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| 1 | Efficacy and safety of metformin and sitagliptin based triple antihyperglycemic therapy(STRATEGY):a multicenter,randomized,controlled,non-inferiority clinical trial显示文摘Despite the current guideline's recommendation of a timely stepwise intensification therapy,the 'clinical inertia',termed as the delayed treatment intensification,commonly exists in the real world,which may be partly due to the relatively little substantial evidence and no clear consensus regarding the efficacy and safety of triple oral agents in patients inadequately controlled with dual therapy.In this clinical trial performed in 237 centers in China,5,535 type 2 diabetic patients inadequately controlled by previous therapies were treated with a stable metformin/sitagliptin dual therapy for 20 weeks.The patients who did not reach the glycated hemoglobin A1c(HbA1c) goal were then further randomized into glimepiride,gliclazide,repaglinide,or acarbose group for an additional 24-week triple therapy.A mean HbAlc reduction of 0.85%was observed when sitagliptin was added to the patients inadequately controlled with metformin in 16 weeks.Further HbAlc reductions in the 24-week triple therapy stage were 0.65%in glimepiride group,0.70%in gliclazide group,0.61%in repaglinide group,and 0.45%in acarbose group.The non-inferiority criterion for primary hypotheses was met for gliclazide and repaglinide,but not for acarbose,compared with glimepiride,when added to metformin/sitagliptin dual therapy.The incidences of adverse events(AEs) were 29.2%in the dual therapy stage and30.3%in the triple therapy stage.Metformin/sitagliptin as baseline therapy,with the addition of a third oral antihyperglycemic agent,including glimepiride,gliclazide,repaglinide,or acarbose,was effective,safe and well-tolerated for achieving an HbAlc<7.0%goal in type 2 diabetic patients inadequately controlled with previous therapies.The timely augmentation of up to three oral antihyperglycemic agents is valid and of important clinical benefit to prevent patients from exposure to unnecessarily prolonged hyperglycemia. | Wen Xu Yiming Mu Jiajun Zhao Dalong Zhu Qiuhe Ji Zhiguang Zhou Bin Yao Anhua Mao Samuel S.Engel Bin Zhao Yan Bi Longyi Zeng Xingwu Ran Juming Lu Linong Ji Wenying Yang Weiping Jia Jianping Weng | 2017 | Science China(Life Sciences)2017，60，3： | 19 |
| 2 | Decreased b-Cell Function is Associated with Cardiovascular Autonomic Neuropathy in Chinese Patients Newly Diagnosed with Type 2 Diabetes显示文摘The influence of b-cell function on cardiovascular autonomic neuropathy(CAN), an important diabetesrelated complication, is still unclear. In this study, we aimed to investigate the association between residual b-cell function and CAN in patients newly diagnosed with type 2 diabetes. We enrolled 90 newly-diagnosed type 2 diabetic patients and 37 participants with normal glucose tolerance as controls. The patients were divided into a CAN? group(diabetic patients with CAN, n = 20) and a CAN-group(diabetic patients without CAN, n = 70) according to the standard Ewing battery of tests. Fasting and postprandial plasma glucose, insulin, and C-peptide were measured.Homeostasis model assessment-beta cells(HOMA-B) and HOMA-insulin resistance(IR) were calculated. The prevalence of CAN in this population was 22.2%. Compared with the CAN-group, the CAN? group had significantly lower fasting plasma insulin(6.60 ± 4.39 vs 10.45 ± 7.82 l/L, P = 0.029), fasting C-peptide(0.51 ± 0.20 vs0.82 ± 0.51 nmol/L, P = 0.004), and HOMA-B(21.44 ± 17.06 vs 44.17 ± 38.49, P = 0.002). Fasting C-peptide was correlated with the Valsalva ratio(r = 0.24, P = 0.043) and the 30:15 test(r = 0.26,P = 0.023). Further analysis showed that fasting C-peptide(OR: 0.041, 95% CI 0.003–0.501, P = 0.012) and HOMAB(OR: 0.965, 95% CI 0.934–0.996, P = 0.028) were independently associated with cardiovascular autonomic nerve function in this population. The patients with fasting C-peptide values \ 0.67 nmol/L were more likely to have CAN than those with C-peptide levels C0.67 nmol/L(OR:6.00, 95% CI 1.815–19.830, P = 0.003). A high prevalence of CAN was found in patients with newly-diagnosed type 2 diabetes. Decreased b-cell function was closely associated with CAN in this population. | Xubin Yang Wen Xu Yanhua Zhu Hongrong Deng Ying Tan Longyi Zeng Jianping Weng | 2019 | Neuroscience Bulletin2019，35，1： | 7 |
