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1.
Bone ; 130: 115121, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678488

RESUMO

BACKGROUND: Osteoporosis and cardiovascular (CV) diseases are closely correlated. RANKL/RANK/OPG pathway and Wnt signalling pathway both implicated in the pathogenesis of osteoporosis and cardiovascular diseases. We aimed to investigate the effect of denosumab or romosozumab therapy on cardiovascular outcomes in patients with primary osteoporosis. METHODS: PubMed, Cochrane library, and EMBASE databases were systematically searched from the inception dates to June 4, 2019. Randomized clinical trials evaluating the effect of denosumab or romosozumab versus active comparators or placebo for at least 6 months in patients with primary osteoporosis or osteopenia were included. Two investigators independently extracted data for study characteristics, outcomes of interest, and risk of bias in accordance with PRISMA guidelines. RESULTS: 17 relevant studies (denosumab: n=11, 13615 participants; romosozumab: n=6, 12219 participants) were included. No associations between denosumab therapy and risk of a composite cardiovascular outcome (1.06 [95 % CI, 0.88-1.28], p=0.54), three-point major adverse cardiovascular event (3P MACE, 1.01 [95 % CI, 0.83-1.23], p=0.93), and four-point major adverse cardiovascular event (4P MACE, 0.99 [95 % CI, 0.83-1.18], p=0.89) were identified. Romosozumab therapy did not increase the risk of composite cardiovascular outcome (1.26 [95 % CI, 0.95-1.68], p=0.11), and 3P MACE (1.41 [95 % CI, 0.99-2.02], p=0.06), while increased the risk of 4P MACE (1.39 [95 % CI, 1.01-1.90], p=0.04) among elderly men and postmenopausal woman with osteoporosis over a period of 12-36 months. Denosumab or romosozumab did not increase or reduce specific cardiovascular outcomes, including CV death or death, myocardial infarction, stroke, atrial fibrillation, heart failure, aortic and intracranial aneurysm, aortic dissection, aortic valve disease and hypertension (all p>0.05). Sensitivity analysis conducted by random effects model altered the result of 4P MACE in romosozumab (1.36 [0.99-1.87], p=0.06). No other significant difference was detected in the sensitivity analyses and subgroup analyses. CONCLUSIONS: Denosumab therapy was not associated with any risk of composite and specific cardiovascular outcomes among patients with primary osteoporosis than active comparators or placebo, while romosozumab therapy might increase the risk of 4P MACE.

2.
J Diabetes Res ; 2019: 1747684, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485449

RESUMO

Introduction: Urinary C-peptide creatinine ratio (UCPCR) is used as a marker of endogenous insulin secretion. This study aims to assess the effectiveness of UCPCR for distinguishing between type 1 diabetes (T1DM) and non-T1DM (monogenic diabetes and T2DM) and predicting therapeutic choices in type 2 diabetes (T2DM) patients. Methods: Twenty-three patients with genetically confirmed monogenic diabetes (median age 35.0 years (interquartile range 30.0-47.0), 13 (56.5%) men), 56 patients with T1DM (median age 46.0 years (interquartile range 26.5-59.5), 28 (50.0%) men), 136 patients with T2DM (median age 53.0 years (interquartile range 42.0-60.0), 87 (64.0%) men), and 59 healthy subjects (median age 36.0 years (30.0-42.0), 26 (44.1%) men) were included. UCPCR was collected in the morning. Receiver operating characteristic (ROC) curves were used to identify optimal UCPCR cut-off values to differentiate T1DM from non-T1DM. This UCPCR cut-off was used to divide T2DM patients into two groups, and the two groups were compared. Results: The UCPCR was lower in patients with T1DM compared with T2DM, monogenic diabetes, and healthy subjects, while the UCPCR was similar in T2DM and monogenic diabetes. A UCPCR cut-off of ≥0.21 nmol/mmol distinguished between monogenic diabetes and T1DM (area under the curve [AUC], 0.949) with 87% sensitivity and 93% specificity. UCPCR ≥ 0.20 nmol/mmol had 82% sensitivity and 93% specificity for distinguishing between T2DM and T1DM, with an AUC of 0.932. UCPCR was not reliable for distinguishing between monogenic diabetes and T2DM (AUC, 0.605). Twenty-five of 136 (18.4%) T2DM patients had UCPCR ≤ 0.20 nmol/mmol. Compared with T2DM patients with a UCPCR > 0.20 nmol/mmol, T2DM patients with UCPCR ≤ 0.20 nmol/mmol had a lower serum C-peptide (fasting C-peptide, 0.39 nmol/L vs. 0.66 nmol/L, P < 0.001; postprandial C-peptide, 0.93 nmol/L vs. 1.55 nmol/L, P < 0.001), lower BMI (22.8 kg/m2 vs. 25.2 kg/m2, P = 0.006), and higher percentage of insulin or secretagogue therapy (92.0% vs. 59.5%, P = 0.002). Conclusions: UCPCR is a practical and noninvasive marker that can distinguish between TIDM and T2DM or monogenic diabetes. UCPCR ≤ 0.20 nmol/mmol reflects severe impaired beta cell function and the need for insulin or secretagogue therapy in T2DM patients.

