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Zhou J.-B.,Capital Medical University | Bai L.,Beijing Haidian Hospital | Wang Y.,Capital Medical University | Yang J.-K.,Capital Medical University | Yang J.-K.,Beijing Key Laboratory of Diabetes Research and Care
International Journal of Clinical Practice | Year: 2016

Aim To assess the efficacy and safety of dipeptidyl peptidase 4-inhibitors (DPP4-I) compared with sulphonylureas in adults with type 2 diabetes (T2D) mellitus. Method Randomised controlled trials were collected from PubMed, EMBASE, Google Scholar and conference. The primary outcome was the change in HbA1c. Secondary outcomes included weight gain, the change in postprandial plasma glucose (PPG), insulin resistance and fasting plasma glucose (FPG), adverse event (AE) and incidence of hypoglycaemia. Results Fourteen studies including 5480 patients randomised to DPP4-I and 5214 patients randomised to sulphonylureas were eligible for the meta-analysis. Compared with sulphonylureas, DPP4-I were associated with a smaller decline in HbA1c (WMD, weighted mean differences 0.08%, 95% CI: 0.03-0.14, p = 0.001), and resulted in weight loss of 1.945 kg (95% CI: -2.237 to -1.653, p < 0.0001). The effect of DPP4-I lowering FPG was inferior to that of sulfonylureas (WMD, 0.268 mmol/l, 95% CI, 0.151-0.385, p < 0.0001), and similar in reducing PPG (WMD, 0.084, 95% CI, -0.701 to 0.869, p = 0.833). According to the follow-up period, the included trials were separated into three groups (group 1: less than half one year, group 2: from half one year to 1 year, group 3: more than 1 year). Subgroup analysis showed that the difference in HbA1c between DPP4-I and sulphonylureas presented a decline curve (group 1: 0.50, 95% CI: 0.15-0.84, group 2: 0.05, 95% CI: -0.05 to 0.15, group 3: 0.09, 95% CI: 0.03-0.15). DPP4-I had a favourable insulin resistance compared with sulfonylureas (WMD, -0.673, 95% CI, -1.248 to -0.097, p = 0.022). In addition, compared with sulfonylureas, DPP4-I was associated with a decrease in overall risk for AE (RR, 0.93, 95% CI, 0.91-0.96, p < 0.0001). The incidence of hypoglycaemia was lower with DPP4-I (RR, 0.24, 95% CI, 0.21-0.27, p < 0.001). Conclusion Patients with T2D who receive DPP4-I could achieve almost similar glycaemic targets with sulphonylureas, with favourable effects on body weight and lower incidence of hypoglycaemia. © 2015 John Wiley & Sons Ltd.

Wang J.-Y.,Capital Medical University | Wang J.-Y.,Beijing Key Laboratory of Diabetes Research and Care | Gao Y.-B.,Capital Medical University | Zhang N.,Capital Medical University | And 9 more authors.
Molecular and Cellular Endocrinology | Year: 2014

Epithelial-to-mesenchymal transition (EMT) plays an important role in renal interstitial fibrosis (RIF) with diabetic nephropathy (DN). Smad7 (a inhibitory smad), a downstream signaling molecules of TGF-β1, represses the EMT. The physiological function of miR-21 is closely linked to EMT and RIF. However, it remained unclear whether miR-21 over-expression affected TGF-β1-induced EMT by regulating smad7 in DN. In this study, real-time RT-PCR, cell transfection, luciferase reporter gene assays, western blot and confocal microscope were used, respectively. Here, we found that miR-21 expression was upregulated by TGF-β1 in time- and concentration -dependent manner. Moreover, miR-21 over-expression enhanced TGF-β1-induced EMT(upregulation of a-SMA and downregulation of E-cadherin) by directly down-regulating smad7/p-smad7 and indirectly up-regulating smad3/p-smad3, accompanied by the decrease of Ccr and the increase of col-IV, FN, the content of collagen fibers, RTBM, RTIAW and ACR. Meantime, the siRNA experiment showed that smad7 can directly regulate a-SMA and E-cadherin expression. More importantly, miR-21 inhibitor can not only inhibit EMT and fibrosis but also ameliorate renal structure and function. In conclusion, our results demonstrated that miR-21 overexpression can contribute to TGF-β1-induced EMT by inhibiting target smad7, and that targeting miR-21 may be a better alternative to directly suppress TGF-β1-mediated fibrosis in DN. © 2014 Elsevier Ireland Ltd.

