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Metabolomics in human type 2 diabetes research

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Frontiers of Medicine 2013年第1期7卷 4-13页

The high prevalence of diabetes and diabetic complications has caused a huge burden on the modern society.Although scientific advances have led to effective strategies for preventing and treating diabetes over the past several decades,little progress has been made toward curing the disease or even getting it under control,from a public health and overall societal standpoint.There is still a lack of reliable biomarkers indicative of metabolic alterations associated with diabetes and different drug responses,highlighting the need for the development of early diagnostic and prognostic markers for diabetes and diabetic complications.The emergence of metabolomics has allowed researchers to systemically measure the small molecule metabolites,which are sensitive to the changes of both environmental and genetic factors and therefore,could be regarded as the link between genotypes and phenotypes.During the last decade,the progression made in metabolomics has provided insightful information on disease development and disease onset prediction.Recent studies using metabolomics approach coupled with statistical tools to predict incident diabetes revealed a number of metabolites that are significantly altered,including branched-chain and aromatic amino acids,such as isoleucine,leucine,valine,tyrosine and phenylalanine,as diagnostic or highly-significant predictors of future diabetes.This review summarizes the current findings of metabolomic studies in human investigations with the most common form of diabetes,type 2 diabetes.

关键词： metabolomics type 2 diabetes metabolic pathway mass spectrometry nuclear magnetic resonance(NMR)

Fibroblast growth factor 21:a novel metabolic regulator from pharmacology to physiology

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Frontiers of Medicine 2013年第1期7卷 25-30页

作者： Huating Li Jing Zhang Weiping Jia Department of Endocrinology and Metabolism Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai Diabetes InstituteShanghai Clinical Center of DiabetesShanghai 200233China

Fibroblast growth factor 21(FGF21)is a member of the fibroblast growth factor family.It actually functions as endocrine hormones but does not regulate cell growth and differentiation.It is demonstrated that FGF21 acts on multiple tissue to coordinate carbohydrate and lipid metabolism,including enhancing insulin sensitivity,decreasing triglyceride concentrations,causing weight loss,ameliorating obesity-associated hyperglycemia and hyperlipidemia.Moreover,FGF21 also plays important roles in some physiological processes,such as fasting and feeding,growth hormone axis and thermogenic function of brown adipose tissue.Clinical relevance of FGF21 in humans is still unclear,and the basis and consequences of increased FGF21 in metabolic disease remain to be determined.Both the pharmacological actions and physiological roles make FGF21 attractive drug candidates for treating metabolic disease,but some questions remain to be answered.This article concentrates on recent advances in our understanding of FGF21.

关键词： FGF21 metabolism pharmacology physiology clinical relevance

Altered intestinal microbiota associated with colorectal cancer

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Frontiers of Medicine 2019年第4期13卷 461-470页

作者： Hong Zhang Ying Chang Qingqing Zheng Rong Zhang Cheng Hu Weiping Jia Shanghai Diabetes Institute Shanghai Key L aboratory of Diabetes Mellitus Shanghai Clinical Center for Diabetes Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 China Digestive Endoscopic Center Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai 200233 China

The gut microbiota plays an important role in the development and progression of colorectal cancer (CRC). To learn more about the dysbiosis of carcinogenesis, we assessed alterations in gut microbiota in patients with CRC. A total of 23 subjects were enrolled in this study: 9 had CRC (CRC group) and 14 had normal colons (normal group). The microbiome of the mucosal-luminal interface of each subject was sampled and analyzed using 16S rRNA gene amplicon sequencing. We also used Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to predict microbial functional profiles. The microbial composition of the mucosal lumen differed between the groups, and the presence of specific bacteria may serve as a potential biomarker for colorectal carcinogenesis. We identified a significant reduction in Eubacterium, which is a butyrate-producing genera of bacteria, and a significant increase in Devosia in the gut microbiota of CRC patients. Different levels of gut microflora in healthy and CRC samples were identified. The observed abundance of bacterial species belonging to Eubacterium and Devosia may serve as a promising biomarker for the early detection of CRC.

