ABSTRACT
AIM: To evaluate the efficacy and safety of janagliflozin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin monotherapy. MATERIALS AND METHODS: This multicentre phase 3 trial included a 24-week, randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. Patients (N = 421) with HbA1c of 7.0% or higher and 10.5% or less were randomized (1:1:1) to receive once-daily placebo, janagliflozin 25 or 50 mg. After the 24-week treatment period, patients on placebo were re-randomized (1:1) to janagliflozin 25 or 50 mg for the additional 28-week treatment, whereas patients on janagliflozin maintained the same therapy. The primary endpoint was the change from baseline in HbA1c to week 24. RESULTS: At week 24, the placebo-adjusted least squares mean changes of HbA1c were -0.58% and -0.58% with janagliflozin 25 and 50 mg, respectively (P < .0001 for both). The proportion of patients achieving HbA1c less than 7.0% was higher with janagliflozin 25 and 50 mg compared with placebo (41.8%, 41.7% and 28.0%, respectively). Both janagliflozin doses provided significant reductions in fasting plasma glucose, 2-hour postprandial glucose, body weight and systolic blood pressure, and improvements in high-density lipoprotein cholesterol and insulin sensitivity compared with placebo (P < .05 for all). The trends in improvement of these variables were retained during the 28-week extension period. No severe hypoglycaemia occurred throughout the whole 52-week treatment. CONCLUSIONS: Janagliflozin 25 or 50 mg once-daily added to metformin therapy significantly improved glycaemic control, reduced body weight and systolic blood pressure, improved high-density lipoprotein cholesterol and insulin sensitivity, and was generally well-tolerated by Chinese T2D patients who had poor glycaemic control with metformin monotherapy.
Subject(s)
Diabetes Mellitus, Type 2 , Insulin Resistance , Metformin , Sodium-Glucose Transporter 2 Inhibitors , Humans , Blood Glucose , Body Weight , Cholesterol , Double-Blind Method , Drug Therapy, Combination , East Asian People , Glycated Hemoglobin , Hypoglycemic Agents/therapeutic use , Lipoproteins, HDL , Metformin/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: Type 2 diabetes mellitus (T2DM) is a worldwide public health concern. Mobile health management platforms could be a potential way to achieve effective glycemic control. OBJECTIVE: This study aimed to evaluate the real-world effectiveness of the Lilly Connected Care Program (LCCP) platform in glycemic control among patients with T2DM in China. METHODS: This retrospective study included Chinese patients with T2DM (aged ≥18 years) from April 1, 2017, to January 31, 2020, for the LCCP group and from January 1, 2015, to January 31, 2020, for the non-LCCP group. Propensity score matching was used to match the LCCP and non-LCCP groups to reduce confounding, with covariates including age, sex, the duration of diabetes, baseline hemoglobin A1c (HbA1c), and the number of oral antidiabetic medication classes. HbA1c reduction over 4 months, the proportions of patients achieving an HbA1c reduction of ≥0.5% or ≥1%, and the proportions of patients reaching to target HbA1c level of ≤6.5% or <7% were compared between the LCCP and non-LCCP groups. Multivariate linear regression was used to assess factors associated with HbA1c reduction. RESULTS: A total of 923 patients were included, among whom 303 pairs of patients were well matched after propensity score matching. HbA1c reduction during the 4-month follow-up was significantly larger in the LCCP group than the non-LCCP group (mean 2.21%, SD 2.37% vs mean 1.65%, SD 2.29%; P=.003). The LCCP group had a higher proportion of patients with an HbA1c reduction of ≥1% (209/303, 69% vs 174/303, 57.4%; P=.003) and ≥0.5% (229/303, 75.6% vs 206/303, 68%; P=.04). The proportions of patients reaching the target HbA1c level of ≤6.5% were significantly different between the LCCP and non-LCCP groups (88/303, 29% vs 61/303, 20.1%; P=.01), whereas the difference in the proportions of patients reaching the target HbA1c level of <7% was not statistically significant (LCCP vs non-LCCP: 128/303, 42.2% vs 109/303, 36%; P=.11). LCCP participation and higher baseline HbA1c were associated with a larger HbA1c reduction, whereas older age, longer diabetes duration, and higher baseline dose of premixed insulin analogue were associated with a smaller HbA1c reduction. CONCLUSIONS: The LCCP mobile platform was effective in glycemic control among patients with T2DM in China in the real world.
