31 results on '"Xiantong Zou"'
Search Results
2. Adrenal limb thickness is associated with metabolism profiles in patients with diabetes: A cross‐sectional study
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Yingning Liu, Xiantong Zou, Wei Zhao, Xun Yao, Lexuan Wang, LingLi Zhou, Rui Zhang, Yingying Luo, Meng Li, Xiuying Zhang, Yu Zhu, Xiaoling Cai, Xianghai Zhou, Xueyao Han, and Linong Ji
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adrenal glands ,diabetes mellitus ,hypertension ,metabolism ,multidetector computed tomography ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Abstract Background The association between adrenal size and metabolic profiles in patients with diabetes mellitus (DM) is unclear. This study was conducted to determine whether the adrenal thickness measured by computed tomography (CT) is correlated with the metabolic profiles of patients with DM. Methods This was a cross‐sectional study including 588 Chinese hospitalized patients with DM without comorbidities or medications known to affect adrenal morphology or hormone secretion. Adrenal limb thickness was measured on unenhanced chest CT. Participants were stratified into tertiles according to their total adrenal limb thickness. Linear and logistic regression models were used to estimate the correlations. Results After adjustment for sex and age, the adrenal thickness was positively associated with body mass index (BMI), waist circumference (WC), urinary albumin/creatinine ratio, and 24‐h urinary free cortisol (UFC) and negatively correlated with high‐density lipoprotein cholesterol. The sequential equation model (SEM) suggested UFC partially mediated the effect of adrenal limb thickness on WC by 12%. Adrenal thickness, but not UFC, was associated with a higher risk of existing hypertension (odds ratio [OR] = 3.78, 95% confidence interval [CI] 1.58, 9.02) and hyperlipidemia (OR = 2.76, 95% CI 1.03, 7.38), independent of age, gender, BMI, and WC. Conclusions The adrenal thickness is independently associated with BMI, WC, cortisol levels, urinary albumin/creatinine ratio, hypertension, and dyslipidemia but not glycemic parameters in patients with diabetes. Our study encourages further studies to investigate the role of adrenal physiology in patients with diabetes.
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- 2024
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3. Differential effects of PGAM5 knockout on high fat high fructose diet and methionine choline-deficient diet induced non-alcoholic steatohepatitis (NASH) in mice
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Li Li, Chengcheng Guo, Yue Yu, Lu Tie, Guotao Lu, Feng Liu, Xueyao Han, Linong Ji, and Xiantong Zou
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PGAM5 ,NASH ,Obesity ,Mitochondria ,Anti-oxidant ,Biotechnology ,TP248.13-248.65 ,Biology (General) ,QH301-705.5 ,Biochemistry ,QD415-436 - Abstract
Abstract Background Phosphoglycerate mutase 5 (PGAM5), a phosphatase involved in mitochondrial homeostasis, is reported to be closely related to the metabolic stress induced by high-fat diet (HFD) or cold. In this study, we aimed to investigate the effects of PGAM5 on hepatic steatosis, inflammation and fibrosis in nonalcoholic steatohepatitis (NASH). Methods and results We generated PGAM5 global knockout (GKO) mice and their wildtype (WT) littermates using CRISPR/CAS9. The mice were fed with a high fat high fructose (HFHF) diet for 12 weeks or a methionine choline-deficient (MCD) diet (methionine choline supplemented (MCS) as control) for 6 weeks. Hepatic PGAM5 expression was up-regulated in humans with NASH and WT mice fed with HFHF and MCS, and reduced in WT mice fed with MCD diet. In HFHF-fed mice, GKO had reduced body weight, hepatic triglyceride (TG) content and serum transaminase along with decreased hepatic pro-inflammatory and pro-fibrotic responses compared with their WT control. GKO had increased expression of antioxidative gene glutathione peroxidase-6 (GPX6) and activation of mammalian target of rapamycin (mTOR). In mice fed with MCS diet, GKO significantly increased serum TNF-α and IL-6 and decreased hepatic GPX6 mRNA expression. There was no difference in hepatic steatosis, inflammation or fibrosis between GKO and WT mice fed with MCD diet. We investigated the role of PGAM5 deficiency in a variety of cell types. In differentiated THP-1 cells, PGAM5 silencing significantly increased pro-inflammatory cytokine secretion and decreased antioxidative proteins, including nuclear factor erythroid 2- related factors (NRF2), heme oxygenase-1 (HO-1) and GPX6 without affecting mTOR activity. In HepG2 cells with steatosis, PGAM5 knockdown reduced insulin sensitivity, increased mTOR phosphorylation and reduced the expression of NRF2, catalase (CAT), HO-1 and GPX6. Conversely, PGAM5 knockdown reduced TG accumulation, increased insulin sensitivity, and increased antioxidative genes in 3T3-L1 cells, despite the up-regulation in mTOR phosphorylation. Conclusions PGAM5-KO relieved hepatic steatosis and inflammation in HFHF model, promoted inflammation in MCS-fed mice and had no effects on the MCD-fed model. The distinct effects may be owing to the different effects of PGAM5-KO on anti-oxidative pathways in energy-dependent, possible involves mTOR, and/or cell type-dependent manner. Our findings suggest that PGAM5 can be a potential therapeutic target for NASH.
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- 2023
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4. Personalized glucose-lowering effect of chiglitazar in type 2 diabetes
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Qi Huang, Xiantong Zou, Yingli Chen, Leili Gao, Xiaoling Cai, Lingli Zhou, Fei Gao, Jian Zhou, Weiping Jia, and Linong Ji
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Endocrinology ,Human metabolism ,Clinical endocrinology ,Machine learning ,Science - Abstract
Summary: Chiglitazar (carfloglitazar) is a peroxisome proliferator-activated receptor pan-agonist presenting non-inferior glucose-lowering efficacy with sitagliptin in patients with type 2 diabetes. To delineate the subgroup of patients with greater benefit from chiglitazar, we conducted a machine learning-based post-hoc analysis in two randomized controlled trials. We established a character phenomap based on 13 variables and estimated HbA1c decline to the effects of chiglitazar in reference to sitagliptin. Out of 1,069 patients, 63.3% were found to have greater reduction in HbA1c levels with chiglitazar, while 36.7% showed greater reduction with sitagliptin. This distinction in treatment response was statistically significant between groups (pinteraction
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- 2023
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5. Review: Machine learning in precision pharmacotherapy of type 2 diabetes—A promising future or a glimpse of hope?
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Xiantong Zou, Yingning Liu, and Linong Ji
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Computer applications to medicine. Medical informatics ,R858-859.7 - Abstract
Precision pharmacotherapy of diabetes requires judicious selection of the optimal therapeutic agent for individual patients. Artificial intelligence (AI), a swiftly expanding discipline, holds substantial potential to transform current practices in diabetes diagnosis and management. This manuscript provides a comprehensive review of contemporary research investigating drug responses in patient subgroups, stratified via either supervised or unsupervised machine learning approaches. The prevalent algorithmic workflow for investigating drug responses using machine learning involves cohort selection, data processing, predictor selection, development and validation of machine learning methods, subgroup allocation, and subsequent analysis of drug response. Despite the promising feature, current research does not yet provide sufficient evidence to implement machine learning algorithms into routine clinical practice, due to a lack of simplicity, validation, or demonstrated efficacy. Nevertheless, we anticipate that the evolving evidence base will increasingly substantiate the role of machine learning in molding precision pharmacotherapy for diabetes.
