Serum lipoprotein (a) concentrations are inversely associated with T2D, prediabetes, and insulin resistance in a middle-aged and elderly Chinese population

Abstract

Lipoprotein (a) [Lp(a)], synthesized by the liver, is a cholesterol-laden LDL-like particle, consisting of a moiety of apo(a) covalently attached to one molecule of apoB100 via a disulfi de bond ( 1 ). The concentration of Lp(a) was found to a large extent genetically determined via variations in the LPA gene, especially the LPA kringle IV repeats, which encode apo(a) and exist in multiple copies ( 2 ). Both serum Lp(a) levels and LPA gene variants have been reported strongly associated with the risk of CVD ( 3-5 ).Because diabetes predisposes individuals toward CVD, a similar association between circulating Lp(a) levels and Abstract Lipoprotein (a) [Lp(a)], an LDL-like particle, has been proposed as a causal risk factor for CVD among general populations. Meanwhile, both serum Lp(a) and diabetes increase the risk of CVD. However, the relationship between serum Lp(a) and T2D is poorly characterized, especially in the Asian population. Therefore, we conducted a cross-sectional study in 10,122 participants aged 40 years or older in Jiading District, Shanghai, China. Our study found that the prevalence of T2D was decreased from 20.9% to 15.0% from the lowest quartile to the highest quartile of serum Lp(a) concentrations ( P for trend <0.0001). Logistic regression analyses showed that the odds ratios and 95% confi dence intervals of prevalent T2D for quartiles 2-4 versus quartile 1 were 0.86 (0.73-1.01), 0.88 (0.75-1.04), and 0.76 (0.64-0.90) ( P for trend = 0.0002), after adjustment for traditional confounding factors. Moreover, the risks for prevalent prediabetes, insulin resistance, and hyperinsulinemia were also decreased from the lowest to the top quartile. This inverse association between serum Lp(a) and T2D was not appreciably changed after we adjusted hypoglycemic medications or excluded the subjects with hypoglycemic and/or lipid-lowering agents and/or a history of self-reported CVD. (81321001, 81390350, 81222008, and 81130016), the Shanghai Municipal of Science and Technology (13495810200) 24 January 2015. Published, JLR Papers in Press, February 3, 2015 DOI 10.1194 Serum lipoprotein (a) concentrations are inversely associated with T2D, prediabetes, and insulin resistance in a middle-aged and elderly Chinese population Abbreviations: 2 hPG, 2 h 75 g oral glucose tolerance test plasma glucose; CCHS, Copenhagen City Heart Study; CI, confi dence interval; DBP, diastolic blood pressure; FPG, fasting plasma glucose; FSI, fasting serum insulin; HbA1C, hemoglobin A1C; HDL-C, high density lipoprotein cholesterol; HOMA-IR, homeostasis model assessment for insulin resistance; LDL-C, low density lipoprotein cholesterol; lg, logarithmically transformed; Lp(a), lipoprotein (a); MET-h/week, metabolic equivalent hours per week; OGTT, oral glucose tolerance test; OR, odds ratio; SBP, systolic blood pressure; TC, total cholesterol; WC, waist circumference; WHS , Women's Health Study. This work was supported by grants from the Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health (1994DP131044), the N...

Lipoprotein (a): impact by ethnicity and environmental and medical conditions

“…Rainwater et al (236) reported significantly lower Lp(a) concentrations in NIDDM patients compared with matched nondiabetic controls in the San Antonio Heart Study. An inverse rela tionship between Lp(a) concentrations and NIDDM has been reported, as well as a negative correlation between Lp(a) and triglyceride levels in diabetic patients, includ ing IDDM and NIDDM (236)(237)(238)(239). In a recent report from the ERICNorfolk study, a strong inverse correlation be tween the Lp(a) level and newonset NIDDM was observed (240).…”

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“…Recent studies, however, have reported the association between very low Lp(a) concentrations and an increased risk of type 2 diabetes mellitus (T2DM) (82)(83)(84)(85).…”

“…Recent epidemiological studies (82)(83)(84)(85) and a Mendelian randomization study surprisingly reported an association between very low Lp(a) concentrations and long apo(a) isoforms with an increased risk of T2DM (83) mostly in Europeans/Whites and Chinese subjects. Some studies used the SNP, rs10455872, to exclude a causal association with T2DM.…”

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