3.
J Diabetes Res ; 2019: 9347132, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31485457

RESUMO

Identifying factors that may impact vildagliptin's efficacy could contribute to individualized treatment for patients with type 2 diabetes. In the current study, we aimed to assess the correlation between patient baseline triglyceride (TG) and efficacy of vildagliptin in Chinese patients with type 2 diabetes in a post hoc analysis of the VISION study. TG-based subgroup analysis was performed to evaluate baseline TG's impact on the decrease of glycated hemoglobin (HbA1c) in patients receiving vildagliptin plus low-dose metformin (VLDM) vs. high-dose metformin (HDM). Additionally, multivariate linear regression was performed to assess the association between baseline TG and HbA1c reduction at weeks 12 and 24 for patients receiving VLDM vs. HDM. For patients receiving VLDM, baseline TG ≤ 2.03 mmol/L was associated with significantly greater HbA1c reduction vs. TG > 2.03 mmol/L at week 12, but not at week 24. Additionally, multivariate linear regression analysis revealed a significant independent association and an association short of statistical significance between patient baseline TG and the HbA1c-reducing efficacy of VLDM at weeks 12 (P < 0.001) and 24 (P = 0.082), respectively, while such association was absent for HDM. Collectively, baseline TG was an independent predictive factor for the efficacy of a dipeptidyl peptidase-IV in treating type 2 diabetes during its initial use.

4.
Medicine (Baltimore) ; 98(37): e16618, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517810

RESUMO

OBJECTIVE: This meta-analysis assessed the effectiveness of probiotics and synbiotics for acute diarrhea (AD) in children and investigated probiotic formulations, types of interventions, and country factors. METHODS: Randomized, double-blind, placebo-controlled trials evaluating the effects of probiotics or synbiotics on AD were analyzed. We followed the recommendations of the Cochrane Handbook and the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. The risks of systematic errors (bias) and random errors were assessed, and the overall quality of the evidence was evaluated using the Grades of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: The meta-analysis included 34 studies with 4911 patients. Five and 29 studies presented the results of synbiotic and probiotic interventions, respectively. After intervention, the durations of diarrhea (weighted mean difference (WMD) = -16.63 [-20.16; -12.51]) and hospitalization (risk ratio (RR) = 0.59 [0.48; 0.73]) were shorter, the stool frequency on day 3 (WMD = -0.98 [-1.55; -0.40]) was decreased, and the incidence of diarrhea lasting 3 days was lower in the probiotic and synbiotic groups than in the control groups. Furthermore, in the subgroup analyses, synbiotics were more effective than probiotics at reducing the durations of diarrhea and hospitalization, and Saccharomyces and Bifidobacterium were more effective than Lactobacillus at reducing the duration of diarrhea. CONCLUSION: This meta-analysis supports the potential beneficial roles of probiotics and synbiotics for AD in children. Further research is needed to determine problems associated with probiotic/synbiotic mixtures and appropriate dosages.