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- 2023
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6. Do East Asians With Normal Glucose Tolerance Have Worse β-Cell Function? A Meta-Analysis of Epidemiological Studies
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Li Li, Xiantong Zou, Qi Huang, Xueyao Han, Xianghai Zhou, and Linong Ji
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diabetes ,β-cell function ,ethical differences ,insulin resistance ,prediabetes ,Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
BackgroundThe difference in the relationship between β-cell function and insulin resistance among Africans, Caucasians and East Asians with normal glucose tolerance (NGT) was not well investigated.MethodsWe searched PubMed and Web of Science with keywords and identified studies that used the homeostasis model assessment (HOMA) model to evaluate β-cell function (HOMA-B) and insulin sensitivity/resistance (HOMA-S/HOMA-IR) in certain ethnic groups. We used random-effect model to pool data of HOMAs and compared the combined data among the three ethnic groups using subgroup analysis. Linear regression analysis was used to estimate the coefficient of HOMA-S on HOMA-B in these ethnic groups.ResultsWe evaluated pooled data of HOMAs in eight African, 26 Caucasian, and 84 East Asian cohorts with NGT, and also 2,392, 6,645 and 67,317 individuals, respectively. The three ethnic groups had distinct HOMA-B but similar HOMA-IR. The regression coefficient of lnHOMA-B on lnHOMA-S was different between Africans and Caucasians (−1.126 vs −0.401, P = 0.0006) or East Asian (−1.126 vs −0.586, P = 0.0087), but similar between Caucasians and East Asians (−0.401 vs −0.586, P = 0.1282). The coefficient in all ethnic groups was similar when age, BMI, and gender were adjusted (African vs Caucasian P = 0.0885, African vs East Asian P = 0.1092, and Caucasian vs East Asian P = 0.6298).ConclusionsIn subjects with NGT, East Asians had lower HOMA-B but similar β-cell response relative to insulin resistance with Caucasians and Africans when age, BMI, and gender were controlled. This result may challenge the allegation that there was an Asian-specific diabetes phenotype with worse β-cell function.
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- 2021
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7. NAFLD or MAFLD: Which Has Closer Association With All-Cause and Cause-Specific Mortality?—Results From NHANES III
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Qi Huang, Xiantong Zou, Xin Wen, Xianghai Zhou, and Linong Ji
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NAFLD ,MAFLD ,mortality ,NHANES ,diagnosis ,Medicine (General) ,R5-920 - Abstract
Background: The recent change of terminology from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) has raised heated discussion. We aim to investigate the association of MAFLD or NAFLD with all-cause and cause-specific mortality to compare the outcomes of the two diagnostic criteria in population-based study.Methods: We recruited 12,480 participants from the Third National Health and Nutrition Examination Survey (NHANES III) with matched mortality data in 2015. Participants were divided into four groups for survival analysis: without NAFLD or MAFLD, with only NAFLD, only MAFLD. Cox proportional hazard regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality. Subgroup analysis were applied in MAFLD patients.Results: The weighted prevalence of MAFLD and NAFLD was relatively 27.4 and 27.9%. Participants with NAFLD or MAFLD were largely overlapped (weighted Cohen's kappa coefficient 0.76). MAFLD increased the overall risk for total mortality in a greater magnitude than NAFLD [HR 2.07 (95% CI 1.86, 2.29) vs. 1.47 (1.20, 1.79)], However, the difference was non-significant after metabolic parameters were adjusted. Risks for cardiovascular, neoplasm, and diabetes-related mortality were similar between MAFLD and NAFLD. Referring to individuals without both NAFLD and MAFLD, individuals with only NAFLD showed reduced total mortality [HR 0.48 (0.34, 0.68)] and neoplasm mortality [HR 0.46 (0.24, 0.89)] in crude. Nevertheless, individuals with only MAFLD independently increased the risk for total mortality [adjusted HR 1.47 (1.22, 1.77)] and neoplasm mortality [aHR 1.58 (1.09, 2.28)]. The risk for overall mortality in MAFLD was consistent between subgroups except for race-ethnicity and whether secondary to viral hepatitis.Conclusions: Participants with MAFLD or NAFLD were highly concordant. MAFLD showed greater risk for all-cause mortality and equal risk for cause-specific mortality referring to NAFLD. The new terminology excluded participants with lower mortality risk and included participants with higher risk. Drug development for MAFLD should consider ethnic differences.
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- 2021
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8. The Association between Non-Alcoholic Fatty Liver Disease (NAFLD) and Advanced Fibrosis with Serological Vitamin B12 Markers: Results from the NHANES 1999–2004
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Li Li, Qi Huang, Linjian Yang, Rui Zhang, Leili Gao, Xueyao Han, Linong Ji, and Xiantong Zou
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vitamin B12 ,homocysteine ,methylmalonic acid ,red blood cell folate ,folate ,Nutrition. Foods and food supply ,TX341-641 - Abstract
Background: There is evidence that vitamin B12 and associated metabolite levels are changed in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH); however, their association has been in dispute. Methods: We included 8397 individuals without previous liver condition or excess alcohol intake from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. NAFLD was diagnosed with Fatty Liver Index (FLI) ≥ 60 or USFLI ≥ 30, and participants with advanced fibrosis risks were identified with elevated non-alcoholic fatty liver disease fibrosis score (NFS), fibrosis 4 index (FIB-4), or aspartate aminotransferase (AST)/platelet ratio index (APRI). Step-wide logistic regression adjusting for confounders was used to detect the association between NAFLD or advanced fibrosis with serum vitamin B12, folate, red blood cell folate (RBC folate), homocysteine (HCY), and methylmalonic acid (MMA). Results: The weighted prevalence of NAFLD was 44.2%. Compared with non-NAFLD participants, patients with NAFLD showed significantly increased RBC folate level and RBC counts, decreased serum vitamin B12 and folate, and similar HCY and MMA levels. NAFLD with advanced fibrosis risk had higher MMA and HCY, reduced serum vitamin B12, and similar serum folate and RBC folate levels than NAFLD with low fibrosis risk. Only RBC folate was independently associated with an increased risk of NAFLD (OR (95% CI): 2.24 (1.58, 3.18)). In all participants, MMA (OR: 1.41 (1.10, 1.80)) and HCY (OR: 2.76 (1.49, 5.11)) were independently associated with increased risk for advanced fibrosis. In participants with NAFLD, this independent association still existed (OR: 1.39 (1.04, 1.85) for MMA and 1.95 (1.09, 3.46) for HCY). In all participants, the area under the receiver operating characteristic curve (ROC AUC) on fibrosis was 0.6829 (0.6828, 0.6831) for MMA and 0.7319 (0.7318, 0.7320) for HCY; in participants with NAFLD, the corresponding ROC AUC was 0.6819 (0.6817, 0.6821) for MMA and 0.6926 (0.6925, 0.6928) for HCY. Conclusion: Among vitamin B12-associated biomarkers, RBC folate was independently associated with elevated NAFLD risk, whereas MMA and HCY were associated with increased risk for advanced fibrosis in the total population and NAFLD participants. Our study highlighted the clinical diagnostic value of vitamin B12 metabolites and the possibility that vitamin B12 metabolism could be a therapeutic target for NASH. Further studies using recent perspective data with biopsy proven NASH could be conducted to validate our results.
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- 2022
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9. A Decision-Support Software to Improve the Standard Care in Chinese Type 2 Diabetes
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Yingying Luo, Yongzan Zhu, Jing Chen, Xueying Gao, Wenjia Yang, Xiantong Zou, Xianghai Zhou, and Linong Ji
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Background. To develop a decision-support software according to the Chinese Diabetes Society guideline in order to improve the standard care in type 2 diabetes. Methods. Firstly, we developed a decision-support software for healthcare professionals. It was an independent software on a tablet to record the data of patients and treatments given by their physicians. A major function of the software was to remind doctors when and how they should implement the standard care as recommended by the Chinese Diabetes Society guideline. Secondly, we compared the baseline data of standard care including statin and aspirin usage with data from a previous “3B study” to see whether there was an improvement of these standard cares. Finally, we further compared the data during four quarters of the whole year to evaluate whether there was a continuous improvement. Results. During the first quarter, 27,291 cases and 27,352 cases were collected with complete information about statin and aspirin usage, respectively. The percentage of patients treated with statins and aspirin in our study was significantly higher than that reported in the 3B study (59.6% vs. 19.9% and 59.8% vs. 18.5%, P0.05). Conclusion. Our decision-support software has been shown to be effective in continuously improving the standardization of comprehensive treatment in type 2 diabetes.
