Abstract
BackgroundCKD, 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.MethodsIn 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.ResultsMild 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.ConclusionsElevated Lp(a) levels have a robust association with mild GFR impairment in type 2 diabetics independent of race, insulin resistance, and albuminuria.
Highlights
Affecting over 20 million patients in the United States alone, chronic kidney disease (CKD) is an independent risk factor for cardiovascular (CV) disease and increased CV mortality [1,2,3,4]
The purpose of this study was to probe whether type 2 diabetes mellitus (T2DM) patients with mild GFR impairment have atherogenic lipid profiles compared to diabetic counterparts with normal renal function
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 estimated glomerular filtration rate (eGFR).60 mL/ min/1.73 m2 determined by the CKD-EPI equation (n51852)
Summary
Affecting over 20 million patients in the United States alone, chronic kidney disease (CKD) is an independent risk factor for cardiovascular (CV) disease and increased CV mortality [1,2,3,4]. CKD has been shown to be the predominant contributor to mortality among patients with type 2 diabetes mellitus (T2DM) [5], which still carries a high absolute risk of CV mortality despite more aggressive treatment of modifiable risk factors [1, 6,7,8,9,10]. The role of early CV prevention for T2DM patients with mild GFR impairment (eGFR 60–90 mL/min/ 1.73 m2) in the absence of albuminuria remains unclear Understudied, this group of diabetics without microalbuminuria does not meet current definitions of CKD and is not considered to be at increased CV risk [2,3,4, 11, 12]. 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. Logistic regression demonstrated a trend towards significance between worse kidney function and apoB (p50.17) as well as apoC-III (p50.067) in the fully adjusted model
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