A multicentre, prospective, non-interventional study evaluating the safety of dapagliflozin in patients with type 2 diabetes in routine clinical practice in China (DONATE).

BACKGROUND: There are few large-scale studies evaluating the safety of the sodium-glucose cotransporter-2 inhibitor, dapagliflozin, in Chinese patients with type 2 diabetes. DONATE, a multicentre, single-arm, prospective, non-interventional study, is the first real-world study evaluating the safety of dapagliflozin in Chinese patients with type 2 diabetes in routine clinical practice. METHODS: Between August 2017 and July 2020, patients with type 2 diabetes who had initiated dapagliflozin therapy and received ≥1 dose were prospectively recruited from 88 hospitals in China. Patients were subsequently followed up for 24 weeks; if patients discontinued dapagliflozin they were followed up for an additional 7 days after treatment discontinuation. The primary outcome was the proportion of patients with adverse events and serious adverse events, particularly key adverse events of special interest (AESI) including urinary tract infection, genital tract infection (typical symptoms with or without microbiological diagnosis) and hypoglycaemia (typical symptoms with or without blood glucose ≤3.9 mmol/L, or blood glucose ≤3.9 mmol/L without symptoms). Exploratory outcomes included the absolute change in metabolic parameters and the proportion of patients with other AESI including volume depletion, abnormal blood electrolytes, polyuria, renal impairment, diabetic ketoacidosis, hepatic impairment and haematuria. RESULTS: A total of 3000 patients were enrolled, of whom 2990 (99.7%) were included in the safety analysis set. Mean (SD) age was 52.6 (12.0) years, and 65.8% of patients were male. Mean (SD) duration of type 2 diabetes at enrolment was 8.4 (7.1) years. Mean (SD) treatment duration of dapagliflozin was 209.1 (157.6) days. Adverse events were reported in 35.4% (n = 1059) of patients during the 24-week follow-up period. Overall, 9.0% (n = 268) were related to treatment and 6.2% (n = 186) were serious. Urinary tract infection, genital tract infection and hypoglycaemia were reported in 2.3% (n = 70), 1.3% (n = 39) and 1.1% (n = 32) of patients, respectively. The proportion of patients with other AESI was also low: polyuria (0.7%; n = 21), volume depletion (0.3%; n = 9), renal impairment (0.3%; n = 8), hepatic impairment (0.2%; n = 7), haematuria (0.2%; n = 6) and diabetic ketoacidosis (0.1%; n = 2). CONCLUSIONS: This study demonstrated that once-daily dapagliflozin was well tolerated in Chinese patients with type 2 diabetes and the overall safety profile of dapagliflozin in clinical practice in China was consistent with that reported in clinical trials. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03156985. Registered on 16 May, 2017.

Knockdown of long non-coding RNA Gm10804 suppresses disorders of hepatic glucose and lipid metabolism in diabetes with non-alcoholic fatty liver disease.

Deregulated glucose and lipid metabolism are the primary underlying manifestations associated with diabetes mellitus (DM) and non-alcoholic fatty liver disease (NAFLD). This study aims to investigate the role of Gm10804, a novel long non-coding RNA (lncRNA), in regulating hepatic glucose and lipid metabolism in DM complicated with NAFLD (DM-NAFLD). Mouse primary hepatocytes exposed to high glucose (HG) were used as a cell model. A mouse DM-NAFLD model was established by high-energy feeding combined with intraperitoneal injection of streptozotocin. The results showed that Gm10804 expression was upregulated in HG-treated hepatocytes and livers from DM-NAFLD mice. Results in hepatocytes in vitro demonstrated that Gm10804 overexpression aggravated, whereas Gm10804 silencing abrogated HG-induced increase in intracellular triglyceride (TG) content, lipid accumulation and expression of hepatic lipogenic proteins (sterol regulatory element-binding proteins 1-c [SREBP-1c] and fatty acid synthase [FAS]) and enzymes for gluconeogenesis (phosphoenolpyruvate carboxykinase [PEPCK] and glucose-6-phosphatase [G6Pase]). Further in vivo assays showed that lentivirus-mediated hepatic knockdown of Gm10804 alleviated hepatic steatosis and lipid accumulation, and decreased expression of hepatic PEPCK, G6Pase, SREBP-1c and FAS in DM-NAFLD mice. In summary, Gm10804 knockdown attenuates hepatic lipid accumulation by ameliorating disorders of hepatic glucose and lipid metabolism in DM-NAFLD. SIGNIFICANCE OF THE STUDY: We first discovered that Gm10804 knockdown attenuated hepatic lipid accumulation by ameliorating disorders of hepatic glucose and lipid metabolism in DM-NAFLD. These results help to understand the pathogenesis and development of DM-NAFLD and provide some clues for further understanding the regulation of lncRNAs in glucose and lipid metabolism.

Association between FABP2 Ala54Thr polymorphisms and type 2 diabetes mellitus risk: a HuGE Review and Meta-Analysis.

