Effects of Adiponectin on T2DM and Glucose Homeostasis: A Mendelian Randomization Study

Overview

Journal Diabetes Metab Syndr Obes

Publisher Dove Medical Press

Specialty Endocrinology

Date 2020 Jun 18

PMID 32547139

Citations 7

Authors

Zefeng Chen

Yulan Bai

Xinyang Long

Qianqian Luo

Zheng Wen

Yuanfan Li

Shengzhu Huang

Yunkun Yan

Zengnan Mo

Affiliations

Soon will be listed here.

Abstract

Purpose: The associations of adiponectin with type 2 diabetes mellitus (T2DM), glucose homeostasis (including β-cell function index (HOMA-β), insulin resistance (HOMA-IR), fasting insulin (FI) and fasting glucose (FG)) have reported in epidemiological studies. However, the previous observational studies are prone to biases, such as reverse causation and residual confounding factors. Herein, a Mendelian Randomization (MR) study was conducted to determine whether causal effects exist among them.

Materials And And Methods: Two-sample MR analyses and multiple sensitivity analyses were performed using the summary data from the ADIPOGen consortium, MAGIC Consortium, and a meta-analysis of GWAS with a considerable sample of T2DM (62,892 cases and 596,424 controls of European ancestry). We got eight valid genetic variants to predict the causal effect among adiponectin and T2DM and glucose homeostasis after excluding the probable invalid or pleiotropic variants.

Results: Adiponectin was not associated with T2DM (odds ratio (OR) = 1.004; 95% confidence interval (CI): 0.740, 1.363) when using MR Egger after removing the invalid SNPs, and the results were consistent when using the other four methods. Similar results existed among adiponectin and HOMA-β, HOMA-IR, FI, FG.

Conclusion: Our MR study revealed that adiponectin had no causal effect on T2DM and glucose homeostasis and that the associations among them in observational studies may be due to confounding factors.

Citing Articles

Effect of Gegen Qinlian Decoction combined with dietary management on patients with damp-heat Type-2 diabetes mellitus and metabolic syndrome.

Nie B, Liu X, Xiao Y, Liu C, Zhao Q Pak J Med Sci. 2024; 40(7):1523-1528.

PMID: 39092028 PMC: 11255807. DOI: 10.12669/pjms.40.7.9476.

Causal relationships between type 2 diabetes, glycemic traits and keratoconus.

Zhu X, Cheng D, Ruan K, Shen M, Ye Y Front Med (Lausanne). 2023; 10:1264061.

PMID: 38020157 PMC: 10658005. DOI: 10.3389/fmed.2023.1264061.

Exploratory analysis of the effect of a controlled lifestyle intervention on inflammatory markers - the Healthy Lifestyle Community Programme (cohort 2).

Koeder C, Anand C, Husain S, Kranz R, Schoch N, Alzughayyar D BMC Nutr. 2023; 9(1):25.

PMID: 36747285 PMC: 9900566. DOI: 10.1186/s40795-023-00684-2.

Mendelian randomization study reveals a causal relationship between adiponectin and LDL cholesterol in Africans.

Meeks K, Bentley A, Doumatey A, Adeyemo A, Rotimi C Sci Rep. 2022; 12(1):18955.

PMID: 36347891 PMC: 9643497. DOI: 10.1038/s41598-022-21922-w.

Causal associations of circulating adiponectin with cardiometabolic diseases and osteoporotic fracture.

Zhang M, Chen X, Zhu Y, Yin L, Quan Z, Ou Y Sci Rep. 2022; 12(1):6689.

PMID: 35461346 PMC: 9035157. DOI: 10.1038/s41598-022-10586-1.

References

Shim H, Chasman D, Smith J, Mora S, Ridker P, Nickerson D . A multivariate genome-wide association analysis of 10 LDL subfractions, and their response to statin treatment, in 1868 Caucasians. PLoS One. 2015; 10(4):e0120758. PMC: 4405269. DOI: 10.1371/journal.pone.0120758. View

Hartwig F, Davies N, Hemani G, Davey Smith G . Two-sample Mendelian randomization: avoiding the downsides of a powerful, widely applicable but potentially fallible technique. Int J Epidemiol. 2017; 45(6):1717-1726. PMC: 5722032. DOI: 10.1093/ije/dyx028. View

Brion M, Shakhbazov K, Visscher P . Calculating statistical power in Mendelian randomization studies. Int J Epidemiol. 2013; 42(5):1497-501. PMC: 3807619. DOI: 10.1093/ije/dyt179. View

