Longitudinal assessment of N-terminal pro-B-type natriuretic peptide and risk of diabetes in older adults

The cardiovascular health study

Erika F. Brutsaert, Mary L. Biggs, Joseph A. Delaney, Luc Djoussé, John S. Gottdiener, Joachim H. Ix, Francis Kim, Kenneth J. Mukamal, David S. Siscovick, Russell P. Tracy, Ian H. de Boer, Christopher R. deFilippi, Jorge Kizer

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Introduction Natriuretic peptides have a well-recognized role in cardiovascular homeostasis. Recently, higher levels of B-type natriuretic peptide (BNP) have also been associated with decreased risk of diabetes in middle-aged adults. Whether this association persists into older age, where the pathophysiology of diabetes changes, has not been established, nor has its intermediate pathways. Methods We investigated the relationship between N-terminal (NT)-proBNP and incident diabetes in 2359 older adults free of cardiovascular disease or chronic kidney disease in the Cardiovascular Health Study. Results We documented 348 incident cases of diabetes over 12.6 years of median follow-up. After adjusting for age, sex, race, body mass index, systolic blood pressure, anti-hypertensive treatment, smoking, alcohol use, and LDL, each doubling of NT-proBNP was associated with a 9% lower risk of incident diabetes (HR = 0.91 [95% CI: 0.84–0.99]). Additional adjustment for waist circumference, physical activity, estimated glomerular filtration rate or C-reactive protein did not influence the association. Among putative mediators, HDL and triglycerides, adiponectin, and especially homeostasis model assessment of insulin resistance, all appeared to account for a portion of the lower risk associated with NT-proBNP. Conclusion In older adults without prevalent cardiovascular or kidney disease, higher NT-proBNP is associated with decreased risk of incident diabetes even after adjustment for traditional risk factors. These findings suggest that the metabolic effects of natriuretic peptides persist late in life and offer a potential therapeutic target for prevention of diabetes in older people.

Original languageEnglish (US)
Pages (from-to)1489-1497
Number of pages9
JournalMetabolism: Clinical and Experimental
Volume65
Issue number10
DOIs
StatePublished - Oct 1 2016

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Brain Natriuretic Peptide
Natriuretic Peptides
Health
Homeostasis
Cardiovascular Diseases
Blood Pressure
Adiponectin
Kidney Diseases
Waist Circumference
Glomerular Filtration Rate
Chronic Renal Insufficiency
C-Reactive Protein
Antihypertensive Agents
Insulin Resistance
Triglycerides
Body Mass Index
Smoking
Alcohols
Exercise
pro-brain natriuretic peptide (1-76)

Keywords

  • BNP
  • Diabetes
  • Elders
  • Natriuretic peptide

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Longitudinal assessment of N-terminal pro-B-type natriuretic peptide and risk of diabetes in older adults : The cardiovascular health study. / Brutsaert, Erika F.; Biggs, Mary L.; Delaney, Joseph A.; Djoussé, Luc; Gottdiener, John S.; Ix, Joachim H.; Kim, Francis; Mukamal, Kenneth J.; Siscovick, David S.; Tracy, Russell P.; de Boer, Ian H.; deFilippi, Christopher R.; Kizer, Jorge.

In: Metabolism: Clinical and Experimental, Vol. 65, No. 10, 01.10.2016, p. 1489-1497.