Assuntos
Diarreia/terapia , Probióticos/uso terapêutico , Simbióticos , Doença Aguda/terapia , Criança , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Sci Rep ; 9(1): 12086, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31427625

RESUMO

To identify the factors associated with serum total bilirubin (STB) and determine whether STB is independently associated with diabetic retinopathy (DR) or diabetic kidney disease (DKD), 1,665 Chinese patients with type 2 diabetes (T2DM) (248 outpatients newly diagnosed with T2DM [NDM] and 1,417 inpatients previously diagnosed with T2DM [PDM]) were studied. Clinical and biochemical information was collected, and a single nucleotide polymorphism (rs6704078) of the UGT1A1 gene was genotyped in 1,059 individuals. Multiple linear regression showed that STB was associated with haemoglobin concentration, platelet count, and serum triglyceride concentration in NDM and PDM patients, and with serum albumin, duration of diabetes, and smoking in PDM patients. In patients with PDM, multiple logistic regression revealed that serum albumin was associated with DR (odds ratio [OR] = 0.92, 95% confidence interval [CI]: 0.87-0.96, p = 0.001) and DKD (OR = 0.93, 95% CI: 0.88-0.98, p = 0.005) after adjustment for STB, STB-related factors, and risk factors for DR and DKD. In addition, patients with the T allele of rs6704078 had higher STB (13.2 [10.4-17.9] µmol/L versus 11.8 (9.4-14.8) µmol/L; p < 0.001) and similar risks of DR or DKD to those without the T allele. Thus, serum albumin, but not STB, is associated with DR and DKD.

6.
J Diabetes Investig ; 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31161658

RESUMO

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.

7.
Sci Rep ; 9(1): 7709, 2019 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-31118445

RESUMO

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.

8.
Clin Lab ; 65(5)2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31115208

RESUMO

BACKGROUND: Tumor-derived exosomal miRNAs secreted by cancer cells play significant roles in the pathological processes of cancer, but no systematic meta-analysis has focused on the diagnostic efficiency of exosomal miRNAs. This meta-analysis assessed the diagnostic value of circulating exosomal miRNA in cancer. METHODS: Studies evaluating the diagnostic value of exosomal miRNA were identified in EMBASE, PubMed, Cochrane Library, and Web of Science up to August 1, 2018. The quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies 2, and STATA 14.0 was used for the analyses. The true positive (TP), false positive (FP), true negative (TN), and false negative (FN) rates were extracted from each study to obtain the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and their 95% confidence intervals (CIs). RESULTS: The meta-analysis included 16 studies with 1,591 patients. Five studies reported sensitivity values, and the pooled sensitivity was 0.86 (95% CI = 0.80 - 0.90, while 29 studies reported specificity values, and the pooled specificity was 0.89 (95% CI = 0.83 - 0.93). The pooled PLR was 7.8 (95% CI = 4.9 - 12.4), the pooled NLR was 0.16 (95% CI = 0.11 - 0.24), the pooled DOR was 48 (95% CI = 23 - 101), and the AUC was 0.94 (0.91 - 0.96). CONCLUSIONS: Our meta-analysis indicated that body fluid exosomal miRNAs are highly accurate for distinguishing patients from healthy individuals, and exosomal miRNAs have superior diagnostic value in plasma, prostate cancer patients, and non-Asian individuals.

