血脂和载脂蛋白与 2 型糖尿病风险的关系；性别和多态性的调节作用；ATTICA 研究。

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

机构信息

Aston Medical School, Aston University, Birmingham, B4 7ET, United Kingdom.

Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece; Medical School, Australian National University, Canberra, Australia; School of Medicine, The University of Notre Dame Australia, Sydney, Australia.

出版信息

Nutr Metab Cardiovasc Dis. 2020 May 7;30(5):788-795. doi: 10.1016/j.numecd.2020.01.008. Epub 2020 Jan 21.

DOI:10.1016/j.numecd.2020.01.008

PMID:32127339

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.

摘要

背景和目的

2 型糖尿病（T2DM）的定义是高血糖，但也常伴有血脂异常和 HDL 胆固醇降低。孟德尔随机化研究表明，低 HDL 胆固醇与 T2DM 之间存在因果关系。然而，性别、多态性和生活方式等已知影响 HDL 胆固醇的因素，在前瞻性队列研究中尚未得到充分探讨。

方法和结果

在 2001-2002 年，ATTICA 研究中随机抽取了 1514 名男性（18-87 岁）和 1528 名女性（18-89 岁）作为研究对象。10 年随访（2011-2012 年）包括 1485 名参与者。测量了血脂和脂蛋白水平、血糖和胰岛素水平，以及已知影响 HDL-胆固醇的载脂蛋白 A1（apoA1）75G/A 基因型。在 10 年的随访期间，总共有 12.9%的研究样本发生了 T2DM。在多变量模型中，男性中 apoA1 水平每增加 1mg/dL，10 年 T2DM 风险降低 1.02%；而 apoB/LDL-胆固醇比值每增加 1 个单位，风险增加 4 倍。最后，三酰甘油/apoA1 比值每增加 1 个单位，风险增加 85%。HOMA-IR 仅对 GG 多态性携带者（均 p<0.05）独立预测 T2DM 10 年发病率，而对 GA 多态性携带者（均 p>0.05）则不预测。

结论

apoA1 与 T2DM 风险降低相关，而 TG/ApoA1 和 apoB/LDL 与 T2DM 风险增加相关，仅在男性中如此。apoA1 多态性与较低的 HDL 胆固醇相关，影响 HOMA-IR 对 T2DM 发病率的预测作用，这种作用似乎受到体力活动的调节，表明可能有更有针对性的预防策略的空间。