Subject(s)
Diabetes Mellitus, Type 2 , Humans , Adolescent , Adult , Diabetes Mellitus, Type 2/drug therapy , Retrospective Studies , Blood Glucose , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic useABSTRACT
Aims: Whether pioglitazone (PIO), a peroxisome proliferator-activated receptor-gamma agonist, increases the risk of developing bladder cancer has been debated for several years. The aim of this study was to investigate the in vitro effects of PIO on normal urothelial transitional epithelium (NUTE) cells and bladder cancer (J82) cells to further evaluate the risk. Methods: NUTE cells were obtained from Sprague-Dawley rats. NUTE and J82 cells were treated with different concentrations of PIO for various time periods. Cell proliferation was tested by the MTT assay. Cell apoptosis was evaluated by flow cytometry. The expressions of p53, cyclin D1, Bcl-2, and Bax were determined by qRT-PCR and western blots. Results: After 24 hours, the treatment of NUTE cells with 10 µmol/L PIO led to morphological changes, without changes in J82 cells. Moreover, PIO inhibited the proliferation and induced apoptosis of NUTE cells, but not J82 cells, in a time- and dose-dependent manner. However, PIO did not alter the growth of cells from other tissues. In addition, treatment with PIO for up to 72 hours did not result in changes in the expressions of p53, cyclin D1, Bcl-2, and Bax in NUTE cells and J82 cells. Interestingly, PIO significantly downregulated the protein levels of p53 and cyclin D1 in J82 cells, but not NUTE cells after more than 192 hours of treatment. Conclusions: PIO did not promote malignant alterations of NUTE cells or stimulate proliferation of J82 cells. PIO decreased the expression of p53 and cyclin D1 in J82 cells after long-term culture, which suggested that PIO may be helpful for diabetic patients with bladder cancer.
Subject(s)
Diabetes Complications/drug therapy , Hypoglycemic Agents/administration & dosage , Thiazolidinediones/administration & dosage , Urinary Bladder Neoplasms/drug therapy , Animals , Apoptosis/drug effects , Cell Proliferation/drug effects , Cyclin D1/genetics , Diabetes Complications/genetics , Diabetes Complications/pathology , Gene Expression Regulation, Neoplastic/drug effects , Humans , PPAR gamma/agonists , Pioglitazone , Proto-Oncogene Proteins c-bcl-2/genetics , Rats , Risk Factors , Tumor Cells, Cultured , Tumor Suppressor Protein p53/genetics , Urinary Bladder Neoplasms/complications , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Urothelium/drug effects , Urothelium/pathologyABSTRACT
BACKGROUND: This study assessed the efficacy and safety of the once-daily glucagon-like peptide-1 receptor agonist, lixisenatide, in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin ± sulfonylurea. METHODS: In this 24-week, double-blind, placebo-controlled, multinational study, patients were randomized to lixisenatide 20 µg once daily or placebo. The primary endpoint was absolute change in glycated haemoglobin (HbA1c ) from baseline to week 24. RESULTS: A total of 391 patients were randomized. Lixisenatide significantly reduced HbA1c levels compared with placebo (LS mean difference: -0.36%, p = 0.0004). A significantly higher proportion of lixisenatide-treated patients achieved HbA1c targets of <7% (p = 0.003) and ≤6.5% (p = 0.001) versus placebo. Lixisenatide was associated with a statistically significant reduction in 2-h postprandial plasma glucose after a standardized breakfast versus placebo (LS mean difference: -4.28 mmol/L, p < 0.0001) and a significant reduction in fasting plasma glucose (p = 0.0109). There was no difference in weight loss versus placebo, with a modest reduction in body weight reported for both groups (lixisenatide: -1.50 kg, placebo: -1.24 kg; p = 0.296). The incidence of treatment-emergent adverse events (TEAEs) was 64.3% with lixisenatide versus 47.4% with placebo, with serious TEAEs reported in 1.5% versus 2.1% of patients, respectively. The most common TEAE in the lixisenatide group was nausea (16.3% vs 2.6% with placebo). The incidence of symptomatic hypoglycaemia was 5.6% with lixisenatide treatment and 2.6% with placebo (p = 0.1321), with no severe symptomatic hypoglycaemia events reported. CONCLUSIONS: In Asian patients with type 2 diabetes mellitus insufficiently controlled on metformin ± sulfonylurea, lixisenatide significantly improved glycaemic control and was well tolerated during the 24-week study.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Drug Resistance , Hyperglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Peptides/therapeutic use , Receptors, Glucagon/agonists , Adult , China , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/metabolism , Double-Blind Method , Drug Resistance, Multiple , Drug Therapy, Combination/adverse effects , Female , Glucagon-Like Peptide-1 Receptor , Glycated Hemoglobin/analysis , Humans , Hypoglycemia/chemically induced , Hypoglycemic Agents/adverse effects , Malaysia , Male , Metformin/adverse effects , Middle Aged , Nausea/chemically induced , Peptides/adverse effects , Receptors, Glucagon/metabolism , Sulfonylurea Compounds/adverse effects , Sulfonylurea Compounds/therapeutic use , ThailandABSTRACT
