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

Duane D. Mellor, Ekavi N. Georgousopoulou, Nathan M. D’cunha, Nenad Naumovski, Christina Chrysohoou, Dimitrios Tousoulis, Christos Pitsavos, Demosthenes B. Panagiotakos

Research output: Contribution to journalArticle

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.
Original languageEnglish
JournalNutrition, Metabolism and Cardiovascular Diseases
Early online date21 Jan 2020
DOIs
Publication statusE-pub ahead of print - 21 Jan 2020

Fingerprint

Apolipoproteins
Type 2 Diabetes Mellitus
Lipids
HDL Cholesterol
Apolipoprotein A-I
Apolipoproteins B
Odds Ratio
Incidence
Dyslipidemias
Random Allocation
Hyperglycemia
LDL Cholesterol
Lipoproteins
Life Style
Triglycerides
Genotype
Insulin
Glucose

Bibliographical note

© 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).

Keywords

  • Lipids
  • HDL cholesterol
  • Apolipoprotein A-1
  • Type 2 Diabetes Risk
  • Prospective cohort

Cite this

Mellor, D. D., Georgousopoulou, E. N., D’cunha, N. M., Naumovski, N., Chrysohoou, C., Tousoulis, D., ... Panagiotakos, D. B. (2020). Association between lipids and apolipoproteins on type 2 diabetes risk; moderating effects of gender and polymorphisms; the ATTICA study. Nutrition, Metabolism and Cardiovascular Diseases. https://doi.org/10.1016/j.numecd.2020.01.008
Mellor, Duane D. ; Georgousopoulou, Ekavi N. ; D’cunha, Nathan M. ; Naumovski, Nenad ; Chrysohoou, Christina ; Tousoulis, Dimitrios ; Pitsavos, Christos ; Panagiotakos, Demosthenes B. / Association between lipids and apolipoproteins on type 2 diabetes risk; moderating effects of gender and polymorphisms; the ATTICA study. In: Nutrition, Metabolism and Cardiovascular Diseases. 2020.
@article{54599353f3f44a1995b4c2956ea7ab92,
title = "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.",
keywords = "Lipids, HDL cholesterol, Apolipoprotein A-1, Type 2 Diabetes Risk, Prospective cohort",
author = "Mellor, {Duane D.} and Georgousopoulou, {Ekavi N.} and D’cunha, {Nathan M.} and Nenad Naumovski and Christina Chrysohoou and Dimitrios Tousoulis and Christos Pitsavos and Panagiotakos, {Demosthenes B.}",
note = "{\circledC} 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).",
year = "2020",
month = "1",
day = "21",
doi = "10.1016/j.numecd.2020.01.008",
language = "English",

}

Mellor, DD, Georgousopoulou, EN, D’cunha, NM, Naumovski, N, Chrysohoou, C, Tousoulis, D, Pitsavos, C & Panagiotakos, DB 2020, 'Association between lipids and apolipoproteins on type 2 diabetes risk; moderating effects of gender and polymorphisms; the ATTICA study', Nutrition, Metabolism and Cardiovascular Diseases. https://doi.org/10.1016/j.numecd.2020.01.008

Association between lipids and apolipoproteins on type 2 diabetes risk; moderating effects of gender and polymorphisms; the ATTICA study. / Mellor, Duane D.; Georgousopoulou, Ekavi N.; D’cunha, Nathan M.; Naumovski, Nenad; Chrysohoou, Christina; Tousoulis, Dimitrios; Pitsavos, Christos; Panagiotakos, Demosthenes B.

In: Nutrition, Metabolism and Cardiovascular Diseases, 21.01.2020.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association between lipids and apolipoproteins on type 2 diabetes risk; moderating effects of gender and polymorphisms; the ATTICA study

AU - Mellor, Duane D.

AU - Georgousopoulou, Ekavi N.

AU - D’cunha, Nathan M.

AU - Naumovski, Nenad

AU - Chrysohoou, Christina

AU - Tousoulis, Dimitrios

AU - Pitsavos, Christos

AU - Panagiotakos, Demosthenes B.

N1 - © 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).

PY - 2020/1/21

Y1 - 2020/1/21

N2 - 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.

AB - 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.

KW - Lipids

KW - HDL cholesterol

KW - Apolipoprotein A-1

KW - Type 2 Diabetes Risk

KW - Prospective cohort

UR - https://linkinghub.elsevier.com/retrieve/pii/S0939475320300247

U2 - 10.1016/j.numecd.2020.01.008

DO - 10.1016/j.numecd.2020.01.008

M3 - Article

ER -

Mellor DD, Georgousopoulou EN, D’cunha NM, Naumovski N, Chrysohoou C, Tousoulis D et al. Association between lipids and apolipoproteins on type 2 diabetes risk; moderating effects of gender and polymorphisms; the ATTICA study. Nutrition, Metabolism and Cardiovascular Diseases. 2020 Jan 21. https://doi.org/10.1016/j.numecd.2020.01.008