Article open access publication

Association of Birth Weight With Type 2 Diabetes and Glycemic Traits

JAMA Network Open, American Medical Association (AMA), ISSN 2574-3805

Volume 2, 9, 2019

DOI:10.1001/jamanetworkopen.2019.10915, Dimensions: pub.1121113248, PMC: PMC6755534, PMID: 31539074,

Authors

Huang, Tao (1) (2)
Wang, Tiange (3) (4) (5)
Zheng, Yan (4) (6)
Ellervik, Christina (4) (7) (8) (9)
Li, Xiang (5)
Gao, Meng (2)
Fang, Zhe (2)
Zhou, Ang (21)
Kleber, Marcus E. (22) (23) (24)
Godfrey, Keith M. (25) (26)
Shi, Yuan (28)
Wang, Carol A. (30) (31)
He, Meian (36)
Lecoeur, Cécile (37) (38)
Corella, Dolores (39) (40)
Moreno, Luis A. (40) (42)
Zhang, Tao (5) (45)
Saw, Seang Mei (10) (28)
Hofman, Albert (4) (14)
Overvad, Kim (51) (52)
Cooper, Cyrus (25) (26) (53)
Liu, Jianjun (10) (20)
Raitakari, Olli (43) (56)
Viikari, Jorma (43) (56)
Lim, Blanche (10) (28)
Froguel, Philippe (37) (38)
Balkau, Beverley (62) (63) (64)
Coltell, Oscar (40) (65)
Pahkala, Katja (43) (67)
Niinikoski, Harri (43) (56)
Hyppönen, Elina (21) (48) (68)
März, Winfried (24) (69) (70)
Inskip, Hazel (25) (26)
Dennison, Elaine (25) (71)
Wong, Tien Yin (10) (28) (72)
Tai, E-Shyong (10) (72)
Estruch, Ramon (40) (80)
Ordovas, Jose M. (41) (81)
Cheng, Ching-Yu (10) (28) (72)
Koh, Woon-Puay (10) (72)
Psaty, Bruce M. (27) (83)
Chasman, Daniel I. (46) (54)
Qi, Lu (4) (5)

