Genome-wide analysis study of gestational diabetes mellitus and related pathogenic factors in a Chinese Han population.

BACKGROUND: Gestational diabetes mellitus (GDM) affects the metabolism of both the mother and fetus during and after pregnancy. Genetic factors are important in the pathogenesis of GDM, and associations vary by ethnicity. However, related studies about the relationship between the susceptibility genes and glucose traits remain limited in China. This study aimed to identify genes associated with GDM susceptibility in Chinese Han women and validate those findings using clinical data during pregnancy and postpartum period. METHODS: A genome-wide association study (GWAS) of 398 Chinese Han women (199 each with and without GDM) was conducted and associations between single nucleotide polymorphisms (SNPs) and glucose metabolism were identified by searching public databases. Relationships between filtered differential SNPs and glucose metabolism were verified using clinical data during pregnancy. The GDM group were followed up postpartum to evaluate the progression of glucose metabolism. RESULTS: We identified five novel SNPs with genome-wide significant associations with GDM: rs62069863 in TRPV3 gene and rs2232016 in PRMT6 gene were positive correlated with 1 h plasma glucose (1hPG) and 2 h plasma glucose (2hPG), rs1112718 in HHEX/EXOC6 gene and rs10460009 in LPIN2 gene were positive associated with fasting plasma glucose, 1hPG and 2hPG, rs927316 in GLIS3 gene was negative correlated with 2hPG. Of the 166 GDM women followed up postpartum, rs62069863 in TRPV3 gene was positively associated with fasting insulin, homoeostasis model assessment of insulin resistance. CONCLUSIONS: The variants of rs62069863 in TRPV3 gene, rs2232016 in PRMT6 gene, rs1112718 in HHEX/EXOC6 gene, rs927316 in GLIS3 gene, and rs10460009 in LPIN2 gene were newly-identified susceptibility loci for GDM in the Chinese Han population. TRPV3 was associated with worse insulin resistance postpartum. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry. TRIAL REGISTRATION NUMBER: ChiCTR2100043762. Date of first registration: 28/02/2021.

Traditional Cantonese puerperal practices and postpartum cardiometabolism in gestational diabetes.

BACKGROUND AND OBJECTIVES: With gestational diabetes (GDM), women have a higher risk for future type 2 diabetes, and risk factors for diabetes for it are amplified. Whether this phenomenon is affected by traditional puerperal or postpartum practices among Chinese women who develop gestational diabetes is unclear. This has been explored in a Cantonese cultural setting to enable relevant risk management. METHODS AND STUDY DESIGN: Some 138 women were followed before, during and after pregnancy in accordance with Cantonese Puerperal Practices (CPP), and occurrence of GDM and exclusive breast-feeding. Body compositional and cardiometabolic information were collected. These included glucose tolerance and insulin resistance. RESULTS: During a median postpartum follow-up of 60.4 days, women with a typical CPP had a greater body weight and weight retention. With artificial feeding, women with a typical CPP had greater OGTT glycemic responses and more insulin resistance. With exclusive breast-feeding, however, no differences in postpartum cardiometabolic measurements were observed, except for a higher early-phase insulin response. CONCLUSIONS: Traditional CPP is associated with early postpartum cardiometabolic impairment in gestational diabetes, but this is avoided with breast-feeding.

Early postpartum abnormal glucose metabolism subtype differs according to mid-trimester lipid profile in women with gestational diabetes mellitus.

BACKGROUND: It is unknown whether early postpartum abnormal glucose metabolism (AGM) in women with previous gestational diabetes mellitus (GDM) is related to their mid-trimester lipid profile. The aim of this study was to characterize the mid-trimester lipid profile of women who experienced GDM and developed into different pathophysiologic subtypes of early postpartum AGM. METHODS: A retrospective cohort study of 498 women with history of GDM was conducted. A 75-g oral glucose tolerance test (OGTT) and plasma lipid measurements were performed at 24-28 weeks of gestation and 6-12 weeks of postpartum. Insulin secretion and sensitivity were estimated using early postpartum OGTT-based indices. RESULTS: Women in the mid-trimester dyslipidemia group had higher postpartum 30-min and 2-h plasma glucose, higher postpartum 2-h plasma insulin, higher postpartum triglyceride (TG), higher postpartum low density lipoprotein cholesterol (LDL-c) concentrations, lower postpartum 30-min insulinogenic index (IGI30), lower postpartum insulin sensitivity index (ISI), and lower postpartum disposition index than those in the normal lipid group (all P < 0.05). Abnormal mid-trimester TG and LDL-c concentrations were associated with postpartum AGM (adjusted odds ratio [OR] = 1.786, 95 % confidence interval [CI] = 1.142-2.425; and adjusted OR = 1.621, 95 % CI = 1.323-2.051, respectively; both P < 0.05). AGM women with low IGI30 and low ISI had higher mid-trimester total cholesterol and LDL-c concentrations, and AGM women with low ISI had higher mid-trimester TG concentrations than women with NGT or other subtypes of AGM (all P < 0.05). CONCLUSIONS: GDM women with abnormal mid-trimester TG and LDL-c were predisposed to early postpartum AGM. Postpartum AGM women who experienced GDM had heterogeneous mid-trimester lipid profile when classified according to their pathophysiologic subtype.

