OBJECTIVEThe two major classes of antidiabetic drugs, sulfonylureas and metformin, may differentially affect macrovascular complications and mortality in diabetic patients. We compared the long-term effects of glipizide and metformin on the major cardiovascular events in type 2 diabetic patients who had a history of coronary artery disease (CAD).RESEARCH DESIGN AND METHODSThis study is a multicenter, randomized, double-blind, placebo-controlled clinical trial. A total of 304 type 2 diabetic patients with CAD, mean age = 63.3 years (range, 36–80 years), were enrolled. Participants were randomly assigned to receive either glipizide (30 mg daily) or metformin (1.5 g daily) for 3 years. The primary end points were times to the composite of recurrent cardiovascular events, including death from a cardiovascular cause, death from any cause, nonfatal myocardial infarction, nonfatal stroke, or arterial revascularization.RESULTSAt the end of study drug administration, both groups achieved a significant decrease in the level of glycated hemoglobin (7.1% in the glipizide group and 7.0% in the metformin group). At a median follow-up of 5.0 years, 91 participants had developed 103 primary end points. Intention-to-treat analysis showed an adjusted hazard ratio (HR) of 0.54 (95% CI 0.30–0.90; P = 0.026) for the composites of cardiovascular events among the patients that received metformin, compared with glipizide. The secondary end points and adverse events were not significantly different between the two groups.CONCLUSIONSTreatment with metformin for 3 years substantially reduced major cardiovascular events in a median follow-up of 5.0 years compared with glipizide. Our results indicated a potential benefit of metformin therapy on cardiovascular outcomes in high-risk patients.

ObjectiveTo evaluate differentially expressed long noncoding RNAs (lncRNAs) and the potential role of lncRNA TUG1 in patients with chronic obstructive pulmonary disease (COPD).MethodsTotal RNA was extracted from both COPD and non-COPD lung tissues, and microarray analysis was performed with 25,628 lncRNA probes and 20,106 mRNA probes. In addition, five up-regulated and five down-regulated lncRNAs were selected for identification using quantitative real-time polymerase chain reaction. COPD cell model was established by transforming growth factor β (TGF-β) treatment. Cell Counting Kit-8 assay was used to detect BEAS-2B and HFL1 cell proliferation after TUG-siRNA transfection with TGF-β treatment. In addition, the expression levels of α-SMA and fibronectin proteins were determined using Western blot in BEAS-2B and HFL1 cells after TUG-siRNA transfection with TGF-β treatment.ResultsThere were 8,376 (32.7%) differentially expressed lncRNAs and 5,094 (25.3%) differentially expressed mRNAs in COPD lung tissues compared with non-COPD lung tissues. Five of the analyzed lncRNAs (BC038205, BC130595, TUG1, MEG3, and LOC646329) were markedly increased, while five lncRNAs (LOC729178, PLAC2, LOC339529, LINC00229, and SNHG5) were significantly decreased in COPD lung tissues compared with non-COPD lung tissues (n=20) (***P<0.001). Knockdown of lncRNA TUG1 promotes BEAS-2B and HFL1 cell proliferation after TGF-β treatment through inhibiting the expression levels of α-SMA and fibronectin.ConclusionAbundant, differentially expressed lncRNAs and mRNAs were identified by microarray analysis and these might play a partial or key role in the diagnosis of patients with COPD. LncRNA TUG1 may become a very important class of biomarker and may act as a potential diagnostic and therapeutic target for patients with COPD.

BackgroundThe lipocalin family proteins, including lipocalin-2 and retinol-binding protein 4 (RBP4), are adipokines closely associated with obesity-related metabolic disorders. In this study, we evaluated the association of serum lipocalin-2 and RBP4 with intima-media thickness (IMT) and subclinical atherosclerosis in type 2 diabetic patients.Methods and ResultsSerum levels of lipocalin-2 and RBP4 were measured in 284 type 2 diabetic patients. Subclinical atherosclerosis was assessed by IMT at carotid, femoral and iliac arteries with ultrasound. Patients with subclinical atherosclerosis showed significantly higher circulating concentrations of lipocalin-2 and RBP4 when compared to those without [112.9 (86.4 to 202.1) µg/L versus 77.2(55.0–150.4) µg/L, 37.1(32.3–40.8) mg/L versus 23.2(20.1–29.2) mg/L, respectively; P = 0.002, P<0.001, respectively]. Moreover, positive correlations were observed between carotid IMT and lipocalin-2 (r = 0.170, P = 0.018) or RBP4 (r = 0.132, P = 0.040), femoral IMT and lipocalin-2 (r = 0.160, P = 0.027), as well as between iliac IMT and RBP4 (r = 0.241, P<0.001). Multiple logistic regression analysis further demonstrated that these two adipokines were independent risk factors for subclinical atherosclerosis in type 2 diabetes.ConclusionCirculating levels of lipocalin-2 and RBP4 are positively correlated with carotid IMT and subclinical atherosclerosis in type 2 diabetes, which suggests a potential role of these two lipid-binding chaperones in the pathogenesis of vascular complications of diabetes.

