Longitudinal assessment of N-terminal pro-B-type natriuretic peptide and risk of diabetes in older adults: The cardiovascular health study

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 have 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.

Natriuretic peptides in the control of lipid metabolism and insulin sensitivity

“…In the Atherosclerosis Risk in Communities Study (a community-based population study), it was shown that having low N-terminal proBNP levels (lowest quartile, <31 pg mL À1 ) was associated with higher risk of incident diabetes over a 12-year follow-up period in subjects without T2DM at baseline. These results were consistent across race, gender and BMI categories (26) and were independent of age (111,112). Of interest, statistical adjustment for BMI did not abrogate the association between low NP levels and diabetes onset (113).…”

“…Another way to link NPs to AT function is the ability of NPs to alter expression and secretion of adiponectin, an adipokine with insulin-sensitizing properties, both in vitro (156) and in vivo (157) in healthy subjects. Moreover, adiponectin is positively associated with NPs (100,111,158,159). Other insulin-desensitizing mediators frequently linked to NPs include tumour necrosis factor-α or interleukin 6.…”

Circulating B‐type natriuretic peptide in women with and without recent gestational diabetes: The impact of current glucose intolerance

“…This finding suggests that, at this early point in the natural history of cardiometabolic disease, the inverse relationship between NT‐proBNP and diabetic risk may predominate over the proposed cardiovascular implications of this biomarker. Notably, several studies have shown that low serum NT‐proBNP can predict incident T2DM . Moreover, a Mendelian randomization study by Pfisters et al demonstrated that a common genetic variant that leads to 20% higher serum BNP levels is associated with a 15% lower risk of T2DM, raising the possibility of a causal relationship.…”

“…Interestingly, it has recently been recognized that BNP also has metabolic implications . Most notably, low serum NT‐proBNP can predict the development of incident type 2 diabetes (T2DM) . Thus, an apparent paradox has emerged; wherein, NT‐proBNP is positively associated with future risk of CVD but inversely related to T2DM (which itself is a predictor of cardiovascular outcomes) …”

“…1 Most notably, low serum NT-proBNP can predict the development of incident type 2 diabetes (T2DM). [7][8][9] Thus, an apparent paradox has emerged; wherein, NT-proBNP is positively associated with future risk of CVD but inversely related to T2DM (which itself is a predictor of cardiovascular outcomes). 1 The diagnosis of gestational diabetes mellitus (GDM) identifies a population of young women who are at risk for the future development of both T2DM and CVD later in life.…”