Article

Diabetologia

, Volume 55, Issue 5, pp 1400-1405

First online:

B-type natriuretic peptide (BNP) affects the initial response to intravenous glucose: a randomised placebo-controlled cross-over study in healthy men

  • B. B. HeinischAffiliated withDepartment of Clinical Pharmacology, Medical University of Vienna
  • , G. VilaAffiliated withDivision of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna
  • , M. ReslAffiliated withDivision of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna
  • , M. RiedlAffiliated withDivision of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna
  • , B. DieplingerAffiliated withDepartment of Medical and Chemical Laboratory Diagnostics, St John of God Hospital
  • , T. MuellerAffiliated withDepartment of Medical and Chemical Laboratory Diagnostics, St John of God Hospital
  • , A. LugerAffiliated withDivision of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna
  • , G. PaciniAffiliated withMetabolic Unit, Institute of Biomedical Engineering, Italian National Research Council
  • , M. ClodiAffiliated withDivision of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna Email author 

Abstract

Aims/hypothesis

B-type natriuretic peptide (BNP) is a hormone released from cardiomyocytes in response to cell stretching and elevated in heart failure. Recent observations indicate a distinct connection between chronic heart failure and diabetes mellitus. This study investigated the role of BNP on glucose metabolism.

Methods

Ten healthy volunteers (25 ± 1 years; BMI 23 ± 1 kg/m2; fasting glucose 4.6 ± 0.1 mmol/l) were recruited to a participant-blinded investigator-open placebo-controlled cross-over study, performed at a university medical centre. They were randomly assigned (sequentially numbered opaque sealed envelopes) to receive either placebo or 3 pmol kg−1 min−1 BNP-32 intravenously during 4 h on study day 1 or 2. One hour after beginning the BNP/placebo infusion, a 3 h intravenous glucose tolerance test (0.33 g/kg glucose + 0.03 U/kg insulin at 20 min) was performed. Plasma glucose, insulin and C-peptide were frequently measured.

Results

Ten volunteers per group were analysed. BNP increased the initial glucose distribution volume (13 ± 1% body weight vs 11 ± 1%, p < 0.002), leading to an overall reduction in glucose concentration (p < 0.001), particularly during the initial 20 min of the test (p = 0.001), accompanied by a reduction in the initial C-peptide levels (1.42 ± 0.13 vs 1.62 ± 0.10 nmol/l, p = 0.015). BNP had no impact on beta cell function, insulin clearance or insulin sensitivity and induced no adverse effects.

Conclusions/interpretation

Intravenous administration of BNP increases glucose initial distribution volume and lowers plasma glucose concentrations following a glucose load, without affecting beta cell function or insulin sensitivity. These data support the theory that BNP has no diabetogenic properties, but improves metabolic status in men, and suggest new questions regarding BNP-induced differences in glucose availability and signalling in various organs/tissues.

Trial registration:

ClinicalTrials.gov: NCT01324739

Funding:

The study was funded by Jubilée Fonds of the Austrian National Bank (OeNB-Fonds).

Keywords

BNP C-peptide Diabetes Glucose Heart failure Healthy volunteers Insulin sensitivity IVGTT