title: 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.
  
  
  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 < .01). Moreover, PCSK9 was positively correlated with multiple metabolic parameters in females: body mass index, systolic blood pressure, fasting glucose, fasting insulin, and C-reactive protein levels (P ≤ .02). In males, PCSK9 levels were decreased overall compared with females (P = .03), and did not differ between the lean, obese, or type 2 diabetes groups.
  
  
  CONCLUSIONS
  Obesity and type 2 diabetes were associated with significantly higher levels of PCSK9 in young women, but not in young men. These data suggest that sex could modify the effects of obesity and diabetes on PCSK9 in young adults.
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Amy E
authors.initials: AE
authors.lastname: Levenson
authors.affiliation: Division of Endocrinology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio.
authors.forename: Amy S
authors.initials: AS
authors.lastname: Shah
authors.affiliation: Division of Cardiology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Khoury
authors.affiliation: Division of Cardiology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kimball
authors.affiliation: Division of Cardiology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Urbina
authors.affiliation: Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sarah D
authors.initials: SD
authors.lastname: de Ferranti
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: David M
authors.initials: DM
authors.lastname: Maahs
authors.affiliation: Division of Endocrinology, Cincinnati Children's Hospital Medical Center and University of Cincinnati, Cincinnati, Ohio.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Dolan
authors.affiliation: Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, Colorado.
authors.forename: R Paul
authors.initials: RP
authors.lastname: Wadwa
authors.affiliation: Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sudha B
authors.initials: SB
authors.lastname: Biddinger
mesh_terms: D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications; D005260:Female; D006801:Humans; D008297:Male; D009765:Obesity / Q000097:blood* / Q000150:complications; D000071449:Proprotein Convertase 9 / Q000097:blood*; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9
keywords: 
  LDL cholesterol; 
  PCSK9
  ; cardiovascular disease; type 2 diabetes; young adult