Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes.

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Fältnamn	Indikatorer	Metadata
000		07487naa a2201501 4500
001		oai:gup.ub.gu.se/196031
003		SwePub
008		240528s2013 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
009		oai:DiVA.org:uu-210192
024	7	a https://gup.ub.gu.se/publication/1960312 URI
024	7	a https://doi.org/10.2337/db13-01282 DOI
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2101922 URI
040		a (SwePub)gud (SwePub)uu
041		a eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Yaghootkar, Hanieh4 aut
245	1 0	a Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes.
264		c 2013-09-17
264	1	b American Diabetes Association,c 2013
520		a 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 -0.07 to 0.11; N = 29,771), nominal evidence of a causal relationship with lower insulin sensitivity (-0.20 SD; 95% CI -0.38 to -0.02; 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: -0.03 SD; 95% CI -0.07 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.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng
653		a Adiponectin
653		a blood
653		a genetics
653		a Blood Glucose
653		a metabolism
653		a Diabetes Mellitus
653		a Type 2
653		a blood
653		a genetics
653		a Female
653		a Genetic Predisposition to Disease
653		a Genetic Variation
653		a Humans
653		a Insulin Resistance
653		a genetics
653		a Male
653		a Mendelian Randomization Analysis
653		a Odds Ratio
653		a Polymorphism
653		a Single Nucleotide
653		a Regression Analysis
700	1	a Lamina, Claudia4 aut
700	1	a Scott, Robert A4 aut
700	1	a Dastani, Zari4 aut
700	1	a Hivert, Marie-France4 aut
700	1	a Warren, Liling L4 aut
700	1	a Stancáková, Alena4 aut
700	1	a Buxbaum, Sarah G4 aut
700	1	a Lyytikäinen, Leo-Pekka4 aut
700	1	a Henneman, Peter4 aut
700	1	a Wu, Ying4 aut
700	1	a Cheung, Chloe Y Y4 aut
700	1	a Pankow, James S4 aut
700	1	a Jackson, Anne U4 aut
700	1	a Gustafsson, Stefanu Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)stegu732
700	1	a Zhao, Jing Hua4 aut
700	1	a Ballantyne, Christie M4 aut
700	1	a Xie, Weijia4 aut
700	1	a Bergman, Richard N4 aut
700	1	a Boehnke, Michael4 aut
700	1	a el Bouazzaoui, Fatiha4 aut
700	1	a Collins, Francis S4 aut
700	1	a Dunn, Sandra H4 aut
700	1	a Dupuis, Josee4 aut
700	1	a Forouhi, Nita G4 aut
700	1	a Gillson, Christopher4 aut
700	1	a Hattersley, Andrew T4 aut
700	1	a Hong, Jaeyoung4 aut
700	1	a Kähönen, Mika4 aut
700	1	a Kuusisto, Johanna4 aut
700	1	a Kedenko, Lyudmyla4 aut
700	1	a Kronenberg, Florian4 aut
700	1	a Doria, Alessandro4 aut
700	1	a Assimes, Themistocles L4 aut
700	1	a Ferrannini, Ele4 aut
700	1	a Hansen, Torben4 aut
700	1	a Hao, Ke4 aut
700	1	a Häring, Hans4 aut
700	1	a Knowles, Joshua W4 aut
700	1	a Lindgren, Cecilia M4 aut
700	1	a Nolan, John J4 aut
700	1	a Paananen, Jussi4 aut
700	1	a Pedersen, Oluf4 aut
700	1	a Quertermous, Thomas4 aut
700	1	a Smith, Ulf,d 1943u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut0 (Swepub:gu)xsmiul
700	1	a Ingelsson, Eriku Uppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)ering425
700	1	a the RISC Consortium,4 aut
700	1	a Lehtimäki, Terho4 aut
700	1	a Liu, Ching-Ti4 aut
700	1	a Loos, Ruth J F4 aut
700	1	a McCarthy, Mark I4 aut
700	1	a Morris, Andrew D4 aut
700	1	a Vasan, Ramachandran S4 aut
700	1	a Spector, Tim D4 aut
700	1	a Teslovich, Tanya M4 aut
700	1	a Tuomilehto, Jaakko4 aut
700	1	a van Dijk, Ko Willems4 aut
700	1	a Viikari, Jorma S4 aut
700	1	a Zhu, Na4 aut
700	1	a Langenberg, Claudia4 aut
700	1	a Ingelsson, Erik4 aut
700	1	a Semple, Robert K4 aut
700	1	a Sinaiko, Alan R4 aut
700	1	a Palmer, Colin N A4 aut
700	1	a Walker, Mark4 aut
700	1	a Lam, Karen S L4 aut
700	1	a Paulweber, Bernhard4 aut
700	1	a Mohlke, Karen L4 aut
700	1	a van Duijn, Cornelia4 aut
700	1	a Raitakari, Olli T4 aut
700	1	a Bidulescu, Aurelian4 aut
700	1	a Wareham, Nick J4 aut
700	1	a Laakso, Markku4 aut
700	1	a Waterworth, Dawn M4 aut
700	1	a Lawlor, Debbie A4 aut
700	1	a Meigs, James B4 aut
700	1	a Richards, J Brent4 aut
700	1	a Frayling, Timothy M4 aut
710	2	a Uppsala universitetb Molekylär epidemiologi4 org
773	0	t Diabetesd : American Diabetes Associationg 62:10, s. 3589-3598q 62:10<3589-3598x 1939-327Xx 0012-1797
856	4	u https://diabetes.diabetesjournals.org/content/diabetes/62/10/3589.full.pdf
856	4 8	u https://gup.ub.gu.se/publication/196031
856	4 8	u https://doi.org/10.2337/db13-0128
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-210192

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