Comparison of exenatide alone or combined with metformin versus metformin in the treatment of polycystic ovaries: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of childbearing age. Randomized controlled trials (RCTs) have reported that exenatide and metformin are effective in the treatment of PCOS. In this meta-analysis, we aimed to compare the effectiveness and safety of exenatide alone or in combination with metformin versus metformin in patients suffering from PCOS. METHODS: RCTs of exenatide therapy were identified through a search of electronic databases in November 2022 and updated in October 2023. Eligible studies were identified independently by the reviewers. Outcomes were analysed with Revman 5.4. RESULTS: Nine RCTs among 214 studies on 1059 women with PCOS were included in the analysis, and among the nine RCTs, eight studies compared exenatide with metformin. Our meta-analysis demonstrated that exenatide was more effective than metformin in terms of pregnancy rate (RR 1.85 [95% CI 1.19,2.86] P = 0.006), sex hormone-binding globulin (SHBG) (MD 5 [95% CI 3.82,6.18] P < 0.001), and follicle-stimulating hormone (FSH) (MD 0.82 [95% 0.41,1.24] P < 0.001). The reductions in total testosterone (TT) (SMD -0.43 [95% CI -0.84, -0.03] P = 0.04) was more significant after treatment with exenatide than after treatment with metformin. In terms of safety, exenatide had a lower diarrhea rate (RR 0.11 [95% CI 0.01, 0.84]) than metformin. In the other three studies, exenatide plus metformin was compared with metformin. Exenatide combined with metformin was more effective in improving SHBG (MD 10.38[95%CI 6.7,14.06] P < 0.001), Matsuda index (MD 0.21[95%CI 0.05,0.37]) and reducing free androgen index (FAI) (MD -3.34 [-4.84, -1.83] P < 0.001), Weight (MD -2.32 [95%CI -3.89, -0.66]) and WC (MD-5.61[95%CI -8.4, -2.82] P < 0.001). The incidence of side effects between exenatide plus metformin and metformin was not statistically significant. CONCLUSIONS: Exenatide alone or in combination with metformin is more effective than metformin for women with PCOS. Considering the evidence on effectiveness and safety, exenatide alone or in combination with metformin may be a better treatment approach than metformin for women with PCOS. TRIAL REGISTRATION: INPLASY https://inplasy.com/inplasy-protocols/ ID: 10.37766/inplasy2022.11.0055.

Effect of type 2 diabetes mellitus and periodontitis on the Th1/Th2 and Th17/Treg paradigm.

PURPOSE: To investigate the effect of type 2 diabetes mellitus (T2DM) and periodontitis on the Th1/Th2/Th17/Treg paradigm. METHODS: A total of 107 volunteers (aged 18-78 years) were recruited. Peripheral blood samples from patients with periodontitis and T2DM (n= 43), patients with periodontitis only (n= 20), patients with T2DM only (n= 23), and healthy controls (n= 21) were collected. Blood pressure, glycated hemoglobin, fasting plasma glucose, probing depth, gingival index, and clinical attachment loss were measured. The circulating proportions of Th1, Th2, Th17, and Treg cells were estimated by flow cytometry. The data were analyzed by a 2x2 factorial ANOVA. RESULTS: We observed higher ratios of Th1/Th2 and Th17/Treg cells among patients with T2DM (P< 0.05) than among healthy controls. The proportion of Th17 cells in patients with periodontitis and T2DM was higher than that in other groups (P< 0.05). T2DM exhibited a predominant effect on the proportion of Th1 cells (F= 18.127, P= 0.000) and the Th17/Treg ratio (F= 45.384, P= 0.000). A significant "T2DM x periodontitis" interaction effect on the proportion of Th2, Th17, Treg cells, and the Th1/Th2 ratio (P< 0.05) was also noticed. The area under curve of Th17 was 0.711 (95% CI= 0.584 to 0.803, P< 0.01) in the receiver operating characteristic curve analysis. CLINICAL SIGNIFICANCE: The results suggest that the proportion of Th2, Th17, Treg cells and the Th1/Th2 ratio is indicative of immune activation and inflammation, which are evident in patients with type 2 diabetes mellitus (T2DM) and periodontitis. The data indicate that the high expression of Th17 cells may be a relevant biological factor that can be associated with an increased risk of developing chronic periodontitis in patients with T2DM.

