Brain natriuretic peptide and insulin resistance in older adults

• Published in: Diabetic medicine 2017-02, Vol.34 (2), p.235-238
• Main Authors: Kim, F., Biggs, M. L., Kizer, J. R., Brutsaert, E. F., Filippi, C., Newman, A. B., Kronmal, R. A., Tracy, R. P., Gottdiener, J. S., Djoussé, L., Boer, I. H., Psaty, B. M., Siscovick, D. S., Mukamal, K. J.
• Format: Article
• Language: English
• Subjects: African Americans - genetics; Aged; Aged, 80 and over; Atrial Natriuretic Factor - genetics; Blood Glucose - metabolism; Brain natriuretic peptide; Cardiovascular disease; Coronary artery disease; Cross-Sectional Studies; Diabetes; Diabetes mellitus; European Continental Ancestry Group - genetics; Fasting; Female; Genetic diversity; Glucose; Glucose Tolerance Test; Health risk assessment; Heart diseases; Humans; Insulin; Insulin - metabolism; Insulin resistance; Insulin Resistance - genetics; Male; Mathematical models; Natriuretic Peptide, Brain - genetics; Natriuretic Peptide, Brain - metabolism; Older people; Peptide Fragments - metabolism; Peptides; Polymorphism, Single Nucleotide; Risk factors; Single-nucleotide polymorphism
• ISSN: 0742-3071; 1464-5491
• DOI: 10.1111/dme.13139

Aims 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. Methods 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. Results 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). Conclusions 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. What's new? In older adults, lower N‐terminal pro‐brain natriuretic peptide is associated with markedly higher insulin resistance even after adjustment for traditional risk factors, but a genetic score using related variants was not.