Association between lipids and apolipoproteins on type 2 diabetes risk; moderating effects of gender and polymorphisms; the ATTICA study

Abstract

Background and Aims Type 2 diabetes mellitus (T2DM) is a condition defined by hyperglycaemia, but also often presents with dyslipidaemia and suppressed HDL cholesterol. Mendelian randomization studies have suggested a causal link between low HDL cholesterol and T2DM. However, influences of gender, polymorphisms and lifestyle, all known to influence HDL cholesterol, have not been fully explored in a prospective cohort. Methods and Results In 2001-2002, a random sample of 1514 males (18-87 years old) and 1528 females (18-89 years old) were recruited in the ATTICA study. The 10-year follow-up (2011-2012) included 1485 participants. Lipids and lipoproteins levels, glucose and insulin levels were measured together with apolipoprotein A1 (apoA1) 75 G/A genotype, which is known to influence HDL-cholesterol. In total, 12.9% of the study sample developed T2DM within the 10-year follow-up period. In multivariable models, for each mg/dL increase in apoA1 levels in males, 10-year T2DM risk decreased 1.02%; while every unit increase in apoB/LDL-cholesterol ratio increased risk 4-fold. Finally, for every unit increase in triglycerides/apoA1 ratio, the risk increased 85%. HOMA-IR independently predicted T2DM 10-year incidence only for carriers of GG polymorphism (all, p<0.05), but not in carriers of the GA polymorphism (all, p>0.05). Conclusion ApoA1 was associated with decreased T2DM risk and TG/ApoA1 and apoB/LDL were associated with increased risk of T2DM, only in males. ApoA1 polymorphism, which is associated with lower HDL cholesterol, influenced the predictive effects of HOMA-IR on T2DM incidence, which appeared to be moderated by physical activity, suggesting potential scope for more targeted preventative strategies.

Publication DOI: https://doi.org/10.1016/j.numecd.2020.01.008
Divisions: College of Health & Life Sciences > Aston Medical School
Additional Information: © 2020, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ Funding: Hellenic Cardiology Society, the Hellenic Atherosclerosis Society, the Graduate Program in Applied Nutrition and Dietetics of Harokopio University and the Coca-Cola SA funded this study by research grants (KE252/ELKE/HUA). The ATTICA Study is funded by research grants from the Hellenic Society of Cardiology (grant –1, 2002).
Uncontrolled Keywords: Apolipoprotein A-1,HDL cholesterol,Lipids,Prospective cohort,Type 2 diabetes risk,Medicine (miscellaneous),Endocrinology, Diabetes and Metabolism,Nutrition and Dietetics,Cardiology and Cardiovascular Medicine
Publication ISSN: 1590-3729
Last Modified: 13 May 2024 17:49
Date Deposited: 27 Jan 2020 14:08
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Related URLs: https://linking ... 939475320300247 (Publisher URL)
http://www.scop ... tnerID=8YFLogxK (Scopus URL)
PURE Output Type: Article
Published Date: 2020-05-07
Published Online Date: 2020-01-21
Accepted Date: 2020-01-07
Authors: Mellor, Duane D. (ORCID Profile 0000-0002-1369-3868)
Georgousopoulou, Ekavi N.
D’cunha, Nathan M.
Naumovski, Nenad
Chrysohoou, Christina
Tousoulis, Dimitrios
Pitsavos, Christos
Panagiotakos, Demosthenes B.

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