title: Overall and central obesity with insulin sensitivity and secretion in a Han Chinese population: a Mendelian randomization analysis.
abstract: Clinical heterogeneity exists in overall obesity and obesity in terms of susceptibility to type 2 diabetes, but the relationship is vulnerable to be confounded by traditional risk factors in epidemiological studies. We aimed to characterize the impact of obesity in insulin secretion and sensitivity by using Mendelian randomization (MR) approach with genetic variants.
  
  
  
  We first constructed two genetic risk scores based on 38 established loci for body mass index (BMI; a surrogate of overall obesity) and 13 waist-to-hip ratio (WHR; a surrogate of central obesity) to assess the causal effects of BMI and WHR on several glycaemic-related traits in 2884 community-based Han Chinese individuals.
  
  
  
  Both of BMI and WHR were observationally correlated with insulin secretion and sensitivity indices. The MR analysis demonstrated that a genetically determined 1 s.d. (3.35 kg m-2) higher BMI caused a unit of 178.18 pmol l-1higher Stumvoll first-phase and 35.52 pmol l-1higher Stumvoll second-phase insulin secretion (P=0.001 and 0.002, respectively), which were even independent of central obesity (P=0.019 and 0.039, respectively). In contrast, a genetically determined 1 s.d. higher WHR (a change of 0.002 in WHR) caused a unit of 1.21 higher homeostasis model assessment of insulin resistance and 18.40 lower Gutt index (representing the insulin sensitivity) (P=0.048 and 0.028, respectively). No substantial heterogeneity existed between the observed associations and the genetic estimated associations (P for difference >0.05).
  
  
  
  We provide new causal evidence that the impact of obesity on insulin secretion and sensitivity could vary between overall obesity and central obesity in Han Chinese populations and also identify the extent to which overall obesity affects compensatory insulin secretion and central obesity inversely links to insulin sensitivity.
authors: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: T
authors: T
authors: Wang
authors: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: X
authors: X
authors: Ma
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors: T
authors: T
authors: Tang
authors: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors: L
authors: L
authors: Jin
authors: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: D
authors: D
authors: Peng
authors: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: R
authors: R
authors: Zhang
authors: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: M
authors: M
authors: Chen
authors: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: J
authors: J
authors: Yan
authors: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: S
authors: S
authors: Wang
authors: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: D
authors: D
authors: Yan
authors: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: Z
authors: Z
authors: He
authors: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: F
authors: F
authors: Jiang
authors: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors: X
authors: X
authors: Cheng
authors: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: Y
authors: Y
authors: Bao
authors: National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China.
authors: Z
authors: Z
authors: Liu
authors: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.|Institute for Metabolic Diseases, Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai, China.
authors: C
authors: C
authors: Hu
authors: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
authors: W
authors: W
authors: Jia
mesh_terms: D044466:Asian People; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D002681:China / Q000208:ethnology; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics* / Q000503:physiopathology; D005006:Ethnicity; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics* / Q000502:physiology; D000078790:Insulin Secretion; D008297:Male; D057182:Mendelian Randomization Analysis; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000235:genetics* / Q000503:physiopathology; D012307:Risk Factors; D049629:Waist-Hip Ratio
chemical_list: D001786:Blood Glucose; D007328:Insulin