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.

Identifying optimal candidates for post-TIPS patients with HCC undergoing TACE: a multicenter observational study.

OBJECTIVE: To develop a prognostic model for post-transjugular intrahepatic portosystemic shunt (TIPS) patients with hepatocellular carcinoma (HCC) beyond the Milan criteria treated by transarterial chemoembolization (TACE). DESIGN: Between January 2013 and January 2020, 512 patients with HCC beyond the Milan criteria who underwent TACE after TIPS were retrospectively recruited from 15 tertiary centers. Patients were randomly sorted into a training set (n = 382) and a validation set (n = 130). Medical data and overall survival were assessed. A prediction model was developed using multivariate Cox regression analyses. Predictive performance and discrimination were evaluated and compared with other prognostic models. RESULTS: Vascular invasion, log10(AFP), 1/creatinine, extrahepatic spread, and log10(ALT) were the most significant prognostic factors of survival. These five parameters were included in a new VACEA score. This score was able to stratify patients in the training set into four distinct risk grades whose median overall survival were 25.2, 15.1, 8.9, and 6.2 months, respectively. The 6-month, 1-year, 2-year, and 3-year AUROC values and C-index of the VACEA model were 0.819, 0.806, 0.779, 0.825, and 0.735, respectively, and higher than those of other seven currently available models in both the training and validation sets, as well as in different subgroups. CONCLUSION: The VACEA score could stratify post-TIPS patients with HCC beyond the Milan criteria treated by TACE and help to identify candidates who benefit from this treatment. KEY POINTS: • Vascular invasion, AFP, creatinine, extrahepatic spread, and ALT were independent significant prognostic factors of survival for HCC patients who underwent TACE after TIPS. • Our new model, named VACEA score, can accurately predict prognosis at the individual level and stratify patients into four distinct risk grades. • The VACEA model showed better prognostic discrimination and calibration than other current TACE-/TIPS-specific models Graphical abstract.

Idarubicin-Loaded DEB-TACE plus Lenvatinib versus Lenvatinib for patients with advanced hepatocellular carcinoma: A propensity score-matching analysis.

AIMS: To investigate the efficacy and safety of lenvatinib and idarubicin-loaded drug-eluting beads transarterial chemoembolization (IDADEB-TACE) in primary advanced hepatocellular carcinoma (HCC). METHODS: This retrospective study included patients with primary advanced HCC who received either lenvatinib monotherapy or lenvatinib plus IDADEB-TACE as first-line treatment from September 2019 to September 2020 at three institutes. Overall survival (OS), time to progression (TTP), objective response rate (ORR), and adverse events were compared. Propensity score-matching was used to reduce the influence of confounding factors on the outcomes. RESULTS: The study reviewed 118 patients who received lenvatinib plus IDADEB-TACE (LIDA group) and 182 who received lenvatinib alone (LEN group). After propensity score-matching, 78 pairs of patients remained. Compared to patients in the LEN group, those in the LIDA group had better post-treatment ORR (57.7% vs. 25.6%, p < 0.001, respectively), median OS and TTP (15.7 vs. 11.3 months, hazard ratio [HR] = 0.50, p < 0.001; 8.0 vs. 5.0 months, HR = 0.60, p = 0.003, respectively), 6- and 12-month OS rates (88.5% vs. 71.4%; 67.6% vs. 43.4%, respectively), and progression-free rates at 6 and 12 months (60.3% vs. 42.3%; 21.1% vs. 10.3%, respectively). Vascular invasion, α-fetoprotein level, and treatment type were independent OS predictors, and vascular invasion and treatment type were independent TTP predictors. Incidences of nausea/vomiting, fever, abdominal pain, and increased ALT/AST were higher in the LIDA group than in the LEN group. CONCLUSIONS: Lenvatinib plus IDADEB-TACE is well-tolerated and more effective than lenvatinib monotherapy in patients with advanced HCC.

Sorafenib plus drug-eluting bead transarterial chemoembolization for early intrahepatic stage-progressed advanced hepatocellular carcinoma refractory to conventional transarterial chemoembolization.