Comparison of Clinical Features between Primary Aldosteronism and Essential Hypertension in Chinese Patients: A Case-Control Study.

Primary aldosteronism (PA) is one of the most common forms of secondary hypertension. Recent studies suggest that, compared with essential hypertension (EH), PA presents more severe disorders of glycolipid metabolism and organ damages. This case-control retrospective study aimed to ascertain clinical features and metabolic parameters between Chinese patients of PA and EH. 174 PA patients and 174 matched EH patients were recruited. Their clinical features, biochemistry parameters, the ventricular septal thickness, and left ventricular mass index (LVMI) were compared. HOMA-ß% and HOMA-IR were calculated to evaluate glucose metabolism. The results showed that there was no significant difference regarding BMI, waist-to-hip ratio, and blood pressure between the two groups. The blood potassium level was significantly lower in PA patients than those in EH patients. The abnormal glucose tolerance and the incidence of diabetes in the PA group were not significantly different from those in EH group, but the insulin secretion levels at 0 min and 30 min were significantly weaker than those in the EH group, and the HOMA-ß% was also lower in the PA group than those in the EH group. Left ventricular structural abnormalities in PA patients were more severe than those in EH patients. Subtype analysis indicated that patient with aldosterone-producing adenoma (APA) has more serious hypokalemia and lower levels of HOMA-ß% and HOMA-IR comparing to those in the idiopathic adrenal hyperplasia (IHA) patient. These findings demonstrated that PA patients showed more impaired insulin secretion function and more severe left ventricular structural damage compared with EH patients.

Forty-eight weeks of statin therapy for type 2 diabetes mellitus patients with lower extremity atherosclerotic disease: Comparison of the effects of pitavastatin and atorvastatin on lower femoral total plaque areas.

AIMS/INTRODUCTION: Type 2 diabetes mellitus is correlated with systemic atherosclerosis. Statin therapies have been proved to reduce low-density lipoprotein cholesterol (LDL-C) level, protecting type 2 diabetes mellitus patients from cardiovascular events. Recently, more interest has been focused on the regression of lower extremity atherosclerotic disease (LEAD) for the potential prevention of amputation. However, the effects of pitavastatin and atorvastatin on LEAD in type 2 diabetes mellitus patients have not been directly compared. MATERIALS AND METHODS: This study compared the effects of pitavastatin and atorvastatin on femoral total plaque areas (FTPA), and lipids and glucose metabolism in type 2 diabetes mellitus patients with elevated LDL-C level and LEAD. Type 2 diabetes mellitus patients with LDL-C level >2.6 mmol/L and LEAD were randomly assigned to receive either pitavastatin 2 mg/day or atorvastatin 10 mg/day for 48 weeks. FTPA were measured at baseline and the end of the study. Levels of glucose and lipids profile were measured periodically. The efficacy was evaluated in 63 patients. RESULTS: The percentage change in FTPA measurements was similar between the pitavastatin group and atorvastatin group (-17.79 ± 21.27% vs -14.34 ± 16.33%), as were the changes in LDL-C (-44.0 ± 18.0% vs -40.3 ± 18.2%) and triglyceride (17.6 ± 20.0% vs 16.2 ± 17.0%). However, the level of high-density lipoprotein cholesterol was significantly higher in the pitavastatin group compared with the atorvastatin group after 48 weeks of treatment (12.9 ± 10.3% vs 7.2 ± 11.7%, P < 0.05). There were no significant differences between groups for the measurements of glucose metabolism. CONCLUSION: In type 2 diabetes mellitus patients with elevated LDL-C level and LEAD, 48 weeks of treatment with either pitavastatin or atorvastatin was associated with significant regression of FTPA. Pitavastatin treatment resulted in a significantly higher high-density lipoprotein cholesterol level compared with atorvastatin treatment.

