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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes
Diabetes, Volume 62, No. 10, Year 2013
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Description
Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic variants at the ADIPOQ gene as instruments to calculate a regression slope between adiponectin levels and metabolic traits (up to 31,000 individuals) and a combination of instrumental variables and summary statistics-based genetic risk scores to test the associations with gold-standard measures of insulin sensitivity (2,969 individuals) and type 2 diabetes (15,960 case subjects and 64,731 control subjects). In conventional regression analyses, a 1-SD decrease in adiponectin levels was correlated with a 0.31-SD (95% CI 0.26-0.35) increase in fasting insulin, a 0.34-SD (0.30-0.38) decrease in insulin sensitivity, and a type 2 diabetes odds ratio (OR) of 1.75 (1.47-2.13). The instrumental variable analysis revealed no evidence of a causal association between genetically lower circulating adiponectin and higher fasting insulin (0.02 SD; 95% CI 20.07 to 0.11; N = 29,771), nominal evidence of a causal relationship with lower insulin sensitivity (20.20 SD; 95% CI 20.38 to 20.02; N = 1,860), and no evidence of a relationship with type 2 diabetes (OR 0.94; 95% CI 0.75-1.19; N = 2,777 case subjects and 13,011 control subjects). Using the ADIPOQ summary statistics genetic risk scores, we found no evidence of an association between adiponectin- lowering alleles and insulin sensitivity (effect per weighted adiponectin-lowering allele: 20.03 SD; 95% CI 20.07 to 0.01; N = 2,969) or type 2 diabetes (OR per weighted adiponectin-lowering allele: 0.99; 95% CI 0.95-1.04; 15,960 case subjects vs. 64,731 control subjects). These results do not provide any consistent evidence that interventions aimed at increasing adiponectin levels will improve insulin sensitivity or risk of type 2 diabetes. © 2013 by the American Diabetes Association.
Authors & Co-Authors
Yaghootkar, Hanieh
United Kingdom, Exeter
University of Exeter Medical School
Lamina, Claudia
Austria, Innsbruck
Medizinische Universitat Innsbruck
Scott, Robert A.
United Kingdom, Cambridge
Wellcome-mrc Institute of Metabolic Science
Dastani, Zari
Canada, Montreal
Institut Lady Davis de Recherches Médicales
Hivert, Marie France
Canada, Sherbrooke
Université de Sherbrooke
United States, Boston
Massachusetts General Hospital
Warren, Liling
United States, Philadelphia
Glaxosmithkline, Usa
Stančáková, Alena
Finland, Kuopio
Itä-suomen Yliopisto
Buxbaum, Sarah G.
United States, Jackson
Jackson State University
Lyytikäinen, Leo Pekka
Finland, Tampere
Fimlab Laboratoriot oy
Finland, Tampere
Tampere University
Henneman, Peter
Netherlands, Leiden
Leids Universitair Medisch Centrum
Wu, Ying
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Cheung, Chloe Y.Y.
Hong Kong
The University of Hong Kong Li ka Shing Faculty of Medicine
Pankow, Jim S.
United States, Minneapolis
University of Minnesota Twin Cities
Jackson, Anne U.
United States, Ann Arbor
University of Michigan, Ann Arbor
Gustafsson, Stefan
Sweden, Uppsala
Uppsala Universitet
Zhao, Jinghua
United Kingdom, Cambridge
Wellcome-mrc Institute of Metabolic Science
Ballantyne, Christie Mitchell
United States, Houston
Baylor College of Medicine
Xie, Weijia
United Kingdom, Exeter
University of Exeter Medical School
Bergman, Richard N.
United States, Los Angeles
Cedars-sinai Medical Center
Boehnke, Michael L.
United States, Ann Arbor
University of Michigan, Ann Arbor
El Bouazzaoui, Fatiha
Netherlands, Leiden
Leids Universitair Medisch Centrum
Collins, Francis S.
United States, Bethesda
National Human Genome Research Institute Nhgri
Dunn, Sandra H.
United States, Pittsburgh
University of Pittsburgh
Dupuis, Josèe
United States, Boston
Boston University
Forouhi, Nita G.
United Kingdom, Cambridge
Wellcome-mrc Institute of Metabolic Science
Gillson, Christopher
United Kingdom, Cambridge
Wellcome-mrc Institute of Metabolic Science
Hattersley, Andrew T.
United Kingdom, Exeter
University of Exeter Medical School
Hong, Jaeyoung
United States, Boston
Boston University
Kähönen, Mika A.P.
Finland, Tampere
University Hospital of Tampere
Kuusisto, Johanna K.
Finland, Kuopio
Itä-suomen Yliopisto
Kedenko, Lyudmyla
Austria, Salzburg
Paracelsus Medizinische Privatuniversitat
Kronenberg, Florian
Austria, Innsbruck
Medizinische Universitat Innsbruck
Doria, Alessandro
United States, Boston
Joslin Diabetes Center
Assimes, Themistocles L.