Research output: Contribution to journalArticle

Brutsaert, EF, Biggs, ML, Delaney, JA, Djoussé, L, Gottdiener, JS, Ix, JH, Kim, F, Mukamal, KJ, Siscovick, DS, Tracy, RP, de Boer, IH, deFilippi, CR & Kizer, J 2016, 'Longitudinal assessment of N-terminal pro-B-type natriuretic peptide and risk of diabetes in older adults: The cardiovascular health study', Metabolism: Clinical and Experimental, vol. 65, no. 10, pp. 1489-1497. https://doi.org/10.1016/j.metabol.2016.06.002
Brutsaert, Erika F. ; Biggs, Mary L. ; Delaney, Joseph A. ; Djoussé, Luc ; Gottdiener, John S. ; Ix, Joachim H. ; Kim, Francis ; Mukamal, Kenneth J. ; Siscovick, David S. ; Tracy, Russell P. ; de Boer, Ian H. ; deFilippi, Christopher R. ; Kizer, Jorge. / Longitudinal assessment of N-terminal pro-B-type natriuretic peptide and risk of diabetes in older adults : The cardiovascular health study. In: Metabolism: Clinical and Experimental. 2016 ; Vol. 65, No. 10. pp. 1489-1497.
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abstract = "Introduction Natriuretic peptides have a well-recognized role in cardiovascular homeostasis. Recently, higher levels of B-type natriuretic peptide (BNP) have also been associated with decreased risk of diabetes in middle-aged adults. Whether this association persists into older age, where the pathophysiology of diabetes changes, has not been established, nor has its intermediate pathways. Methods We investigated the relationship between N-terminal (NT)-proBNP and incident diabetes in 2359 older adults free of cardiovascular disease or chronic kidney disease in the Cardiovascular Health Study. Results We documented 348 incident cases of diabetes over 12.6 years of median follow-up. After adjusting for age, sex, race, body mass index, systolic blood pressure, anti-hypertensive treatment, smoking, alcohol use, and LDL, each doubling of NT-proBNP was associated with a 9{\%} lower risk of incident diabetes (HR = 0.91 [95{\%} CI: 0.84–0.99]). Additional adjustment for waist circumference, physical activity, estimated glomerular filtration rate or C-reactive protein did not influence the association. Among putative mediators, HDL and triglycerides, adiponectin, and especially homeostasis model assessment of insulin resistance, all appeared to account for a portion of the lower risk associated with NT-proBNP. Conclusion In older adults without prevalent cardiovascular or kidney disease, higher NT-proBNP is associated with decreased risk of incident diabetes even after adjustment for traditional risk factors. These findings suggest that the metabolic effects of natriuretic peptides persist late in life and offer a potential therapeutic target for prevention of diabetes in older people.",
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AU - Djoussé, Luc

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AU - Mukamal, Kenneth J.

AU - Siscovick, David S.

AU - Tracy, Russell P.

AU - de Boer, Ian H.

AU - deFilippi, Christopher R.

AU - Kizer, Jorge

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N2 - Introduction Natriuretic peptides have a well-recognized role in cardiovascular homeostasis. Recently, higher levels of B-type natriuretic peptide (BNP) have also been associated with decreased risk of diabetes in middle-aged adults. Whether this association persists into older age, where the pathophysiology of diabetes changes, has not been established, nor has its intermediate pathways. Methods We investigated the relationship between N-terminal (NT)-proBNP and incident diabetes in 2359 older adults free of cardiovascular disease or chronic kidney disease in the Cardiovascular Health Study. Results We documented 348 incident cases of diabetes over 12.6 years of median follow-up. After adjusting for age, sex, race, body mass index, systolic blood pressure, anti-hypertensive treatment, smoking, alcohol use, and LDL, each doubling of NT-proBNP was associated with a 9% lower risk of incident diabetes (HR = 0.91 [95% CI: 0.84–0.99]). Additional adjustment for waist circumference, physical activity, estimated glomerular filtration rate or C-reactive protein did not influence the association. Among putative mediators, HDL and triglycerides, adiponectin, and especially homeostasis model assessment of insulin resistance, all appeared to account for a portion of the lower risk associated with NT-proBNP. Conclusion In older adults without prevalent cardiovascular or kidney disease, higher NT-proBNP is associated with decreased risk of incident diabetes even after adjustment for traditional risk factors. These findings suggest that the metabolic effects of natriuretic peptides persist late in life and offer a potential therapeutic target for prevention of diabetes in older people.

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