Lin Jennie, Reilly Muredach P, Terembula Karen, Wilson F Perry
Renal Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States of America.
PLoS One. 2014 Dec 9;9(12):e114397. doi: 10.1371/journal.pone.0114397. eCollection 2014.
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.
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.
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.
Elevated Lp(a) levels have a robust association with mild GFR impairment in type 2 diabetics independent of race, insulin resistance, and albuminuria.
慢性肾脏病（CKD）是心血管疾病的独立危险因素，会增加2型糖尿病（T2DM）患者的死亡率。治疗可改变的心血管风险因素可降低微量白蛋白尿糖尿病患者的死亡率，但仅根据肾小球滤过率（GFR）标准进行早期心血管预防在轻度CKD糖尿病患者中的作用仍不明确。本研究的目的是探讨与肾功能正常的糖尿病患者相比，轻度GFR受损的T2DM患者是否具有致动脉粥样硬化的血脂谱。
在宾夕法尼亚糖尿病心脏研究（PDHS）中，对一组无临床心血管疾病的T2DM患者进行单中心观察性队列研究，对1852例根据CKD-EPI方程确定的估算肾小球滤过率（eGFR）>60 mL/min/1.73 m²的受试者（n = 1852）直接测量的血脂成分进行横断面分析。在增量线性和逻辑回归模型中（以eGFR 90 mL/min/1.73 m²为切点），对eGFR与对数转换后的血脂参数进行未调整和多变量分析。
即使在对人口统计学、药物、代谢参数和白蛋白尿进行全面调整后，轻度GFR受损（eGFR 60 - 90 mL/min/1.73 m²，尿白蛋白肌酐比值（ACR）中位数为5.25 mg/g）仍与对数转换后的脂蛋白（a）[Lp(a)]值升高相关（比值比[OR]为1.17，p = 0.005），且与临床致动脉粥样硬化的Lp(a)水平高于30 mg/dL相关（OR为1.35，p = 0.0!13）。逻辑回归显示，在完全调整模型中，肾功能越差与载脂蛋白B（apoB）（p = 0.17）以及载脂蛋白C-III（apoC-III）（p = 0.067）之间存在显著趋势。
在2型糖尿病患者中，Lp(a)水平升高与轻度GFR受损密切相关，且不受种族、胰岛素抵抗和白蛋白尿的影响。
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