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- 2019
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10. Gender‐specific data‐driven adiposity subtypes using deep‐learning‐based abdominal <scp>CT</scp> segmentation
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Xiantong Zou, Xianghai Zhou, Yufeng Li, Qi Huang, Yuan Ni, Ruiming Zhang, Fang Zhang, Xin Wen, Jiayu Cheng, Yanping Yuan, Yue Yu, Chengcheng Guo, Guotong Xie, and Linong Ji
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Nutrition and Dietetics ,Endocrinology ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) - Published
- 2023
11. How does obesity affect mortality through blood pressure and blood glucose in Chinese and US citizens? Insights from a causal mediation analysis of two large cohorts
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Qi Huang, Xiantong Zou, Pei Gao, Xueyao Han, Xianghai Zhou, and Linong Ji
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Health Policy ,Public Health, Environmental and Occupational Health - Published
- 2023
12. Urinary C‐peptide/creatinine ratio: A useful biomarker of insulin resistance and refined classification of type 2 diabetes mellitus
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Lingli Zhou, Ling Chen, Simin Li, Wei Liu, Xiaoling Cai, Yanai Wang, Xiantong Zou, Ying Gao, Linong Ji, Xueyao Han, Yingying Luo, Rui Zhang, and Siqian Gong
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Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,030204 cardiovascular system & hematology ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Insulin resistance ,Internal medicine ,Diabetes mellitus ,Glucose Intolerance ,medicine ,Humans ,Glycated Hemoglobin ,Type 1 diabetes ,Creatinine ,C-Peptide ,business.industry ,Type 2 Diabetes Mellitus ,Odds ratio ,Middle Aged ,Prognosis ,medicine.disease ,Cross-Sectional Studies ,Diabetes Mellitus, Type 2 ,chemistry ,Cardiovascular Diseases ,Biomarker (medicine) ,Female ,Insulin Resistance ,business ,Body mass index ,Biomarkers ,Follow-Up Studies - Abstract
The urinary C-peptide/creatinine ratio (UCPCR) is low in patients with type 1 diabetes mellitus, but it has not been well characterized in patients with type 2 diabetes mellitus (T2DM). We aimed to measure the UCPCRs in patients with T2DM and explore the relationships among UCPCR, insulin resistance (IR), and chronic vascular complications of diabetes.A cross-sectional study was performed of 1299 Chinese hospitalized patients with T2DM. Binary logistic regression was used to evaluate the relationships between the chronic vascular complications of diabetes and UCPCR. K-means analysis was used to allocate participants to subgroups with five to six variables (age at diagnosis, body mass index [BMI], glycosylated hemoglobin, homoeostasis model assessment 2-estimated beta-cell function (HOMA2-B), and HOMA2-insulin resistance (HOMA2-IR), with or without UCPCR).UCPCR positively correlated with HOMA2-IR (r = 0.448, P .001). After adjustment for sex, age, duration of diabetes, and other cardiovascular risk factors, UCPCR was positively associated with diabetic kidney disease (DKD) (odds ratio [OR] = 1.198, 95% CI 1.019-1.408, P = .029) and coronary heart disease (CHD) (OR = 1.312, 95% CI 1.079-1.594, P = .006). When UCPCR was added, cluster analysis using the six variables identified five subgroups of T2DM, characterized by differing age at diagnosis, BMI, beta-cell function, IR, and prevalence of vascular complications.UCPCR is positively associated with IR, DKD, and CHD and represents a promising biomarker that could refine the classification of T2DM.背景: 1型糖尿病患者尿C肽/肌酐比值水平低。但尿C肽/肌酐比值在2型糖尿病患者中并没有被充分评估, 本研究拟测定2型糖尿病患者的尿C肽/肌酐比值水平, 探讨尿C肽/肌酐比值与胰岛素抵抗及糖尿病慢性血管并发症的相关性, 并评估尿C肽/肌酐比值改善2型糖尿病精准分型的可能性。 方法: 本研究共纳入北京大学人民医院内分泌科住院2型糖尿病患者1299名。采集所有患者的临床资料, 测定其空腹尿C肽/肌酐比, 通过二元Logistic回归分析尿C肽/肌酐比值与糖尿病血管并发症的相关性。并分别用传统的五个变量[诊断年龄, 体重指数, 糖化血红蛋白, 改良稳态模型计算的β细胞功能指数(HOMA2-B)及胰岛素抵抗指数(HOMR2-IR)]和加入尿C肽/肌酐比值后的六个变量, 通过相同的k-means聚类算法对2型糖尿病患者进行聚类分组, 比较不同亚组的临床特点。 结果: 尿C肽/肌酐比值与HOMA2-IR水平 (r=0.448, P0.001)正相关。在调整了性别, 年龄, 病程及其他心血管疾病危险因素后, 尿C肽/肌酐比值水平与糖尿病肾病 [比值比(OR) =1.198, 95%CI (1.019, 1.408), P=0.029]及冠状动脉粥样硬化性心脏病的发生风险呈正相关 [OR=1.312, 95%CI (1.079, 1.594), P=0.006]。在五个传统临床变量基础上, 加入尿C肽/肌酐比值后再进行聚类分型, 可以清晰地将患者分为五组:两组具有早发糖尿病特征[早发胰岛素缺乏型糖尿病(n=350)和早发胰岛素抵抗型糖尿病(n=176)], 两组具有晚发糖尿病特征[晚发胰岛素缺乏型糖尿病(n=318)和晚发胰岛素抵抗型糖尿病(n=133)]及轻型糖尿病(n=299)。各组间诊断年龄, 体重指数, 胰岛β细胞功能, 胰岛素抵抗水平以及糖尿病血管并发症比例显著不同。 结论: 尿C肽/肌酐比值与胰岛素抵抗水平及糖尿病肾病, 冠状动脉粥样硬化性心脏病发生风险正相关。在传统临床变量基础上引入尿C肽/肌酐比值, 可以改善2型糖尿病的精准分型。.
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- 2021
13. Do East Asians With Normal Glucose Tolerance Have Worse β-Cell Function? A Meta-Analysis of Epidemiological Studies
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Xueyao Han, Linong Ji, Qi Huang, Xianghai Zhou, Li Li, and Xiantong Zou
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Blood Glucose ,medicine.medical_specialty ,β cell function ,endocrine system diseases ,β-cell function ,Endocrinology, Diabetes and Metabolism ,prediabetes ,Diseases of the endocrine glands. Clinical endocrinology ,Cohort Studies ,Endocrinology ,ethical differences ,Asian People ,Internal medicine ,insulin resistance ,Epidemiology ,medicine ,Diabetes Mellitus ,Homeostasis ,Humans ,Normal glucose tolerance ,B-Lymphocytes ,diabetes ,business.industry ,Asia, Eastern ,nutritional and metabolic diseases ,Glucose Tolerance Test ,RC648-665 ,Epidemiologic Studies ,Meta-analysis ,Systematic Review ,business - Abstract
BackgroundThe difference in the relationship between β-cell function and insulin resistance among Africans, Caucasians and East Asians with normal glucose tolerance (NGT) was not well investigated.MethodsWe searched PubMed and Web of Science with keywords and identified studies that used the homeostasis model assessment (HOMA) model to evaluate β-cell function (HOMA-B) and insulin sensitivity/resistance (HOMA-S/HOMA-IR) in certain ethnic groups. We used random-effect model to pool data of HOMAs and compared the combined data among the three ethnic groups using subgroup analysis. Linear regression analysis was used to estimate the coefficient of HOMA-S on HOMA-B in these ethnic groups.ResultsWe evaluated pooled data of HOMAs in eight African, 26 Caucasian, and 84 East Asian cohorts with NGT, and also 2,392, 6,645 and 67,317 individuals, respectively. The three ethnic groups had distinct HOMA-B but similar HOMA-IR. The regression coefficient of lnHOMA-B on lnHOMA-S was different between Africans and Caucasians (−1.126 vs −0.401, P = 0.0006) or East Asian (−1.126 vs −0.586, P = 0.0087), but similar between Caucasians and East Asians (−0.401 vs −0.586, P = 0.1282). The coefficient in all ethnic groups was similar when age, BMI, and gender were adjusted (African vs Caucasian P = 0.0885, African vs East Asian P = 0.1092, and Caucasian vs East Asian P = 0.6298).ConclusionsIn subjects with NGT, East Asians had lower HOMA-B but similar β-cell response relative to insulin resistance with Caucasians and Africans when age, BMI, and gender were controlled. This result may challenge the allegation that there was an Asian-specific diabetes phenotype with worse β-cell function.