9.
BMC Med Inform Decis Mak ; 19(Suppl 2): 65, 2019 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-30961622

RESUMO

BACKGROUND: The Named Entity Recognition (NER) task as a key step in the extraction of health information, has encountered many challenges in Chinese Electronic Medical Records (EMRs). Firstly, the casual use of Chinese abbreviations and doctors' personal style may result in multiple expressions of the same entity, and we lack a common Chinese medical dictionary to perform accurate entity extraction. Secondly, the electronic medical record contains entities from a variety of categories of entities, and the length of those entities in different categories varies greatly, which increases the difficult in the extraction for the Chinese NER. Therefore, the entity boundary detection becomes the key to perform accurate entity extraction of Chinese EMRs, and we need to develop a model that supports multiple length entity recognition without relying on any medical dictionary. METHODS: In this study, we incorporate part-of-speech (POS) information into the deep learning model to improve the accuracy of Chinese entity boundary detection. In order to avoid the wrongly POS tagging of long entities, we proposed a method called reduced POS tagging that reserves the tags of general words but not of the seemingly medical entities. The model proposed in this paper, named SM-LSTM-CRF, consists of three layers: self-matching attention layer - calculating the relevance of each character to the entire sentence; LSTM (Long Short-Term Memory) layer - capturing the context feature of each character; CRF (Conditional Random Field) layer - labeling characters based on their features and transfer rules. RESULTS: The experimental results at a Chinese EMRs dataset show that the F1 value of SM-LSTM-CRF is increased by 2.59% compared to that of the LSTM-CRF. After adding POS feature in the model, we get an improvement of about 7.74% at F1. The reduced POS tagging reduces the false tagging on long entities, thus increases the F1 value by 2.42% and achieves an F1 score of 80.07%. CONCLUSIONS: The POS feature marked by the reduced POS tagging together with self-matching attention mechanism puts a stranglehold on entity boundaries and has a good performance in the recognition of clinical entities.

10.
J Enzyme Inhib Med Chem ; 34(1): 799-807, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30879343

RESUMO

mPGES-1 is a terminal rate-limiting enzyme responsible for inflammation-induced PGE2 production. The inhibition of mPGES-1 has been considered as a safe and effective target for the treatment of inflammation and cancer. However, a specific, efficient, and simple method for high-throughput screening of mPGES-1 inhibitors is still lacking. In this study, we developed a fluorescence imaging strategy to monitor the expression of mPGES-1 via CRISPR/Cas9 knock-in system. Immunofluorescence colocalisation, Sanger sequencing, RNAi, and IL-1ß treatment all confirmed the successful construction of mPGES-1 reporter cells. The fluorescence signal intensity of the reporter cells treated with four conventional mPGES-1 inhibitors was considerably attenuated via flow cytometry and fluorescent microplate reader, demonstrating that the reporter cells can be used as an efficient and convenient means for screening and optimising mPGES-1 inhibitors. Moreover, it provides a new technical support for the development of targeted small molecule compounds for anti-inflammatory and tumour therapy.


Assuntos
Sistemas CRISPR-Cas , Inibidores Enzimáticos/farmacologia , Fígado/efeitos dos fármacos , Prostaglandina-E Sintases/antagonistas & inibidores , Citometria de Fluxo , Fluorescência , Imunofluorescência , Células HEK293 , Células Hep G2 , Ensaios de Triagem em Larga Escala , Humanos , Interleucina-1beta/farmacologia , Fígado/citologia , Fígado/enzimologia , Prostaglandina-E Sintases/genética , Interferência de RNA , Reação em Cadeia da Polimerase em Tempo Real , Bibliotecas de Moléculas Pequenas/farmacologia
11.
J Diabetes ; 11(9): 729-743, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30615306

RESUMO

BACKGROUND: Metformin is first-line therapy for patients with diabetes. However, it may lower vitamin B12 concentrations, which could have hematological or neurological implications. This meta-analyses reviewed all available studies on associations between metformin use and vitamin B12 levels, anemia, and neuropathy in diabetic patients. METHODS: PubMed, Web of Knowledge, Cochrane Library, and Embase were searched to identify all relevant studies published in English prior to March 2018. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were calculated for dichotomous outcomes and pooled mean differences (MDs) and 95% CIs were calculated for continuous outcomes. RESULTS: Thirty-one studies were included in the meta-analyses. Compared with diabetic patients not taking metformin, patients taking metformin had a significantly higher risk of vitamin B12 deficiency (RR 2.09; 95% CI 1.49, 2.93; P < 0.0001; I2 = 64%) and significantly lower serum vitamin B12 concentrations (MD -63.70; 95% CI -74.35, -53.05] pM; P < 0.00001; I2 = 87%), which depended on dose and duration of treatment. Metformin use was also associated with significantly greater percentage decrease in serum vitamin B12 concentrations from baseline in diabetic patients (MD -14.68%; 95% CI -17.98%, -11.39%; P < 0.00001; I2 = 33%). Analyses revealed no significant association between metformin use and the prevalence of anemia or neuropathy. CONCLUSIONS: Metformin use led to significantly lowered vitamin B12 concentrations and significantly higher risk of vitamin B12 deficiency in diabetic patients. More quality studies are needed to explore the associations between metformin use and anemia and neuropathy in these patients. Annual vitamin B12 assessment in diabetic patients taking metformin is recommended.