OBJECTIVE: To investigate whether the existence of obstructive sleep apnea syndrome (OSAS) in patients with type 2 diabetes (T2DM) is associated with low grade chronic inflammation. METHODS: Fifty-four patients hospitalized for poor glycemic control from 12/2008 to 12/2009 were divided into 2 groups, OSAS group (T2DM with OSAS, 27 cases) and NOSAS group (T2DM without OSAS, 27 cases). The control group consisted of 26 people from a health check-up program without diabetes and OSAS. Biochemical indexes were analyzed in central laboratory of the hospital. Serum tumor necrosis factor-α(TNF-α), lipopolysaccharides (LPS), monocyte chemoattractant protein-1 (MCP), and plasminogen activator inhibitor-1 (PAI) levels were determined with commercial ELISA kits. Apnea hypopnea index (AHI), the lowest pulse oxygen saturation (LSpO2) at night were measured with a portable home sleep monitor. RESULTS: Homeostasis model assessment insulin resistance index (HOMA-IR), AHI in OSAS group were higher than those in NOSAS group and control group [for HOMA-IR, 2.7 ± 1.5 vs 1.7 ± 0.9 vs 1.2 ± 0.7, and for AHI, (17.0 ± 13.0) vs (3.4 ± 1.3) vs (3.2 ± 1.2) per hour], and LSpO2 was lower than that in NOSAS group and control group [(78 ± 11)% vs (87 ± 4)% vs (89 ± 6)%]. Compared with normal control, levels of TNF-α [(0.73 ± 0.19) vs (1.97 ± 0.13) vs (1.09 ± 0.29) ng/ml], LPS [(50 ± 11) vs (303 ± 70) vs (171 ± 49) pg/ml], MCP [(302 ± 41) vs (514 ± 122) vs (473 ± 134) pg/ml] and PAI [(0.89 ± 0.25) vs (2.27 ± 0.85) vs (1.59 ± 0.13) ng/ml] in patients with OSAS and with NOSAS group increased significantly. Pearson univariate correlation analysis revealed that TNF-α and PAI were both positively associated with HOMA-IR, FBG and AHI, and negatively with LSpO2, LPS, MCP were both associated positively with FBG and AHI, and negatively with LSpO2. Multiple linear regression stepwise analysis found that TNF-α and LPS were independently associated with AHI and FBG, MCP with LSpO2, PAI with both AHI and HOMA-IR. CONCLUSIONS: Patients with diabetes and OSAS show raised level of chronic inflammatory activity.
Subject(s)
Diabetes Mellitus, Type 2/complications , Inflammation/blood , Insulin Resistance , Sleep Apnea, Obstructive/blood , Tumor Necrosis Factor-alpha/blood , Aged , Blood Glucose/metabolism , Case-Control Studies , Chemokine CCL2/blood , Diabetes Mellitus, Type 2/blood , Female , Humans , Inflammation/complications , Inflammation/pathology , Lipopolysaccharides/blood , Male , Middle Aged , Oxygen/blood , Polysomnography , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/pathologyABSTRACT
OBJECTIVE: Study of Once-daily LeVEmir(®) (SOLVE(TM)) was a 24-week international observational study to evaluate the safety and effectiveness of initiating once-daily insulin detemir (Levemir) as add-on therapy in patients with type 2 diabetes mellitus (T2DM) who failed treatment of oral anti-diabetic drugs (OAD). METHODS: The present study was derived from the data of Chinese cohort. A total of 3272 patients with T2DM failing OAD were enrolled in the study. Determir were prescribed to the patients by the decision of the physician. Clinical data were collected at baseline, week 12 and week 24 to evaluate the safety and effectiveness of detemir. RESULTS: The age of the patients was (56.2 ± 10.8) years with a diabetes duration of (7.1 ± 5.2) years. Their BMI was (25.3 ± 3.3) kg/m(2). No patient experienced any major or nocturnal hypoglycaemic event during the study. After 24 weeks of treatment, the glycosylated hemoglobin A1c (HbA1c) decreased from (8.33 ± 1.69)% to (7.16 ± 1.18)% with a mean change of -1.17%, the fasting plasma glucose decreased from (9.52 ± 2.59) mmol/L to (6.84 ± 1.42) mmol/L with a mean change of -2.7 mmol/L, and the 7-point blood glucose profile improved overall. Totally 49.1% of patients achieved HbA1c < 7%. The mean body weight decreased by 0.15 kg. CONCLUSIONS: Insulin detemir administered once daily as add-on therapy in patients with T2DM failing OAD regimen significantly reduces the risk of major hypoglycemia, improves glycemic control, increases the percentage of patients achieving treatment target with neutral effect on body weight.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin, Long-Acting/therapeutic use , Aged , Female , Humans , Insulin Detemir , Male , Middle Aged , Prospective Studies , Treatment OutcomeABSTRACT
OBJECTIVE: To characterize the baseline status of Chinese diabetic patients based on data derived from Chinese cohort from SOLVE(TM) study. METHODS: Patients with type 2 diabetes initiating basal insulin detemir at the decision of the physician were eligible for the study. Data on demographics, medical history, glycemic profile and treatment regimen at baseline were collected by physicians. RESULTS: A total of 3272 patients [female 42%, male 58%, mean age (56.2 ± 10.8) years] were included in the study. Their BMI was (25.3 ± 3.3) kg/m(2). The duration of diabetes was 4.0 (0.1 - 27.0) years, and the duration of treatment with oral antidiabetic drugs (OADs) was 3.0 (0.0 - 20.2) years. The proportions of subjects with diabetic macro- and micro-vascular complications were 15.8% (515 cases) and 27.1% (866 cases), respectively. The hemoglobin A1c (HbA1c) at baseline was (8.33 ± 1.70)%, and the fasting blood glucose (FPG) was (9.5 ± 2.6) mmol/L. CONCLUSIONS: A large proportion of patients with type 2 diabetes remain in poor glycemic control, and the prevalence of diabetic complications is high, which requires optimal therapeutic strategy for the patients with suboptimal glycemic control.
Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin/administration & dosage , Adult , Aged , Blood Glucose/analysis , Cohort Studies , Diabetes Mellitus, Type 2/blood , Drug Administration Schedule , Female , Glycated Hemoglobin/analysis , Humans , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Male , Middle Aged , Treatment OutcomeABSTRACT
Induced pluripotent stem cell (iPSC) line, SJHi001-A, was generated from a diabetic patient carrying a heterozygous c.G248A mutation in GCGR gene that generated the p.W83X. The PBMCs from her father (no diabetes and no mutation site) were also prepared into iPSC (SJHi002-A) as a control. Both two cell lines had normal karyotype, expressed pluripotency markers and could differentiate into the three germ layers in vivo.
Subject(s)
Diabetes Mellitus , Induced Pluripotent Stem Cells , Cell Line , Diabetes Mellitus/genetics , Diabetes Mellitus/metabolism , Female , Humans , Induced Pluripotent Stem Cells/metabolism , Mutation/genetics , Receptors, Glucagon/genetics , Receptors, Glucagon/metabolismABSTRACT
Background: The pathogenesis of the progressive loss of beta cell function latent autoimmune diabetes in adults (LADA) remains still elusive. We aim to study the fatty acid (FA) profile in LADA. Subjects and methods: Data from 116 patients with diabetes and GADA and 249 diabetes controls without GADA selected by Propensity Score Matching were collected. FA was analyzed with liquid chromatography-tandem mass spectrometry analysis. Results: Principal factor analysis found component 1 explains 82.6% of total variance contained fatty acids from a mixed of lard oil, seafood, and vegetable diet, followed by diet predominantly from vegetable oil, a diet of high fat diet, and a diet of seafood diet. The FA heatmap looked clearly different among the three groups with more similar type 1 (t1dm) and LADA fatty acid profile. n-3 α-linolenic acid (ALA), n-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA), such as Eicosapentaenoic Acid and Docosapentaenoic Acid, n-3/n-6 ratio and triene/tetraene ratio were higher in patients with type 2 diabetes (t2dm) compared with LADA and t1dm. Saturated FAs were lower in t2dm than t1dm and LADA. Arachidic acid and n-6 LC-PUFAs were lower in t2dm than in t1dm and LADA. The characteristics of FAs in LADA were in between of classical t1dm and t2dm. Patients were classified into 6 clusters by FA clusters. Only cluster 2, 3, 5 contained enough patients to be analyzed. Cluster 5 showed an insulin deficient phenotype containing more than 60% of patients with t1dm and LADA and only 12.8% of t2dm. Cluster 2 and 3 were similar. ß cell function and glycemic control was better in cluster 3 homing 25% of t2dm. Cluster 2 held 28% of t1dm and LADA, in this cluster more than 60% of patients was t2dm. n-3 linolenic acid, n-3 LC-PUFAs, some n-6 LC-PUFAs, n-3/n-6 ratio and triene/tetraene ratio were negatively associated with GADA positivity while n-6 Arachidonic Acid was associated positively with GADA. Similar findings were found for insulin sensitivity and beta cell function. Conclusion: PUFA are associated with insulin sensitivity and beta cell function, and like other clinical features, FA profile distributed differently, but could not be used as makers to differentiate LADA from t1dm and t2dm. Ethics and Dissemination: This study has been approved by the Ethical Review Committee of Second Hospital of Dalian Medical University (approval number: 2021-005). Clinical Trial Registration: none.
Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Glucose Intolerance , Insulin Resistance , Latent Autoimmune Diabetes in Adults , Autoantibodies , Autoimmunity , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/complications , Fatty Acids , Glucose Intolerance/complications , Glutamate Decarboxylase , HumansABSTRACT
Improving glucose sensitivity remains an unmet medical need in treating type 2 diabetes (T2D). Dorzagliatin is a dual-acting, orally bioavailable glucokinase activator that enhances glucokinase activity in a glucose-dependent manner, improves glucose-stimulated insulin secretion and demonstrates effects on glycemic control in patients with T2D. We report the findings of a randomized, double-blind, placebo-controlled phase 3 clinical trial to evaluate the efficacy and safety of dorzagliatin in patients with T2D. Eligible drug-naïve patients with T2D (n = 463) were randomly assigned to the dorzagliatin or placebo group at a ratio of 2:1 for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin from baseline to week 24. Safety was assessed throughout the trial. At week 24, the least-squares mean change in glycated hemoglobin from baseline (95% confidence interval) was -1.07% (-1.19%, -0.95%) in the dorzagliatin group and -0.50% (-0.68%, -0.32%) in the placebo group (estimated treatment difference, -0.57%; 95% confidence interval: -0.79%, -0.36%; P < 0.001). The incidence of adverse events was similar between the two groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin group. In summary, dorzagliatin improved glycemic control in drug-naïve patients with T2D and showed a good tolerability and safety profile.
Subject(s)
Diabetes Mellitus, Type 2 , Blood Glucose , Diabetes Mellitus, Type 2/drug therapy , Double-Blind Method , Drug Therapy, Combination , Glucokinase , Glucose , Glycated Hemoglobin/analysis , Glycated Hemoglobin/therapeutic use , Humans , Hypoglycemic Agents , Pyrazoles , Treatment OutcomeABSTRACT
B-cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1) is highly expressed in several malignant tumors and its expression level is positively correlated with tumor invasion, distant metastasis, prognosis, and recurrence. In the present study, the biological effect of small interfering RNA (siRNA) that targeted Bmi-1 expression was studied in human cervical carcinoma cell line HeLa cells. Bmi-1 siRNA inhibited the expression of Bmi-1 at the mRNA and protein levels in HeLa cells, which significantly affected proliferation, colony formation, and migration of HeLa cells in vitro and in vivo. Therefore, silencing Bmi-1 may be a potential therapeutic option for the management of some human cancers.
Subject(s)
Gene Silencing , Nuclear Proteins/antagonists & inhibitors , Proto-Oncogene Proteins/antagonists & inhibitors , RNA, Small Interfering/genetics , Repressor Proteins/antagonists & inhibitors , Animals , Cell Movement , Cell Proliferation , G1 Phase , HeLa Cells , Humans , Mice , Mice, Nude , Nuclear Proteins/genetics , Polycomb Repressive Complex 1 , Proto-Oncogene Proteins/genetics , Repressor Proteins/geneticsABSTRACT
AIMS/INTRODUCTION: Data of nationwide glycemic control and hypoglycemic treatment patterns in newly diagnosed type 2 diabetes patients in China are absent. The aim of this study was to assess the evolution of treatment patterns for newly diagnosed type 2 diabetes patients and the clinical outcomes during 12-month follow up. MATERIALS AND METHODS: This is an observational prospective cohort study with 12 months of follow up. Patients with a diagnosis of type 2 diabetes for <6 months were enrolled. Glycated hemoglobin A1c (HbA1c) levels and hypoglycemic treatment patterns were collected at baseline and at every 3 months of follow up. RESULTS: A total of 79 hospitals were recruited, consisting of 5,770 participants. The mean HbA1c was 8.4 ± 2.5% at baseline, and decreased to 6.7 ± 1.2% at 12 months with 68.5% of patients achieving HbA1c <7%. At baseline, 44.6% of the patients were without hypoglycemic medications, 37.7% had oral hypoglycemic agents and 17.7% received insulin treatment. Determinants of change in HbA1c were treatment patterns, comorbidities, baseline characteristics such as obesity and smoking, regions, and tiers of hospitals. Associated factors with treatment alterations were time of follow up, treatment patterns, patient-reported reasons such as the economic factors and poor efficacy. CONCLUSIONS: In newly diagnosed type 2 diabetes patients, compared with patients without medications, patients with one oral hypoglycemic agent had higher possibilities of reaching glycemic control, whereas patients using insulin had lower possibilities of reaching the target. Factors associated with change in HbA1c and treatment alterations were also revealed.