PURPOSE: To investigate the effectiveness and safety of the combination of sorafenib and drug-eluting bead transarterial chemoembolization (DEB-TACE) in the treatment of early intrahepatic stage-progressed advanced hepatocellular carcinoma (ISPA-HCC). METHODS: This study was approved by the ethics committees of six tertiary medical centers in China. Between October 2017 and October 2020, 213 patients with advanced HCC received either sorafenib combined with on-demand DEB-TACE (DTS group, n = 103) or sorafenib monotherapy (S group, n = 110). Overall survival (OS), time to progression (TTP), local tumor response, and adverse events (AEs) were compared between the two groups. RESULTS: The incidences of nause/vomiting, abdonimal pain, hyperbilirubinemia, fever and ALT/AST increasing were higher in the DTS group. The post-treatment partial response, objective response, and disease control rates were significantly higher in the DTS group than in the S group (51.5% vs. 23.6%; 56.3% vs. 25.5%; 77.7% vs. 56.4%, respectively). The median OS was significantly longer in the DTS group than in the S group [16.3 vs. 10.0 months; hazard ratio (HR) = 0.43; P < 0.001], as was the TTP (6.7 vs. 4.3 months; HR = 0.60; P = 0.001). In the DTS group, patients who received ≥ 2 sessions of DEB-TACE benefited more than those who received two sessions of DEB-TACE. Multivariate analysis revealed that the α-fetoprotein level and treatment allocation were independent predictors of OS and TTP. CONCLUSION: The combination of sorafenib and DEB-TACE is safe and effective for the treatment of early ISPA-HCC.

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.

Translation and validation of the Chinese version of medical maximizer-minimizer scale: a cross-sectional study.

OBJECTIVE: Medical overutilisation and underutilisation affect optimal healthcare. The Medical Maximizer-Minimizer Scale (MMS) was developed to assess individual medical maximising and minimising tendencies. Despite significant improvement in the healthcare system over the past four decades, no psychometric scales to examine treatment maximising and minimising preferences are available in China. This study aimed to translate the MMS into Chinese and examine its reliability and validity in a Chinese population. DESIGN: This cross-sectional study was conducted in December 2019 through an online survey panel. METHODS: The MMS was translated into a Chinese version (CN-MMS) using a forward-backward translation procedure. Next, a random online survey of the general population in China was conducted. Exploratory factor analysis (EFA) and confirmatory factor analysis were performed to examine the underlying factor structure of the CN-MMS. The internal consistency reliability of the scale was determined using Cronbach's α coefficient and corrected item-total correlation. A multivariate linear regression analysis was used to examine associations between medical maximising and minimising preferences and demographic variables in the Chinese population. RESULTS: This study included 984 participants aged 18-80 years. The CN-MMS retained 10 items, and the EFA supported a two-factor structure. The model fit for this two-factor structure of the CN-MMS was acceptable with χ2/df=3.7, comparative fit index=0.958, goodness-of-fit index=0.951, Tucker-Lewis Index=0.944 and root mean square error of approximation=0.074. The scale had a Cronbach's α coefficient of 0.864, corrected item-total correlation of 0.451-0.667, and test-retest reliability of 0.815. Significant predictors of CN-MMS total score were nationality and household monthly income. CONCLUSIONS: The CN-MMS showed satisfactory psychometric properties. Therefore, it can be used to investigate the individual medical maximising and minimising tendencies among the general Chinese population.

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.

The Relationship between Neutrophil-to-Lymphocyte Ratio and Intracerebral Hemorrhage in Type 2 Diabetes Mellitus.

INTRODUCTION: Chronic systematic inflammation has been suggested to be associated with the occurrence and development of cardiovascular events. Low-grade systematic inflammation persists in type 2 diabetes mellitus (T2DM) patients. In addition, the risk of cerebral hemorrhage in these patients is increased compared with non-diabetic patients. Neutrophil-to-lymphocyte ratio (NLR) is the ratio derived by dividing the neutrophil count with the lymphocyte count from a peripheral blood sample. This study aimed to explore the relation between NLR and cerebral hemorrhage, and to prove that NLR is an independent risk factor of cerebral hemorrhage in T2DM patients. METHODS: In total, 429 cases of T2DM patients were included. The patients were divided into two groups depending on the presence of cerebral hemorrhage: the cerebral hemorrhage group (n = 87) and the control group (n = 342). Based on clinical and laboratory data of diabetes diagnosis, this article investigates the relationship between NLR and the risk of cerebral hemorrhage. RESULTS: Increase in NLR was positively correlated with the incidence of cerebral hemorrhage in T2DM patients and might serve as an independent risk factor of cerebral hemorrhage in T2DM patients (OR: 4.451, 95% CI: 2.582-7.672). NLR >2.58 might be useful in predicting the threshold value of cerebral hemorrhage risk in newly diagnosed T2DM patients (area under the curve: .72, 95% CI: .659-.780, P < .001) CONCLUSION: As an indicator of the degree of systematic inflammation, NLR is an independent risk factor of cerebral hemorrhage in T2DM patients.