Racial/ethnic differences in circulating natriuretic peptide levels: The Diabetes Prevention Program

Abstract

Natriuretic peptides are cardiac-derived hormones that enhance insulin sensitivity and reduce fat accumulation. Low natriuretic peptide levels are associated with increased risk of type 2 diabetes mellitus (DM2); a condition with variable prevalence across racial/ethnic groups. Few studies have examined whether circulating natriuretic peptide levels and their response to preventive interventions for DM2 differ by race/ethnicity. The Diabetes Prevention Program (DPP) is a clinical trial (July 31, 1996- July 31, 2001) that randomized participants to preventive interventions for DM2. Using stored serum samples, we examined N-terminus pro-B-type natriuretic peptide (NT-proBNP) levels in 3,220 individuals (56% white; 19% African-American; 15% Hispanic; 5% American-Indian; 5% Asian). The influence of race/ethnicity on NT-proBNP concentrations at baseline and after two years of treatment with placebo, lifestyle, or metformin was examined with multivariable-adjusted regression. At baseline, NT-proBNP differed significantly by race (P < .001), with the lowest values in African-American individuals. Hispanic individuals also had lower baseline NT-proBNP levels compared with whites (P< .001), while NT-proBNP levels were similar between white, American-Indian, and Asian individuals. At two years of follow-up, NT-proBNP levels decreased in African-Americans in each of the DPP study arms, whereas they were stable or increased in the other racial/ethnic groups. In the DPP, African-American individuals had lower circulating NT-proBNP levels compared with individuals in other racial/ethnic groups at baseline and after two years of preventive interventions. Further studies should examine the cardio-metabolic implications of lower natriuretic peptide levels in African-Americans. Trial Registration: ClinicalTrials.gov NCT00004992.

Fig 1. Baseline multivariable-adjusted least-square mean NT-proBNP levels in the DPP according to race/ethnicity.

Least square mean log_e NT-proBNP values (95% confidence interval) calculated from multivariable linear regression adjusted for: age, gender, body mass index, systolic blood pressure, diastolic blood pressure, history of hypertension, insulin sensitivity, estimated glomerular filtration rate, education and income. ANCOVA P < .005 considered statistically significant to account for multiple comparisons.

Fig 2. Multivariable adjusted percent differences in baseline NT-proBNP levels by race/ethnicity compared with white individuals in the DPP.

Percent difference (95% confidence interval) in NT-proBNP by race/ethnicity compared with white individuals. Values calculated from multivariable linear regression adjusted for: age, gender, body mass index, systolic blood pressure, diastolic blood pressure, history of hypertension, insulin sensitivity, estimated glomerular filtration rate, education and income. ANCOVA P < .005 considered statistically significant to account for multiple comparisons.

Fig 3. Multivariable adjusted percent change in NT-proBNP levels from baseline to two year follow up according to treatment randomization and race/ethnicity in the DPP.

Percent change in NT-proBNP values (95% confidence interval) calculated from multivariable linear regression adjusted for: age, gender, body mass index, systolic blood pressure, diastolic blood pressure, history of hypertension, insulin sensitivity, estimated glomerular filtration rate, education and income, and NT-proBNP measured at baseline, as well as change in body mass index, change in insulin sensitivity, change in estimated glomerular filtration rate at 2 years of follow-up. ANCOVA P<0.05 considered statistically significant.