Non-Classical 21-Hydroxylase Deficiency: Analysis of a Mutant Gene in a Uyghur Family and Literature Review.

OBJECTIVE: The gene mutation and clinical characteristics of a patient with non-classical 21-hydroxylase deficiency and his family were analyzed. METHODS: A patient was diagnosed with non-classical 21-hydroxylase deficiency in the Department of Endocrinology of People's Hospital of Xinjiang Uygur Autonomous Region in December 2016. The clinical data and related gene-sequencing results were analyzed. The detected mutations were verified in nine members of the family. RESULTS: Gene-sequencing results revealed that the proband and the other three members of the family (proband, proband's mother's younger brother and the proband's mother's younger brother's younger daughter, and proband's second elder sister) shared the following mutations: Ile173Asn, Ile237Asn, Val238Glu, Met240Lys, Val282Leu, Leu308Phefs*6, Gln319Ter, Arg357Trp, and Arg484Profs. The Val282Leu mutation was heterozygous in the proband's mother's younger brother's younger daughter, but homozygous in the other three individuals. The father of the proband, the elder brother of the father of the proband, the third younger brother of the father of the proband, and the elder sister of the proband all carried only the Val282Leu mutation. CONCLUSION: Val282Leu is the gene responsible for non-classical 21-hydroxylase deficiency. Screening for this gene in the offspring of patients with non-classical 21-hydroxylase deficiency may help to identify cases early.

Regulation of lncRNA PVT1 on miR-125 in metastasis of gastric cancer cells.

Regulation of long non-coding RNA (lncRNA) PVT1 on miR-125 affecting the metastasis of gastric cancer cells and the mechanism were investigated. qPCR was used to detect the expression of PVT1 and miR-125 in gastric cancer and paracancerous tissues, and the relationship between PVT1 and clinicopathological parameters of gastric cancer patients. Dual luciferase reporter gene was used to detect the mutual effect between PVT1 and miR-125. The clone formation assay was used to detect changes of proliferation behavior of gastric cancer cells after inhibition of PVT1. Transwell invasion assay was used to detect the changes of invasion ability of gastric cancer cells after inhibition of PVT1. Subcutaneous tumor formation in nude mice inhibited the effect of PVT1 on the tumor size and volume of gastric cancer cells. Compared with paracancerous tissues, the expression of PVT1 and miR-125 was significantly increased in gastric cancer tissues. There were no significant differences in the expression level of PVT1 between gastric cancer patients of different genders and ages. The higher the gastric cancer staging was, the more obvious the expression level of PVT1 in the tissues of patients with gastric cancer was, and the more obvious the expression of PVT1 in the tissues of patients with gastric lymph node metastasis was. PVT1 specifically bound to the 3'UTR of miR-125, whereas the inhibition of PVT1 inhibited the ability of proliferation and invasion of gastric cancer cells. In vitro experiment of tumor formation in nude mice showed that the tumor volume and weight of the tumor-bearing mice in the si-PVT1 group were significantly reduced. PVT1 plays an important role in the occurrence and development of gastric cancer, it can regulate the proliferation and invasion of gastric cancer cells by targeting miR-125 activity.

Comparison of Androgen Levels, Endocrine and Metabolic Indices, and Clinical Findings in Women with Polycystic Ovary Syndrome in Uygur and Han Ethnic Groups from Xinjiang Province in China.