United States, Stanford
Stanford University School of Medicine
Ferrannini, Ele
Italy, Pisa
Università Di Pisa
Hansen, Torben Frøstrup
Denmark, Copenhagen
Novo Nordisk Foundation Center for Basic Metabolic Research
Denmark, Odense
Faculty of Health Sciences, University of Southern Denmark
Hao, Ke
United States, New York
Icahn School of Medicine at Mount Sinai
Häring, Hans Ulrich
Germany, Tubingen
Eberhard Karls Universität Tübingen
Knowles, Joshua W.
United States, Stanford
Stanford University School of Medicine
Lindgren, Cecilia M.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Nolan, John J.
Denmark, Herlev
Steno Diabetes Center Copenhagen
Paananen, Jussi
Finland, Kuopio
Itä-suomen Yliopisto
Pedersen, Oluf Borbye
Denmark, Copenhagen
Novo Nordisk Foundation Center for Basic Metabolic Research
Denmark, Gentofte
Hagedorn Research Institute
Denmark, Copenhagen
Det Sundhedsvidenskabelige Fakultet
Denmark, Aarhus
Fakultetet Health
Assimes, Themistocles L.
United States, Stanford
Stanford University School of Medicine
Smith, Ulf P.G.
Sweden, Gothenburg
Sahlgrenska Akademin
Lehtimäki, Terho J.
Finland, Tampere
Fimlab Laboratoriot oy
Finland, Tampere
Tampere University
Liu, Chingti
United States, Boston
Boston University
Loos, Ruth J.F.
United Kingdom, Cambridge
Wellcome-mrc Institute of Metabolic Science
United States, New York
Icahn School of Medicine at Mount Sinai
McCarthy, Mark I.
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
United Kingdom, Oxford
University of Oxford Medical Sciences Division
United Kingdom, Oxford
Churchill Hospital
Morris, Andrew D.
United Kingdom, Dundee
University of Dundee
Ramachandran, Vasan S.
United States, Boston
Boston University
United States, Framingham
Framingham Heart Study
Spector, Tim David
United Kingdom, London
King's College London
Teslovich, Tanya M.
United States, Ann Arbor
University of Michigan, Ann Arbor
Tuomilehto, Jaakko O.I.
Finland, Helsinki
Terveyden ja Hyvinvoinnin Laitos
Saudi Arabia, Jeddah
King Abdulaziz University
Spain, Madrid
Hospital Universitario la Paz
Austria, Krems an Der Donau
Donau-universität Krems
van Dijk, Ko Willems
Netherlands, Leiden
Leids Universitair Medisch Centrum
Viikari, Jorma S.A.
Finland, Turku
Turun Yliopistollinen Keskussairaala
Finland, Turku
Turun Yliopisto
Zhu, Na
United States, Minneapolis
University of Minnesota Twin Cities
Langenberg, Claudia C.
United Kingdom, Cambridge
Wellcome-mrc Institute of Metabolic Science
Ingelsson, Erik
Sweden, Uppsala
Uppsala Universitet
United Kingdom, Oxford
The Wellcome Centre for Human Genetics
Semple, Robert K.
United Kingdom, Birmingham
National Institute for Health Research
United Kingdom, Cambridge
University of Cambridge
Sinaiko, Alan R.
United States, Minneapolis
University of Minnesota Twin Cities
Palmer, Colin Neil Alexander
United Kingdom, Dundee
University of Dundee
Walker, Mark A.
United Kingdom, Newcastle
School of Medical Education
Lam, Karen S.L.
Hong Kong
The University of Hong Kong Li ka Shing Faculty of Medicine
Paulweber, Bernhard
Austria, Salzburg
Paracelsus Medizinische Privatuniversitat
Mohlke, Karen
United States, Chapel Hill
The University of North Carolina at Chapel Hill
van Duijn, Cornelia M.
Netherlands, Rotterdam
Erasmus Mc
Raitakari, Olli T.
Finland, Turku
Turun Yliopistollinen Keskussairaala
Finland, Turku
Lääketieteellinen Tiedekunta
Bidulescu, Aurelian
United States, Atlanta
Morehouse School of Medicine
Wareham, Nicholas J.
United Kingdom, Cambridge
Wellcome-mrc Institute of Metabolic Science
Laakso, M. M.
Finland, Kuopio
Itä-suomen Yliopisto
Waterworth, Dawn M.
United States, Philadelphia
Glaxosmithkline, Usa
Lawlor, Debbie A.
United Kingdom, Bristol
University of Bristol
Meig, James B.
United Kingdom, Newcastle
School of Medical Education
Richards, John Brent
United Kingdom, London
King's College London
Canada, Montreal
Université Mcgill
Frayling, Tim M.
United Kingdom, Exeter
University of Exeter Medical School
Statistics
Citations: 118
Authors: 76
Affiliations: 56
Identifiers
Doi:
10.2337/db13-0128
ISSN:
00121797
e-ISSN:
1939327X
Research Areas
Genetics And Genomics
Noncommunicable Diseases
Study Design
Randomised Control Trial
Case-Control Study