Subject(s)
Biomarkers/analysis , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Blood Glucose/analysis , China/epidemiology , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Female , Follow-Up Studies , Glycated Hemoglobin/analysis , Humans , Male , Middle Aged , Prognosis , Prospective StudiesABSTRACT
INTRODUCTION: Early screening for diabetic retinopathy (DR) with an efficient and scalable method is highly needed to reduce blindness, due to the growing epidemic of diabetes. The aim of the study was to validate an artificial intelligence-enabled DR screening and to investigate the prevalence of DR in adult patients with diabetes in China. RESEARCH DESIGN AND METHODS: The study was prospectively conducted at 155 diabetes centers in China. A non-mydriatic, macula-centered fundus photograph per eye was collected and graded through a deep learning (DL)-based, five-stage DR classification. Images from a randomly selected one-third of participants were used for the DL algorithm validation. RESULTS: In total, 47 269 patients (mean (SD) age, 54.29 (11.60) years) were enrolled. 15 805 randomly selected participants were reviewed by a panel of specialists for DL algorithm validation. The DR grading algorithms had a 83.3% (95% CI: 81.9% to 84.6%) sensitivity and a 92.5% (95% CI: 92.1% to 92.9%) specificity to detect referable DR. The five-stage DR classification performance (concordance: 83.0%) is comparable to the interobserver variability of specialists (concordance: 84.3%). The estimated prevalence in patients with diabetes detected by DL algorithm for any DR, referable DR and vision-threatening DR were 28.8% (95% CI: 28.4% to 29.3%), 24.4% (95% CI: 24.0% to 24.8%) and 10.8% (95% CI: 10.5% to 11.1%), respectively. The prevalence was higher in female, elderly, longer diabetes duration and higher glycated hemoglobin groups. CONCLUSION: This study performed, a nationwide, multicenter, DL-based DR screening and the results indicated the importance and feasibility of DR screening in clinical practice with this system deployed at diabetes centers. TRIAL REGISTRATION NUMBER: NCT04240652.
Subject(s)
Diabetes Mellitus , Diabetic Retinopathy , Adult , Aged , Artificial Intelligence , China/epidemiology , Diabetic Retinopathy/diagnosis , Diabetic Retinopathy/epidemiology , Female , Humans , Mass Screening , Middle Aged , Prospective StudiesABSTRACT
Nationwide data on glycemic control, blood pressure (BP) control and lipid control in patients with newly diagnosed type 2 diabetes were vacant in China. The aim of this study was to assess the clinical outcomes for these patients. This is an observational prospective cohort study with 12 months of follow up. Patients with a diagnosis of type 2 diabetes less than 6 months were enrolled. Hemoglobin A1c (HbA1c) levels, BP levels and lipid levels were collected at baseline and the follow-ups. This study was registered at www.clinicaltrials.gov (NCT01525693). A total of 5770 participants from 79 hospitals across six geographic regions of China were recruited. After 12 months of treatment, 68.5% of these patients achieved HbA1c <7.0%; 83.7% reached BP <140/90 mmHg; 48.2% met low density lipoprotein cholesterol (LDL-c) <2.6 mmol/L; and 29.5% of patients reached the combined three therapeutic targets. Compared to those patients with baseline HbA1c <7.0%, patients with baseline HbA1c ≥7.0% had higher failure rate to reach glycemic control (relative risk (RR) = 2.04, p < 0.001), BP control (RR = 1.21, p < 0.001) and LDL-c control (RR = 1.11, p < 0.001). Obese patients had higher possibilities of failure in glucose control (RR = 1.05, p = 0.004), BP control (RR = 1.62, p < 0.001) and lipid control (RR = 1.09, p = 0.001) than patients with normal weight. The active smokers were more likely to fail in glycemic control than non-smokers (RR = 1.06, p = 0.002), and patients with physical activities were less likely to fail in lipid control than patients without exercises (RR = 0.93, p = 0.008). This study outlined the burdens of glycemic control, blood pressure control, lipid control in newly diagnosed type 2 diabetic patients in China, identified gaps in the quality of care and risk-factor control and revealed the factors influencing these gaps.
Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Adult , Aged , Aged, 80 and over , Blood Glucose/analysis , China/epidemiology , Cholesterol, LDL/blood , Combined Modality Therapy , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/therapy , Dyslipidemias/complications , Dyslipidemias/drug therapy , Female , Glycated Hemoglobin/analysis , Humans , Hypertension/complications , Hypertension/drug therapy , Hypoglycemia/chemically induced , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Male , Middle Aged , Obesity/complications , Obesity/therapy , Prevalence , Prospective Studies , Risk Factors , Smoking/epidemiology , Socioeconomic Factors , Young AdultABSTRACT
Vaccines are commonly used in the prevention of infectious diseases. The basic principle of vaccination is to use specific antigens, endogenous or exogenous to stimulate immunity against the specific antigens or cells producing them. Autoantigen or oligo vaccination has been used for disease animal models. More recently humanized monoclonal antibodies have been successfully used for the treatment of neoplastic disorders or familial hypercholesterolemia. Humanized monoclonal antibody therapy needs repeated injection, and the therapy is expensive. Therapeutic vaccination can lead to persistent immunized or immune tolerant against the therapeutic molecule(s) or site. However, immunization against those endogenous substances may also elicit persistent autoimmune reaction or destruction that do harm to health. Therefore, rigorous studies are needed before any clinical application. In this review, we briefly reviewed vaccines used in protection against common metabolic diseases including atherosclerosis, hypertension, and diabetes mellitus.
