Lack of association between plasma PCSK9 and LDL-apoB100 catabolism in patients with uncontrolled type 2 diabetes

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• 作者：Bruno  ; Verg&egrave ; s^a ;   ; ^{bruno.verges@chu-dijon.fr} ; Laurence  ; Duvillard^a ; Marie Claude  ; Brindisi^a ; Emmanuel  ; Gautier^c ; Michel  ; Krempf^b ;   ; ^c ;   ; ^d ; Philippe  ; Costet^b ;   ; ^c ; Bertrand  ; Cariou^b ;   ; ^c ;   ; ^d
• 关键词：Lipoprotein kinetics ; PCSK9 ; Diabetes ; LDL catabolism ; Apolipoprotein B
• 刊名：Atherosclerosis
• 出版年：2011
• 出版时间：November 2011
• 年：2011
• 卷：219
• 期：1
• 页码：342-348
• 全文大小：224 K

文摘

Objective

Pro-protein convertase subtilisin/kexin type 9 (PCSK9) is a post-transcriptional inhibitor of LDL-receptor. In non-diabetic men, plasma PCSK9 levels were found to be inversely correlated with low-density lipoprotein (LDL) apolipoprotein B100 (apoB) fractional catabolic rate (FCR). Here, we aimed to determine the effect of type 2 diabetes on the association between plasma PCSK9 and FCR of LDL.

Methods

A kinetic study of LDL-apoB100, using stable isotopes, was performed in 38 individuals (20 men, 18 women) including 23 non-diabetic normolipidemic subjects and 15 patients with type 2 diabetes.

Results

In the non-diabetic group, plasma PCSK9 was positively correlated with LDL-C (r = 0.64, p = 0.001), apoB (r = 0.67, p < 0.001), and inversely correlated with LDL-apoB FCR (r = ?.61, p = 0.002). In contrast, in type 2 diabetic patients, plasma PCSK9 was not associated with LDL-C, apoB and LDL-apoB FCR. However, the lack of association between PCSK9 and LDL-apoB FCR seemed to be limited to the patients with ¡°uncontrolled?diabetes (HbA1c > 7 % ) since a borderline significant negative correlation between PCSK9 and LDL FCR (r = ?.70, p = 0.08) was retrieved in patients with HbA1c ?7 % . In multivariate analysis, LDL-apoB FCR was independently associated with PCSK9 (p = 0.001) and fasting glycaemia (log) (p = 0.030) in the non-diabetic population and with PCSK9 (p = 0.040) and HbA1c (p = 0.029) in diabetic patients.

Conclusion

Our data indicate that both PCSK9 and glycaemia are independent factors influencing LDL catabolism. Plasma PCSK9 influences significantly the catabolism of LDL-apoB100 in individuals without diabetes, but not in patients with uncontrolled type 2 diabetes. Thus, the influence of diabetes on LDL-apoB FCR catabolism may overwhelm the influence of PCSK9.