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Screening cardiovascular risk factors of diabetes patients in the primary diabetes clinics.
An, L, Wang, Y, Cao, C, Chen, T, Zhang, Y, Chen, L, Ren, S, Tang, M, Ma, F, Li, X, et al
Medicine. 2021;(30):e26722
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Abstract
To evaluate the atherosclerotic cardiovascular diseases (ASCVD) risk factors in type 2 diabetes patients from the primary diabetes clinics for further comprehensive intervention in China.A cross-sectional study was conducted in 5 primary diabetes chain hospitals in Beijing, Lanzhou, Harbin, Chengdu, and Taiyuan in continuous patients with type 2 diabetes from March 2016 to December 2019. The data collected at the first visit were analyzed, and proportions of patients reached the targets (glycosylated hemoglobin [HbA1c] < 7%, blood pressure < 130/80 mm Hg, and low-density lipoprotein cholesterol [LDL-C] < 2.6mmol/l) were calculated. The clinical characteristics and the associated factors with achievement in HbA1c, blood pressure, and LDL-C targets were analyzed.A total of 20,412 participants, including 11,353 men (55.6%), with an average age of (59.4 ± 10.4) years were enrolled. Nearly 95% diabetes had one or more ASCVD risk factors other than hyperglycemia. The control rates of HbA1c, blood pressure, and LDL-C were 26.5%, 27.8%, and 42.6%, respectively. Only 4.1% patients achieved all 3 targets. Nearly 95% patients had one or more ASCVD risk factors other than hyperglyciemia. Diabetes duration, family history, and overweight/obesity were associated with the number of aggregated ASCVD risk factors. The patients with older age, no overweight/obesity, not smoking, less ASCVD risk factors, and having special diabetes care insurance (Chengdu) were associated with a higher control rates.To deal with poor control status, global management of ASCVD risk factors, weight loss, and smoking cessation must be emphasized in the primary diabetes care settings. Special diabetes care insurance should be advocated.Current ClinicalTrial.gov protocol ID NCT03707379. Date of Registration: October 16, 2018. https://clinicaltrials.gov.
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Effects of sodium-glucose cotransporter 2 inhibitors on non-alcoholic fatty liver disease in patients with type 2 diabetes: A meta-analysis of randomized controlled trials.
Xing, B, Zhao, Y, Dong, B, Zhou, Y, Lv, W, Zhao, W
Journal of diabetes investigation. 2020;(5):1238-1247
Abstract
AIMS/INTRODUCTION Non-alcoholic fatty liver disease (NAFLD) is increasingly common in patients with type 2 diabetes mellitus. Currently, some studies have found that sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new hypoglycemic drug, can improve non-alcoholic fatty liver in addition to its hypoglycemic effect. Thus, we undertook a meta-analysis of randomized controlled trials to evaluate the efficacy of SGLT2 inhibitors on the treatment of NAFLD. MATERIALS AND METHODS PubMed, Embase and the Cochrane Library were searched for randomized controlled trials of SGLT2 inhibitors in patients with NAFLD and type 2 diabetes mellitus up to 1 October 2019. Differences were expressed as weight mean difference (WMD) with 95% confidence interval (CI) for continuous outcomes. The I2 statistic was applied to evaluate the heterogeneity of studies. RESULTS A total of six trials including 309 patients were selected into our meta-analysis. SGLT2 inhibitors could reduce alanine aminotransferase (WMD -11.05 IU/L, 95% CI -19.85, -2.25, P = 0.01) and magnetic resonance imaging proton density fat fraction (WMD -2.07%, 95% CI -3.86, -0.28, P = 0.02). However, SGLT2 inhibitors did not reduce aspartate aminotransferase (WMD -1.11 IU/L, 95% CI -2.39, 0.17, P = 0.09). In addition, secondary outcomes, such as bodyweight and visceral fat area, were also reduced (WMD -1.62 kg, 95% CI -2.02, -1.23, P < 0.00001; WMD -19.98 cm2 , 95% CI -27.18, -12.79, P < 0.00001, respectively). CONCLUSIONS SGLT2 inhibitors can significantly decrease alanine aminotransferase and liver fat, accompanied with weight loss, which might have a positive effect on fatty liver in patients with type 2 diabetes mellitus. The limitation is that the sample size of the studies was small. Therefore, more large randomized controlled trials specified on NAFLD are required to evaluate these results.
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Dorzagliatin monotherapy in Chinese patients with type 2 diabetes: a dose-ranging, randomised, double-blind, placebo-controlled, phase 2 study.