Subject(s)
Atherosclerosis/prevention & control , Diabetes Mellitus/prevention & control , Hypertension/prevention & control , Vaccination , Vaccines , Animals , Autoantigens/immunology , HumansABSTRACT
The oncogene Bmi-1 regulates cell proliferation and senescence. It is reported that it controlled the self-renewal of leukemic and breast cancer stem cell and was overexpressed in some solid tumors and hematologic malignancies. In this study, the effects of inactivation of Bmi-1 mediated by a plasmid-expressing antisense Bmi-1 RNA on the proliferation of lung cancer cell line A549 were investigated. As a result, when the plasmid was stably introduced into the cell line, the Bmi-1 protein level was specifically downregulated, and the cell proliferation was significantly inhibited as shown by the cell growth curve and colony forming assay. The cells were found mostly in the phase of G(0)/G(1) and cells in S phase were significantly decreased. Our results suggest that targeting Bmi-1 might be a therapeutic potential for the treatment of non-small-cell lung cancer.
Subject(s)
Carcinoma, Non-Small-Cell Lung/pathology , Cell Proliferation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , RNA, Antisense/pharmacology , Repressor Proteins/genetics , Repressor Proteins/metabolism , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/genetics , Cell Line, Tumor , G1 Phase/drug effects , Humans , Polycomb Repressive Complex 1 , RNA, Antisense/metabolism , Resting Phase, Cell Cycle/drug effectsABSTRACT
The present study aimed to evaluate the diagnostic value of echocardiography in measuring the thickness of epicardial adipose tissue (EAT) of the patients of type 2 diabetes mellitus (T2DM) and its correlation with the intimal-medial thickness of the carotid artery (cIMT) to investigate the relationship between EAT and cIMT. 68 patients of T2DM were enrolled and were divided into 2 groups: group of T2DM with duration≤10 years (35 cases) and group of T2DM with duration>10 years (33 cases). And 30 healthy subjects were enrolled as the control group. The thickness of EAT and cIMT were measured by echocardiography and high-frequency ultrasonography. The thickness of EAT and IMT of the carotid artery of 2 type 2 diabetic groups (duration≤10 years and>10 years) were significantly higher than that of the control group (all p<0.05), and the thickness of EAT and cIMT of the group of T2DM with duration>10 years were significantly higher than that of the group of T2DM with duration≤10 years (p<0.05). In univariate analysis, the thickness of EAT was positively and significantly associated with age (r=0.412, p<0.05), BMI (r=0.566, p<0.05), waist circumference (r=0.475, p<0.05), LDL (r=0.425, p<0.05), TG (r=0.496, p<0.05), duration of diabetes (r=0.384, p<0.05) and cIMT (r=0.456, p<0.05). In multiple stepwise regression analyses, age, BMI and IMT of carotid artery were appeared to be significantly associated with EAT (p<0.05 for all). In conclusion, routine screening of EAT and cIMT by ultrasonography in type 2 diabetic patients helps us to predict cardiovascular risks and prevent further development of cardiovascular complications.
Subject(s)
Adipose Tissue/metabolism , Carotid Intima-Media Thickness , Diabetes Mellitus, Type 2/diagnosis , Echocardiography , Pericardium/diagnostic imaging , Pericardium/metabolism , Adipose Tissue/diagnostic imaging , Adipose Tissue/pathology , Adult , Aged , Case-Control Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Diabetic Angiopathies/diagnosis , Echocardiography/methods , Female , Humans , Male , Middle Aged , Pericardium/pathology , Predictive Value of Tests , PrognosisABSTRACT
Our study was aimed to investigate the gender disparities in lipid goal attainment among type 2 diabetes outpatients with concomitant coronary heart disease (CHD) and explore potential risk factors. We performed the present analysis using data from a nationally representative epidemiologic study. The therapeutic goal was defined as achieving a low-density lipoprotein cholesterol (LDL-C) <1.8 mmol/L. A total of 1721 male and 2072 female type 2 diabetes outpatients with established CHD were identified. Compared with men, women had higher levels of total cholesterol (4.98 vs. 4.46 mmol/L; p < 0.001), LDL-C (2.82 vs. 2.54 mmol/L; p < 0.001), and triglycerides (2.02 vs. 1.79 mmol/L; p < 0.001), but not hemoglobin A1c (7.47% vs. 7.50%; p = 0.597). The proportion of women received lipid-lowering therapy was lower (38.1% vs. 48.2%; p < 0.001). The percentages of patients who achieved the LDL-C goal were higher among men. Multivariable regression analysis indicated that the odds ratio for lipid goal attainment due to the gender difference was 0.61 after adjusting confounders. The inability to achieve LDL-C goals in women with type 2 diabetes and CHD is apparently greater than that in men. This finding underscores the importance of initiatives to establish a more aggressive lipid management strategy for women to overcome gender imbalances.
