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

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/m 2 ; 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).

Defective Natriuretic Peptide Receptor Signaling in Skeletal Muscle Links Obesity to Type 2 Diabetes

“…Furthermore, no acute effect of NP on glucose uptake was observed in human primary myotubes. These findings are in agreement with at least one human study reporting no acute effect of BNP on insulin sensitivity and insulin secretion (42). Altogether these data indicate that NP signaling does not acutely modulate skeletal muscle glucose uptake in vivo.…”

Changes in N-terminal pro-B-type natriuretic peptide and incidence of diabetes: The Multi-Ethnic Study of Atherosclerosis (MESA)

“…However, a Mendelian randomization study by Pfister et al [2] supports causality by documenting that a genetic variant of the BNP gene associated with increased levels of NT-proBNP is inversely associated with incident diabetes. Furthermore, the lowering of blood glucose during an oral glucose tolerance test (OGTT) associated with an intravenous infusion of BNP [27] favours the notion that natriuretic peptides may be on the causal pathway in the development of T2D. Future research should be aimed at elucidating whether either stimulating an increase in synthesis and release or administering natriuretic peptides in individuals with low baseline levels could initially improve insulin sensitivity and, thus, prevent the further development of obesity and T2D compared with those who maintain low levels of natriuretic peptide.…”

B-type natriuretic peptide and glycaemia: an emerging cardiometabolic pathway?

“…Of potential relevance, any lipolytic effect of natriuretic peptides might be expected to contribute to a reduction in insulin sensitivity. Thus, there are several strands of evidence that ANP may have some contextdependent influence on glucose metabolism, although these strands are disparate and any effect of BNP on glucose metabolism is even less clear.In this issue of Diabetologia, Heinisch and co-authors describe a study of the effects of short-term infusion of BNP on circulating glucose, insulin and C-peptide concentrations during an IVGTT [9]. The study involved ten healthy male volunteers who received both BNP and placebo, infused for 1 h prior to and during the IVGTT, in random order using a single-blinded crossover design.…”

“…In this issue of Diabetologia, Heinisch and co-authors describe a study of the effects of short-term infusion of BNP on circulating glucose, insulin and C-peptide concentrations during an IVGTT [9]. The study involved ten healthy male volunteers who received both BNP and placebo, infused for 1 h prior to and during the IVGTT, in random order using a single-blinded crossover design.…”

“…There may, however, be other explanations. Pre-infusion of BNP may have stimulated diuresis and urinary glucose loss [12,13] (unfortunately, urinary glucose was not measured in the study by Heinisch and co-workers [9]). It is of note that the circulating BNP level achieved following infusion was extremely high (∼400 pg/ml; a concentration normally consistent with heart failure), perhaps increasing the likelihood of an appreciable diuretic effect even over the short term.…”