Zhu, D, Gan, S, Liu, Y, Ma, J, Dong, X, Song, W, Zeng, J, Wang, G, Zhao, W, Zhang, Q, et al
The lancet. Diabetes & endocrinology. 2018;(8):627-636
Abstract
BACKGROUND Glucokinase acts as a glucose sensor in the pancreas and a glucose processor in the liver, and has a central role in glucose homoeostasis. Dorzagliatin is a new, dual-acting, allosteric glucokinase activator that targets both pancreatic and hepatic glucokinases. Dorzagliatin has good pharmacokinetic and pharmacodynamic properties in humans, and provides effective 24-h glycaemic control and improves glucose sensitivity in patients with type 2 diabetes. We aimed to assess the efficacy and safety of dorzagliatin monotherapy at different doses in Chinese patients with type 2 diabetes. METHODS In this multicentre, randomised, double-blind, placebo-controlled, phase 2 study, we randomly assigned (1:1:1:1:1) patients to receive oral placebo or one of four doses of oral dorzagliatin (75 mg once a day, 100 mg once a day, 50 mg twice a day, or 75 mg twice a day) using permuted-block randomisation, with a block size of ten and without stratification. Eligible patients were men or non-fertile women (aged 40-75 years) with type 2 diabetes who had a BMI of 19·0-30·0 kg/m2, were on a diet and exercise regimen, and were previously untreated or treated with metformin or α-glucosidase inhibitor monotherapy. The study started with a 4-week placebo run-in period followed by a 12-week treatment period. The primary endpoint was the change in HbA1c from baseline to week 12, which was assessed in all patients who received at least one dose of study drug and had both baseline and at least one post-baseline HbA1c value. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02561338. FINDINGS Between Sept 29, 2015, and Aug 17, 2016, we randomly assigned 258 patients to one of the five study groups. At the end of 12 weeks, the least squares mean change in HbA1c from baseline was -0·35% (95% CI -0·60 to -0·10) in the placebo group, -0·39% (-0·64 to -0·14) in the 75 mg once daily group, -0·65% (-0·92 to -0·38) in the 100 mg once daily group, -0·79% (-1·06 to -0·52) in the 50 mg twice daily group, and -1·12% (-1·39 to -0·86) in the 75 mg twice daily group. Compared with the placebo group, the change in HbA1c between baseline and 12 weeks was significant in the 50 mg twice daily (p=0·0104) and the 75 mg twice daily (p<0·0001) groups. The number of adverse events was similar between the treatment groups and the placebo group. There were no reports of drug-related serious adverse events or severe hypoglycaemia. INTERPRETATION Dorzagliatin had a beneficial effect on glycaemic control and was safe and well tolerated over 12 weeks in Chinese patients with type 2 diabetes. FUNDING Hua Medicine, National Major Scientific and Technological Special Project for Significant New Drugs Development, Shanghai Science and Technology Innovation Action Project, Shanghai Pudong District Science and Technology Innovation Action Project, and Shanghai Municipal Commission of Economy and Informatisation Innovation Action Project.
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Sequence data and association statistics from 12,940 type 2 diabetes cases and controls.
Flannick, J, Fuchsberger, C, Mahajan, A, Teslovich, TM, Agarwala, V, Gaulton, KJ, Caulkins, L, Koesterer, R, Ma, C, Moutsianas, L, et al
Scientific data. 2017;:170179
Abstract
To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (>80% of low-frequency coding variants in ~82 K Europeans via the exome chip, and ~90% of low-frequency non-coding variants in ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
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Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes.
Imamura, M, Takahashi, A, Yamauchi, T, Hara, K, Yasuda, K, Grarup, N, Zhao, W, Wang, X, Huerta-Chagoya, A, Hu, C, et al
Nature communications. 2016;:10531
Abstract
Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P<5 × 10(-8)), rs1116357 near CCDC85A, rs147538848 in FAM60A, rs1575972 near DMRTA1, rs9309245 near ASB3, rs67156297 near ATP8B2, rs7107784 near MIR4686 and rs67839313 near INAFM2. Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P<0.007). These results indicate that expansion of single ethnic GWAS is still useful to identify novel susceptibility loci to complex traits not only for ethnicity-specific loci but also for common loci across different ethnicities.
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Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin.
Liu, CT, Raghavan, S, Maruthur, N, Kabagambe, EK, Hong, J, Ng, MC, Hivert, MF, Lu, Y, An, P, Bentley, AR, et al
American journal of human genetics. 2016;(1):56-75
Abstract
Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.
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The genetic architecture of type 2 diabetes.
Fuchsberger, C, Flannick, J, Teslovich, TM, Mahajan, A, Agarwala, V, Gaulton, KJ, Ma, C, Fontanillas, P, Moutsianas, L, McCarthy, DJ, et al
Nature. 2016;(7614):41-47
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Abstract
The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
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Metabolic effects of fluoxetine in adults with type 2 diabetes mellitus: a meta-analysis of randomized placebo-controlled trials.
Ye, Z, Chen, L, Yang, Z, Li, Q, Huang, Y, He, M, Zhang, S, Zhang, Z, Wang, X, Zhao, W, et al
PloS one. 2011;(7):e21551
Abstract
BACKGROUND The prevalence of obesity and diabetes is increasing dramatically throughout the world. Studies have shown that excess adiposity is a critical predictor of new onset T2DM. This meta-analysis is aimed to assess the metabolic effects of fluoxetine in T2DM. METHODS AND FINDINGS Electronic search was conducted in the database Medline, PubMed, EMBASE, and the Cochrane library, from inception through to March 2011. A systematic review of the studies on the metabolic effects of fluoxetine in T2DM was performed. The weighted mean difference (WMD) and its 95% CI were calculated from the raw data extracted from the original literature. The software Review Manager (version 4.3.1) and Stata (version 11.0) were applied for meta-analysis. Five randomized, placebo-controlled trials were included in the meta-analysis. According to WMD calculation, fluoxetine therapy led to 4.27 Kg of weight loss (95%CI 2.58-5.97, P<0.000 01), 1.41 mmol/L of fasting plasma glucose (FPG) decrement (95%CI 0.19-2.64, P = 0.02) and 0.54 mmol/L of triglyceride (TG) reduction (95%CI 0.35-0.73, P<0.000 01) compared with placebo. Moreover, fluoxetine therapy produced 0.78% of HbA1c decrement (95%CI -0.23-1.78). However, this effect was not statistically significant (P = 0.13). CONCLUSIONS Short period of fluoxetine therapy can lead to weight loss as well as reduction of FPG, HbA1c and TG in T2DM.