Early postpartum dyslipidemia and its potential predictors during pregnancy in women with a history of gestational diabetes mellitus.

BACKGROUND: This study aimed to analyze the incidence of early postpartum dyslipidemia and its potential predictors in women with a history of gestational diabetes mellitus (GDM). METHODS: This was a retrospective study. Five hundred eighty-nine women diagnosed with GDM were enrolled and followed up at 6-12 weeks after delivery. A 75 g oral glucose tolerance test (OGTT) and lipid levels were performed during mid-trimester and the early postpartum period. Participants were divided into the normal lipid group and dyslipidemia group according to postpartum lipid levels. Demographic and metabolic parameters were analyzed. Multiple logistic regression was performed to analyze the potential predictors for early postpartum dyslipidemia. A receiver operating characteristic curve (ROC) was calculated to determine the cut-off values. RESULTS: A total of 38.5% of the 589 women developed dyslipidemia in early postpartum and 60% of them had normal glucose metabolism. Delivery age, systolic blood pressure (SBP), glycated hemoglobin (HbA1c) and low-density lipoprotein cholesterol (LDL-C) were independent predictors of early postpartum dyslipidemia in women with a history of GDM. The cut-offs of maternal age, SBP, HbA1c values, and LDL-C levels were 35 years, 123 mmHg, 5.1%, and 3.56 mmol/L, respectively. LDL-C achieved a balanced mix of high sensitivity (63.9%) and specificity (69.2%), with the highest area under the receiver operating characteristic curve (AUC) (0.696). When LDL-C was combined with age, SBP, and HbA1c, the AUC reached to 0.733. CONCLUSIONS: A lipid metabolism evaluation should be recommended in women with a history of GDM after delivery, particularly those with a maternal age > 35 years, SBP > 123 mmHg before labor, HbA1c value > 5.1%, or LDL-C levels > 3.56 mmol/L in the second trimester of pregnancy.

ACCURACY OF PLASMA FREE METANEPHRINES IN THE DIAGNOSIS OF PHEOCHROMOCYTOMA AND PARAGANGLIOMA: A SYSTEMATIC REVIEW AND META-ANALYSIS.

OBJECTIVE: Various studies have validated plasma free metanephrines (MNs) as biomarkers for pheochromocytoma and paraganglioma (PPGL). This meta-analysis aimed to estimate the overall diagnostic accuracy of this biochemical test for PPGL. METHODS: We searched the PubMed, the Cochrane Library, Web of Science, Embase, Scopus, OvidSP, and ProQuest Dissertations & Theses databases from January 1, 1995 to December 2, 2016 and selected studies written in English that assessed plasma free MNs in the diagnosis of PPGL. Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) was used to evaluate the quality of the included studies. We calculated pooled sensitivities, specificities, positive and negative likelihood ratios, diagnostic odds ratios (DORs) and areas under curve (AUCs) with their 95% confidence intervals (95% CIs). Heterogeneity was assessed by I2. To identify the source of heterogeneity, we evaluated the threshold effect and performed a meta-regression. Deeks' funnel plot was selected for investigating any potential publication bias. RESULTS: Although the combination of metanephrine (MN) and normetanephrine (NMN) carried lower specificity (0.94, 95% CI 0.90-0.97) than NMN (0.97, 95% CI 0.92-0.99), NMN was generally more accurate than individual tests, with the highest AUC (0.99, 95% CI 0.97-0.99), DOR (443.35, 95% CI 216.9-906.23), and pooled sensitivity (0.97, 95% CI 0.94-0.98) values. Threshold effect and meta-regression analyses showed that different cut-offs, blood sampling positions, study types and test methods contributed to heterogeneity. CONCLUSION: This meta-analysis suggested an effective value for combined plasma free MNs for the diagnosis of PPGL, but testing for MNs requires more standardization using tightly regulated studies. ABBREVIATIONS: AUC = area under curve; CI = confidence interval; DOR = diagnostic odds ratio; EIA = enzyme immunoassay; LC-ECD = liquid chromatography-electrochemical detection; LC-MS/MS = liquid chromatography-tandem mass spectrometry; MN = metanephrine; NMN = normetaneprhine; PPGL = pheochromocytoma and paraganglioma; QUADAS-2 = Quality Assessment of Diagnostic Accuracy Studies 2.