BACKGROUND The aim of this study was to compare androgen levels, endocrine and metabolic indices, and clinical findings in women with polycystic ovary syndrome (PCOS) in Uygur and Han ethnic groups from Xinjiang Province, China. MATERIAL AND METHODS Between January 2016 to May 2017 clinical data were collected from Uygur (N=82) and Han (N=100) women diagnosed with PCOS, including age, body mass index (BMI), the Ferriman-Gallwey (mFG) hirsutism score, and waist-to-hip ratio (WHR). Blood samples obtained from all study participants were used to measure androgenic steroid levels, including androgen, androstenedione, dehydroepiandrosterone (DHEA), dihydrotestosterone (DHT), and the free androgen index (FAI). Endocrine indices measured included sex-hormone binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and prolactin (PL). Metabolic indices measured included insulin, glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), triglyceride (TG), and low-density lipoprotein (LDL). RESULTS The FAI in Uygur women with PCOS (4.89) was significantly increased compared with Han women with PCOS (2.78) (p<0.05); androgen levels were significantly correlated with the FAI, glucose, insulin, TC, HDL, and LDL (p<0.05); androstenedione levels were positively correlated with glucose and insulin levels (p<0.05). In Han women with PCOS, androgen levels were negatively correlated with TG levels and positively correlated with TC levels (p<0.05); the FAI was positively correlated with glucose and insulin levels (p<0.05). CONCLUSIONS There were significant differences in androgen levels, endocrine, and metabolic indices in women with PCOS between the Uygur and Han ethnic groups from Xinjiang Province in China.

Different lipid profiles, insulin sensitivity, and insulin resistance among Han, Uygur, and Kazak men with normal glucose tolerance in Xinjiang, China.

BACKGROUND: This study aimed to determine the differences in clinical parameters among Han, Uygur, and Kazak men with normal glucose tolerance. METHODS: Participants' data from the China National Diabetes and Metabolic Disorders Study pertaining to Han, Uygur, and Kazak men from the Xinjiang province were used (n = 930). Pearson's correlation was used to examine the relationship between HOMA-IR, Matsuda Index, and clinical characteristics. RESULTS: HOMA-IR of Han men was significantly higher than in Uygurs and Kazaks (P < 0.001). The Matsuda Index of Kazaks was significantly higher than that of Hans and Uygurs (P < 0.001). While Kazaks had the highest BMI, WC, SBP, and DBP; they also had the highest HDL-C and lowest TG (P < 0.001). TG of Uygurs was significantly higher than that of Hans and Kazaks (P < 0.001). In Hans and Kazaks, the TG/HDL-C ratio increased with HOMA-IR quartiles; there was no association in Uygurs. In Hans and Kazaks, the TG/HDL-C ratio decreased with Matsuda index quartiles; there was no association in Uygurs. Multivariate linear regression showed that HOMA-IR was independently associated with ethnicity, BMI and TG/HDL-C ratio (P < 0.01), while Matsuda index was independently associated with ethnicity, BMI, LDL-C levels (P < 0.001) and TG/HDL-C ratio (P < 0.001). CONCLUSIONS: In conclusion, Han, Uygur, and Kazak men had different lipid profiles, BMI, and WC. Han men had the highest insulin resistance while Kazak men had the highest insulin sensitivity.

Risk factors associated with nonalcohol fatty liver disease and fibrosis among patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is closely related to hepatic steatosis and fibrosis. The aim of this study was to analyze the occurrence of hepatic steatosis and fibrosis in patients with T2DM and to explore the risk factors.A total of 629 patients with T2DM were enrolled. Liver stiffness value (LSV) and controlled attenuation parameters (CAP) were measured using Fibroscan. Liver fibrosis was diagnosed when LSV was greater than 7.4 kPa, and advanced liver fibrosis was diagnosed when LSV was greater than 10.6 kPa. Hepatic steatosis diagnosis was made when CAP value was greater than 238 dB/m. Demographic information, physical examination data, and laboratory tests results were collected. The 629 patients were classified into 2 groups by the liver fibrosis and liver steatosis, and then the difference was analyzed.Among patients enrolled, 231 patients were diagnosed as liver fibrosis. The age of the patients in the fibrosis group was significantly greater than that in the non-fibrosis group, and similar trends were observed in the waist-hip ratio (WHR), systolic blood pressure, and diastolic blood pressure. The proportion of smoking and alcoholic consumption was significantly lower in patients with non-fibrosis group. A total of 426 patients were diagnosed with liver steatosis. Body mass index (BMI), WHR, systolic blood pressure, and diastolic blood pressure in patients with steatosis were significantly higher than those in non-steatosis group. We observed that the LSV (P = .042) and CAP value (P < .001) are positively correlated with metabolic syndrome components in T2DM patients. Older age (OR = 1.099, P = .001), high BMI (OR = 1.088, P = .003), low platelet level (OR = 0.996, P = .014), and smoking (OR = 1.653, P = .013) were independent risk factors of liver fibrosis among T2DM patients. High BMI (OR = 1.369, P < .001), high diastolic blood pressure (OR = 1.048, P < .001), and high gamma glutamyl transpeptidase (OR = 1.018, P = .009) were independent risk factors for liver steatosis among T2DM patients.This study suggested risk factors screening of liver fibrosis and steatosis. Timely intervention should be taken into consideration among high risk patients to prevent progress liver diseases.

