Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes
| العنوان: | 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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| المؤلفون: | Claudia Lamina, Dawn M. Waterworth, Ramachandran S. Vasan, Alan R. Sinaiko, Jorma Viikari, Alena Stančáková, Nita G. Forouhi, Leo-Pekka Lyytikäinen, Chloe Y Y Cheung, Torben Hansen, Bernhard Paulweber, Ying Wu, Christie M. Ballantyne, Jaakko Tuomilehto, Karen S.L. Lam, Jussi Paananen, James B. Meigs, Jing Hua Zhao, Francis S. Collins, Hans U. Häring, Marie-France Hivert, Joshua W. Knowles, Zari Dastani, Andrew T. Hattersley, Ele Ferrannini, Ching-Ti Liu, Sarah Buxbaum, Mika Kähönen, Peter Henneman, Aurelian Bidulescu, Michael Boehnke, Ruth J. F. Loos, Fatiha el Bouazzaoui, Ulf Smith, Tim D. Spector, Josée Dupuis, Weijia Xie, Thomas Quertermous, Robert K. Semple, Lyudmyla Kedenko, John J. Nolan, Andrew D. Morris, Anne U. Jackson, Cornelia M. van Duijn, Ko Willems van Dijk, Markku Laakso, Robert A. Scott, Na Zhu, Oluf Pedersen, Terho Lehtimäki, Claudia Langenberg, Ke Hao, Christopher J. Gillson, Olli T. Raitakari, Mark I. McCarthy, Florian Kronenberg, Jaeyoung Hong, James S. Pankow, Debbie A Lawlor, Nicholas J. Wareham, Karen L. Mohlke, Timothy M. Frayling, Tanya M. Teslovich, Sandra H. Dunn, Alessandro Doria, Cecilia M. Lindgren, Richard N. Bergman, Johanna Kuusisto, Hanieh Yaghootkar, Liling Warren, Stefan Gustafsson, Erik Ingelsson, Colin N. A. Palmer, Mark Walker, Themistocles L. Assimes, J. Brent Richards |
| المساهمون: | Epidemiology, Medical Microbiology & Infectious Diseases |
| المصدر: | Diabetes, 62(10), 3589-3598 Yaghootkar, H, Lamina, C, Scott, R A, Dastani, Z, Hivert, M F, Warren, L L, Stancakova, A, Buxbaum, S G, Lyytikaeinen, L P, Henneman, P, Wu, Y, Cheung, C Y Y, Pankow, J S, Jackson, A U, Gustafsson, S, Zhao, J H, Ballantyne, C M, Xie, W J, Bergman, R N, Boehnke, M, el Bouazzaoui, F, Collins, F S, Dunn, S H, Dupuis, J, Forouhi, N G, Gillson, C, Hattersley, A T, Hong, J Y, Kaehoenen, M, Kuusisto, J, Kedenko, L, Kronenberg, F, Doria, A, Assimes, T L, Ferrannini, E, Hansen, T, Hao, K, Haering, H, Knowles, J W, Lindgren, C M, Nolan, J J, Paananen, J, Pedersen, O, Quertermous, T, Smith, U, Lehtimaeki, T, Liu, C T, Loos, R J F, McCarthy, M I, Morris, A D, Vasan, R S, Spector, T D, Teslovich, T M, Tuomilehto, J, van Dijk, K W, Viikari, J S, Zhu, N, Langenberg, C, Ingelsson, E, Semple, R K, Sinaiko, A R, Palmer, C N A, Walker, M, Lam, K S L, Paulweber, B, Mohlke, K L, van Duijn, C, Raitakari, O T, Bidulescu, A, Wareham, N J, Laakso, M, Waterworth, D M, Lawlor, D A, Meigs, J B, Richards, J B, Frayling, T M, Consortium, G & Consortium, R 2013, ' Mendelian Randomization Studies Do Not Support a Causal Role for Reduced Circulating Adiponectin Levels in Insulin Resistance and Type 2 Diabetes ', Diabetes, vol. 62, pp. 3589-3598 . https://doi.org/10.2337/db13-0128Test Diabetes Yaghootkar, H, Lamina, C, Scott, R A, Dastani, Z, Hivert, M F, Warren, L L, Stancáková, A, Buxbaum, S G, Lyytikäinen, L P, Henneman, P, Wu, Y, Cheung, C Y Y, Pankow, J S, Jackson, A U, Gustafsson, S, Zhao, J H, Ballantyne, C M, Xie, W, Bergman, R N, Boehnke, M, El Bouazzaoui, F, Collins, F S, Dunn, S H, Dupuis, J, Forouhi, N G, Gillson, C, Hattersley, A T, Hong, J, Kähönen, M, Kuusisto, J, Kedenko, L, Kronenberg, F, Doria, A, Assimes, T L, Ferrannini, E, Hansen, T, Hao, K, Häring, H, Knowles, J W, Lindgren, C M, Nolan, J J, Paananen, J, Pedersen, O, Quertermous, T, Smith, U, Lehtimäki, T, Liu, C T, Loos, R J F, McCarthy, M I, Morris, A D, Vasan, R S, Spector, T D, Teslovich, T M, Tuomilehto, J, Van Dijk, K W, Viikari, J S, Zhu, N, Langenberg, C, Ingelsson, E, Semple, R K, Sinaiko, A R, Palmer, C N A, Walker, M, Lam, K S L, Paulweber, B, Mohlke, K L, Van Duijn, C, Raitakari, O T, Bidulescu, A, Wareham, N J, Laakso, M, Waterworth, D M, Lawlor, D A, Meig, J B, Richards, J B & Frayling, T M 2013, ' Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes ', Diabetes, vol. 62, no. 10, pp. 3589-3598 . https://doi.org/10.2337/db13-0128Test Diabetes, 62(10), 3589-3598. American Diabetes Association Inc. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | Blood Glucose, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, ADIPOQ Gene, Biology, Polymorphism, Single Nucleotide, 03 medical and health sciences, MOLECULAR-WEIGHT ADIPONECTIN GREATER-THAN-G PLASMA ADIPONECTIN ADIPOSE-TISSUE ASSOCIATION ANALYSES METABOLIC PROFILE GENETIC-VARIANTS SUPPRESSION TEST GLYCEMIC TRAITS OBESE WOMEN, 0302 clinical medicine, Insulin resistance, SDG 3 - Good Health and Well-being, Diabetes mellitus, Internal medicine, Mendelian randomization, Odds Ratio, Internal Medicine, medicine, Humans, Genetic Predisposition to Disease, Original Research, 030304 developmental biology, 0303 health sciences, Adiponectin, Genetic Variation, Genetics/Genomes/Proteomics/Metabolomics, Mendelian Randomization Analysis, Odds ratio, medicine.disease, 3. Good health, Endocrinology, Diabetes Mellitus, Type 2, Regression Analysis, Female, Insulin Resistance |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0012-1797 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3f2386755cd164d07f113ab70cbd80feTest https://ora.ox.ac.uk/objects/uuid:fd376590-520a-44d4-a377-1d5ba7bc4b0cTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3f2386755cd164d07f113ab70cbd80fe |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 00121797 |
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