Wenhuan Feng

Comparative efficacy of anti‐diabetic agents on nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus: a systematic review and meta‐analysis of randomized and non‐randomized studies

Nonalcoholic fatty liver disease (NAFLD) has a high prevalence in patients with type 2 diabetes mellitus (T2DM). In this study, we sought to provide a comprehensive assessment regarding the effects of anti‐diabetic agents on NAFLD in patients with T2DM.

Randomized trial comparing the effects of gliclazide, liraglutide, and metformin on diabetes with non-alcoholic fatty liver disease†

The aim of the present study was to compare the effects of gliclazide, liraglutide, and metformin in type 2 diabetes mellitus (T2DM) patients with non‐alcoholic fatty liver disease (NAFLD).

Effects of liraglutide, metformin and gliclazide on body composition in patients with both type 2 diabetes and non-alcoholic fatty liver disease: A randomized trial

To compare the effects of gliclazide, liraglutide and metformin on body composition in patients with type 2 diabetes mellitus with non‐alcoholic fatty liver disease.

Effects of Exenatide on Metabolic Changes, Sexual Hormones, Inflammatory Cytokines, Adipokines, and Weight Change in a DHEA-Treated Rat Model

Insulin resistance and hyperandrogenism are the main features of polycystic ovarian syndrome (PCOS). Low-grade inflammation is also involved in PCOS. This study was performed to evaluate the effect of exenatide on metabolic changes, sexual hormones, inflammatory cytokines, adipokines, and weight changes in a dehydroepiandrosterone (DHEA)-treated rat model. After the model was produced by daily subcutaneous injections of DHEA, rats were given metformin (265 mg/kg), exenatide (10 μg/kg), and saline (1 mL). One group served as a control group. Blood samples and ovarian tissues were removed and prepared for biochemical and hormonal analyses. Exenatide significantly reduced body weight and insulin, testosterone, interleukin 6 (IL-6), PEDF, and visfatin levels. Exenatide also ameliorated changes in ovarian morphology, as evidenced by decreased numbers of cystic follicles and various follicles and elevated numbers of granular cell layers. The effects observed with exenatide were comparable to those observed with metformin. This study has provided evidence that exenatide may be efficient in the treatment of PCOS.

Clinical and Pathological Characteristics of Hypertensive and Normotensive Adrenal Pheochromocytomas

INTRODUCTION Pheochromocytoma/Paraganglioma (PPGL) present with an extremely variable clinical picture which ranges from dramatic, to mild, to silent, depending on tumor attitude to release catecholamines. Hypertension is the hallmark of these tumors but is not always present. Distinct differences of clinical manifestations exist in hypertensive pheochromocytomas (HPs) and normotensive pheochromocytomas (NPs), however the comparative analysis is lacking. METHODS The objective was to assess the clinical symptoms, hemodynamics, metabolism, radiological and histological features of patients with HPs and NPs. This study included 104 pheochromocytoma patients who were categorized into HPs (n=69) and NPs (n=35) groups. All clinical records were reviewed. Tumor samples were examined to determine the Adrenal Gland Scale Score and were available for measurement of gene transcriptions. Biochemical examinations of 95 subjects with primary hypertension (PH) were recorded for comparative study. RESULTS Patients with NPs showed lower proportion of clinical triad, inapparent metabolic disorders and lower urinary catecholamine levels than HPs, but higher than PH. Tumor weight positively correlated with 24 h urinary norepinephrine level in patients with HPs (P=0.028), and tumor diameter negatively correlated with phenylethanolamine-N-methyltransferase (PNMT) immunohistochemistry (P=0.011) in NPs but not in HPs. The Adrenal Gland Scale Score of NPs group was similar to that of HPs group. The positive percentage of epinephrine type (E-type) of catecholamine in HPs group was higher than that in the NPs. The transcript gene levels of PNMT, secretogranin II (SGII) and neuropeptide Y (NPY) from tissue samples were significantly lower in NPs than in HPs (PPNMT=0.038, PSGII=0.040, PNPY=0.032), while vesicular monoamine transporter 1 (VMAT1) had no difference between HPs and NPs (PVMAT1=0.053). CONCLUSION HPs and NPs have distinct differences in clinical, biochemical and pathological phenotypes, which are closely related with productions involved in tumor occurrence and development.

Adrenal androgen measurement for assessing the selectivity of adrenal venous sampling in primary aldosteronism

HighlightsCompared to cortisol, the AV/PV ratios of androstenedione and DHEA in AV samples were larger in AVS.Compared to cortisol, the concentrations of androstenedione and DHEA in AV samples were less variable over time in AVS.An SI ≥ 3 for androstenedione or DHEA provided optimal sensitivity and specificity in AVS. &NA; Adrenal venous sampling (AVS) is the reference standard for primary aldosteronism (PA) subtyping. Cortisol is widely used to assess the success of selective AVS, but it is not always reliable. The aim of the present study was to investigate the usefulness of adrenal androgens, compared to cortisol, in assessing the selectivity of AVS. We consecutively recruited 37 patients with PA undergoing AVS. AVS procedures were performed with the bilateral simultaneous technique without cosyntropin stimulation. We collected two baseline blood samples from 10 patients with a 15‐min interval between time‐15 (t‐15) and time 0 (t0) to measure the variability in the levels of the tested hormones over time. Cortisol, androstenedione, dehydroepiandrosterone (DHEA), and DHEA sulfate (DHEAS) concentrations were measured in adrenal and peripheral venous (AV and PV, respectively) samples. The selectivity index (SI) values for androstenedione and DHEA were on average 3.0‐ and 2.0‐fold higher, respectively, than those for cortisol, respectively (P < 0.05). However, the SI for DHEAS was 5.0‐fold lower than the SI for cortisol (P < 0.05). Plasma androstenedione and DHEA concentrations positively correlated with cortisol and aldosterone concentrations in AV samples (P < 0.01). Compared to cortisol, the variation ratio of AV androstenedione and DHEA decreased from t‐15 to t0 (0.23 and 0.43 vs. 0.52; P = 0.001 and P = 0.061, respectively). Using receiver operating characteristic curves, an SI ≥ 3 for androstenedione or DHEA provided optimal sensitivity and specificity in AVS. Given the much larger AV/PV ratios and reduced variability compared to cortisol, the adrenal androgens androstenedione and DHEA are useful for assessing the selectivity of AVS without cosyntropin stimulation and may be superior analytes in conditions with marked variability of cortisol levels or with adrenocortical tumors cosecreting cortisol and aldosterone.

