Circulating mir-200c and mir-33a may be used as biomarkers for predicting high fructose corn syrup-induced fatty liver and vitamin D supplementation-related liver changes.

BACKGROUND: Nonalcoholic fatty liver is one of the most common forms of liver disease and role of microRNAs (miRNAs) on this illness is currently unclear. It was aimed to evaluate the predictive role of circulating miR-33a and mir-200c on high fructose corn syrup (HFCS)-induced fatty liver and vitamin D3 supplementation-related hepatic changes. METHODS: Twenty-four rats were randomized into three groups: sham (n = 8), experimental fatty liver group (n = 8), and fatty liver + vitamin D3 supplementation group (n = 8). In the treatment group, 10 µg/kg/week of vitamin D3 was given by orogastric tube weekly for 4 weeks in addition to a high fructose diet. Serum AST, ALT, TNF-α, and MDA levels were tested. Liver tissue samples were examined using hematoxylin/eosin, periodic acid-Schif (PAS) and Masson's Trichrome staining. Circulating miR-33a and mir-200c were quantified by qRT-PCR method. Moreover, in silico analyses were accomplished. RESULTS: In the vitamin D3 group, results of biochemical parameters were significantly different than those of the fatty liver group (p < 0.001). Moreover, significant differences in serum levels of circulating miR-33a and mir-200c were identified among all groups (p < 0.05). Finally, more favorable histopathological changes were noticed in the vitamin D3 supplementation group. The expressions of Ki-67 were also considerably reduced in the vitamin D3 group. According to KEGG pathway analysis, mir-33a and mir-200c were found to play a common role in the Hippo signaling pathway, lysine degradation, and protein processing. DISCUSSION: Our current experimental fatty liver study showed that, in a specified dose, vitamin D3 supplementation could alleviate adverse undesirable hepatic effects of HFCS via miR-33a and mir-200c.

Kisspeptin levels in idiopathic hypogonadotropic hypogonadism diagnosed male patients and its relation with glucose-insulin dynamic.

Male hypogonadism is defined as the deficiency of testosterone or sperm production synthesized by testicles or the deficiency of both. The reasons for hypogonadism may be primary, meaning testicular or secondary, meaning hypothalamohypophyseal. In hypogonadotropic hypogonadism (HH), there is indeficiency in gonadotropic hormones due to hypothalamic or hypophyseal reasons. Gonadotropin-releasing hormone (GnRH) is an important stimulant in releasing follicular stimulant hormone (FSH), mainly luteinizing hormone (LH). GnRH omitted is under the effect of many hormonal or stimulating factors. Kisspeptin is present in many places of the body, mostly in hypothalamic anteroventral periventricular nucleus and arcuate nucleus. Kisspeptin has a suppressor effect on the metastasis of many tumors such as breast cancer and malign melanoma metastases, and is called "metastin" for this reason. Kisspeptin is a strong stimulant of GnRH. In idiopathic hypogonadotropic hypogonadism (IHH) etiology, there is gonadotropic hormone release indeficiency which cannot be clearly described. A total of 30 male hypogonatropic hypogonadism diagnosed patients over 30 years of age who have applied to Haydarpasa Education Hospital Endocrinology and Metabolic Diseases Service were included in the study. Compared to the control group, the effect of kisspeptin on male patients with hypogonatropic hypogonadism and on insulin resistance developing in hypogonadism patients was investigated in our study. A statistically significant difference was detected between average kisspeptin measurements of the groups (p < 0.01). Kisspeptin measurement of the cases in the patient group were detected significantly high. No statistically significant relation was detected among kisspeptin and LH/FSH levels. Although a positive low relation was detected between kisspeptin measurements of patient group cases and homeostasis model assessment of insulin resistance (HOMA-IR) measurements, this relation was statistically insignificant. When the patient and control groups were compared for HOMA-IR, no statistically significant difference was detected. The reason for high kisspeptin levels in the patient group compared to the control group makes us consider that there may be a GPR54 resistance or GnRH neuronal transfer pathway defect. When patients and control groups were compared for HOMA-IR, the difference was not statistically significant. It is considered that kisspeptin is one of the reasons for hypogonatropic hypogonadism and has less effect on insulin resistance.

Early Neurodegeneration of the Inner Retinal Layers in Type 1 Diabetes Mellitus.