Subject(s)
Anticholesteremic Agents/administration & dosage , Cholesterol, LDL/blood , Coronary Disease/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Aged , Anticholesteremic Agents/adverse effects , Cholesterol, HDL/blood , Coronary Disease/blood , Coronary Disease/complications , Coronary Disease/epidemiology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Female , Glycated Hemoglobin/metabolism , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Lipids/blood , Male , Middle Aged , Outpatients , Risk Factors , Sex Characteristics , Triglycerides/bloodABSTRACT
BACKGROUND: To study the relationship between positivity for hepatitis B surface antibody (HBsAb) and the risk of diabetes mellitus in the retired Chinese population. METHODS: A cross-sectional analysis was conducted in 900 retired Chinese workers attending a health check-up program. HBsAb, hepatitis B surface antigen, oral glucose tolerance test (OGTT), fasting plasma glucose (FBG), 2-h plasma glucose 2hBG, and insulin levels were collected. RESULTS: Participants positive for HBsAb were younger, with lower blood pressure, lower FBG and 2hBG serum uric acid, and glutamic pyruvic transaminase than those who were HbsAb negative. There were 306 subjects with impaired glucose tolerance and 121 with type 2 diabetes (T2D) in the present cohort. Using Chi-squared analysis to assess the risk of diabetes, women positive for HBsAb had a lower prevalence of T2D than those negative for HBsAb (15.7% vs 26.5%, respectively; P < 0.01). Multivariate analysis revealed family history of diabetes, age, and waist circumference were independently associated with a higher prevalence of diabetes, and that HBsAb positivity was independently associated with a lower prevalence of diabetes (odds ratio 0.579; 95% confidence interval 0.388-0.918) when adjusted for sex, family history of hypertension and dyslipidemia, and body mass index. CONCLUSIONS: An HBsAb-positive status is associated with a low rate of diabetes and better metabolic status. A prospective study of patients with known vaccination records is needed to investigate whether hepatitis B virus vaccination could protect against the development of diabetes.
Subject(s)
Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/immunology , Hepatitis B Antibodies/blood , Hepatitis B Surface Antigens/immunology , Hepatitis B/immunology , Asian People/ethnology , Biomarkers/blood , Blood Glucose/metabolism , Blood Pressure/physiology , China/epidemiology , Cross-Sectional Studies , Diabetes Mellitus, Type 2/ethnology , Female , Glucose Tolerance Test , Hepatitis B/epidemiology , Hepatitis B virus/immunology , Humans , Insulin/blood , Male , Middle Aged , PrevalenceABSTRACT
BACKGROUND: There are few data on the prevalence of obesity and its influence on achieving blood glucose, blood pressure, and blood lipid (3B) goals in Chinese type 2 diabetes outpatients. METHODS: Patient demographic data, anthropometric measurements, medications, and blood glucose and lipid profiles of 24,512 type 2 diabetes patients from a large, geographically diverse study (CCMR-3B) were analyzed. Using cut-points for body mass index (BMI) and waist circumference (WC) recommended by the Working Group on Obesity in China, overweight and obesity were defined as BMIs of 24-27.9 kg/m2 and ≥28.0 kg/m2. Central obesity was defined as a waist circumference ≥80 cm in women and ≥85 cm in men. The 3B therapeutic goals were HbA1c<7.0%, BP<140/90 mmHg and LDL-C<2.6 mmol/L. RESULTS: Overall, 43.0% of type 2 diabetes patients were overweight and 16.7% were obese; 13.3% of overweight and and 10.1% of obese patients achieved all the 3B target goals. Overweight or obese patients were less likely to achieve 3B goals than those with normal BMIs. More than a half the overweight or obese patients (69.6%) were centrally obese. Patients with abdominal obesity were less likely to achieve cardiometabolic targets than those without abdominal obesity. In multivariate logistic regression analysis, female, higher BMI and waist circumference, smoking, drinking, sedentary lifestyle, and longer diabetes duration were significantly correlated with failure to achieve 3B control goals. CONCLUSIONS: Obesity is highly prevalent and associated with poor 3B control in Chinese type 2 diabetes patients. In clinical practice, more attention and resources should focus on weight loss for such patients.