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Li Q.,Capital Medical University | Li Q.,Beijing Key Laboratory of Diabetes Research and Care | Lu J.,Capital Medical University | Lu J.,Beijing Key Laboratory of Diabetes Research and Care | And 8 more authors.
Hormone and Metabolic Research | Year: 2016

This study was aimed to evaluate the relationship between normal serum uric acid (SUA) level and metabolic syndrome (MetS) risk. This cross-sectional study involved 1914 subjects with MetS and 3 659 healthy controls aged 18–79 years. All participants filled out questionnaires and underwent physical examination and blood sample collection for biochemical examination. Demographic and clinical characteristics data were analyzed by t-test or chi-squared test. Normal SUA levels were divided into quartiles. Associations between quartiles of normal SUA level and the risk of MetS were explored using logistic regression analysis and receiver operating characteristic (ROC) curve analysis. Values of age, waist circumference, blood lipid, blood pressure, fasting plasma glucose, SUA, and body mass index were all higher in subjects with MetS than that of healthy controls significantly. The frequency of MetS increased with SUA level within the normal range. Compared with Q1, the risk of MetS was greater in the other quartiles of SUA level in men (OR, 1.495–2.288); this difference was significant for Q3 and Q4 (p<0.05), but not for Q2. Among women, the risk of MetS also increased with SUA level within the normal range, with all differences showing statistical significance (p<0.05). The area under the ROC curve of normal SUA level for MetS presence was larger for women than for men. In conclusion, the results provide support for the use of normal SUA level as a contributing clinical predictor of MetS, especially in women. Copyright © 2016, Georg Thieme Verlag KG. All rights reserved.


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.


Li H.-X.,Capital Medical University | Li H.-X.,Baoding No1 Central Hospital | Zhang F.,Capital Medical University | Zhang F.,Beijing Key Laboratory of Diabetes Research and Care | And 11 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.


Chen Y.-W.,Capital Medical University | Wang Y.-Y.,Capital Medical University | Wang Y.-Y.,Beijing Key Laboratory of Diabetes Research and Care | Zhao D.,Capital Medical University | And 14 more authors.
PLoS ONE | Year: 2015

Little is known about the relationship between lower extremity peripheral arterial disease (PAD) and proliferative diabetic retinopathy (PDR) in type 2 diabetes (T2D). Here, we explored the relationship between sight-threatening PDR and PAD.We screened for diabetic retinopathy (DR) and PAD in hospitalized patients with T2D. Patients with a diabetic duration of more than 10 years, HbA1c ≥7.5%, eGFR ≥60mL/min/1.73m2 and with PDR or with no diabetic retinopathy (NDR) were eligible for this cross-sectional study. Severities of DR were graded by digital retinal photographs according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale.We assessed PAD by measuring Ankle Brachial Index (ABI), Toe Brachial Index (TBI) and Doppler ultrasound. Statistical analyses were performed using SPSS 17.0 software. Of the 1544 patients, 169 patients with extreme eye (57 PDR and 112 NDR) phenotypes met the inclusion criteria. Patients with PDR had a significantly higher proportion of low ABI (≤0.99) and high ABI (≥1.3) than patients with NDR (28.1% and 15.8%vs. 14.3% and 6.2% respectively, P<0.05). PDR patients also had lower TBI than NDR patients (0.56±0.09 vs. 0.61±0.08, P<0.01). The proportion of patients with abnormal duplex ultrasound was higher in PDR than in NDR (21.1% vs. 9.8%, P<0.001). This showed that PDR associated with PAD could be defined in multiple ways: abnormal ABI (≤ 0.9) (OR = 3.61, 95% CI: 1.15-11.26), abnormal TBI (OR = 2.84, 95% CI: 1.19-6.64), abnormal duplex (OR = 3.28, 95% CI: 1.00-10.71), and critical limb ischemia (OR = 5.52, 95% CI: 2.14-14.26). Moreover, PDR was a stronger independent correlation factor for PAD than a diabetic duration of 10 years. In conclusion, PAD is more common in PDR than in NDR. It implies that PDR and PAD are mostly concomitant in T2D.We should focus on screening PAD in patients with PDR in clinical practice. © 2015 Chen et al.


Li Q.,Capital Medical University | Cao X.,Capital Medical University | Cao X.,Beijing Key Laboratory of Diabetes Research and Care | Qiu H.-Y.,Capital Medical University | And 9 more authors.
Gene | Year: 2016

To establish a three-step programmed method to find gene mutations related to maturity onset diabetes of the young (MODY). Target region capture and next-generation sequencing (NGS) were performed using customized oligonucleotide probes designed to capture suspected genes for MODY in 11 probands with clinically diagnosed MODY. The suspected associations of certain genes with MODY were then confirmed by Sanger sequencing in the probands and their family members. Finally, to validate variants of one of the genes of interest (glucokinase, GCK) as pathogenic mutations, protein function editing by the variant genes was assessed. In the target region capture and NGS phase, a total of nine variants of seven genes (GCK, WFS1, SLC19A2, SH2B1, SERPINB4, RFX6, and GATA6) were identified in eight probands. Two heterozygous GCK mutations located on the same allele (p.Leu77Arg and p.Val101Met) were identified in a MODY family. Sanger sequencing was used to confirm the variants identified by NGS to be present in probands and their diabetic family members, but not in non-diabetic family members. Finally, enzyme kinetic and thermal stability analyses revealed that the p.Leu77Arg mutation or the p.Leu77Arg mutation in combination with the p.Val101Met mutation inactivates GCK function and stability, while mutation of p.Val101Met alone does not. The p.Leu77Arg but not p.Val101Met GCK mutation is therefore considered a pathogenic mutation associated with MODY. Genetic screening coupled with gene-editing protein function testing is an effective and reliable method by which causative gene mutations of MODY can be identified. © 2016 Elsevier B.V.


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.


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.


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.


Qiu H.-Y.,Capital Medical University | Qiu H.-Y.,Beijing Key Laboratory of Diabetes Research and Care | Yuan S.-S.,Capital Medical University | Yuan S.-S.,Beijing Key Laboratory of Diabetes Research and Care | And 6 more authors.
Journal of Diabetes Research | Year: 2016

The purpose of this study was to investigate the effect of moxifloxacin on HERG channel protein and glucose metabolism. HERG expression was investigated using immunohistochemistry. The whole-cell patch clamp method was used to examine the effect of moxifloxacin on HERG channel currents. A glucose tolerance test was used to analyze the effects of moxifloxacin on blood glucose and insulin concentrations in mice. Results show that HERG protein was expressed in human pancreatic β-cells. Moxifloxacin inhibited HERG time-dependent and tail currents in HEK293 cells in a concentration-dependent manner. The IC50 of moxifloxacin inhibition was 36.65 mol/L. Moxifloxacin (200 mg/kg) reduced blood glucose levels and increased insulin secretion in wild-type mice at 60 min after the start of the glucose tolerance test. In contrast, moxifloxacin did not significantly alter blood glucose and insulin levels in HERG knockout mice. Serum glucose levels increased and insulin concentrations decreased in HERG knockout mice when compared to wild-type mice. The moxifloxacin-induced decrease in blood glucose and increase in insulin secretion occurred via the HERG protein; thus, HERG protein plays a role in insulin secretion. © 2016 Hai-Yan Qiu et al.

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