Brain natriuretic peptide and insulin resistance in older adults.
Higher levels of brain natriuretic peptide (BNP) have been associated with a decreased risk of diabetes in adults, but whether BNP is related to insulin resistance in older adults has not been established.



N-terminal of the pro hormone brain natriuretic peptide (NT-pro BNP) was measured among Cardiovascular Health Study participants at the 1989-1990, 1992-1993 and 1996-1997 examinations. We calculated measures of insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Gutt index, Matsuda index] from fasting and 2-h concentrations of glucose and insulin among 3318 individuals with at least one measure of NT-proBNP and free of heart failure, coronary heart disease and chronic kidney disease, and not taking diabetes medication. We used generalized estimating equations to assess the cross-sectional association of NT-proBNP with measures of insulin resistance. Instrumental variable analysis with an allele score derived from nine genetic variants (single nucleotide polymorphisms) within or near the NPPA and NPPB loci was used to estimate an un-confounded association of NT-proBNP levels on insulin resistance.



Lower NT-proBNP levels were associated with higher insulin resistance even after adjustment for BMI, waist circumference and other risk factors (P < 0.001 for all four indices). Although the genetic score was strongly related to measured NT-proBNP levels amongst European Americans (F statistic = 71.08), we observed no association of genetically determined NT-proBNP with insulin resistance (P = 0.38; P = 0.01 for comparison with the association of measured levels of NT-proBNP).



In older adults, lower NT-proBNP is associated with higher insulin resistance, even after adjustment for traditional risk factors. Because related genetic variants were not associated with insulin resistance, the causal nature of this association will require future study.
Department of Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
F
F
Kim
Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA.
M L
ML
Biggs
Department of Medicine and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, NY, USA.
J R
JR
Kizer
Department of Medicine and Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, NY, USA.
E F
EF
Brutsaert
School of Medicine, University of Maryland, Baltimore, MD, USA.
C
C
de Filippi
Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA.
A B
AB
Newman
Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seattle, WA, USA.
R A
RA
Kronmal
Department of Pathology and Biochemistry, University of Vermont, College of Medicine, Burlington, VT, USA.
R P
RP
Tracy
School of Medicine, University of Maryland, Baltimore, MD, USA.
J S
JS
Gottdiener
Division of Aging, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
L
L
Djoussé
Department of Medicine, School of Medicine, University of Washington, Seattle, WA, USA.
I H
IH
de Boer
Cardiovascular Health Research Unit, Department of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA, USA.|Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA.
B M
BM
Psaty
New York Academy of Medicine, New York, NY.
D S
DS
Siscovick
Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA, USA.
K J
KJ
Mukamal
D001741:Black or African American / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D009320:Atrial Natriuretic Factor / Q000235:genetics; D001786:Blood Glucose / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005215:Fasting; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000235:genetics*; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
D001786:Blood Glucose; D007328:Insulin; C472955:NPPA protein, human; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor