NH2-terminal probrain natriuretic peptide is associated with diabetes complications in the EURODIAB Prospective Complications Study: the role of tumor necrosis factor-α.
OBJECTIVE
Circulating levels of NH(2)-terminal probrain natriuretic peptide (NT-proBNP), a marker of acute heart failure, are associated with increased risk of cardiovascular disease (CVD) in the general population. However, there is little information on the potential role of NT-proBNP as a biomarker of vascular complications in type 1 diabetic patients. We investigated whether serum NT-proBNP levels were associated with micro- and macrovascular disease in type 1 diabetic subjects.


METHODS
A cross-sectional nested case-control study from the EURODIAB Prospective Complications Study of 507 type 1 diabetic patients was performed. Case subjects (n = 345) were defined as those with one or more complications of diabetes; control subjects (n = 162) were those with no evidence of any complication. We measured NT-proBNP levels by a two-site sandwich electrochemiluminescence immunoassay and investigated their associations with complications.


RESULTS
Mean NT-proBNP levels were significantly higher in case than in control subjects. In logistic regression analyses, NT-proBNP values >26.46 pg/mL were independently associated with a 2.56-fold increased risk of all complications. Odds ratios of CVD (3.95 [95% CI 1.26-12.35]), nephropathy (4.38 [1.30-14.76]), and distal symmetrical polyneuropathy (4.32 [1.41-13.23]) were significantly increased in patients with NT-proBNP values in the highest quartile (>84.71 pg/mL), independently of renal function and known risk factors. These associations were no longer significant after inclusion of TNF-α into the model.


CONCLUSIONS
In this large cohort of type 1 diabetic subjects, we found an association between NT-proBNP and diabetic micro- and macrovascular complications. Our results suggest that the inflammatory cytokine TNF-α may be involved in this association.
Department of Internal Medicine, University of Turin, Turin, Italy. gabriella.gruden@unito.it
Gabriella
G
Gruden
Federica
F
Barutta
Nish
N
Chaturvedi
Casper
C
Schalkwijk
Coen D
CD
Stehouwer
Silvia
S
Pinach
Maria
M
Manzo
Maria
M
Loiacono
Marinella
M
Tricarico
Giulio
G
Mengozzi
Daniel R
DR
Witte
John H
JH
Fuller
Paolo Cavallo
PC
Perin
Graziella
G
Bruno
D000328:Adult; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000378:metabolism*; D005260:Female; D006801:Humans; D007118:Immunoassay; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D010446:Peptide Fragments; D014409:Tumor Necrosis Factor-alpha; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain