The predictive utility of circulating PCSK9 levels on diabetes mellitus

Jia, Peng; Zhu, Cheng‐Gang; Li, Jianjun

doi:10.1186/s12933-021-01226-5

Cited by 5 publications

(3 citation statements)

References 9 publications

(13 reference statements)

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“…Third, although we could speculate on the neutralizing function of the PCSK9-Abs, it remains unclear. Fourth, although it has been reported that the concentration of circulating PCSK9 might be a predictor for the development of type 2 DM 31 , we could not follow up the HD population; consequently, we do not know whether their PCSK9-Ab levels will relate with the new onset of diabetes in this population.…”

Section: Discussionmentioning

confidence: 95%

Association of high proprotein convertase subtilisin/kexin type 9 antibody level with poor prognosis in patients with diabetes: a prospective study

Yamagata

Hayashi

Yoshida

et al. 2023

Sci Rep

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In addition to pathogenic autoantibodies, polyclonal autoantibodies with unknown physiological roles and pathogenicity are produced in the body. Moreover, serum antibodies against the proprotein convertase subtilisin/kexin type 9 (PCSK9) protein, which is integral to cholesterol metabolism, have also been observed. PCSK9 was also reported to be associated with insulin secretion and diabetes mellitus (DM). Therefore, we aimed to examine the clinical significance of PCSK9 antibodies (PCSK9-Abs) levels. We measured blood PCSK9-Abs and PCSK9 protein levels in 109 healthy donors (HDs) and 274 patients with DM (type 2 DM: 89.8%) using an amplified luminescence proximity homogeneous assay-linked immunosorbent assay. Subsequently, patients with DM were followed up (mean: 4.93 years, standard deviation: 2.77 years, maximum: 9.58 years, minimum: 0.07 years) to examine associations between antibody titers and mortality, myocardial infarction, stroke onset, and cancer. The primary endpoint of this study was to examine whether PCSK9-Abs can be a prognostic marker for overall mortality among the patients with diabetes. The secondary endpoint was to examine the relationship between PCSK9-Abs and clinical parameters. Although both PCSK9-Abs and PCSK9 protein levels were significantly higher in the DM group than in the HD group (p < 0.008), PCSK9-Abs and PCSK9 protein levels showed no correlation in either group. Mortality was significantly associated with higher PCSK9-Ab levels, but unrelated to PCSK9 protein levels. After investigating for potential confounding factors, higher PCSK9-Ab levels were still associated with increased mortality among the patients with DM. PCSK9-Abs may be a novel prognostic marker for overall mortality in patients with diabetes, and further studies are warranted to verify its usefulness.

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Section: Discussionmentioning

confidence: 95%

Association of high proprotein convertase subtilisin/kexin type 9 antibody level with poor prognosis in patients with diabetes: a prospective study

Yamagata

Hayashi

Yoshida

et al. 2023

Sci Rep

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“…13 Emerging data suggest PCSK9 as a risk factor for type 2 diabetes mellitus (T2DM) with several preclinical and clinical studies indicating a role for this molecule in glycometabolic disturbances and as a predictor of CV outcome in diabetic patients with coronary artery disease (CAD). [14][15][16] Yet, reports are often conflicting and whether PCSK9 levels could work as a reliable marker of vascular stiffness in such population remains unclear. 17 The aim of the present study is to evaluate the associations between circulating PCSK9 levels and arterial stiffness assessed as carotid-femoral PWV.…”

Section: Introductionmentioning

confidence: 99%

“…Emerging data suggest PCSK9 as a risk factor for type 2 diabetes mellitus (T2DM) with several preclinical and clinical studies indicating a role for this molecule in glycometabolic disturbances and as a predictor of CV outcome in diabetic patients with coronary artery disease (CAD) 14–16 …”

Section: Introductionmentioning

confidence: 99%

Serum proprotein convertase subtilisin/Kexin type 9 and vascular disease in type 2 diabetic patients