- Published
- 2021
14. NAFLD or MAFLD: Which Has Closer Association With All-Cause and Cause-Specific Mortality?—Results From NHANES III
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Linong Ji, Xiantong Zou, Xin Wen, Qi Huang, and Xianghai Zhou
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0301 basic medicine ,medicine.medical_specialty ,Medicine (General) ,National Health and Nutrition Examination Survey ,diagnosis ,Population ,MAFLD ,Subgroup analysis ,Disease ,03 medical and health sciences ,0302 clinical medicine ,R5-920 ,Internal medicine ,NAFLD ,medicine ,NHANES ,education ,Survival analysis ,Original Research ,education.field_of_study ,business.industry ,Fatty liver ,Hazard ratio ,General Medicine ,medicine.disease ,mortality ,Confidence interval ,030104 developmental biology ,Medicine ,030211 gastroenterology & hepatology ,business - Abstract
Background: The recent change of terminology from non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) has raised heated discussion. We aim to investigate the association of MAFLD or NAFLD with all-cause and cause-specific mortality to compare the outcomes of the two diagnostic criteria in population-based study.Methods: We recruited 12,480 participants from the Third National Health and Nutrition Examination Survey (NHANES III) with matched mortality data in 2015. Participants were divided into four groups for survival analysis: without NAFLD or MAFLD, with only NAFLD, only MAFLD. Cox proportional hazard regression was used to estimate multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality. Subgroup analysis were applied in MAFLD patients.Results: The weighted prevalence of MAFLD and NAFLD was relatively 27.4 and 27.9%. Participants with NAFLD or MAFLD were largely overlapped (weighted Cohen's kappa coefficient 0.76). MAFLD increased the overall risk for total mortality in a greater magnitude than NAFLD [HR 2.07 (95% CI 1.86, 2.29) vs. 1.47 (1.20, 1.79)], However, the difference was non-significant after metabolic parameters were adjusted. Risks for cardiovascular, neoplasm, and diabetes-related mortality were similar between MAFLD and NAFLD. Referring to individuals without both NAFLD and MAFLD, individuals with only NAFLD showed reduced total mortality [HR 0.48 (0.34, 0.68)] and neoplasm mortality [HR 0.46 (0.24, 0.89)] in crude. Nevertheless, individuals with only MAFLD independently increased the risk for total mortality [adjusted HR 1.47 (1.22, 1.77)] and neoplasm mortality [aHR 1.58 (1.09, 2.28)]. The risk for overall mortality in MAFLD was consistent between subgroups except for race-ethnicity and whether secondary to viral hepatitis.Conclusions: Participants with MAFLD or NAFLD were highly concordant. MAFLD showed greater risk for all-cause mortality and equal risk for cause-specific mortality referring to NAFLD. The new terminology excluded participants with lower mortality risk and included participants with higher risk. Drug development for MAFLD should consider ethnic differences.
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- 2021
15. 1167-P: Nonalcoholic Fatty Liver Disease, Metabolic Dysfunction Associated Fatty Liver Disease, and Associations with All-Cause and Cause-Specific Mortality
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Linong Ji, Qi Huang, Xiantong Zou, and Xianghai Zhou
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education.field_of_study ,medicine.medical_specialty ,National Health and Nutrition Examination Survey ,business.industry ,Endocrinology, Diabetes and Metabolism ,Fatty liver ,Population ,Subgroup analysis ,Disease ,medicine.disease ,Internal medicine ,Nonalcoholic fatty liver disease ,Cohort ,Internal Medicine ,medicine ,education ,business ,Survival analysis - Abstract
The change in terminology from nonalcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) has raised heated discussion. Our study aims to investigate which has closer association with all-cause and cause-specific mortality in a population-based cohort. We investigated the association between fatty liver disease and mortality in 12,480 adults from National Health and Nutrition Examination Survey III with a medium follow-up time of 22.7 years. Characteristics were compared in participants without NAFLD or MAFLD, with only NAFLD, only MAFLD, or both; survival analysis and subgroup analysis were applied. Participants with NAFLD or MAFLD were highly overlapped (Weighted Cohen’s kappa coefficient 0.78). MAFLD increased the risk for total mortality in a greater magnitude than NAFLD (HR: 2.07 [95% CI 1.86, 2.29] vs. 1.48 [1.35, 1.65]) in crude, but the risks were neglectable when metabolic parameters were adjusted. The risk for cardiovascular, neoplasm and diabetes-related mortality was similar between MAFLD and NAFLD. In reference to participants without NAFLD or MAFLD, patients with only NAFLD showed a reduced risk for total (0.48 [0.34, 0.68]) and neoplasm mortality (0.46 [0.24, 0.89]), while participants with only MAFLD was independently associated with enhanced risk for total (1.74 [1.40, 2.15]), neoplasm (1.94 [1.30, 2.90]) and diabetes-related mortality (3.24 [1.05, 9.97]) after adjustment. The risk of MAFLD for overall mortality was consistence between subgroups except for race-ethnicity. In conclusion, participants with MAFLD or NAFLD were highly concordant. Compared with NAFLD, MAFLD was certified with greater risk in all-cause mortality and similar risk in cause-specific mortality. The new terminology excluded participants with lower mortality risk and included participants with higher risk. Drug development for MAFLD should consider ethnicity difference. Disclosure Q. Huang: None. X. Zou: None. X. Zhou: None. L. Ji: None. Funding National Key Research and Development Program of China (2016YFC1304901, 2016YFC1305603); National Natural Science Foundation of China (81800515); Beijing Nova Program of Science and Technology (Z191100001119026)
- Published
- 2021
16. 1070-P: Relationships between ß-Cell Function and Insulin Sensitivity in East Asians and Caucasians during Progression from NGT to Diabetes: A Meta-analysis
- Author
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Linong Ji, Li Li, and Xiantong Zou
- Subjects
medicine.medical_specialty ,β cell function ,endocrine system diseases ,business.industry ,Endocrinology, Diabetes and Metabolism ,nutritional and metabolic diseases ,Insulin sensitivity ,medicine.disease ,Endocrinology ,Insulin resistance ,Meta-analysis ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Pooled data ,Cell response ,business ,hormones, hormone substitutes, and hormone antagonists - Abstract
Aim: To investigate the relationships of β cell function and insulin resistance in East Asians and Caucasians. Methods: We searched for studies that used homeostasis model assessment to evaluate β cell function (HOMA-β) and insulin sensitivity/resistance (HOMA-S/HOMA-IR) in the two races. Random-effect model was used to analyze pooled HOMAs in NGT, IGR and T2DM. Linear regression was used to compare the coefficient of log transformed HOMA-S on log transformed HOMA-β between races. Results: We evaluated pooled data of HOMAs in 208 studies (110 NGT, 52 IGR and 46 T2DM). In NGT, East Asians had lower HOMA-β [103.1 (93.9,112.4) vs. 131.0 (117.9,144.0)] and HOMA-IR [1.7 (1.6,1.8) vs. 1.9 (1.6,2.3)] versus Caucasians. Similar pattern was found in IGR and T2DM. In both races, HOMA-β progressively decreased in NGT, IGR and T2DM and HOMA-IR increased accordingly. The coefficients of lnHOMA-S on lnHOMA-β were similar between East Asians and Caucasians with NGT (P=0.128) or IGR (P=0.672) (Figure). In T2DM, HOMA-S and HOMA-β did not fit the hyperbola. Conclusion: East Asians and Caucasians had similar β cell response relative to insulin resistance. During the progression from NGT to T2DM, the relationships between HOMA-β and HOMA-S changed in a similar pattern between the two races. Our study challenges the previous saying that East Asians had worse β cell function. Disclosure L. Li: None. X. Zou: None. L. Ji: None.