Dupuis J, Langenberg C, Prokopenko I, Saxena R, Soranzo N, Jackson A . New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat Genet. 2010; 42(2):105-16. PMC: 3018764. DOI: 10.1038/ng.520. View

Au Yeung S, Schooling C . Adiponectin and coronary artery disease risk: A bi-directional Mendelian randomization study. Int J Cardiol. 2018; 268:222-226. DOI: 10.1016/j.ijcard.2018.03.132. View

Dastani Z, Johnson T, Kronenberg F, Nelson C, Assimes T, Marz W . The shared allelic architecture of adiponectin levels and coronary artery disease. Atherosclerosis. 2013; 229(1):145-8. PMC: 6139652. DOI: 10.1016/j.atherosclerosis.2013.03.034. View

Xu Y, Wang L, He J, Bi Y, Li M, Wang T . Prevalence and control of diabetes in Chinese adults. JAMA. 2013; 310(9):948-59. DOI: 10.1001/jama.2013.168118. View

Li J, Ni J, Wu Y, Zhang H, Liu J, Tu J . Sex Differences in the Prevalence, Awareness, Treatment, and Control of Diabetes Mellitus Among Adults Aged 45 Years and Older in Rural Areas of Northern China: A Cross-Sectional, Population-Based Study. Front Endocrinol (Lausanne). 2019; 10:147. PMC: 6426742. DOI: 10.3389/fendo.2019.00147. View

Bowden J, Del Greco M F, Minelli C, Davey Smith G, Sheehan N, Thompson J . A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization. Stat Med. 2017; 36(11):1783-1802. PMC: 5434863. DOI: 10.1002/sim.7221. View

10.

Pereira R, Snell-Bergeon J, Erickson C, Schauer I, Bergman B, Rewers M . Adiponectin dysregulation and insulin resistance in type 1 diabetes. J Clin Endocrinol Metab. 2012; 97(4):E642-7. PMC: 3319187. DOI: 10.1210/jc.2011-2542. View

11.

Xue A, Wu Y, Zhu Z, Zhang F, Kemper K, Zheng Z . Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes. Nat Commun. 2018; 9(1):2941. PMC: 6063971. DOI: 10.1038/s41467-018-04951-w. View

12.

Bowden J, Davey Smith G, Haycock P, Burgess S . Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator. Genet Epidemiol. 2016; 40(4):304-14. PMC: 4849733. DOI: 10.1002/gepi.21965. View

13.

Miguel-Escalada I, Bonas-Guarch S, Cebola I, Ponsa-Cobas J, Mendieta-Esteban J, Atla G . Human pancreatic islet three-dimensional chromatin architecture provides insights into the genetics of type 2 diabetes. Nat Genet. 2019; 51(7):1137-1148. PMC: 6640048. DOI: 10.1038/s41588-019-0457-0. View

14.

Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M . Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med. 2007; 13(3):332-9. DOI: 10.1038/nm1557. View

15.

Zheng Y, Ley S, Hu F . Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2017; 14(2):88-98. DOI: 10.1038/nrendo.2017.151. View

16.

Juma P, Mohamed S, Matanje Mwagomba B, Ndinda C, Mapa-Tassou C, Oluwasanu M . Non-communicable disease prevention policy process in five African countries. BMC Public Health. 2018; 18(Suppl 1):961. PMC: 6117619. DOI: 10.1186/s12889-018-5825-7. View

17.

Venkatrao M, Nagarathna R, Patil S, Singh A, Rajesh S, Nagendra H . A composite of BMI and waist circumference may be a better obesity metric in Indians with high risk for type 2 diabetes: An analysis of NMB-2017, a nationwide cross-sectional study. Diabetes Res Clin Pract. 2020; 161:108037. DOI: 10.1016/j.diabres.2020.108037. View

18.

Basu R, Pajvani U, Rizza R, Scherer P . Selective downregulation of the high molecular weight form of adiponectin in hyperinsulinemia and in type 2 diabetes: differential regulation from nondiabetic subjects. Diabetes. 2007; 56(8):2174-7. DOI: 10.2337/db07-0185. View

19.

Willemsen G, Ward K, Bell C, Christensen K, Bowden J, Dalgard C . The Concordance and Heritability of Type 2 Diabetes in 34,166 Twin Pairs From International Twin Registers: The Discordant Twin (DISCOTWIN) Consortium. Twin Res Hum Genet. 2015; 18(6):762-71. DOI: 10.1017/thg.2015.83. View

20.

Lee J, Yang J, Han B, Choi S, Kim J . Adiponectin for the treatment of diabetic nephropathy. Korean J Intern Med. 2019; 34(3):480-491. PMC: 6506734. DOI: 10.3904/kjim.2019.109. View