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 - Funding Information:
This work was supported by the Hellenic Cardiology Society , the Hellenic Atherosclerosis Society , the Graduate Program in Applied Nutrition and Dietetics, 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 ).
Publisher Copyright:
© 2020 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University
PY - 2020/5/7
Y1 - 2020/5/7
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 - Apolipoprotein A-1
KW - HDL cholesterol
KW - Lipids
KW - Prospective cohort
KW - Type 2 diabetes risk
UR - http://www.scopus.com/inward/record.url?scp=85080067757&partnerID=8YFLogxK
U2 - 10.1016/j.numecd.2020.01.008
DO - 10.1016/j.numecd.2020.01.008
M3 - Article
SN - 0939-4753
VL - 30
SP - 788
EP - 795
JO - Nutrition, Metabolism and Cardiovascular Diseases
JF - Nutrition, Metabolism and Cardiovascular Diseases
IS - 5
ER -