- Published
- 2021
17. Mitochondria-derived methylmalonic acid is associated with advanced fibrosis risks in metabolic dysfunction-associated fatty liver disease (MAFLD): results from the NHANES 1999–2004
- Author
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Qi Huang, Li Li, Linjian Yang, Linong Ji, and Xiantong Zou
- Subjects
Hepatology - Published
- 2022
18. FOXO1 inhibition prevents renal ischemia–reperfusion injury via cAMP‐response element binding protein/PPAR‐γ coactivator‐1α‐mediated mitochondrial biogenesis
- Author
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Lu Tie, Jing Su, Yundi Shi, Yanqing Wang, Xiantong Zou, Qian Liu, Fengxue Zhang, Xuejun Li, Di Wang, Tianru Huyan, and Qi Wang
- Subjects
0301 basic medicine ,Mitochondrial ROS ,Male ,FOXO1 ,Apoptosis ,Quinolones ,CREB ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Mitophagy ,Coactivator ,Animals ,Humans ,EP300 ,Cyclic AMP Response Element-Binding Protein ,Transcription factor ,Pharmacology ,Organelle Biogenesis ,biology ,Chemistry ,Forkhead Box Protein O1 ,Research Papers ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,Cell biology ,Mitochondria ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Kidney Tubules ,Mitochondrial biogenesis ,Reperfusion Injury ,biology.protein ,Kidney Diseases ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
BACKGROUND AND PURPOSE: Growing evidence indicates targeting mitochondrial dynamics and biogenesis could accelerate recovery from renal ischemia–reperfusion (I/R) injury, but the underlying mechanisms remain elusive. Transcription factor forkhead box O1 (FOXO1) is a key regulator of mitochondrial homeostasis and plays a pathological role in the progression of renal disease. EXPERIMENTAL APPROACH: A mouse model of renal I/R injury and a hypoxia/reoxygenation (H/R) injury model for human renal tubular epithelial cells were used. KEY RESULTS: I/R injury up‐regulated renal expression of FOXO1 and treatment with FOXO1‐selective inhibitor AS1842856 prior to I/R injury decreased serum urea nitrogen, serum creatinine and the tubular damage score after injury. Post‐I/R injury AS1842856 treatment could also ameliorate renal function and improve the survival rate of mice following injury. AS1842856 administration reduced mitochondrial‐mediated apoptosis, suppressed the overproduction of mitochondrial ROS and accelerated recovery of ATP both in vivo and in vitro. Additionally, FOXO1 inhibition improved mitochondrial biogenesis and suppressed mitophagy. Expression of PPAR‐γ coactivator 1α (PGC‐1α), a master regulator of mitochondrial biogenesis, was down‐regulated in both I/R and H/R injury, which could be abrogated by FOXO1 inhibition. Experiments using integrated bioinformatics analysis and coimmunoprecipitation established that FOXO1 inhibited PGC‐1α transcription by competing with cAMP‐response element binding protein (CREB) for its binding to transcriptional coactivators CREBBP/EP300 (https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2734/https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2737). CONCLUSION AND IMPLICATIONS: These findings suggested that FOXO1 was critical to maintain mitochondrial function in renal tubular epithelial cells and FOXO1 may serve as a therapeutic target for pharmacological intervention in renal I/R injury.
- Published
- 2019
19. Novel subgroups of patients with adult-onset diabetes in Chinese and US populations
- Author
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Linong Ji, Xiantong Zou, Xianghai Zhou, and Zhanxing Zhu
- Subjects
medicine.medical_specialty ,Endocrinology ,Text mining ,business.industry ,Endocrinology, Diabetes and Metabolism ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,MEDLINE ,Medicine ,Adult Onset Diabetes ,business ,medicine.disease - Published
- 2019
20. A Decision-Support Software to Improve the Standard Care in Chinese Type 2 Diabetes
- Author
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Linong Ji, Xueying Gao, Yongzan Zhu, Yingying Luo, Xiantong Zou, Wenjia Yang, Xianghai Zhou, and Jing Chen
- Subjects
Blood Glucose ,medicine.medical_specialty ,Decision support system ,China ,Statin ,Standardization ,Article Subject ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,MEDLINE ,Blood Pressure ,Hyperlipidemias ,Type 2 diabetes ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Diabetes mellitus ,Secondary Prevention ,Medicine ,Humans ,Hypoglycemic Agents ,030212 general & internal medicine ,Antihypertensive Agents ,Quality of Health Care ,Aspirin ,lcsh:RC648-665 ,business.industry ,Guideline ,medicine.disease ,Decision Support Systems, Clinical ,Quality Improvement ,Metformin ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Emergency medicine ,Practice Guidelines as Topic ,030221 ophthalmology & optometry ,Guideline Adherence ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,Platelet Aggregation Inhibitors ,Software ,medicine.drug ,Research Article - Abstract
Background. To develop a decision-support software according to the Chinese Diabetes Society guideline in order to improve the standard care in type 2 diabetes. Methods. Firstly, we developed a decision-support software for healthcare professionals. It was an independent software on a tablet to record the data of patients and treatments given by their physicians. A major function of the software was to remind doctors when and how they should implement the standard care as recommended by the Chinese Diabetes Society guideline. Secondly, we compared the baseline data of standard care including statin and aspirin usage with data from a previous “3B study” to see whether there was an improvement of these standard cares. Finally, we further compared the data during four quarters of the whole year to evaluate whether there was a continuous improvement. Results. During the first quarter, 27,291 cases and 27,352 cases were collected with complete information about statin and aspirin usage, respectively. The percentage of patients treated with statins and aspirin in our study was significantly higher than that reported in the 3B study (59.6% vs. 19.9% and 59.8% vs. 18.5%, P<0.001). There were no significant differences among the four quarters for the percentage of the patients who were taking statin or aspirin (P>0.05). Conclusion. Our decision-support software has been shown to be effective in continuously improving the standardization of comprehensive treatment in type 2 diabetes.
