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Obesity and type 2 diabetes are associated with elevated PCSK9 levels in young women.

ABSTRACT: BACKGROUND:Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein cholesterol and cardiovascular disease risk, and is an emerging therapeutic target. OBJECTIVE:We compared serum PCSK9 levels in young adults, with and without type 2 diabetes. SUBJECTS AND METHODS:Cross-sectional analysis was conducted in a cohort, aged 15 to 26?years, in Cincinnati, OH, from 2005 to 2010. Serum PCSK9 levels were measured in 94 youth with type 2 diabetes, 93 obese control subjects, and 99 lean control subjects. Correlative analyses were conducted to determine significant covariates of PCSK9 by group and sex, and multivariate linear regression models were used to study the independent determinants of PCSK9. RESULTS:In females, PCSK9 levels were significantly increased in the obese and type 2 diabetes subjects relative to the lean controls (P?

SUBMITTER: Levenson AE

PROVIDER: S-EPMC5513789 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Obesity and type 2 diabetes are associated with elevated PCSK9 levels in young women.

Levenson Amy E AE Shah Amy S AS Khoury Philip R PR Kimball Thomas R TR Urbina Elaine M EM de Ferranti Sarah D SD Maahs David M DM Dolan Lawrence M LM Wadwa R Paul RP Biddinger Sudha B SB

Pediatric diabetes 20170117 8

<h4>Background</h4>Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of low-density lipoprotein cholesterol and cardiovascular disease risk, and is an emerging therapeutic target.<h4>Objective</h4>We compared serum PCSK9 levels in young adults, with and without type 2 diabetes.<h4>Subjects and methods</h4>Cross-sectional analysis was conducted in a cohort, aged 15 to 26 years, in Cincinnati, OH, from 2005 to 2010. Serum PCSK9 levels were measured in 94 youth with type 2 di ...[more]

PMID: 28093849

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Project description:PurposeThe 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.MethodsPCSK9 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).ResultsPCSK9 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 m2. 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 m2, respectively.ConclusionSerum 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.

Dataset Information

Obesity and type 2 diabetes are associated with elevated PCSK9 levels in young women.

Publications

Obesity and type 2 diabetes are associated with elevated PCSK9 levels in young women.

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