12.
Diabetes Care ; 42(4): 644-650, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30679305

RESUMO

OBJECTIVE: Individualized treatment of patients with diabetes requires detailed evaluation of risk factor dynamics at the population level. This study evaluated the persistent glycemic and cardiovascular (CV) risk factor burden over 2 years after treatment intensification (TI). RESEARCH DESIGN AND METHODS: From U.S. Centricity Electronic Medical Records, 276,884 patients with incident type 2 diabetes who intensified metformin were selected. Systolic blood pressure (SBP) ≥130/140 mmHg and LDL ≥70/100 mg/dL were defined as uncontrolled for those with/without a history of CV disease at TI. Triglycerides ≥150 mg/dL and HbA1c ≥7.5% (58 mmol/mol) were defined as uncontrolled. Longitudinal measures over 2 years after TI were used to define risk factor burden. RESULTS: With 3.7 years' mean follow-up, patients were 59 years; 70% were obese; 22% had a history of CV disease; 60, 30, 50, and 48% had uncontrolled HbA1c, SBP, LDL, and triglycerides, respectively, at TI; and 81% and 69% were receiving antihypertensive and lipid-modifying therapies, respectively. The proportion of patients with consistently uncontrolled HbA1c increased from 31% in 2005 to 41% in 2014. Among those on lipid-modifying drugs, 41% and 37% had consistently high LDL and triglycerides over 2 years, respectively. Being on antihypertensive therapies, 29% had consistently uncontrolled SBP. Among patients receiving cardioprotective therapies, 63% failed to achieve control in HbA1c + LDL, 57% in HbA1c + SBP, 55% in LDL + SBP, and 63% in HbA1c + triglycerides over 2 years after TI. CONCLUSIONS: Among patients on multiple therapies for risk factor control, more than one-third had uncontrolled HbA1c, lipid, and SBP levels, and more than one-half had two CV risk factors that were simultaneously uncontrolled after TI.


Assuntos
Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Feminino , Humanos , Lipídeos/sangue , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
14.
J Med Econ ; 22(4): 336-343, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30663458

RESUMO

BACKGROUND AND OBJECTIVE: Dapagliflozin is the first SGLT2 inhibitor available in China, where the disease burden of diabetes and its complications is very heavy. Because a new diabetes treatment strategy for diabetes should consider its cost-effectiveness, compared with an existing treatment, this study aimed to examine the cost-effectiveness between dapagliflozin and metformin treatment in China. METHODS: The Cardiff Diabetes Model (CDM) was used to estimate cost effectiveness and macro- and micro-vascular outcomes of dapagliflozin vs metformin. The CDM effectiveness inputs were derived from indirect comparative efficacy data from meta-analysis of 71 studies comparing monotherapy and add-on therapy of dapagliflozin vs metformin: dapagliflozin or metformin monotherapy, add-on therapy with other oral hypoglycemic agents, and add-on therapy with insulin. Direct medication costs and medical costs on treating diabetes were calculated based on published and local sources. A discount rate of 3% was applied to both costs and health effects. Univariate and probabilistic sensitivity analyses (PSA) were performed to assess uncertainties. RESULTS: The total healthcare costs accumulated over the lifetime on dapagliflozin treatment arm was 8,626 Chinese yuan higher than the metformin treatment arm for an individual patient, and the quality adjusted life years (QALYs) gained with dapagliflozin treatment was 0.8 more than metformin treatment. Therefore, an incremental cost-effectiveness ratio was 10,729 yuan per QALY gained for dapagliflozin treatment arm vs metformin treatment arm. The cost-effectiveness results were robust to various sensitivity analyses. CONCLUSION: Dapagliflozin treatment was more cost-effective compared with metformin treatment for Chinese type 2 diabetes patients. However, the findings of favorable cost-effectiveness results for dapagliflozin are largely driven by the effects of favorable weight profile on clinical, utility, and costs in the Cardiff model.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Hipoglicemiantes/economia , Hipoglicemiantes/uso terapêutico , Metformina/economia , Metformina/uso terapêutico , Administração Oral , Fatores Etários , Idade de Início , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/economia , Peso Corporal , China , Colesterol/sangue , Análise Custo-Benefício , Complicações do Diabetes/economia , Complicações do Diabetes/epidemiologia , Quimioterapia Combinada , Feminino , Glucosídeos/administração & dosagem , Glucosídeos/economia , Hemoglobina A Glicada , Gastos em Saúde , Humanos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/administração & dosagem , Metformina/efeitos adversos , Pessoa de Meia-Idade , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de Vida , Índice de Gravidade de Doença , Fatores Sexuais , Fatores Socioeconômicos , Inibidores do Transportador 2 de Sódio-Glicose/economia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
15.
Genet Med ; 2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30245511