PURPOSE: This study explores retinal structural changes in type 1 diabetes without clinically diagnosed diabetic retinopathy (DR). METHODS: Peripapillary retinal nerve fiber layer (RNFL) thickness, macular ganglion cell complex (GCC) thickness, and macular thickness (MT) were measured in 90 type 1 diabetic patients by using spectral domain optical coherence tomography. The values were compared with 100 sex- and age-matched healthy controls. The independent t test was used to assess differences in the mean age, mean diabetic and ocular parameters, and the thickness values between the diabetic and control groups. Multiple linear regression analysis was performed to investigate the correlation between the thickness values and diabetic and ocular parameters. RESULTS: Whole-RNFL, the superior and inferior quadrants, and the superior half of the peripapillary RNFL thicknesses were significantly thinner in diabetic patients compared with controls (p < 0.05). GCC thicknesses in the average macular, outer temporal superior and outer temporal inferior sectors were significantly thinner in diabetic patients (p < 0.05). Central and average MTs were similar in both groups (p > 0.05). There were significant negative correlations of the duration of type 1 diabetes with the inner nasal MT, inner temporal superior GCC thickness, inner nasal inferior GCC thickness, and outer nasal superior GCC thickness (p < 0.05). Similarly, there were significant negative correlations of the level of HbA1c with the whole-RNFL thickness, superior-half-RNFL thickness, and superior-quadrant-RNFL thickness (p < 0.05). CONCLUSIONS: Type 1 diabetic patients without clinically diagnosed DR had neurodegeneration in the inner retinal layers compared with healthy controls.

Publication Rate of Abstracts Presented at the Annual Congress of the European Society for Surgical Research during 2008-2011.

BACKGROUND/PURPOSE: The presentation of scientific studies at major meetings serves to rapidly share study results with the scientific community. On the other hand, full-text publication of abstracts in peer-reviewed journals ensures the dissemination of science. This study examines the publication rate (PR) of meeting abstracts presented at the European Society for Surgical Research (ESSR) congresses and determines/compares the factors affecting the PRs. METHODS: All presentations at the ESSR congresses held during 2008-2011 were retrospectively assessed. Manuscripts indexed in PubMed were included. The meeting year, journal impact factor (IF) in the publication year, study type, presentation type, time to publication and geographic origin of studies were assessed. RESULTS: Among a total of 1,368 oral and poster abstracts, 48.7% (n = 391) of the oral presentations (OPs) and 29.7% (n = 168) of the poster presentations (PPs) were published in medical journals indexed in PubMed. The mean IF of the journals was 2.696 (0.17-14.95). The journals that published OPs had a higher IF than the journals in which PPs were published (2.944 vs. 2.118; p < 0.001). The PR was also higher in the OP group than in the PP group of journals (p < 0.001). The time to publication was 17.5 months (-166 to 82) and was shorter for PPs than for OPs (14.02 vs. 19.09 months; p = 0.01). According to the study type, experimental studies had a significantly higher PR (53.7%; p < 0.001); however, there was no significant difference in PR in terms of the prospective or retrospective nature of clinical studies. The clinical studies were also compared according to the IF values of the journals in terms of the prospective or retrospective nature of the study, and no significant difference was found (p = 0.62). CONCLUSION: The ESSR congress is an efficient meeting for researchers from varied surgical disciplines and has a PR equivalent to that of similar scientific meetings. The congress has achieved a PR of 40.9% over 4 years with an average IF of 2.696 and a mean time to publication of 17.5 months, which is equivalent to that of similar scientific meetings. OPs have a higher PR in journals with greater IF values as compared with PPs.

Insulinoma Misdiagnosed as Post-bariatric Hypoglycemia: A Case Report and Review of the Literature.

Hypoglycemia is seen with increasing frequency after bariatric surgery. After the diagnosis of hypoglycemia has been clarified, malnutrition, drugs, hormone deficiencies, insulinoma, extra-islet tumors, post-bariatric hypoglycemia (PBH), early or late dumping syndrome, and nesidioblastosis should be considered in the differential diagnosis. A few case reports of insulinomas presenting after bariatric surgery have been reported in the literature. The coexistence of insulinoma and type 2 diabetes mellitus (T2D) is very rare. We herein report a clinical case of insulinoma presenting with severe hypoglycemia in a patient with a history of gastric transit bipartition. A patient with type 2 diabetes mellitus underwent gastric transit bipartition surgery due to the inability of medical therapy to provide adequate hyperglycemia control. After the operation, hypoglycemic symptoms appeared, and a reversal operation was performed, considering the diagnosis as PBH. After the reverse operation, the patient's hypoglycemia symptoms did not regress. The patient was admitted to our endocrinology clinic due to the persistence of hypoglycemia and symptoms such as fatigue, palpitation, and syncope. The patient's detailed anamnesis was examined, additional tests were performed, and the patient was diagnosed with insulinoma. The symptoms of hypoglycemia and the need for treatment for diabetes mellitus disappeared after the Whipple operation. This is the first case of insulinoma after gastric transit bipartition and subsequent reversal operations. In addition, the patient's diagnosis of diabetes mellitus makes this case unique. Although this is a very rare case, clinicians must be aware of it, especially if the patient has hypoglycemic symptoms during the fasting state.