[Analysis of androgen receptor gene mutation in complete androgen insensitivity syndrome in a Uygur family].

OBJECTIVE: To identify the mutation of androgen receptor (AR) gene in a Uygur family with complete androgen insensitivity syndrome and elucidate its pathogenesis. METHODS: Two males with pseudohermaphroditism in this family were clinically diagnosed complete androgen insensitivity syndrome and by polymerase chain reaction (PCR) and DNA sequencing, we checked possible mutation of all exons and its splice site in AR gene. Two males with pseudohermaphroditism in this family were clinically diagnosed as complete androgen insensitivity syndrome and confirmed by PCR and DNA sequencing. And the possible mutations of all exons and splice sites in AR gene were examined. RESULTS: A proband and another family member had c.2157G > A, p.W719X nonsense mutation of AR gene and their mother was a mutation carrier of AR gene. Substitution (G- > A) at position 2 157 of exon 4 of AR resulted in mutation (TGG- > TGA) at codon 719 (termination codon). The nonsense mutation led to a truncation of 202 amino acids in AR protein. The mutations were absent in other family members. CONCLUSION: The nonsense mutation at AR gene W719X, a confirmed cause of disease, is first-ever found in Chinese, especially Uygur population.

[Secretion and action of insulin among Han and Uygur subjects with impaired fasting glucose and impaired glucose tolerance from Xinjiang].

OBJECTIVE: To compare insulin secretion and action with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and combined glucose intolerance (CGI, IFG and IGT) between Han and Uygur populations living in Xinjiang. METHODS: A multicenter cross-section survey (The Third Diabetes Epidemiological Survey in China) was conducted in Xinjiang from 2007 to 2008 including 2203 subjects (Han 1118, Uygur 1085) underwent an oral glucose test (OGTT). Homeostasis model assessment on insulin resistance (HOMA-IR) and ß cell function (HOMA-ß) were calculated. The ratio of incremental insulin (ΔI30) and glucose (ΔG30) response was used to evaluate the early insulin secretion. ΔI30/ΔG30/HOMA-IR was used to evaluate the glucose disposition index (DI). RESULTS: There were differences noticed regarding the waist circumstances (WC), body mass index (BMI), lipids, 0 and 120 min insulin levels in different glucose tolerance status between the Hans and Uygurs. Data related to NGT, IFG, CGI, WC from the Uygurs was significantly different from that of the Hans (P < 0.01), while the NGT, IFG, IGT and 120-minute plasma insulin levels of the Hans were significantly different from that of the Uygurs (P < 0.01). HOMA-IR and HOMA-ß in Hans were significantly different from those of the Uygurs (P < 0.01). There were significant differences noticed on data related to ΔI30/ΔG30, and DI among the two populations with different ethnicities. CONCLUSION: Regarding the regulation of impaired glucose, the insulin resistance among the Hans was significantly different from that of the Uygurs, while there seemed to be a compensatory secretion of pancreatic ß cells which played the role of maintaining blood glucose homeostasis.