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.

Conflict of interest statement

Merck KGaA provides medication for DPPOS. DPP/DPPOS have also received donated materials from Bristol-Myers Squibb, Parke-Davis, and LifeScan Inc. This research was also supported, in part, by the intramural research program of the NIDDK. LifeScan Inc., Health O Meter, Hoechst Marion Roussel, Inc., Merck-Medco Managed Care, Inc., Merck and Co., Nike Sports Marketing, Slim Fast Foods Co., and Quaker Oats Co. donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices Corp., Matthews Media Group, Inc., and the Henry M. Jackson Foundation provided support services under subcontract with the Coordinating Center. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products to declare.

Figures

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

Least square mean loge 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.