| 3 | Glucokinase activator improves glucose tolerance and induces hepatic lipid accumulation in mice with diet-induced obesity显示文摘Background and aims:Type 2 diabetes mellitus remains a substantial medical problem with increasing global prevalence.Pharmacological research is becoming increasingly focused on personalized treatment strategies.Drug development based on glucokinase(GK)activation is an important strategy for lowering blood glucose.This study aimed to investigate the effect of GK activation on glucose and lipid metabolism in diet-induced obese mice.Materials and methods:Mice were fed with a high-fat diet(HFD)for 16 weeks to induce obesity,followed by a GK activator(GKA,AZD1656)or vehicle treatment by gavage for 4 weeks.The effect of GKA treatment on glucose metabolism was evaluated using glucose and insulin tolerance tests.Hepatic lipid accumulation was assessed by hematoxylin and eosin staining,Oil Red O staining,and transmission electron microscopy.The underlying mechanism of GK activation in glucose and lipid metabolism in the liver was studied using transcriptomic analysis,with a mechanistic study in mouse livers in vivo and AML12 cells in vitro.Results:GK activation by GKA treatment improved glucose tolerance in HFD-fed mice while increasing hepatic lipid accumulation.Transcriptomic analysis of liver tissues indicated the lipogenesis and protein kinase RNA-like endoplasmic reticulum kinase(PERK)-unfolded protein response(UPR)pathway activations in GKA-treated HFD-fed mice.Inhibition of the ACC activity,which is an important protein in lipogenesis,attenuated GKA treatment-induced lipid accumulation and PERK-UPR activation in vitro.Conclusions:GK activation improved glucose tolerance and insulin sensitivity while inducing hepatic lipid accumulation by increasing the lipogenic gene expression,which subsequently activated the hepatic PERK-UPR signaling pathway. | Nan Cai a Xuanrong Chen Jia Liu Zheyao Wen Siyin Wen Wen Zeng Shuo Lin Yanming Chen Guojun Shi Longyi Zeng | 2023 | Liver Research2023，7，2： | 0 |
| 4 | Existing tests vs. novel non-invasive assays for detection of invasive aspergillosis in patients with respiratory diseases显示文摘Background: Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-β-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-basedAspergillus assays.Methods: Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM andAspergillus-specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed.Results: The entire cohort included 3530 admissions (proven/probable IPA=66, no IPA=3464) and the subcohort included 127 admissions (proven/probable IPA=38, no IPA=89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) (χ^(2)=19.83,P<0.001), serum BDG (≥70 pg/mL: 33% [31/95]) (χ^(2)=24.65,P<0.001), and fungal culture (33% [84/253]) (χ^(2)=29.38,P<0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher’s exactP=1.000) to and slightly lower specificity (87% [77/89]) (χ^(2)=5.52,P=0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812-0.953]) and BAL GM (0.901 [0.824-0.977]) (P=0.734). Sputum LFD had similar specificity (91% [81/89]) (χ^(2)=0.89,P=0.345) to and lower sensitivity (63% [24/38]) (χ^(2)=4.14,P=0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) (χ^(2)=6.95,P=0.008), BDG (χ^(2)=10.43,P=0.001), and fungal culture (χ^(2)=12.70,P<0.001).Conclusions: Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test. | Wei Xiao Longyi Du Linli Cai Tiwei Miao Bing Mao Fuqiang Wen Peter Gerard Gibso Deying Gong Yan Zeng Mei Kang Xinmiao Du Junyan Qu Yan Wang Xuemei Liu Ruizhi Feng Juanjuan Fu | 2022 | Chinese Medical Journal2022，，13： | 0 |
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