RESUMO

PURPOSE: To estimate the prevalence of glucokinase variant-induced diabetes (GCK-DM) in a general population and to establish a clinical strategy for identifying GCK-DM from type 2 diabetes (T2DM). METHODS: A population-based study of diabetes in a rural region of Beijing, China, was conducted using two-stage stratified random cluster sampling. The glucokinase exons were sequenced in patients with diabetes. RESULTS: A total of 3345 subjects, including 545 patients with diabetes, participated in this study. Seven patients with GCK-DM were identified. The estimated prevalence rates of GCK-DM were 0.21% and 1.3% in the whole population and the diabetic patients, respectively. In the newly diagnosed diabetic patients (New-DM), a triglyceride cutoff ≤1.43 mmol/L (126.55 mg/dl) could discriminate GCK-DM from T2DM with 100% sensitivity and 68.4% specificity. Its effectiveness was confirmed in an additional 134 early-onset young patients with T2DM and mild hyperglycemia. A clinical criterion based on triglyceride and mild hyperglycemia could differentiate GCK-DM from T2DM in New-DM and was shown to be effective in identifying GCK-DM from 559 early-onset young patients with T2DM in the hospital. CONCLUSIONS: The prevalence of GCK-DM is approximately 1.3% in the Chinese population with diabetes, and the new clinical screening strategy is helpful for identifying GCK-DM.

16.
J Diabetes Res ; 2018: 7842064, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30155490

RESUMO

miR-122, the expression of which is regulated by several transcription factors, such as HNF1A, was recently reported to be associated with type 2 diabetes (T2DM) and hepatocellular carcinoma. HNF1A variants can cause diabetes and might be involved in the development of primary liver neoplasm. Differences in miR-122 expression among different types of diabetes have not been studied. This study aimed to investigate differences in serum miR-122 levels in Chinese patients with different forms of diabetes, including T2DM, type 1 diabetes (T1DM), HNF1A variant-induced diabetes (HNF1A-DM), glucokinase variant-induced diabetes (GCK-DM), and mitochondrial A3243G mutation-induced diabetes (MDM). In total, 12 HNF1A-DM patients, 24 gender-, age-, and body mass index-matched (1 : 2) T2DM patients and 24 healthy subjects were included in this study. In addition, 30 monogenic diabetes (11 GCK-DM and 19 MDM) and 17 T1DM patients were included. Fasted blood biochemistry and miR-122 were measured. The results showed that the HNF1A-DM patients had lower miR-122 levels [0.046 (0.023, 0.121)] than T2DM patients [0.165 (0.036, 0.939), P = 0.02] and healthy controls [0.249 (0.049, 1.234), P = 0.019]. The area under the curve of the receiver operating characteristic curve for miR-122 to discriminate HNF1A-DM and T2DM was 0.687 (95% CI: 0.52-0.86, P = 0.07). There was no difference in serum miR-122 among HNF1A-DM, GCK-DM, MDM, and T1DM patients. Lower serum miR-122 is a unique feature of HNF1A-DM patients and might partially explain the increased risk for liver neoplasm and abnormal lipid metabolism in HNF1A-DM patients.