Affiliations

Organisations

  1. (1) Key Laboratory of Molecular Cardiovascular Sciences, Peking University, Ministry of Education, Beijing, China
  2. (2) Peking University, grid.11135.37
  3. (3) Shanghai Jiao Tong University, grid.16821.3c
  4. (4) Harvard University, grid.38142.3c
  5. (5) Tulane University, grid.265219.b
  6. (6) Fudan University, grid.8547.e
  7. (7) Boston Children's Hospital, grid.2515.3
  8. (8) Region Zealand, grid.480615.e
  9. (9) University of Copenhagen, grid.5254.6, KU
  10. (10) National University of Singapore, grid.4280.e
  11. (11) Steno Diabetes Center, grid.419658.7, Capital Region
  12. (12) Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
  13. (13) University of North Carolina System, grid.410711.2
  14. (14) Erasmus University Medical Center, grid.5645.2
  15. (15) Leiden University Medical Center, grid.10419.3d
  16. (16) Baylor College of Medicine, grid.39382.33
  17. (17) Leipzig University, grid.9647.c
  18. (18) Lund University, grid.4514.4
  19. (19) RIKEN Center for Integrative Medical Sciences, Laboratory for Statistical Analysis, Yokohama, Japan
  20. (20) Genome Institute of Singapore, grid.418377.e
  21. (21) University of South Australia, grid.1026.5
  22. (22) Competence Cluster of Nutrition and Cardiovascular Health, Halle-Jena-Leipzig, Germany
  23. (23) Friedrich Schiller University Jena, grid.9613.d
  24. (24) Heidelberg University, grid.7700.0
  25. (25) MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Southampton, United Kingdom
  26. (26) NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, University of Southampton, Southampton, United Kingdom
  27. (27) University of Washington, grid.34477.33
  28. (28) Singapore National Eye Center, grid.419272.b
  29. (29) Tampere University, grid.502801.e
  30. (30) University of Newcastle Australia, grid.266842.c
  31. (31) University of Western Australia, grid.1012.2
  32. (32) Ludwig Maximilian University of Munich, grid.5252.0
  33. (33) Institute of Epidemiology, Helmholtz Zentrum München German Research Center for Environmental Health, Neuherberg, Germany
  34. (34) Klinikum der Universität München, grid.411095.8
  35. (35) Queen Mary University of London, grid.4868.2
  36. (36) Huazhong University of Science and Technology, grid.33199.31
  37. (37) University of Lille Nord de France, grid.412304.0
  38. (38) Pasteur Institute of Lille, grid.8970.6
  39. (39) University of Valencia, grid.5338.d
  40. (40) Institute of Health Carlos III, grid.413448.e
  41. (41) Tufts University, grid.429997.8
  42. (42) University of Zaragoza, grid.11205.37
  43. (43) University of Turku, grid.1374.1
  44. (44) University College Dublin, grid.7886.1
  45. (45) Shandong University, grid.27255.37
  46. (46) Brigham and Women's Hospital, grid.62560.37
  47. (47) University of Pittsburgh, grid.21925.3d
  48. (48) University College London, grid.83440.3b
  49. (49) University of Bristol, grid.5337.2
  50. (50) Danish Cancer Society, grid.417390.8
  51. (51) Aalborg Hospital, grid.27530.33, North Denmark Region
  52. (52) Aarhus University, grid.7048.b, AU
  53. (53) University of Oxford, grid.4991.5
  54. (54) Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
  55. (55) University of San Carlos, grid.267101.3
  56. (56) Turku University Hospital, grid.410552.7
  57. (57) Department of Clinical Physiology, Tampere University Hospital, and Finnish Cardiovascular Research Center–Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland
  58. (58) Department of Paediatrics and NICU, CHC-Site St-Vincent, Liège-Rocourt, Belgium
  59. (59) Rovira i Virgili University, grid.410367.7
  60. (60) University of Milan, grid.4708.b
  61. (61) Harokopio University, grid.15823.3d
  62. (62) Centre for research in epidemiology and population health, grid.463845.8
  63. (63) University of Paris-Sud, grid.5842.b
  64. (64) Versailles Saint-Quentin-en-Yvelines University, grid.12832.3a
  65. (65) Jaume I University, grid.9612.c
  66. (66) Hôpital Jeanne de Flandre, grid.414184.c
  67. (67) Paavo Nurmi Centre, Sports and Exercise Medicine Unit, Department of Physical Activity and Health, Turku, Finland
  68. (68) South Australian Health and Medical Research Institute, grid.430453.5
  69. (69) Medical University of Graz, grid.11598.34
  70. (70) Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany
  71. (71) Victoria University of Wellington, grid.267827.e
  72. (72) Duke NUS Graduate Medical School, grid.428397.3
  73. (73) University of North Carolina at Chapel Hill, grid.10698.36
  74. (74) Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Crawley, Western Australia, Australia
  75. (75) Children's Memorial Health Institute, grid.413923.e
  76. (76) King Abdulaziz University, grid.412125.1
  77. (77) University of Massachusetts Lowell, grid.225262.3
  78. (78) Centre de Recherche des Cordeliers, grid.417925.c
  79. (79) University of Paris Diderot, Sorbonne Paris Cité, UMR_S 1138, Centre de Recherche des Cordeliers, Paris, France
  80. (80) Department of Internal Medicine, Hospital Clinic, IDIBAPS, Barcelona, Spain
  81. (81) Spanish National Centre for Cardiovascular Research, grid.467824.b
  82. (82) University of Kentucky, grid.266539.d
  83. (83) Kaiser Permanent Washington Health Research Institute, Seattle

Description

Importance: Observational studies have shown associations of birth weight with type 2 diabetes (T2D) and glycemic traits, but it remains unclear whether these associations represent causal associations. Objective: To test the association of birth weight with T2D and glycemic traits using a mendelian randomization analysis. Design, Setting, and Participants: This mendelian randomization study used a genetic risk score for birth weight that was constructed with 7 genome-wide significant single-nucleotide polymorphisms. The associations of this score with birth weight and T2D were tested in a mendelian randomization analysis using study-level data. The association of birth weight with T2D was tested using both study-level data (7 single-nucleotide polymorphisms were used as an instrumental variable) and summary-level data from the consortia (43 single-nucleotide polymorphisms were used as an instrumental variable). Data from 180 056 participants from 49 studies were included. Main Outcomes and Measures: Type 2 diabetes and glycemic traits. Results: This mendelian randomization analysis included 49 studies with 41 155 patients with T2D and 80 008 control participants from study-level data and 34 840 patients with T2D and 114 981 control participants from summary-level data. Study-level data showed that a 1-SD decrease in birth weight due to the genetic risk score was associated with higher risk of T2D among all participants (odds ratio [OR], 2.10; 95% CI, 1.69-2.61; P = 4.03 × 10-5), among European participants (OR, 1.96; 95% CI, 1.42-2.71; P = .04), and among East Asian participants (OR, 1.39; 95% CI, 1.18-1.62; P = .04). Similar results were observed from summary-level analyses. In addition, each 1-SD lower birth weight was associated with 0.189 SD higher fasting glucose concentration (β = 0.189; SE = 0.060; P = .002), but not with fasting insulin, 2-hour glucose, or hemoglobin A1c concentration. Conclusions and Relevance: In this study, a genetic predisposition to lower birth weight was associated with increased risk of T2D and higher fasting glucose concentration, suggesting genetic effects on retarded fetal growth and increased diabetes risk that either are independent of each other or operate through alterations of integrated biological mechanisms.

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