Inverse Association of Lipoprotein (a) With Markers of Insulin Resistance in Dyslipidemic Subjects

Abstract

Lipoprotein (a) [Lp(a)] is an LDL-like particle that contains an apolipoprotein B100 molecule covalently bound to a plasminogen-like glycoprotein, apolipoprotein (a) [apo(a)]. Epidemiological evidence supports a direct and causal association between Lp(a) levels and coronary risk. On the contrary, a few prospective findings demonstrate inverse association of Lp(a) levels with risk of type 2 diabetes (T2DM). The aim of our study was to evaluate the association of Lp(a) with indicators of insulin resistance (IR) and metabolic syndrome (MS), which precede development of T2DM. We enrolled 607 asymptomatic dyslipidemic subjects (295 men and 312 women, mean age 45.6±14.0 years) into our cross-sectional study. Lp(a) concentrations correlated inversely with TG, AIP, insulin, HOMA, C-peptide, BMI, waist circumference, and number of MS components (p<0.01 for all). Subjects with MS had significantly lower Lp(a) concentrations in comparison with those without the presence of this phenotype (p<0.0001). Serum concentrations of Lp(a) in the lower (1th-3rd) quartiles of insulin and HOMA were significantly higher than in the 4th quartile of these insulin resistance markers (p<0.001). Odds ratios of having increased markers of IR (TG, HOMA) and MS in top quartile of Lp(a) also indicate inverse association of Lp(a) with IR. The results of our study support an inverse association of Lp(a) levels with IR and MS that precedes overt T2DM diagnosis.

Biomarker potential of C-peptide for screening of insulin resistance in diabetic and non-diabetic individuals

“…Borai et al (2011) have shown that HbA1c may serve as a simple and reliable marker for IR in adults with normal glucose tolerance. Vaverková et al (2017) observed an inverse association between lipoprotein-a and IR as well as metabolic syndrome that precedes an overt T2DM diagnosis.…”

Sleep Duration, Lipid Profile and Insulin Resistance: Potential Role of Lipoprotein(a)

“…Although no consensus goal of Lp(a) is established, the general recommendation is to treat other cardiovascular risk factors in patients with high Lp(a) in combination with other hypolipidemic and glucose-lowering drugs [ 2 , 15 ]. At the same time, recent studies have demonstrated that, while increased Lp(a) levels are associated with enhanced atherogenesis, proinflammatory and prothrombotic states [ 16 ], a greater risk of cardiovascular events, and poorer prognosis [ 2 , 15 , 17 , 18 ], the decreased serum concentrations of Lp(a) are related to the insulin resistance state [ 19 ]. These findings suggest that any shift (either to increase or decrease) of Lp(a) might be associated with an unfavorable outcome and should be monitored, so the association between Lp(a) levels and cardiometabolic disease might be U-shaped.…”

In search of a physiological function of lipoprotein(a): causality of elevated Lp(a) levels and reduced incidence of type 2 diabetes

“…T2D can have a lag phase of 10-20 years before it is diagnosed, and in the preceding timespan, patients will develop insulin resistance and elevated insulin levels. Several studies have shown an inverse association between insulin levels and Lp(a) levels (11), even before a frank diagnosis of T2D is made (12,13). Furthermore, physiological doses of insulin have been suggested to suppress apolipoprotein(a) mRNA and protein production in cynomolgous monkey hepatocytes (14).…”