17.
Diabetes Ther ; 9(5): 1995-2014, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30155646

RESUMO

INTRODUCTION: The aim of this study was to evaluate the efficacy and safety of initial combination therapy compared with monotherapy in drug-naïve type 2 diabetes patients. METHODS: MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched for randomized clinical trials of initial combination therapy with hypoglycemic agents compared with monotherapy. Those which satisfied the search criteria were included in the meta-analysis. Weighted mean difference and relative risks were calculated. RESULTS: A total of 36 studies were included in the meta-analysis. Compared with metformin monotherapy, initial combination therapy with metformin plus another anti-diabetes drug exhibited significant reductions in glycated hemoglobin (HbA1c) (p < 0.001). Most of the combination therapies had a similar risk of hypoglycemia (p > 0.05), with the exception of combinations of sulfonylurea/glinide and metformin or combinations of thiazolidinedione and metformin. Compared with dipeptidyl peptidase-4 (DPP-4) inhibitor monotherapy, initial combination therapy with DPP-4 inhibitor plus another anti-diabetes drug showed a significant decrease in HbA1c (p < 0.001) and a similar risk of hypoglycemia (p > 0.05). Compared with monotherapy with other anti-diabetes drugs, initial combination therapies also resulted in significant HbA1c reductions, a similar risk of hypoglycemia and similar risks of other adverse events. CONCLUSION: Compared with monotherapy, all initial combination therapies resulted in significant HbA1c reductions. Compared with metformin monotherapy, initial combination therapies with DPP-4 inhibitors plus metformin, sodium/glucose cotransporter 2 inhibitors and metformin, respectively, were associated with similar risks of hypoglycemia, but initial combination therapies with sulfonylurea plus metformin, thiazolidinedione and metformin, respectively, were associated with higher risks of hypoglycemia. FUNDING: AstraZeneca Ltd. (China). TRIAL REGISTRATION: Registration number CRD42017060717 in PROSPERO.

18.
Endocrine ; 62(2): 299-306, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30128962

RESUMO

PURPOSE: To clarify the relevance between smoking and diabetic retinopathy in patients with type 1 and type 2 diabetes mellitus. METHODS: Published evidence were searched in MEDLINE and EMBASE from the databases began until Feb. 2017. Studies evaluating the association between smoking and diabetic retinopathy or evaluating the risk factors of diabetic retinopathy including smoking were included. RESULTS: Totally 73 studies were identified, among which 19 studies included type 1 diabetes patients and 56 studies included type 2 diabetes patients. In type 1 diabetes, compare with non-smokers, the risk of diabetic retinopathy significantly increased in smokers (risk ratio (RR) = 1.23, 95% CI 1.14, 1.33, P < 0.001), and the risk of proliferative diabetic retinopathy also significantly increased in smokers (RR = 1.48, 95% CI 1.20, 1.81, P < 0.001). In type 2 diabetes, compare with non-smokers, the risk of diabetic retinopathy significantly decreased in smokers (RR = 0.92, 95% CI 0.86, 0.98, P = 0.02) and the risk of proliferative diabetic retinopathy also significantly decreased in smokers (RR = 0.68, 95% CI 0.61, 0.74, P < 0.001). CONCLUSIONS: Compare with non-smokers, the risk of diabetic retinopathy significantly increased in smokers with type 1 diabetes while significantly decreased in smokers with type 2 diabetes. However, this result did not change the importance of smoking cessation for public health.