BackgroundFibroblast growth factor 21 (FGF21), a glucose and lipid metabolic regulator, has recently been demonstrated to be associated with cardiovascular diseases (CVD) such as carotid atherosclerosis, coronary heart disease and carotid artery plaques. However, the relationship between circulating FGF21 and subclinical atherosclerosis or atherosclerosis of other arteries such as the femoral and iliac artery remains unclear. In this study, we evaluated the association of serum FGF21 with intima-media thickness (IMT) and subclinical atherosclerosis in type 2 diabetic patients.MethodsSerum FGF21 levels were detected by enzyme-linked immunosorbent assay in 212 newly diagnosed type 2 diabetic patients without clinical symptoms of atherosclerosis or cardiovascular diseases. IMT of the carotid, femoral, and iliac arteries were measured by high-resolution B-mode ultrasound to determine the presence of subclinical atherosclerosis, which was defined as having an IMT > 1.0 mm and/or plaque on one or more of the three arteries without any clinical manifestations. The relationship between serum FGF21 levels and subclinical atherosclerosis was analyzed.ResultsSerum FGF21 levels were significantly higher in patients with subclinical atherosclerosis compared to those without [261.3 (135.1–396.4) versus 144.9 (95.9–223.0) ng/L, P < 0.001]. These differences were also observed in both men and women with subclinical atherosclerosis compared to their respective groups without [men: 243.2 (107.6–337.0) versus 136.8 (83.6–212.8) ng/L, P = 0.048; women: 292.4 (174.2–419.9) versus 160.4 (115.3–258.5) ng/L, P = 0.001]. Moreover, serum FGF21 levels showed a significantly positive correlation with carotid IMT in women (r = 0.23, P = 0.018) and with iliac IMT in both genders (women: r = 0.27, P = 0.005; men: r = 0.22, P = 0.024). Multiple logistic regression analysis further showed that serum FGF21 was an independent impact factor for subclinical atherosclerosis in patients with type 2 diabetes.ConclusionsSerum FGF21 is elevated in newly diagnosed type 2 diabetes, and positively correlates with carotid and iliac lesions in patients with subclinical atherosclerosis, especially in women. High levels of FGF21 may be a compensatory reaction to offset atherosclerosis.

Background: To evaluated and compared the efficacy and safety of 3 prostaglandin analogues (0.005% latanoprost, 0.004% travoprost, and 0.03% bimatoprost) in treatment of primary open-angle glaucoma (POAG) or ocular hypertension (OHT). Methods: PubMed, Embase, Cochrane library, Web of science, CNKI, Wanfang, and Vip database, published between January 1, 2000 and June 1, 2018, were systematically examined for randomized controlled trials (RCT) based on prostaglandin analogues for POAG or OHT treatment. Statistical analyses including weighted mean difference (WMD) calculation and odds ratio (OR) were performed using Review Manager Software version 5.3. Result: The 17 studies were included in this analysis (N = 2433 participants) with 1∼12 months’ follow-ups. The difference of intraocular pressure (IOP) reduction between latanoprost and travoprost group had not significant; there was significant difference of IOP reduction between latanoprost and bimatoprost group in the third month and sixth month; Travoprost was significantly different from bimatoprost in reducing IOP in the third month. Travoprost revealed an elevated risk of conjunctival hyperemia compared with latanoprost. An elevated risk of conjunctival hyperemia and growth of lashes compared with latanoprost. Bimatoprost shows lower ocular tolerability with higher incidence of side effects such as conjunctival hyperemia. Conclusions: 0.03% bimatoprost appears more effective following long time use (3 and 6 month post-treatment) for IOP control compared to 0.005% latanoprost, and is more effective compared to 0.004% travoprost after being used for a certain period of time (3 months post-treatment); nevertheless, 0.005% latanoprost is better tolerated in patients with POAG or OHT.