NH2-Terminal Pro–Brain Natriuretic Peptide and Risk of Diabetes

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.

[1]  Pedro Lozano.  Natriuretic peptides. , 2020, The Journal of the Arkansas Medical Society.

[2]  C. Moro.  Natriuretic peptides and fat metabolism , 2013, Current opinion in clinical nutrition and metabolic care.

[3]  J. Pankow,et al.  Validity and reliability of self-reported diabetes in the Atherosclerosis Risk in Communities Study. , 2012, American journal of epidemiology.

[4]  G. Pacini,et al.  B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men , 2012, Diabetologia.

[5]  A. Vidal-Puig,et al.  NPs -- heart hormones that regulate brown fat? , 2012, The Journal of clinical investigation.

[6]  G. Ailhaud,et al.  Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. , 2012, The Journal of clinical investigation.

[7]  Thomas J. Wang,et al.  Low plasma level of atrial natriuretic peptide predicts development of diabetes: the prospective Malmo Diet and Cancer study. , 2012, The Journal of clinical endocrinology and metabolism.

[8]  Inês Barroso,et al.  Mendelian Randomization Study of B-Type Natriuretic Peptide and Type 2 Diabetes: Evidence of Causal Association from Population Studies , 2011, PLoS medicine.

[9]  D. Levy,et al.  Cardiac natriuretic peptides, obesity, and insulin resistance: evidence from two community-based studies. , 2011, The Journal of clinical endocrinology and metabolism.

[10]  V. Salomaa,et al.  Thirty-One Novel Biomarkers as Predictors for Clinically Incident Diabetes , 2010, PloS one.

[11]  K. Nakao,et al.  Natriuretic Peptides/cGMP/cGMP-Dependent Protein Kinase Cascades Promote Muscle Mitochondrial Biogenesis and Prevent Obesity , 2009, Diabetes.

[12]  M. Volpe,et al.  Natriuretic peptides: an update on bioactivity, potential therapeutic use, and implication in cardiovascular diseases. , 2008, American journal of hypertension.

[13]  D. Lloyd‐Jones,et al.  Multiple biomarker panels for cardiovascular risk assessment. , 2008, The New England journal of medicine.

[14]  A. Bayés‐Genís,et al.  Understanding amino-terminal pro-B-type natriuretic peptide in obesity. , 2008, The American journal of cardiology.

[15]  D. Levy,et al.  Association of Plasma Natriuretic Peptide Levels With Metabolic Risk Factors in Ambulatory Individuals , 2007, Circulation.

[16]  M. Drazner,et al.  Impact of Body Mass and Body Composition on Circulating Levels of Natriuretic Peptides: Results From the Dallas Heart Study , 2005, Circulation.

[17]  Mark A Miller,et al.  Oral Human Brain Natriuretic Peptide Activates Cyclic Guanosine 3,5-Monophosphate and Decreases Mean Arterial Pressure , 2005, Circulation.

[18]  A. Jaffe,et al.  Quality specifications for B-type natriuretic peptide assays. , 2005, Clinical chemistry.

[19]  L. Køber,et al.  N-terminal pro-B-type natriuretic peptide and long-term mortality in stable coronary heart disease. , 2005, The New England journal of medicine.

[20]  D. Levy,et al.  Impact of Obesity on Plasma Natriuretic Peptide Levels , 2004, Circulation.

[21]  Robert Gray,et al.  A Proportional Hazards Model for the Subdistribution of a Competing Risk , 1999 .

[22]  P. Dessı̀-Fulgheri,et al.  Expression of natriuretic peptide receptors in human adipose and other tissues , 1996, Journal of endocrinological investigation.

[23]  Aric Invest.  The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators , 1989 .

[24]  A. Folsom,et al.  The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators. , 1989, American journal of epidemiology.

[25]  G. Novo,et al.  Biomarkers in heart failure. , 2009, Frontiers in bioscience.

[26]  A. Dyer,et al.  Association of traditional risk factors with cardiovascular death across 0 to 10, 10 to 20, and >20 years follow-up in men and women. , 2008, The American journal of cardiology.