19.
Diabetes Technol Ther ; 20(10): 704-714, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30095971

RESUMO

BACKGROUND: As initial combination therapy of metformin and dipeptidyl peptidase-4 (DPP-4) inhibitor, the efficacy and safety for the use of high dose of metformin or low dose of metformin and the efficacy and safety for the combination use for Asian and Caucasian patients were not clear. METHODS: Double-blind randomized controlled trials comparing the efficacy of initial combination therapy of metformin and DPP-4 inhibitors with metformin monotherapy were included. The primary outcome was a result of comparisons between high-dose combination therapy and low-dose combination therapy in terms of efficacy and safety. RESULTS: A total of 11 studies were included. The results indicated that the high-dose combination therapy showed significant decreases in hemoglobin A1c (HbA1c) (-0.32%, P < 0.05), fasting plasma glucose (FPG) (-0.63 mmol/L, P < 0.05), and postprandial glucose (PPG) (-0.99 mmol/L, P < 0.05), but less increase in body weight (-0.54 kg, P < 0.05) when compared with low-dose combination therapy, corrected by metformin monotherapy. Moreover, the high-dose combination therapy exhibited significant decreases in HbA1c (-0.24%, P < 0.05), FPG (-0.54 mmol/L, P < 0.05), and PPG (-0.94 mmol/L, P < 0.05) in the Caucasian population than in the Asian population, corrected by metformin monotherapy. CONCLUSION: As an initial treatment, the high dose of metformin in combination with DPP-4 inhibitors not only provided better glycemic control but also had less effect on weight gain compared with the low-dose combination therapy through the correction of metformin monotherapy. Moreover, initial combination therapy in the Caucasian population showed better glycemic control and less increase in body weight compared with the Asian population.

20.
Chin Med J (Engl) ; 131(13): 1605-1612, 2018 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-29941715

RESUMO

Background: Placebo was defined as any therapy that is used for its nonspecific psychological and physiologic effect but has no specific pharmacologic impact on the condition being treated. Besides medication therapies, studies have found that the optimal dietary approach as well as physical activity and education are useful to control hyperglycemia in patients with type 2 diabetes (T2DM). The aim of this study was to evaluate the placebo effects of antidiabetic therapies in Asian and Caucasian T2DM patients and make a comparison between the two ethnicities. Methods: A search using the MEDLINE database, EMBASE, and Cochrane Database was performed, from when recording began until December 2016. The main concepts searched in English were sulfonylurea (SU); alpha glucosidase inhibitors (AGI); metformin (MET); thiazolidinediones (TZD); dipeptidyl peptidase-4 inhibitors (DPP-4i); sodium-glucose cotransporter 2 inhibitors (SGLT2i); glucagon-like peptide-1 receptor agonist (GLP-1RA); type 2 diabetes (T2DM); placebo controlled; and randomized controlled trials. Using the Cochrane instrument, we evaluated the adequacy of randomization, allocation concealment procedures, and blinding. Results: This study included 63 studies with a total of 7096 Asian patients involved and 262 studies with a total of 27,477 Caucasian patients involved. In Caucasian population, the use of placebo led to significant reductions of glycosylated hemoglobin (HbA1c), -0.683% (P = 0.008) in SU monotherapy treatment, -0.193% (P = 0.001) in DPP-4i treatment, and -0.230% (P < 0.001) in SGLT2i treatment, respectively. In Asian population, the use of placebo resulted in significant decreases of HbA1c, -0.162% (P = 0.012) in DPP-4i treatment and -0.269% (P = 0.028) in GLP-1RA add-on therapy, respectively. The placebo also significantly reduced body weight. In Caucasian population, placebo use resulted in 0.833 kg (P = 0.006) weight loss by SU treatment and 0.953 kg (P = 0.006) weight loss by GLP-1RA treatment. In Asian population, the placebo led to a weight change of 0.612 kg (P < 0.001) by GLP-1RA analog treatment. The changes of HbA1c and weight due to the placebo effect in other treatments were not significant in both Asian and Caucasian population. Comparisons of the placebo effect on HbA1c change and weight change in each treatment group indicated that no significant difference was found between Asian and Caucasian population. Conclusions: The overall differences of the placebo effect on HbA1c changes as well as on body weight changes were not significant between Asian and Caucasian T2DM patients. The placebo effect on HbA1c changes and weight changes was not associated with baseline age, gender, baseline body mass index, baseline HbA1c, duration of diabetes, or study duration.

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