title: Cardiac natriuretic peptides, obesity, and insulin resistance: evidence from two community-based studies.
abstract: BACKGROUND
  The natriuretic peptides play an important role in salt homeostasis and blood pressure regulation. It has been suggested that obesity promotes a relative natriuretic peptide deficiency, but this has been a variable finding in prior studies and the cause is unknown.
  
  
  OBJECTIVE
  The aim of this study was to examine the association between obesity and natriuretic peptide levels and evaluate the role of hyperinsulinemia and testosterone as mediators of this interaction.
  
  
  METHODS
  We studied 7770 individuals from the Framingham Heart Study (n = 3833, 54% women) and the Malmö Diet and Cancer study (n = 3918, 60% women). We examined the relation of plasma N-terminal pro-B-type natriuretic peptide levels (N-BNP) with obesity, insulin resistance, and various metabolic subtypes.
  
  
  RESULTS
  Obesity was associated with 6-20% lower levels of N-BNP (P < 0.001 in Framingham, P = 0.001 in Malmö), whereas insulin resistance was associated with 10-30% lower levels of N-BNP (P < 0.001 in both cohorts). Individuals with obesity who were insulin sensitive had only modest reductions in N-BNP compared with nonobese, insulin-sensitive individuals. On the other hand, individuals who were nonobese but insulin resistant had 26% lower N-BNP in Framingham (P < 0.001) and 10% lower N-BNP in Malmö (P < 0.001), compared with nonobese and insulin-sensitive individuals. Adjustment for serum-free testosterone did not alter these associations.
  
  
  CONCLUSIONS
  In both nonobese and obese individuals, insulin resistance is associated with lower natriuretic peptide levels. The relative natriuretic peptide deficiency seen in obesity could be partly attributable to insulin resistance, and could be one mechanism by which insulin resistance promotes hypertension.
authors.affiliation: Cardiology Division, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Abigail May
authors.initials: AM
authors.lastname: Khan
authors.forename: Susan
authors.initials: S
authors.lastname: Cheng
authors.forename: Martin
authors.initials: M
authors.lastname: Magnusson
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Elizabeth L
authors.initials: EL
authors.lastname: McCabe
authors.forename: Andrea D
authors.initials: AD
authors.lastname: Coviello
authors.forename: Jose C
authors.initials: JC
authors.lastname: Florez
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.forename: Daniel
authors.initials: D
authors.lastname: Levy
authors.forename: Sander J
authors.initials: SJ
authors.lastname: Robins
authors.forename: Pankaj
authors.initials: P
authors.lastname: Arora
authors.forename: Shalender
authors.initials: S
authors.lastname: Bhasin
authors.forename: Carolyn S P
authors.initials: CS
authors.lastname: Lam
authors.forename: Ramachandran S
authors.initials: RS
authors.lastname: Vasan
authors.forename: Olle
authors.initials: O
authors.lastname: Melander
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Wang
mesh_terms: D000328:Adult; D000728:Androgens / Q000097:blood; D015992:Body Mass Index; D015331:Cohort Studies; D004032:Diet; D005260:Female; D006801:Humans; D006946:Hyperinsulinism / Q000150:complications; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain / Q000097:blood; D045265:Natriuretic Peptides / Q000378:metabolism*; D009765:Obesity / Q000453:epidemiology / Q000378:metabolism*; D011237:Predictive Value of Tests; D013739:Testosterone / Q000097:blood
chemical_list: D000728:Androgens; D045265:Natriuretic Peptides; D020097:Natriuretic Peptide, Brain; D013739:Testosterone