NH2-terminal pro-brain natriuretic peptide and risk of diabetes

Abstract

Brain natriuretic peptide (BNP) has an established role in cardiovascular disease (CVD). However, recent animal studies suggest direct metabolic effects of BNP. To determine the association of BNP with the risk of diabetes, we conducted a prospective analysis of participants from the Atherosclerosis Risk in Communities (ARIC) study. We included 7,822 men and women without history of diabetes, CVD, or reduced kidney function at baseline. At baseline, NH2-terminal (NT)-proBNP, a cleavage product of BNP, was inversely associated with adiposity, fasting glucose, insulin, and cholesterol but positively associated with blood pressure and C-reactive protein levels. During a median follow-up of 12 years, 1,740 participants reported a new diagnosis of diabetes or medication use for diabetes. Baseline quartiles of NT-proBNP were inversely associated with diabetes risk, even after multivariable adjustment including fasting glucose. The adjusted HRs for diabetes were 1.0 (reference), 0.84 (95% CI 0.74-0.96), 0.79 (95% CI 0.68-0.90), and 0.75 (95% CI 0.64-0.87) for the 1st, 2nd, 3rd, and 4th quartiles of baseline NT-proBNP, respectively (P for trend <0.001). This inverse association was robust across sex, race, and obesity subgroups. Our results extend animal studies and support a direct and important metabolic role of BNP in humans.

FIG. 1.

Cumulative incidence (%) of diagnosed diabetes by quartiles (Q) of NT-proBNP at baseline.

FIG. 2.

Adjusted* HR (95% CI) of incident diagnosed diabetes by baseline NT-proBNP level overlaid on the distribution (frequency histogram) of NT-proBNP in the study population. HRs are presented using a logarithmic scale. Linear spline centered at 14.7 (10th percentile), with knots at the 33rd and 66th percentiles (24.9 and 76.2, respectively), after excluding values ≥99 percentile (NT-proBNP ≥611 pg/mL). *Adjusted for weight, height, age, race/center, sex, systolic blood pressure, diastolic blood pressure, smoking, LDL cholesterol, HDL cholesterol, C-reactive protein, fasting glucose, and family history of diabetes.