- Published
- 2019
21. 1644-P: Novel Subgroups of Prediabetes and Their Clinical Outcomes: A Data-Driven Analysis
- Author
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Linong Ji, Xianghai Zhou, Xiantong Zou, Zhanxing Zhu, Yufeng Li, and Yingying Luo
- Subjects
education.field_of_study ,medicine.medical_specialty ,business.industry ,Endocrinology, Diabetes and Metabolism ,Population ,medicine.disease ,Placebo ,law.invention ,NHANES III ,Randomized controlled trial ,law ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,In patient ,Prediabetes ,education ,business ,Pioglitazone ,medicine.drug - Abstract
The progression of prediabetes to diabetes and the reversion of them to NGT are highly heterogeneous. To develop a refined classification of prediabetes, we used data-driven K-means clustering in patients diagnosed with IGT and IFG according to WHO 1999 criteria in Pinggu Study (a prospective population-based survey for diabetes in suburban Beijing, n=628), NHANES III study (a cross-sectional population-based survey in the U.S., n=1532) and Beijing Prediabetes Reversion Program (BPRP, a RCT to evaluate the efficacy of lifestyle and/or pioglitazone on prediabetes reversion, n=1905). Based on five variables including HbA1c, BMI, age, HOMAIR and HOMAB, we identified four replicable clusters across all three datasets including high glucose group (HGG), lean group (LG), early-onset group (EOG) and insulin resistant group (IRG) (Figure). HRG had significant higher 1-year diabetes progression rate (15.4% in BPRP and 25.6% in Pinggu study) and the LG had the lowest diabetes progression rate (7.1% in BPRP and 11.1% in Pinggu Study). In BPRP, HGG treated with Intensive lifestyle plus pioglitazone had significant higher reversion rate to NGT and EOG treated with intensive life style plus placebo had least reversion rate compared to other treatment. Our study provides risk stratification for prediabetes and can potentially facilitate clinical decision, representing a first step towards precision management. Disclosure X. Zou: None. Z. Zhu: None. Y. Luo: None. Y. Li: None. X. Zhou: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi. Funding The Major Chronic Non-Communicable Disease Prevention and Control Research of China; Beijing Science and Technology Committee; National Natural Science Foundation of China
- Published
- 2019
22. 1521-P: An Efficacy Evaluation on Prediabetes Management Using a Machine Learning-Based Risk Stratification Approach
- Author
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Xianghai Zhou, Zhanxing Zhu, Linong Ji, Yingying Luo, Xiantong Zou, and Yufeng Li
- Subjects
education.field_of_study ,Diabetes risk ,business.industry ,Endocrinology, Diabetes and Metabolism ,Population ,Psychological intervention ,medicine.disease ,Machine learning ,computer.software_genre ,law.invention ,Randomized controlled trial ,law ,Diabetes mellitus ,Risk stratification ,Internal Medicine ,medicine ,Prediabetes ,Artificial intelligence ,education ,business ,computer ,Pioglitazone ,medicine.drug - Abstract
The progression of prediabetes towards diabetes was heterogeneous, suggesting a demand for individualized management. We aim to investigate whether stratifying participants with prediabetes according to their progression risk could affect the response to interventions. We developed a 1-year diabetes progression risk evaluating model with a panel of diabetes risk factors using a machine learning method (i.e., Bagging algorithm with 300 decision trees) in prediabetes participants in Pinggu Study (a prospective population-based survey in suburban Beijing, n=622). The model training phase was conducted on 2/3 randomly selected participants and the validation phase was conducted on other 1/3. This model successfully predicted the 1-year progression of prediabetes participants in Pinggu study (internal ROC AUC 1.000, external ROC AUC 0.883). In Beijing Prediabetes Reversion Program (BPRP, a multi-central RCT to evaluate the efficacy of lifestyle and/or pioglitazone on prediabetes reversion, n=1897), subjects were divided into tertiles as high, medium and low risk groups according to their progression probability predicted by the model. Pioglitazone plus intensive lifestyle significantly increased reversion and reduced diabetes progression only in high risk group. This study suggests personalized treatment on prediabetes according to their progression risk is necessary. Disclosure X. Zou: None. Z. Zhu: None. Y. Luo: None. Y. Li: None. X. Zhou: None. L. Ji: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck KGaA, Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis AG, Roche Pharma, Sanofi. Funding The Major Chronic Non-Communicable Disease Prevention and Control Research of China; Beijing Science and Technology Committee; National Natural Science Foundation of China
- Published
- 2019
23. Decreased Glycemic Difference Between Diabetes and Nondiabetes in the Elderly Leads to the Reduced Diagnostic Accuracy of Hemoglobin A1c for Diabetes Screening in an Aged Chinese Population
- Author
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Simin Zhang, Xiaoling Cai, Xianghai Zhou, Xueyao Han, Linong Ji, Xiuying Zhang, Yufeng Li, and Xiantong Zou
- Subjects
Adult ,Blood Glucose ,Aging ,China ,medicine.medical_specialty ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Population ,030209 endocrinology & metabolism ,Prediabetic State ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Endocrinology ,Predictive Value of Tests ,Internal medicine ,Diabetes mellitus ,Prevalence ,medicine ,Humans ,Mass Screening ,030212 general & internal medicine ,Diagnostic Errors ,education ,Mass screening ,Aged ,Glycemic ,Glycated Hemoglobin ,Glucose tolerance test ,education.field_of_study ,medicine.diagnostic_test ,Receiver operating characteristic ,business.industry ,Area under the curve ,Glucose Tolerance Test ,Middle Aged ,Nutrition Surveys ,Postprandial Period ,medicine.disease ,Health Surveys ,Surgery ,Medical Laboratory Technology ,Cross-Sectional Studies ,Diabetes Mellitus, Type 2 ,ROC Curve ,chemistry ,Glycated hemoglobin ,business - Abstract
This study investigated the impact of age on the accuracy of glycated hemoglobin (HbA1c) for diabetes screening and explored the possible cause(s).Data from 3,050 Chinese participants 25-75 years of age without known diabetes in a population-based cross-sectional survey were analyzed. Diabetes was diagnosed by the oral glucose tolerance test (OGTT). The performance of HbA1c for detecting OGTT-defined diabetes in tertile groups (divided by age) was evaluated by the area under the curve (AUC) of the receiver operating characteristic curve (ROC). The effect of age on the difference in glucose levels between participants with and without diabetes and the impact of this difference on the performance of HbA1c were evaluated.In young (25-41 years old), middle-aged (41-53 years old), and old (55-72 years old) participants, the ROC AUC (95% confidence interval) of HbA1c for detecting OGTT-defined diabetes was 0.958 (0.915, 1.000), 0.891 (0.852, 0.930), and 0.861 (0.821, 0.901), respectively (P = 0.005). The difference of fasting plasma glucose between participants with diabetes and those without diabetes decreased with increasing age: 3.01 (2.80, 3.22) mmol/L, 2.90 (2.71, 3.09) mmol/L, and 2.33 (2.16, 2.50) mmol/L in the three consecutive age groups, respectively. A similar pattern was found in 2-h postprandial plasma glucose. The impact of age on the diagnostic power of HbA1c diminished after data were rearranged to artificially increase the difference between participants without diabetes and those with diabetes.The accuracy of HbA1c for detecting OGTT-defined diabetes declines with age. This is largely due to the decreased separation in glycemic levels between participants with diabetes and without diabetes in the elderly.
- Published
- 2016
24. 11Beta-hydroxysteroid dehydrogenase-1 deficiency or inhibition enhances hepatic myofibroblast activation in murine liver fibrosis
- Author
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Xiantong, Zou, Prakash, Ramachandran, Timothy J, Kendall, Antonella, Pellicoro, Elena, Dora, Rebecca L, Aucott, Kajal, Manwani, Tak Yung, Man, Karen E, Chapman, Neil C, Henderson, Stuart J, Forbes, Scott P, Webster, John P, Iredale, Brian R, Walker, and Zoi, Michailidou
- Subjects
Liver Cirrhosis ,Male ,Mice, Inbred C57BL ,Disease Models, Animal ,Mice ,Hepatocytes ,Animals ,11-beta-Hydroxysteroid Dehydrogenases ,Myofibroblasts - Abstract
A hallmark of chronic liver injury is fibrosis, with accumulation of extracellular matrix orchestrated by activated hepatic stellate cells (HSCs). Glucocorticoids limit HSC activation in vitro, and tissue glucocorticoid levels are amplified by 11beta-hydroxysteroid dehydrogenase-1 (11βHSD1). Although 11βHSD1 inhibitors have been developed for type 2 diabetes mellitus and improve diet-induced fatty liver in various mouse models, effects on the progression and/or resolution of liver injury and consequent fibrosis have not been characterized. We have used the reversible carbon tetrachloride-induced model of hepatocyte injury and liver fibrosis to show that in two models of genetic 11βHSD1 deficiency (global, Hsd11b111βHSD1 deficiency enhances myofibroblast activation and promotes initial fibrosis following chemical liver injury; hence, the effects of 11βHSD1 inhibitors on liver injury and repair are likely to be context-dependent and deserve careful scrutiny as these compounds are developed for chronic diseases including metabolic syndrome and dementia. (Hepatology 2018;67:2167-2181).
