT) levels (SMD=-1.02 U/L; 95% CI: -2.23 to 0.20) and non-significantly increase aspartate aminotransferase (AST) levels (SMD = 0.17 U/L; 95% CI: -0.26–0.61). Conclusion. Realsil intake was associated with a significantly decreased circulating GGT level without any significant effect on AST and ALT levels.

Context. Pituitary adenomas are benign tumors, usually found in men in their 3rd and 5th decades of life, representing 10-15% of all intracranial tumors. The clinical manifestations include important endocrinological disturbances and visual impairment. Objective. This study aimed to determine the most suitable neurosurgical approach regarding the dimensions, extensions and invasiveness of tumor extensions. Design. This was a systematic review of the literature from 2002-2022, focused on clinical outcome, especially endocrinological state according to the surgical approach. Subjects and Methods. We performed an advanced search on Web of Science and PubMed databases on October 10th, 2022. The literature showed 300 studies in the last 20 years, and after we applied the inclusion and exclusion criteria’s, 19 studies were fully read and analyzed. Results. Postoperative complications were reviewed in each surgical approach group, including visual impairment, new endocrinological disturbances, diabetes insipidus and cerebrospinal fluid leakage. Analyze of the endocrinological findings did not determined differences in transcranial groups from transsphenoidal groups. Overall complications were identified in the transcranial cohorts, while cerebrospinal fluid leakage still represent the main problem in transsphenoidal groups. The majority of studies found included extended endoscopic transsphenoidal approach, which shows results of great potential. Conclusions. For the surgical treatment of pituitary adenoma, transsphenoidal procedure with or without extended approaches is preferred, but they’re cases when a craniotomy is mandatory for a feasible gross tumor resection. Combined “above and below” simultaneous procedure or a two-staged intervention is recommended for giant pituitary adenoma, to maximize tumor resection and lower the risk of cerebrospinal fluid leakage.

Background. The high recurrence rate and low survival rate of ovarian cancer (OC) patients are closely related to an anoxic environment. We aim to study the mechanism of long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) on hypoxia ovarian cancer cells (OCC) and its mechanism was investigated. Methods. Knockdown and overexpression of HOTTIP in human OCC (SKOV-3, OVCAR3) were performed. The expression levels of HOTTIP and HIF- 1α were monitored by qRT-PCR and WB. Transwell was conducted to validate the cell migration and invasion. ELISA was performed to calculate VEGF concentration in cells. Cell viability was monitored by CCK-8. Cell apoptosis and cycle were tested by flow cytometry. RNA pull-down was used to analyze the interaction between HIF-1α and HOTTIP. Results. HOTTIP was highly expressed in OCC. After HOTTIP knockdown, HIF-1α expression and VEGF concentration in OCC were decreased. Cell migration, invasion, and cell viability were decreased. Cell apoptosis rate and G0/G1 phase cells were increased. RNA pull-down indicated a direct interaction between HIF-1α and HOTTIP. Conclusions. HOTTIP formed a positive feedback loop with HIF-1α to promote the development and metastasis of hypoxia ovarian cancer. This study provided theoretical support for the development of new OC treatment strategies.

Background. Type 1 diabetes mellitus is a common disorder which causes a variety of complications such as cognitive deficits in central nervous system. Auditory P300 event related potential is a wellestablished neurophysiologic approach in the assessment of cognitive performance. In this study, we aimed to evaluate the cognitive performance in insulin dependent diabetic patients by auditory event related potentials. Methods. In this descriptive analytical and non-interventional study, auditory P300 event related potential was measured in oddball paradigm by using two tone burst stimuli (1000 & 2000 Hz) on 25 diabetic patients and 25 age, education and sex matched healthy controls, with mean age 28.76±4.1 in patients and 29.68±3.6 in controls. Results. The mean P300 latency of the diabetic patients was significantly prolonged and the mean P300 amplitude of the diabetic patients was significantly lower when compared with that of controls at all electrode sites (p<0.01). Also there was a strong correlation between P300 latency and glucose level, HbA1c and diabetes duration (p<0.01). Conclusion. Auditory information processing is slower and the speed of information categorizing is lower in diabetic patients than in controls.

Background. Diabetes mellitus (DM) is considered as an important health confounder in our world, which necessitates its better management by new methods. In this study, we have evaluated the effects of oral Arnebia Euchroma (AE) extract on different stereological parameters of the pancreas as well as blood glucose in Streptozotocin (STZ)-induced diabetes in rats. Methods. We divided 48 Wistar rats into 4 groups: C1 including normal rats, C2 not-treated diabetic rats, E1 with diabetic rats receiving 100 mg/kg AE extract orally, and E2 including diabetic rats treated with 300 mg/kg AE extract. Stereological study was done and the levels of blood glucose were also estimated and compared between experimental and control groups. Results. There were significant differences in volumes of pancreatic islets, β cell populations, blood glucose levels in AE treated groups compared with nottreated diabetic group. Conclusion. Although AE did not completely prevent or heal the pancreatic damage, its oral administration showed promising effects on maintaining the population of beta cells, the main insulin secreting cells, after STZ-induced injury and also lowered blood glucose levels compared to the not-treated diabetic group.

recently. However, the nature of the signals that may connect body fat/muscle tissues with the central nervous system governing energy homeostasis remains to be elucidated. Objective. The present study was designed to investigate the effects of peripheral kisspeptin-10 administration on irisin release in human males. Subjects and methods. Kisspeptin-10 was administered to normal weight (n=8) and obese (n=8) men. Sequential blood sampling was performed for 30 minutes pre and 210 minutes post kisspeptin injection at 30 minutes interval. ELISA kit was used to detect plasma irisin levels. Results. There is a significant (P<0.0001) effect of Kisspeptin-10 administration on irisin release in both normal weight and obese participants. Mean irisin levels (96.24 ± 1.351 ng/mL) at 210 minutes were significantly (P<0.0001) enhanced as compared to pre-kisspeptin (59.18 ± 4.815 ng/ mL) in normal weight subjects. In obese subjects mean irisin levels (75.76 ± 4.06 ng/mL) were significantly (P<0.0001) elevated at 180 minutes post-kisspeptin when compared with pre-kisspeptin irisin levels (41.28 ± 2.89 ng/mL). Conclusion. Our findings suggest that kisspeptin may have a novel therapeutic potential to induce irisin release in humans which may have anti-obesity effects.