Abstract
The connection between lipoprotein (a) [Lp(a)] levels and the risks of cardiovascular disease and diabetes remains poorly understood. Lp(a) is encoded by the LPA gene, and evidence suggests that the kringle IV type 2 (KIV-2) variant is particularly important to Lp(a) isoform size. A large isoform size, represented as a high number of KIV-2 repeats in LPA, is associated with low serum Lp(a) concentrations and an increased risk of type 2 diabetes. We investigated the associations among Lp(a) concentrations, LPA KIV-2 repeats, and type 2 diabetes in a Chinese population of 1,863 consecutive patients with very high cardiovascular risk, as identified by coronary angiography. Individuals with Lp(a) levels in the top tertile [67.86 (35.34-318.50) mg/dl] had a lower risk of diabetes compared with those in the bottom tertile [7.38 (0.60-12.91) mg/dl]. There was an inverse association between the number of KIV-2 repeats and serum Lp(a) concentrations. This study demonstrated that a high number of LPA KIV-2 repeats are associated with increased risk of type 2 diabetes in a Chinese population with very high cardiovascular risk, which suggests that large Lp(a) isoform size, associated with low Lp(a) concentration, has a causal effect on type 2 diabetes.
Highlights
The connection between lipoprotein (a) [Lp(a)] levels and the risks of cardiovascular disease and diabetes remains poorly understood
Several studies using Mendelian randomization approaches have demonstrated that LPA variants were associated with the risk of coronary heart disease (CHD) and myocardial infarction [14,15,16,17], which supports a causal role of Lp(a) in ischemic cardiovascular disease
Serum Lp(a) levels were inversely associated with fasting plasma glucose (FPG), 2 h 2 h postprandial plasma glucose (PPG), glycosylated hemoglobin (HbA1c), diabetes, and triglyceride, and positively associated with total cholesterol, LDL cholesterol (LDL-C), apoB, and significant coronary stenosis
Summary
The connection between lipoprotein (a) [Lp(a)] levels and the risks of cardiovascular disease and diabetes remains poorly understood. A large isoform size, represented as a high number of KIV-2 repeats in LPA, is associated with low serum Lp(a) concentrations and an increased risk of type 2 diabetes. This study demonstrated that a high number of LPA KIV-2 repeats are associated with increased risk of type 2 diabetes in a Chinese population with very high cardiovascular risk, which suggests that large Lp(a) isoform size, associated with low Lp(a) concentration, has a causal effect on type 2 diabetes.—Mu-Han-Ha-Li, D-L-D-E., T-Y. One study using a novel genetic approach confirmed that it is a high number of KIV-2 repeats that is causally associated with increased risk of type 2 diabetes, and not low Lp(a) concentrations per se [20]
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