Prolactin improves hepatic steatosis via CD36 pathway

BACKGROUND & AIMS Prolactin (PRL) is a multifunctional polypeptide with effects on metabolism, however, little is known about its effect on hepatic steatosis and lipid metabolism. Herein, we aimed to assess the role of PRL in the development of non-alcoholic fatty liver disease (NAFLD). METHODS The serum PRL levels of 456 patients with NAFLD, 403 controls without NAFLD diagnosed by ultrasound, and 85 individuals with liver histology obtained during metabolic surgery (44 female and 30 male patients with NAFLD and 11 age-matched non-NAFLD female individuals) were evaluated. The expression of the gene encoding the prolactin receptor (PRLR) and signalling molecules involved in hepatic lipid metabolism were evaluated in human liver and HepG2 cells. The effects of overexpression of PRLR or fatty acid translocase (FAT)/CD36 or knockdown of PRLR on hepatic lipid metabolism were tested in free fatty acid (FFA)-treated HepG2 cells. RESULTS Circulating PRL levels were lower in individuals with ultrasound-diagnosed NAFLD (men: 7.9 [range, 5.9-10.3] µg/L; women: 8.7 [range, 6.1-12.4] µg/L) than those with non-NAFLD (men: 9.1 [range, 6.8-13.0] µg/L, p = 0.002; women: 11.6 [range, 8.2-16.1] µg/L, p <0.001). PRL levels in patients with biopsy-proven severe hepatic steatosis were lower compared with those with mild-to-moderate hepatic steatosis in both men (8.3 [range, 5.4-9.5] µg/L vs. 9.7 [range, 7.1-12.3] µg/L, p = 0.031) and women (8.5 [range, 4.2-10.6] µg/L vs. 9.8 [range, 8.2-15.7] µg/L, p = 0.027). Furthermore, hepatic PRLR gene expression was significantly reduced in patients with NAFLD and negatively correlated with CD36 gene expression. In FFA-induced HepG2 cells, PRL treatment or PRLR overexpression significantly reduced the expression of CD36 and lipid content, effects that were abrogated after silencing of PRLR. Furthermore, overexpression of CD36 significantly reduced the PRL-mediated improvement in lipid content. CONCLUSIONS Our results reveal a novel association between the central nervous system and the liver, whereby PRL/PRLR improved hepatic lipid accumulation via the CD36 pathway. LAY SUMMARY Our clinical study suggests a negative association between prolactin (PRL)/prolactin receptor (PRLR) and the presence of non-alcoholic fatty liver disease (NAFLD). Using cell experiments, we found that PRL ameliorates hepatic steatosis via the hepatic PRLR and fatty acid translocase (FAT)/CD36, a key transporter of free fatty acid uptake in liver. Our findings suggest a novel approach to improving NAFLD using PRL and PRLR. Clinical trial number: NCT03296605.

Expression and Histopathological Significance of Disabled-2 in Aldosterone-Producing Adenoma

The current pathological diagnosis of aldosterone-producing adenoma (APA) is challenging because no histological markers of aldosterone production are available in routine practice. A previous study demonstrated that Disabled-2 (DAB2) is a specific marker of the zona glomerulosa (ZG) in rodents. The aim of the present study was to investigate the significance of immunohistochemical staining to detect DAB2 in the adrenal tissue of patients with APA. We investigated the expression of DAB2 in 36 adrenal glands with APA, 23 adrenal glands with cortisol-producing adenoma (CPA), and 33 adrenal glands with non-functioning adenoma (NFA). Immunohistochemical staining was performed using anti-DAB2 antibodies on paraffin-embedded sections. We analysed the expression of DAB2 semi-quantitatively by scoring staining intensity, and assessed the correlation of this information with the clinical findings. DAB2 mRNA expression in adenoma tissues was evaluated by RT-PCR. DAB2 was highly expressed in the ZG in normal human adrenal glands. DAB2 expression was heterogeneous in APA, with spotted, strong staining noted in most samples (25 of 36 APA). CPA and NFA also exhibited extensive low or moderate DAB2 expression. DAB2 mRNA was significantly increased and positively correlated with CYP11B2 in APA (p<0.05). In APA, the DAB2 score adjusted for tumour volume was positively correlated with plasma aldosterone (p<0.05). Patients with low or moderate DAB2 staining more frequently exhibited high blood pressure and were diagnosed at a younger age compared with patients with high DAB2 staining. The present study clearly demonstrates that DAB2 is a specific marker of the ZG in normal human adrenal glands but that DAB2 immunostaining is not sufficiently powerful for histopathological diagnosis of APA. DAB2 might be involved in excessive aldosterone biosynthesis and correlate with specific clinical characteristics of APA patients.