关键词： colorectal cancer (CRC) gut microbiota intestinal Eubacterium Devosia

Advancement in genetic variants conferring obesity susceptibility from genome-wide association studies

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Frontiers of Medicine 2015年第2期9卷 146-161页

作者： Tao Wang Weiping Jia Cheng Hu Shanghai Diabetes Institute Shanghai Key Laboratory of Diabetes Mellitus Shanghai Clinical Center for Diabetes Shanghai Jiao TongUniversity Affiliated Sixth People's Hospital Shanghai 200233 China

Obesity prevalence has increased in recent years. Lifestyle change fuels obesity, but genetic factors cause more than 50% of average variations in obesity. The advent of genome-wide association studies （GWAS） has hastened the progress of polygenic obesity research. As of this writing, more than 73 obesity susceptibility loci have been identified in ethnic groups through GWAS. The identified loci explain only 2% to 4% of obesity heritability, thereby indicating that a large proportion of loci remain undiscovered. Thus, the next step is to identify and confirm novel loci, which may exhibit smaller effects and lower allele frequencies than established loci. However, achieving these tasks has been difficult for researchers. GWAS help researchers discover the causal loci. Moreover, numerous biological studies have been performed on the polygenic effects on obesity, such as studies on fat mass- and obesity-associated gene （FTO）, but the role of these polygenic effects in the mechanism of obesity remains unclear. Thus, obesity-causing variations should be identified, and insights into the biology of polygenic effects on obesity are needed.

关键词： obesity genetics genome-wide association studies body mass index fat mass- and obesity-associated gene

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新形势、新理念下的慢性病防控

中华内科杂志 2022年第1期61卷 1-3页

作者：贾伟平上海交通大学附属第六人民医院内分泌代谢科上海200233

慢性病成为对人民健康的主要威胁,防控策略要以疾病诊治为主的传统临床医学模式向早期监测、早期干预、预防为主的大健康模式转变。“关口前移、健康优先、主动健康”是抗击慢性病更为合理和经济的举措。要践行科学技术“面向人民生命... 详细信息

慢性病成为对人民健康的主要威胁,防控策略要以疾病诊治为主的传统临床医学模式向早期监测、早期干预、预防为主的大健康模式转变。“关口前移、健康优先、主动健康”是抗击慢性病更为合理和经济的举措。要践行科学技术“面向人民生命健康”的国家战略,持续开展技术创新和集成,构建“医防融合”“医管融合”的协同管理体系,推动慢性病防控的全人群、全周期、全方位管理。

关键词：慢性病预防治疗健康

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强基固本,全专结合,做好健康守护人

中华内科杂志 2024年第5期63卷 427-429页

作者：贾伟平上海交通大学附属第六人民医院内分泌代谢科上海200233

2024年我们面临的健康挑战仍然十分严峻。伴随人口老龄化、疾病谱的改变,心脑血管疾病、恶性肿瘤、慢性呼吸系统疾病和糖尿病等重大慢性病成为危害我国人民生命健康的主要疾病。针对我国慢性病影响人民健康的巨大挑战,党中央国务院颁布... 详细信息

2024年我们面临的健康挑战仍然十分严峻。伴随人口老龄化、疾病谱的改变,心脑血管疾病、恶性肿瘤、慢性呼吸系统疾病和糖尿病等重大慢性病成为危害我国人民生命健康的主要疾病。针对我国慢性病影响人民健康的巨大挑战,党中央国务院颁布实施了《健康中国2030规划纲要》,提出了慢性病的综合防控战略。在学习了国家一系列政策文件后,笔者结合在临床一线工作40年的诊治经验,以及近20年间探索不同层级医疗机构优质医疗资源整合,推动医疗与预防融合方面的体会,撰写此篇随笔与读者分享。

关键词：慢性病健康教育科普

Decreasing complexity of glucose time series derived from continuous glucose monitoring is correlated with deteriorating glucose regulation

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Frontiers of Medicine 2023年第1期17卷 68-74页

作者： Cheng Li Xiaojing Ma Jingyi Lu Rui Tao Xia Yu Yifei Mo Wei Lu Yuqian Bao jian Zhou Weiping Jia Department of Endocrinology and Metabolism Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s HospitalShanghai Clinical Center for DiabetesShanghai Diabetes InstituteShanghai Key Laboratory of Diabetes MellitusShanghai 200233China College of Information Science and Engineering Northeastern UniversityShenyang 110819China