The effects of glucagon like peptide-1 (GLP-1) on cardiac remodeling: exploring the role of medication and physiological modulation after metabolic surgery.

Obesity and associated comorbidities reach epidemic proportions nowadays. Several treatment strategies exist, but bariatric surgery has the only longstanding effects. Since a few years, there is increasing interest in the effects of gastro-intestinal hormones, in particular Glucagon-Like Peptide-1 (GLP-1) on the remission of Type 2 Diabetes (T2DM) and its effects on cardiac cardiovascular morbidity, cardiac remodeling, and mortality. In the past years several high quality multicenter randomized controlled trials were developed to assess the effects of GLP-1 receptor agonist therapy on cardiovascular morbidity and mortality. Most of the trials were designed and powered as non-inferiority trials to demonstrate cardiovascular safety. Most of these trials show a reduction in cardiovascular morbidity in patients with T2DM. Some follow-up studies indicate potential beneficial effects of GLP-1 receptor agonists on cardiovascular function in patients with heart failure, however the results are contradictory, and we need long-term studies to make firm conclusions about the pleiotropic properties of incretin-based therapies. However, it seems that GLP-1 receptor agonists have different effects than the increased GLP-1 production after bariatric surgery on cardiovascular remodeling. One of the hypotheses is that the blood concentrations of GLP-1 receptor agonists are three times higher compared to GLP-1 increase after bariatric and metabolic surgery. The purpose of this narrative review is to summarize the effects of GLP-1 on cardiovascular morbidity, mortality and remodeling due to medication but also due to bariatric and metabolic surgery. The second objective is to explain the possible differences in effects of GLP-1 agonists and bariatric and metabolic surgery.

The vasoactive intestinal polypeptide (VIP) levels at the patients with ankylosing spondylitis and its association with inflammation markers.

Vasoactive intestinal polypeptide (VIP) is a neuropeptide from secretin/glukagon family. Recently, the importance of VIP is becoming more evident, and it is thought that VIP is playing an important regulatory role between neuroendocrine-immune-gastrointestinal systems. In this study, we have tried to evaluate the potential role of VIP in patients with ankylosing spondylitis (AS). In this study, 40 patients (30 male and 10 female) with AS and 40 healthy controls were included. X-ray examinations and scoring of sacroiliac joints of the patients with AS were done according to 1984 Modified New York Criteria for AS. All patients have been assessed with Bath Ankylosing Spondylitis Disease Activity Index. Platelet counts were significantly higher in study group (P < 0.05) in contrast to levels of the hemoglobin. The mean VIP levels were 4.2 ± 1.8 (pg/mL) for study group and 2.8 ± 0.8 (pg/mL) for controls. These results were statistically significant (P < 0.05). There was not any correlation between plasma VIP levels with CRP, ESR, Hb, BASDAI results and radiological scoring of the patients (P > 0.05) in contrast to our expectations. However, platelet counts and VIP levels were correlated significantly (P = 0.03). Our data demonstrate that VIP tended to be high in patients with AS when compared with healthy subjects and correlated with platelet counts significantly, for the first time at the literature. According to this study, VIP may have potential role in the pathogenesis of AS, and it is a potential candidate for many kinds of therapies.

The Prophylactic Effects of Metoprolol, Diltiazem, and Pilocarpine on Hypoglycemia-Induced Prolongation of QT Interval.

