title: Diabetes and Risk of Arterial Stiffness: A Mendelian Randomization Analysis.
abstract: We aimed to explore the causal association between type 2 diabetes (T2D) and increased arterial stiffness. We performed a Mendelian randomization (MR) analysis in 11,385 participants from a well-defined community study in Shanghai during 2011-2013. We genotyped 34 T2D-associated common variants identified in East Asians and created a genetic risk score (GRS). We assessed arterial stiffness noninvasively with the measurement of brachial-ankle pulse wave velocity (baPWV). We used the instrumental variable (IV) estimator to qualify the causal relationship between T2D and increased arterial stiffness. We found each 1-SD increase in T2D_GRS was associated with 6% higher risk in increased arterial stiffness (95% CI 1.01, 1.12), after adjustment of other metabolic confounders. Using T2D_GRS as the IV, we demonstrated a causal relationship between T2D and arterial stiffening (odds ratio 1.24, 95% CI 1.06, 1.47; P = 0.008). When categorizing the genetic loci according to their effect on insulin secretion or resistance, we found genetically determined decrease in insulin secretion was associated with increase in baPWV (βIV = 122.3 cm/s, 95% CI 41.9, 204.6; P = 0.0005). In conclusion, our results provide evidence supporting a causal association between T2D and increased arterial stiffness in a Chinese population.
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Min
authors.initials: M
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing, China.
authors.forename: Lan
authors.initials: L
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Kui
authors.initials: K
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Po
authors.initials: P
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Mingli
authors.initials: M
authors.lastname: Hao
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Biomedical Engineering, Medical Systems Biology Research Center, Tsinghua University School of Medicine, Beijing, China National Engineering Research Center for Beijing Biochip Technology, Beijing, China gning@sibs.ac.cn byf10784@rjh.com.cn ymsun@capitalbio.com.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Weiqing
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China gning@sibs.ac.cn byf10784@rjh.com.cn ymsun@capitalbio.com.
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
authors.affiliation: State Key Laboratory of Medical Genomics, Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, and Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China Department of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China gning@sibs.ac.cn byf10784@rjh.com.cn ymsun@capitalbio.com.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Bi
mesh_terms: D000328:Adult; D000368:Aged; D055109:Ankle Brachial Index; D044466:Asian People / Q000235:genetics*; D002681:China; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D000078790:Insulin Secretion; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D016017:Odds Ratio; D063177:Pulse Wave Analysis; D012307:Risk Factors; D059289:Vascular Stiffness / Q000235:genetics*
chemical_list: D007328:Insulin