- Published
- 2016
25. Search for genetic determinants of sulfonylurea efficacy in type 2 diabetic patients from China
- Author
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Linong Ji, Simin Zhang, Hechao Li, Yong Tang, Xueyao Han, Xiaoling Cai, Xiantong Zou, Lihua Zhang, Xiuying Zhang, and Qian Ren
- Subjects
Male ,China ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,Pharmacology ,Bioinformatics ,Polymorphism, Single Nucleotide ,Glibenclamide ,Double-Blind Method ,Glyburide ,Genetic variation ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,SNP ,In patient ,Cyclin-Dependent Kinase Inhibitor p16 ,Cyclin-Dependent Kinase Inhibitor p15 ,business.industry ,fungi ,food and beverages ,Human physiology ,Middle Aged ,medicine.disease ,Sulfonylurea ,Sulfonylurea Compounds ,Diabetes Mellitus, Type 2 ,Female ,business ,Pharmacogenetics ,medicine.drug - Abstract
The aim of this study was to investigate whether genetic variance can influence the efficacy of glibenclamide in patients with type 2 diabetes.A total of 747 patients with type 2 diabetes was enrolled from the Xiaoke Pills Clinical Trial, which is a double-blind, randomised controlled trial. All the patients had been treated with glibenclamide for 48 weeks, with strict drug dose adjustment and data collection. Treatment failure was confirmed when patients reached the criteria for terminating their participation in the study (fasting blood glucose level ≥ 7.0 mmol/l on two consecutive tests 4 weeks after reaching the pre-set maximal dose or maximal tolerated dose). Using this cohort, we tested 44 single-nucleotide polymorphisms (SNPs) in 27 gene regions. The genes in our study were involved in the metabolism of sulfonylureas, islet beta cell function, insulin resistance and beta cell growth and differentiation. A logistic regression model was used to evaluate the relationship between genetic variants and treatment failure over a period of 48 weeks.We found that no SNP reached the significance level of p0.00125 if Bonferroni correction was performed for multiple testing in the logistic regression model used in this pharmacogenetic study. Participants with the minor allele C of rs10811661 in CDKN2A/CDKN2B showed a significantly greater reduction in fasting blood glucose (TT vs TC vs CC: 9.3% (0-20.0%) vs 9.2% (0.9-20.5%) vs 12.7% (5.2-24.4%), p = 0.008) after the initial 4 weeks of treatment independent of age, sex and BMI. There was a significant difference in beta cell function among carriers of different genotypes of rs10811661.Our study demonstrated that the CDKN2A/CDKN2B gene may be nominally associated with the efficacy of glibenclamide, and that CDKN2A/CDKN2B is associated with beta cell function.
- Published
- 2013
26. Increased Angiogenesis Protects against Adipose Hypoxia and Fibrosis in Metabolic Disease-resistant 11 beta-Hydroxysteroid Dehydrogenase Type 1 (HSD1)-deficient Mice
- Author
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Zoi Michailidou, Brian R. Walker, Nicholas M. Morton, John P. Iredale, Sophie Turban, Patrick W. F. Hadoke, Jonathan R. Seckl, Xiantong Zou, Peter J. Ratcliffe, Joerg Schrader, and Eileen Miller
- Subjects
Male ,Vascular Endothelial Growth Factor A ,Angiogenesis ,Adipose tissue ,Weight Gain ,Biochemistry ,Mice ,0302 clinical medicine ,Transforming Growth Factor beta ,11β-hydroxysteroid dehydrogenase type 1 ,Fibrosis ,11-beta-Hydroxysteroid Dehydrogenase Type 1 ,Hypoxia ,Mice, Knockout ,Extracellular Matrix Proteins ,0303 health sciences ,biology ,Molecular Bases of Disease ,3. Good health ,Apelin ,Adipose Tissue ,Fibroblast ,Intercellular Signaling Peptides and Proteins ,Collagen ,Signal Transduction ,medicine.medical_specialty ,Adipose tissue macrophages ,Neovascularization, Physiologic ,Adipokine ,030209 endocrinology & metabolism ,Angiopoietin-like 4 Protein ,03 medical and health sciences ,Adipokines ,Internal medicine ,medicine ,Angiopoietin-Like Protein 4 ,Animals ,Obesity ,Smad3 Protein ,Glucocorticoids ,Molecular Biology ,030304 developmental biology ,Cell Biology ,Hypoxia-Inducible Factor 1, alpha Subunit ,medicine.disease ,Actins ,PPAR gamma ,Endocrinology ,biology.protein ,Insulin Resistance ,Angiopoietins - Abstract
Background: Adipose hypertrophy limits fat cell oxygenation, promotes scarring, and associates with increased local glucocorticoid regeneration (higher 11βHSD1 enzyme). Results: 11βHSD1 knock-out mice have reduced scarring and better vascularization and oxygenation in their adipose tissue. Conclusion: Elevated adipose 11βHSD1 contributes to obesity pathogenesis by suppressing adipose angiogenesis. Significance: Enhancement of adipose oxygenation and vascularization is a novel therapeutic modality for 11βHSD1 inhibitors., In obesity, rapidly expanding adipose tissue becomes hypoxic, precipitating inflammation, fibrosis, and insulin resistance. Compensatory angiogenesis may prevent these events. Mice lacking the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1−/−) have “healthier” adipose tissue distribution and resist metabolic disease with diet-induced obesity. Here we show that adipose tissues of 11βHSD1−/− mice exhibit attenuated hypoxia, induction of hypoxia-inducible factor (HIF-1α) activation of the TGF-β/Smad3/α-smooth muscle actin (α-SMA) signaling pathway, and fibrogenesis despite similar fat accretion with diet-induced obesity. Moreover, augmented 11βHSD1−/− adipose tissue angiogenesis is associated with enhanced peroxisome proliferator-activated receptor γ (PPARγ)-inducible expression of the potent angiogenic factors VEGF-A, apelin, and angiopoietin-like protein 4. Improved adipose angiogenesis and reduced fibrosis provide a novel mechanism whereby suppression of intracellular glucocorticoid regeneration promotes safer fat expansion with weight gain.