Gao L.,Capital Medical University | Xin Z.,Capital Medical University | Yuan M.-X.,Capital Medical University | Cao X.,Beijing Key Laboratory of Diabetes Research and Care | And 5 more authors.
PLoS ONE | Year: 2016

Objective: To evaluate the relationship between metabolic syndrome (MetS) and the prevalence of diabetic retinopathy (DR). Research Design and Methods: We conducted a case-controlled study, with data obtained from 2,551 Chinese participants between 18-79 years of age (representing a population of 1,660,500 in a district of Beijing). 74 cases of DR were found following data assessment by two 45° digital retinal images. Subjects without DR (NDR group) selected from the remaining 2,477 subjects were matched 1:1 to the DR group by HbA1c. MetS was defined by incorporating diagnostic criteria of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF). Results: There were no statistical differences between the DR group and NDR group in a number of biological or laboratory tests. However, the percentage of patients with DR increased vs. patients without DR with the number of MetS components from 1 to 5 (14.3% vs. 85.7%, 38.9% vs. 61.1%, 49.1%vs. 50.9%, 61.4% vs. 38.6% and 83.3%vs. 16.7%, respectively) (Pearson χ2 = 9.938, P = 0.037). The trend to develop DR with MetS was significantly higher than that without MetS (NMetS) (χ2 = 5.540, P = 0.019). MetS was an independent statistical indicator of the presence of DR after adjusting for age and sex [odds ratio (95% CI): 2.701 (1.248-5.849), P = 0.012], which is still the case with an additional adjustment for WC, SBP, TC, HbA1c and duration of diabetes [odds ratio (95% CI): 2.948(1.134-7.664), P = 0.027]. Conclusion: DR is one of the diabetic microvascular complications. Apart from poor glycemic control, the concomitance of other metabolic factors can also influence DR. MetS, defined as a cluster of metabolic risk factors, is a strong and independent indicator of DR, even to the same extent as glycemic control. © 2016 Gao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Li H.-X.,Capital Medical University | Zhang F.,Capital Medical University | Zhang F.,Beijing Key Laboratory of Diabetes Research and Care | Zhao D.,Capital Medical University | And 10 more authors.
BMC Public Health | Year: 2014

Background: Visceral adipose tissue (VAT) is a unique pathogenic fatty deposit, in that it is closely correlated with risk of cardiovascular diseases. The present study is to investigate the usefulness of neck circumference (NC) to indicate VAT. Methods. Participants aged 35 to 75 years who had taken abdomen and neck computer tomography (CT) examination were included in this study. Neck adipose tissue, abdominal VAT and subcutaneous adipose tissue (SAT) areas, as well as sagittal abdominal diameter (SAD) were measured by CT. Body anthropometrics and metabolic parameters including blood glucose, lipid profiles and blood pressure were also measured. Results: A lower abdomen CT examination was carried out on a total of 177 patients (87 male and 90 female) with a mean age of 59 years. Of the 177 participants, 15 men and 15 women also took a neck CT examination. With a comparable age and BMI, neck adipose area was correlated with abdominal VAT area significantly in men (r = 0.57, p = 0.028) and women (r = 0.53, p = 0.041). NC is positively correlated with VAT both in men (r = 0.49, p < 0.001) and women (r = 0.25, p = 0.012). Meanwhile, SAD is the best predictor for visceral fat both in men (r = 0.83, p < 0.001) and women (r = 0.73, p < 0.001). Body mass index (BMI), waist circumference (WC), and waist to height ratio (WHtR) correlated significantly with VAT both in men and women (r = 0.68, 0.42, 0.46 in men and 0.50, 0.23, 0.39 in women, p < 0.001), while waist hip ratio (WHR) displayed the weakest least correlation in men (r = 0.32, p = 0.001) and no correlation in women (r = 0.08, p = 0.442). Additionally, BMI was more strongly correlated with VAT than NC in both sexes (both p < 0.01). Conclusion: Significant correlation between NC and VAT was present in Chinese men and women, which may be accounted by the fact that neck fat area is significantly correlated with abdominal VAT. Meanwhile, SAD is the best predictor for visceral fat in the Chinese population. © 2014 Li et al.; licensee BioMed Central Ltd.

Cao X.,Capital Medical University | Cao X.,Beijing Key Laboratory of Diabetes Research and Care | Yang F.-Y.,Capital Medical University | Yang F.-Y.,Beijing Key Laboratory of Diabetes Research and Care | And 6 more authors.
Molecular and Cellular Endocrinology | Year: 2014

Blocking the renin-angiotensin system (RAS) can reduce the risk of diabetes. Meanwhile, the angiotensin (Ang)-converting enzyme-2 (ACE2)/Ang-(1-7)/Mas axis has recently been proposed to function as a negative regulator of the RAS. In previous studies, we first demonstrated that ACE2 knockout (ACE2-/y) mice exhibit impaired glucose tolerance or diabetes. However the precise roles of ACE2 on glucose metabolism are unknown. Here we show that the ACE2/Ang-(1-7)/Mas axis can ameliorate insulin resistance in the liver. Activation of the ACE2/Ang-(1-7)/Mas axis increases glucose uptake and decreases glycogen synthesis in the liver accompanied by increased expression of glucose transporters, insulin receptor substrates and decreased expression of enzymes for glycogen synthesis. ACE2 knockout mice displayed elevated levels of oxidative stress and exposure to Ang-(1-7) reduced the stress in hepatic cells. As a consequence of anti-oxidative stress, activation of the ACE2/Ang-(1-7)/Mas axis led to improved hepatic insulin resistance through the Akt/PI3K/IRS-1/JNK insulin signaling pathway. This is the first time documented that the ACE2/Ang-(1-7)/Mas axis can ameliorate insulin resistance in the liver. As insulin resistance in the liver is considered to be the primary cause of the development of type 2 diabetes, this axis may serve as a new diabetes target. © 2014 Elsevier Ireland Ltd.

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