Lipoprotein Subfractions and Glucose Homeostasis in Prediabetes and Diabetes in Taiwan

Abstract

Aims: Prediabetes and diabetes are associated with increased insulin resistance and decreased insulin production, dyslipidemia, and increased cardiovascular disease (CVD) risk. Our goals were to assess lipoprotein subfractions using novel assays in such subjects.Methods: Fasting normal, prediabetic, and diabetic Taiwanese men and women (n = 2,049) had their serum glucose, glycosylated hemoglobin, insulin, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), HDL3-C, apolipoprotein E-HDL-C, direct low-density lipoprotein cholesterol (LDL-C), small dense LDL-C (sdLDL-C), LDL-TG, and remnant lipoprotein cholesterol (RLP-C) levels measured using novel assays. HDL2-C, LDL-C, and large-buoyant LDL-C (lbLDL-C) were calculated.Results: Prediabetic male and female subjects had significantly higher levels of TG, RLP-C, sdLDL-C, the sdLDL-C/LDL-C ratio, and LDL-TG than normal subjects, and statin treatment abolished this effect in men, but not in women. Diabetic male and female subjects had significantly higher TG and sdLDL-C/LDL-C ratios, and significantly lower levels of HDL-C, HDL2-C, HDL3-C, and apoE HDL-C than normal subjects, as did prediabetic women. Median direct LDL-C levels were > 100 mg/dL in all groups, even in those receiving statin therapy. Calculated LDL-C significantly underestimated direct LDL-C by > 10% in diabetic subjects.Conclusions: Our data indicate that prediabetic subjects were more likely to have significantly elevated RLP-C, sdLDL-C, and LDL-TG, while diabetic subjects were more likely to have significantly decreased HDL-C, HDL2-C, HDL3-C, and apoE HDL-C than normal subjects, and calculated LDL-C significantly underestimated their direct LDL-C. In our view, direct LDL-C and sdLDL-C should be measured and optimized in both diabetic and prediabetic subjects to reduce CVD risk.

High sdLDL Cholesterol can be Used to Reclassify Individuals with Low Cardiovascular Risk for Early Intervention: Findings from the Chinese Multi-Provincial Cohort Study

“…Therefore, it is apparent that the measurement of LDLC quantifies the cholesterol content of LDL particles but does not take into account the vast heterogeneity of LDL particles among individuals, and the use of LDLC to evaluate cholesterol-related cardiovascular risk may actually underestimate future risk in individuals who have a high level of circulating sdLDLC. Except for the atherogenic role of sdLDLC, it was also found that sdLDLC levels were strongly associated with atherosclerotic risk markers such as inflammation, thrombosis, hematologic markers 26 ) , and prediabetes 27 ) , which was further demonstrated in our study where sdLDLC levels were significantly correlated with hs-CRP and fasting blood glucose in the general population. Taking all these findings into account, the measurement of sdLDLC may therefore help clinicians to reclassify individuals thought to be at low risk into the high-risk category, for early intervention.…”

Association of small dense low-density lipoprotein with cardiovascular outcome in patients with coronary artery disease and diabetes: a prospective, observational cohort study

“…However, routine lipid measures may not well reflect the compositional changes of lipid parameters in DM and Pre-DM patients. For example, no significant increase in LDL-C levels was found in some DM and Pre-DM patients [16]. In patients with metabolic disorder, the increase in very low-density lipoprotein (VLDL) particles could initiate a sequence of hydrolysis process and result in higher plasma sdLDL levels [6].…”

“…In hyperglycemic status, the HL-mediated pathway is more active [6]. Thus, the plasma level of sdLDL is significantly elevated in pre-diabetes (Pre-DM) and DM individuals [13,16]. Furthermore, sdLDL is more susceptible to glycation than lbLDL, which may increase its atherogenicity [17].…”

Long-term prognostic utility of low-density lipoprotein (LDL) triglyceride in real-world patients with coronary artery disease and diabetes or prediabetes

“…However, even after intensive lowering of LDL-C, the absolute risk of events in DM patients is still higher than that in non-diabetic patients. Hypertriglyceridemia is the main feature of lipid disorder in DM and Pre-DM and could induce a sequence of compositional changes for lipid parameters including low HDL-cholesterol and type B pattern of LDL distribution [32,33]. Despite the undisputable causal role of elevated LDL-C in patients with DM [34], TG-enriched lipoproteins were significantly elevated while plasma levels of LDL-C were usually within the normal range [12].…”