Plasma lipoprotein(a) levels are associated with mild renal impairment in type 2 diabetics independent of albuminuria

Abstract

Background: CKD, an independent risk factor for CV disease, increases mortality in T2DM. Treating modifiable CV risk factors decreases mortality in diabetics with microalbuminuria, but the role of early CV prevention in diabetics with mild CKD by GFR criteria alone remains unclear. The purpose of this study was to probe whether T2DM patients with mild GFR impairment have atherogenic lipid profiles compared to diabetic counterparts with normal renal function.

Methods: In the Penn Diabetes Heart Study (PDHS), a single-center observational cohort of T2DM patients without clinical CVD, cross-sectional analyses were performed for directly measured lipid fractions in 1852 subjects with eGFR>60 mL/min/1.73 m² determined by the CKD-EPI equation (n = 1852). Unadjusted and multivariable analyses of eGFR association with log-transformed lipid parameters in incremental linear and logistic regression models (with eGFR 90 mL/min/1.73 m² as a cut-point) were performed.

Results: Mild GFR impairment (eGFR 60-90 mL/min/1.73 m², median urinary ACR 5.25 mg/g) was associated with higher log-transformed Lp(a) values (OR 1.17, p = 0.005) and with clinically atherogenic Lp(a) levels above 30 mg/dL (OR 1.35, p = 0.013) even after full adjustment for demographics, medications, metabolic parameters, and albuminuria. Logistic regression demonstrated a trend towards significance between worse kidney function and apoB (p = 0.17) as well as apoC-III (p = 0.067) in the fully adjusted model.

Conclusions: Elevated Lp(a) levels have a robust association with mild GFR impairment in type 2 diabetics independent of race, insulin resistance, and albuminuria.

Figure 1. Odds of Lower eGFR Category by Lipid Parameters.

Multivariable analysis adjusted for the following co-variates: age, race, gender, body mass index, hypertension (definition includes use of anti-hypertensive medications), use of lipid-lowering medication, hemoglobin A1c, HOMA-IR, duration on insulin, urinary albumin to creatinine ratio. Abbreviations: TC total cholesterol, HDL-C high density lipoprotein cholesterol, LDL-C low density lipoprotein cholesterol, VLDL-C very low density lipoprotein cholesterol, TG trigylcerides, Lp(a) lipoprotein(a), apoA-I apolipoprotein A-I, apoA-II apolipoprotein A-II, apoB apolipoprotein B, apoC-III apolipoprotein C-III, apoE apolipoprotein E, FFA free fatty acids.