Changes in N-terminal pro-B-type natriuretic peptide and incidence of diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA)

Abstract

Aims This study looked at whether the inverse association of circulating N-terminal pro-B-type natriuretic peptide (NT-proBNP) with incident diabetes is modified by changes in NT-proBNP (ΔNT-proBNP) levels. Methods lasma NT-proBNP was assayed at baseline and 3.2 years later (visit 3) in the Multi-Ethnic Study of Atherosclerosis (MESA).ΔNT-proBNP was calculated as NT-proBNPvisit3 − NT-proBNPbaseline. A Poisson distribution was fitted to determine the incidence density of diabetes, adjusted for age, race, gender, educational attainment, antihypertensive medication, total intentional exercise and plasma IL-6 levels. In the primary analysis (n = 3236 without diabetes up to visit 3, followed for a mean of 6.3 years), incidence density was regressed for the following categories of baseline NT-proBNP: (1) <54.4 pg/mL; (2) 54.4–85.9 pg/mL; and (3) 86–54.2 pg/mL. This was crossed with categories of ΔNT-proBNP as medians (ranges): (1) −6.2 (−131–11.7) pg/mL; (2) 19.8 (11.8–30.1) pg/mL; (3) 44.0 (30.2–67.9) pg/mL; and (4) 111.2 (68.0–3749.9) pg/mL. Results The incidence density of diabetes followed a U-shaped association across categories of ΔNT-proBNP within categories of baseline NT-proBNP after adjusting for other covariates (P = 0.02). At each level of baseline NT-proBNP, the incidence density of diabetes was lowest for small-to-moderate increases in NT-proBNP. Conclusion This analysis suggests that NT-proBNP has a biphasic association with diabetes in which the risk of incident diabetes decreases within a ‘physiological range’ of ΔNT-proBNP, and plateaus or increases as NT-proBNP concentrations increase, probably in response to pathophysiological conditions leading to high levels of NT-proBNP.

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

“…33 Comparison of the upper versus the lowest three sextiles of baseline NT-proBNP was associated with a 32% lower adjusted risk of this outcome, but attenuation of the association occurred at levels toward the upper limit of the fifth sextile (>150 pg/ml), 33 consistent with similar flattening of NT-proBNP’s associations with metabolic risk factors as concentrations reached a higher range. 11, 12 The same study 33 reported a U-shaped association for subsequent 3-year interval change in NT-proBNP and diabetes. Taken together with the ARIC results, these findings are consistent with the adverse metabolic impact of pathologic elevations of NT-proBNP into the higher range, as compared with physiologic elevations.…”

Differences in Natriuretic Peptide Levels by Race/Ethnicity (From the Multi-Ethnic Study of Atherosclerosis)

“…1,2 Animal and human studies demonstrate that relative NP deficiencies are associated with the development of salt-sensitive hypertension, insulin resistance, diabetes mellitus, and obesity. 3–8 These cardiovascular risk factors disproportionately affect certain races/ethnicities, suggesting that relatively low NP concentrations may contribute to racial differences in susceptibility to cardiometabolic disease 9,10 However, whether NPs concentrations differ between racial/ethnic groups, with relatively low concentrations corresponding with those groups carrying the highest burden of cardiometabolic disease, has not been completely characterized. 11–13 Furthermore, a substantial proportion of the inter-individual variation in circulating NP concentrations has been attributed to genetic factors.…”

Computerized tomography measured liver fat is associated with low levels of N-terminal pro-brain natriuretic protein (NT-proBNP). Multi-Ethnic Study of Atherosclerosis

“…Low plasma NT-proBNP has been associated in cross sectional studies with greater BMI [5, 33], increased visceral adipose tissue [6], presence of metabolic syndrome [34, 35] and in longitudinal studies low levels of NT-proBNP have shown to be predictive of incident diabetes [8, 36-38]. The epidemiological associations between natriuretic peptides with obesity and incident diabetes could result from reverse causality.…”