Armentaro

Carbone

Cassano

et al. 2022

Eur J Clin Investigation

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Background Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) levels have been suggested as novel atherosclerotic biomarker. PCSK9 plays important roles in the pathogenesis of atherosclerosis by regulating the degradation of low‐density lipoprotein receptor as well as different inflammatory pathways. Considering the important prognostic role of arterial stiffness in cardiovascular disease (CVD), the aim of the study is to investigate the correlation between PCSK9 levels and arterial stiffness in a cohort of diabetic patients, without previous CV events. Methods This cross‐sectional analysis enrolled 401 Caucasian patients with type II diabetes mellitus (T2DM). PCSK9 levels were measured by ELISA test, arterial stiffness was estimated by measuring carotid‐femoral pulse wave velocity (PWV). Results Patients were divided in three tertiles according to increasing value of PCSK9. From the I to the III tertiles, there was a significant increase in high sensitivity C‐reactive protein (hs‐CRP), fibrinogen and white blood cells (WBC) and a reduction in estimated glomerular filtration rate (e‐GFR). Patients with higher levels of PCSK9 presented increased systolic, diastolic blood pressure, pulse pressure and PWV. PWV was significantly and directly correlated with PCSK9, fibrinogen, age, BMI and PP, and indirectly correlated with diet, lifestyle and e‐GFR. Serum PCSK9 was the major predictor of PWV, justifying a 16.9% of its variation. Conclusion Our study demonstrates a close association between circulating PCSK9 levels and PWV in T2DM subjects without previous CV events even after adjusting for well‐known CV risk factor and pharmacological medications. Serum PCSK9 could be a useful biomarker for CV risk stratification in diabetic subjects.

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Increased serum PCSK9 levels are associated with renal function impairment in patients with type 2 diabetes mellitus

Feng,

Liao,

Zhang

et al. 2023

Renal Failure

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Purpose The purpose of this study was to investigate the association between serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels and renal function impairment in type 2 diabetes mellitus (T2DM) patients. Methods PCSK9 levels were measured in T2DM patients, streptozotocin plus high-fat diet (STZ + HFD) mice, human proximal tubular epithelial (HK-2) cells treated with high glucose plus palmitic acid (HGPA) and the corresponding control groups. The T2DM patients were further divided into three groups according to serum PCSK9 levels. An analysis of clinical data was conducted, and a binary logistic regression model was used to test the relationship between potential predictors and urine albumin/urine creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). Results PCSK9 levels were higher in the DM group than in the control group in humans, mice and HK-2 cells. The systolic blood pressure (SBP), serum creatinine (Scr), blood urea nitrogen (BUN), triglyceride (TG), and urine α1-MG/urine creatinine ratio (UαCR) values in PCSK9 tertile 3 were significantly higher than those in PCSK9 tertile 1 ( p < 0.05). The DBP and UACR values were significantly higher in PCSK9 tertile 3 than in PCSK9 tertile 1 and PCSK9 tertile 2 (both p < 0.05). In addition, URCR values were significantly higher in PCSK9 tertile 3 and PCSK9 tertile 2 than in PCSK9 tertile 1 (both p < 0.05). Serum PCSK9 levels were positively correlated with SBP, Scr, BUN, TG, URCR, UαCR and UACR but inversely correlated with eGFR. In STZ + HFD mice, serum PCSK9 levels were positively correlated with Scr, BUN and UACR, which was consistent with the findings in the patients. A logistic regression model revealed that serum PCSK9 is an independent risk factor for UACR ≥30 mg/g and eGFR <60 mL/min/1.73 m 2 . The ROC curve showed that 170.53 ng/mL and 337.26 ng/mL PCSK9 were the best cutoff values for UACR ≥30 mg/g and eGFR <60 mL/min/1.73 m 2 , respectively. Conclusion Serum PCSK9 levels are associated with renal function impairment in T2DM patients and in some patients lower PCSK9 may be helpful to decrease chronic kidney disease.

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The predictive utility of circulating PCSK9 levels on diabetes mellitus

Cited by 5 publications

References 9 publications

Association of high proprotein convertase subtilisin/kexin type 9 antibody level with poor prognosis in patients with diabetes: a prospective study

Association of high proprotein convertase subtilisin/kexin type 9 antibody level with poor prognosis in patients with diabetes: a prospective study

Serum proprotein convertase subtilisin/Kexin type 9 and vascular disease in type 2 diabetic patients

Increased serum PCSK9 levels are associated with renal function impairment in patients with type 2 diabetes mellitus

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