Background Insulin-induced hypoglycemia has been demonstrated to prolong the corrected QT (QTc) interval. Prolongation of the QTc interval, especially in diabetic patients using insulin, can cause fatal ventricular arrhythmias. The aim of this study was to evaluate the effects of metoprolol, diltiazem, and pilocarpine on hypoglycemia-induced QTc prolongation. Methods Thirty male rats were randomly distributed into the following five groups: Group 1 (1 mL/kg saline, n=6), Group 2 (40 U/kg crystalline insulin + saline, n=6), Group 3 (40 U/kg crystalline insulin + 1 mg/kg metoprolol, n=6), Group 4 (40 U/kg crystalline insulin + 0.8 mg/kg pilocarpine, n=6), and Group 5 (40 U/kg crystalline insulin + 2 mg/kg diltiazem, n=6). Three hours after insulin injection, the blood glucose level was measured in all groups. Blood glucose <40 mg/dl was defined as hypoglycemia. Electrocardiograms (ECG) were taken in lead I (DI), and QTc was calculated by using Bazett's formula. Results Group 2 (insulin + saline) showed that it had a significantly prolonged QTc interval as compared to the control group (p<0.0001). However, treatments of the rats with metoprolol, pilocarpine, and diltiazem significantly prevented prolongation of the QTc interval as compared to the insulin + saline group (p<0.005, p<0.005, and p<0.01, respectively). Conclusion The findings of the present study demonstrated the efficacy of metoprolol, pilocarpine, and diltiazem in the prevention of hypoglycemia-induced QTc prolongation in male rats.

Effects of Bariatric Surgery on Heart Rhythm Disorders: a Systematic Review and Meta-Analysis.

The aim of this systematic review is to provide an overview of the literature on the effects of bariatric surgery on obesity-associated electrocardiogram (ECG) abnormalities and cardiac arrhythmias. Fourteen studies were included with a methodological quality ranging from poor to good. Majority of the studies showed a significant decrease of QT interval and related measures after bariatric surgery. Seven studies were included in the meta-analysis on effects of bariatric surgery on QTc interval and a significant decrease in QTc interval of - 33.6 ms, 95%CI [- 49.8 to - 17.4] was seen. Bariatric surgery results in significant decrease in QTc interval and P-wave dispersion, i.e., a normalization of initial pathology. The effects on atrial fibrillation are conflicting and not yet fully understood.

Biochemical characteristics and calcium and PTH levels of patients with high normal and elevated serum 25(OH)D levels in Turkey: DeVIT-TOX survey.

Vitamin D intake over the recommended dose is usually associated with high serum 25(OH)D levels and generally not associated with symptoms of hypercalcemia. High doses of cholecalciferol need to be avoided to protect against vitamin D toxicity and related complications. Strict adherence to the clinical guidelines for treating vitamin D deficiency can ensure safe and effective treatment. PURPOSE: We observed a tendency to use high doses of cholecalciferol for vitamin D deficiency treatment or vitamin D supplementation. We aimed to determine the biochemical characteristics of patients with high normal and elevated serum 25(OH)D levels. METHODS: An online invitation was sent to all tertiary endocrinology clinics in Turkey to complete an online retrospective survey (DeVIT-TOX Survey) for patients diagnosed with high serum 25(OH)D levels (> 88 ng/mL) between January 2019 and December 2019. The patients were evaluated according to the presence of signs and symptoms of hypercalcemia and doses of vitamin D intake, evaluated into the following three groups according to their 25(OH)D levels: group 1, > 150 ng/mL; group 2, 149-100 ng/mL; and group 3, 99-88 ng/mL. RESULTS: A total of 253 patients were included in the final analysis (female/male: 215/38; mean age, 51.5 ± 15.6 years). The average serum 25(OH)D level was 119.9 ± 33 (range, 88-455) ng/mL, and the average serum calcium level was 9.8 ± 0.7 (range, 8.1-13.1) mg/dL. Most (n = 201; 75.4%) patients were asymptomatic despite having high serum 25(OH)D and calcium levels. The serum 25(OH)D level was significantly higher in the symptomatic groups than in the asymptomatic groups (138.6 ± 64 ng/mL vs. 117.7 ± 31 ng/mL, p < 0.05). The most common cause (73.5%) associated with high serum 25(OH)D levels was the inappropriate prescription of a high dose of oral vitamin D (600.000-1.500.000 IU) for treating vitamin D deficiency/insufficiency in a short time (1-3 months). The cut-off value of 25 (OH) D level in patients with hypercalcemia was found to be 89 ng/mL [median 116.5 (89-216)]. CONCLUSIONS: High dose of vitamin D intake is associated with a high serum 25 OH D level, without symptoms of hypercalcemia. Inappropriate prescription of vitamin D is the primary cause for elevated 25(OH) D levels and related hypercalcemia. Hypercalcemia may not be observed in every patient at very high 25(OH) D levels. Adherence to the recommendation of guidelines is essential to ensure safe and effective treatment of vitamin D deficiency.