- Published
- 2012
- Full Text
- View/download PDF
27. Metabolic pathways promoting intrahepatic fatty acid accumulation in methionine and choline deficiency: implications for the pathogenesis of steatohepatitis
- Author
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Ruth Andrew, John P. Iredale, Xiantong Zou, Nicholas M. Morton, Moffat J. Nyirenda, Rebecca L. Aucott, David P. Macfarlane, Dawn E W Livingstone, and Brian R. Walker
- Subjects
nonalcoholic fatty liver disease ,Male ,Physiology ,Endocrinology, Diabetes and Metabolism ,Hepatitis ,Eating ,Mice ,chemistry.chemical_compound ,methionine- and choline-deficient diet ,Methionine ,0302 clinical medicine ,Nonalcoholic fatty liver disease ,chemistry.chemical_classification ,0303 health sciences ,Fatty Acids ,Fatty liver ,free fatty acids ,Articles ,Organ Size ,Immunohistochemistry ,Choline Deficiency ,3. Good health ,choline-deficient diet ,Adipose Tissue ,Liver ,Lipogenesis ,030211 gastroenterology & hepatology ,Metabolic Networks and Pathways ,medicine.medical_specialty ,steatohepatitis ,Palmitic Acids ,Biology ,Gas Chromatography-Mass Spectrometry ,03 medical and health sciences ,Physiology (medical) ,Internal medicine ,medicine ,Animals ,Triglycerides ,030304 developmental biology ,Triglyceride ,Fatty acid metabolism ,Fatty acid ,medicine.disease ,Diet ,Fatty Liver ,Mice, Inbred C57BL ,Kinetics ,B vitamins ,de novo lipogenesis ,Endocrinology ,chemistry ,Hepatocytes ,Steatohepatitis - Abstract
The pathological mechanisms that distinguish simple steatosis from steatohepatitis (or NASH, with consequent risk of cirrhosis and hepatocellular cancer) remain incompletely defined. Whereas both a methionine- and choline-deficient diet (MCDD) and a choline-deficient diet (CDD) lead to hepatic triglyceride accumulation, MCDD alone is associated with hepatic insulin resistance and inflammation (steatohepatitis). We used metabolic tracer techniques, including stable isotope ([13C4]palmitate) dilution and mass isotopomer distribution analysis (MIDA) of [13C2]acetate, to define differences in intrahepatic fatty acid metabolism that could explain the contrasting effect of MCDD and CDD on NASH in C57Bl6 mice. Compared with control-supplemented (CS) diet, liver triglyceride pool sizes were similarly elevated in CDD and MCDD groups (24.37 ± 2.4, 45.94 ± 3.9, and 43.30 ± 3.5 μmol/liver for CS, CDD, and MCDD, respectively), but intrahepatic neutrophil infiltration and plasma alanine aminotransferase (31 ± 3, 48 ± 4, 231 ± 79 U/l, P < 0.05) were elevated only in MCDD mice. However, despite loss of peripheral fat in MCDD mice, neither the rate of appearance of palmitate (27.2 ± 3.5, 26.3 ± 2.3, and 28.3 ± 3.5 μmol·kg−1·min−1) nor the contribution of circulating fatty acids to the liver triglyceride pool differed between groups. Unlike CDD, MCDD had a defect in hepatic triglyceride export that was confirmed using intravenous tyloxapol (142 ± 21, 122 ± 15, and 80 ± 7 mg·kg−1·h−1, P < 0.05). Moreover, hepatic de novo lipogenesis was significantly elevated in the MCDD group only (1.4 ± 0.3, 2.3 ± 0.4, and 3.4 ± 0.4 μmol/day, P < 0.01). These findings suggest that important alterations in hepatic fatty acid metabolism may promote the development of steatohepatitis. Similar mechanisms may predispose to hepatocyte damage in human NASH.
- Published
- 2011
28. 11[b]HSD1 deficiency increases susceptibility to liver fibrosis by activating hepatic stellate cells
- Author
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Rebecca L. Aucott, Xiantong Zou, Brian R. Walker, Antonella Pellicoro, Michelle Clarkson, Scott Peter Webster, Zoi Michailidou, John P. Iredale, and Prakash Ramachandran
- Subjects
medicine.medical_specialty ,Endocrinology ,Chemistry ,Liver fibrosis ,Internal medicine ,medicine ,Hepatic stellate cell ,Beta (finance) - Published
- 2013
29. Metabolic pathways promoting intrahepatic fatty acid accumulation in methionine and choline deficiency: implications for the pathogenesis of steatohepatitis.
- Author
-
Macfarlane, David P., Xiantong Zou, Andrew, Ruth, Morton, Nicholas M., Livingstone, Dawn E. W., Aucott, Rebecca L., Nyirenda, Moffat J., Iredale, John P., and Walker, Brian R.
- Subjects
- *
FATTY acid synthesis , *CIRRHOSIS of the liver , *LIVER cancer , *TRIGLYCERIDES , *INSULIN resistance , *METABOLISM , *LIVER cells - Abstract
The pathological mechanisms that distinguish simple steatosis from steatohepatitis (or NASH, with consequent risk of cirrhosis and hepatocellular cancer) remain incompletely defined. Whereas both a methionine- and choline-deficient diet (MCDD) and a choline-deficient diet (CDD) lead to hepatic triglyceride accumulation, MCDD alone is associated with hepatic insulin resistance and inflammation (steatohepatitis). We used metabolic tracer techniques, including stable isotope ([13C4]palmitate) dilution and mass isotopomer distribution analysis (MIDA) of [13C2]acetate, to define differences in intrahepatic fatty acid metabolism that could explain the contrasting effect of MCDD and CDD on NASH in C57Bl6 mice. Compared with control-supplemented (CS) diet, liver triglyceride pool sizes were similarly elevated in CDD and MCDD groups (24.37 ± 2.4, 45.94 ± 3.9, and 43.30 ± 3.5 μmol/liver for CS, CDD, and MCDD, respectively), but intrahepatic neutrophil infiltration and plasma alanine aminotransferase (31 ± 3, 48 ± 4, 231 ± 79 U/l, P < 0.05) were elevated only in MCDD mice. However, despite loss of peripheral fat in MCDD mice, neither the rate of appearance of palmitate (27.2 ± 3.5, 26.3 ± 2.3, and 28.3 ± 3.5 μmol·kg-1·min-1) nor the contribution of circulating fatty acids to the liver triglyceride pool differed between groups. Unlike CDD, MCDD had a defect in hepatic triglyceride export that was confirmed using intravenous tyloxapol (142 ± 21, 122 ± 15, and 80 ± 7 mg·kg-1·h-1, P < 0.05). Moreover, hepatic de novo lipogenesis was significantly elevated in the MCDD group only (1.4 ± 0.3, 2.3 ± 0.4, and 3.4 ± 0.4 μmol/day, P < 0.01). These findings suggest that important alterations in hepatic fatty acid metabolism may promote the development of steatohepatitis. Similar mechanisms may predispose to hepatocyte damage in human NASH. [ABSTRACT FROM AUTHOR]
- Published
- 2011
- Full Text
- View/download PDF
30. The Effect of Glimepiride Compared With Sitagliptin as an add-on Therapy to Metformin in Severe Insulin Deficiency Diabetes
- Author
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Peking University First Hospital, Jiangsu Province Geriatric Institute, and Xiantong Zou, MD. Ph.D., Attending Physician of the Department of Endocrinology and Metabolism
- Published
- 2022
31. Increased Angiogenesis Protects against Adipose Hypoxia and Fibrosis in Metabolic Disease-resistant 11β-Hydroxysteroid Dehydrogenase Type 1 (HSD1)-deficient Mice.
- Author
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Michailidou, Zoi, Turban, Sophie, Miller, Eileen, Xiantong Zou, Schrader, Joerg, Ratcliffe, Peter J., Hadoke, Patrick W. F., Walker, Brian R., Iredale, John P., Morton, Nicholas M., and Seckl, Jonathan R.
- Subjects
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METABOLIC disorders , *NEOVASCULARIZATION , *HYDROXYSTEROID dehydrogenases , *ADIPOSE tissues , *HYPOGLYCEMIC agents , *PANCREATIC secretions - Abstract
In obesity, rapidly expanding adipose tissue becomes hypoxic, precipitating inflammation, fibrosis, and insulin resistance. Compensatory angiogenesis may prevent these events. Mice lacking the intracellular glucocorticoid-amplifying enzyme 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1-/-) have "healthier" adipose tissue distribution and resist metabolic disease with diet-induced obesity. Here we show that adipose tissues of 11βHSD1-/- mice exhibit attenuated hypoxia, induction of hypoxia-inducible factor (HIF-1α) activation of the TGF- β/Smad3/α-smooth muscle actin (α-SMA) signaling pathway, and fibrogenesis despite similar fat accretion with diet-induced obesity. Moreover, augmented 11βHSD1-/- adipose tissue angiogenesis is associated with enhanced peroxisome proliferator- activated receptor γ (PPARγ)-inducible expression of the potent angiogenic factors VEGF-A, apelin, and angiopoietinlike protein 4. Improved adipose angiogenesis and reduced fibrosis provide a novel mechanism whereby suppression of intracellular glucocorticoid regeneration promotes safer fat expansion with weight gain. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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