Most information used to evaluate diabetic statuses is collected at a special time-point,such as taking fasting plasma glucose test and providing a limited view of individual’s health and disease risk.As a new parameter for continuously evaluating personal clinical statuses,the newly developed technique“continuous glucose monitoring”(CGM)can characterize glucose dynamics.By calculating the complexity of glucose time series index(CGI)with refined composite multi-scale entropy analysis of the CGM data,the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes(P for trend<0.01).Furthermore,CGI was significantly associated with various parameters such as insulin sensitivity/secretion(all P<0.01),and multiple linear stepwise regression showed that the disposition index,which reflectsβ-cell function after adjusting for insulin sensitivity,was the only independent factor correlated with CGI(P<0.01).Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.

关键词： complexity of glucose time series continuous glucose monitoring impaired glucose regulation insulin secretion and sensitivity refined composite multi-scale entropy

坚持系统理念, 融合创新发展, 做好健康服务

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中华内科杂志 2023年第1期62卷 1-3页

作者：贾伟平上海交通大学医学院附属第六人民医院内分泌代谢科上海200233

2022年是抗击新型冠状病毒感染疫情第3年, 《中华内科杂志》在各方的努力、支持和关爱下, 如期完成了全年的出版计划。新的一年, 2023年, 也是《中华内科杂志》创刊70周年, 70年来无数医学大家对本刊无私奉献, 杂志获得了长足发展和诸... 详细信息

2022年是抗击新型冠状病毒感染疫情第3年, 《中华内科杂志》在各方的努力、支持和关爱下, 如期完成了全年的出版计划。新的一年, 2023年, 也是《中华内科杂志》创刊70周年, 70年来无数医学大家对本刊无私奉献, 杂志获得了长足发展和诸多的荣誉。展望未来, 我们将始终坚持为不同学科间搭建共享平台, 推动学科间学术交流与合作。传承前辈的敬业奉献精神, 在新时代、新时期, 本届编委及编辑部专职人员一定会齐心合力, 砥砺奋进, 使《中华内科杂志》成为临床医生的良师益友, 并在办刊水准上更上一层楼。

关键词：慢性病预防治疗健康

Targeted gene panel provides advantages over whole-exome sequencing for diagnosing obesity and diabetes mellitus

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Journal of Molecular Cell Biology 2023年第6期15卷 40-52页

作者： Hairong Yu Haoyong Yu Rong Zhang Danfeng Peng Dandan Yan Yunjuan Gu Yuqian Bao Weiping Jia Hong Zhang Cheng Hu Shanghai Diabetes Institute Shanghai Key Laboratory of Diabetes MellitusShanghai Clinical Center for DiabetesShanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China Department of Endocrinology Affiliated Hospital of Nantong UniversityNantong 226001China Institute for Metabolic Disease Fengxian Central Hospital Affiliated to Southern Medical UniversityShanghai 201499China

A small fraction of patients diagnosed with obesity or diabetes mellitus has an underlying monogenic cause.Here,we constructed a targeted gene panel consisting of 83 genes reported to be causative for monogenic obesity or diabetes.We performed this panel in 481 patients to detect causative variants and compared these results with whole-exome sequencing(WES)data available for 146 of these patients.The coverage of targeted gene panel sequencing was significantly higher than that of WES.The diagnostic yield in patients sequenced by the panel was 32.9%with subsequent WES leading to three additional diagnoses with two novel genes.In total,178 variants in 83 genes were detected in 146 patients by targeted sequencing.Three of the 178 variants were missed by WES,although the WES-only approach had a similar diagnostic yield.For the 335 samples only receiving targeted sequencing,the diagnostic yield was 32.2%.In conclusion,taking into account the lower costs,shorter turnaround time,and higher quality of data,targeted sequencing is a more effective screening method for monogenic obesity and diabetes compared to WES.Therefore,this approach could be routinely established and used as a first-tier test in clinical practice for specific patients.

关键词： molecular diagnosis monogenic diabetes mellitus monogenic obesity targeted panel whole-exome sequencing