Many studies have examined the association between the FABP2 (rs1799883) Ala54Thr gene polymorphism and type 2 diabetes mellitus risk (T2DM) in various populations, but their results have been inconsistent. To assess this relationship more precisely, A HuGE review and meta-analysis were performed. The PubMed and CNKI database was searched for case-control studies published up to April 2014. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. Ultimately, 13 studies, comprising 2020 T2DM cases and 2910 controls were included. Overall, for the Thr carriers (Ala/Thr and Thr/Thr) versus the wild-type homozygotes (Ala/Ala), the pooled OR was 1.18 (95% CI = 1.04-1.34, P = 0.062 for heterogeneity), for Thr/Thr versus Ala/Ala the pooled OR was 1.17 (95% CI = 1.05-1.41 P = 0.087 for heterogeneity). In the stratified analysis by ethnicity, the significantly risks were found among Asians but not Caucasians. This meta-analysis suggests that the FABP2 (rs1799883) Ala54Thr polymorphisms are associated with increased susceptibility to T2DM risk among Asians but not Caucasians.

The intervention dilemma and high burden of children with autism in Guizhou province, Southwest China.

Background: Autism spectrum disorder (ASD) is a highly disabling neurodevelopmental disorder, and the burden is high. Data on the burden of ASD are limited in China, especially in the southwest. Therefore, the aims of this study were to investigate the intervention status and burden of children with ASD in Southwest China. Materials and methods: Families of children with ASD were recruited from hospitals, special education schools, and private rehabilitation centers; they participated in the survey and completed the questionnaire. Descriptive analysis was conducted on the questionnaire results, which included basic demographic characteristics, rehabilitation status, and burden. Multivariate analysis was used to analyze the association of basic family demographic characteristics, rehabilitation status, and costs of ASD. Results: A total of 231 families of children with ASD participated in this survey, and 78.35% (181/231) of the children with ASD were male. The mean age was 4.34 ± 2.09 years. A total of 55.84% (129/231) of the children with ASD had an intellectual disability. Only 46.32% (107/231) started receiving intervention within 1 month after diagnosis. The institutions for rehabilitation interventions for children with ASD were mainly tertiary hospitals (39.39%), special education schools (29.87%) and private rehabilitation institutions (21.64%). For a total of 42.86% (99/231) of the children with ASD, the duration of the intervention was less than 10 h per week. A total of 74.89% (173/231) of the children with ASD received a rehabilitation intervention at home. A total of 66.67% of the parents were satisfied with the treatment. The monthly cost of medical intervention for the patients of children with autism was 7,225 ± 474 RMB ($1,134 ± 74), and the non-medical intervention cost was 2,133 ± 107 RMB ($334 ± 17). The annual burden of patients with autism was 86,700 ± 5,688 RMB ($13,596 ± 892). The estimated total annual burden of ASD was 5.548 billion RMB ($870 million) in Guizhou province. Conclusion: The results revealed that rehabilitation resources are limited and that the burden of ASD is high in Guizhou province; therefore, improving the rehabilitation status and easing the burden of children with ASD is urgent in these regions.

Surface-based morphometry study of the brain in benign childhood epilepsy with centrotemporal spikes.

BACKGROUND: The study aimed to explore cortical morphology in benign childhood epilepsy with centrotemporal spikes (BECTS) and the relationship between cortical characteristics and age of onset and intelligence quotient (IQ). METHODS: Cortical morphometry with surface-based morphometry (SBM) was used to compare changes in cortical thickness, gyrification, sulcal depth, and fractal dimension of the cerebral cortex between 25 BECTS patients and 20 healthy controls (HCs) with two-sample t-tests [P<0.05, family-wise error (FWE) corrected]. Relationships between abnormal cortical morphological changes and age of onset and IQ, which included verbal intelligence quotient (VIQ), performance intelligence quotient (PIQ), and full-scale intelligence quotient (FIQ) were investigated with Spearman correlation analysis (P<0.05, uncorrected). RESULTS: The BECTS patients showed extensive cortical thinning predominantly in bilateral frontal, temporal regions, and limbic system. Cortical gyrification increased in the left hemisphere and partial right hemisphere, and the decreased cortical gyrification was only in the left hemisphere. The increased sulcal depth was the left fusiform gyrus. There are no statistically significant differences in the fractal dimension. Correlation analysis revealed the negative correlation between age of onset and cortical thickness in the right precentral gyrus. It also revealed the negative correlation between the age of onset and cortical gyrification in the left inferior parietal gyrus. Also, there was negative correlation between VIQ and cortical gyrification in the left supramarginal gyrus of BECTS patients. CONCLUSIONS: This study reveals aberrant cortical thickness, cortical gyrification, and sulcal depth of BECTS in areas related to cognitive functions including language, attention and memory, and the correlation between some brain regions and VIQ and age of onset, providing a potential marker of early neurodevelopmental disturbance and cognitive dysfunction in BECTS.

Increased serum pigment epithelium-derived factor in women with gestational diabetes is associated with type 2 diabetes.

Background. Pigment epithelium-derived factor (PEDF) is demonstrated to be elevated in diabetes patients. However, no reports have emerged in pregnant women with gestational diabetes mellitus (GDM). This study was undertaken to investigate serum PEDF levels in GDM women and to evaluate PEDF as a biomarker to predict diabetes postpartum. Methods. Serum PEDF concentration and clinical characteristics were detected in the pregnant women with GDM (n = 120) and without GDM (control group, n = 120). Results. PEDF levels were elevated in subjects with GDM versus controls. Univariate correlations showed that serum PEDF levels were positively correlated with fasting glucose and fasting insulin levels, respectively, and negatively correlated with adiponectin. Receiver operating characteristic (ROC) analysis demonstrated that the AUC of serum PEDF for diabetes mellitus in women postpartum was 0.893. Conclusion. Serum PEDF was elevated in pregnant women with GDM, which is probably an early detection marker for predicting development of GDM to diabetes mellitus.