Amino-Terminal Brain Natriuretic Peptide is Related to the Presence of Diabetic Polyneuropathy Independently of Cardiovascular Disease

Diabetic polineuropathy (DPN) is among the most common long-term complications of diabetes, affecting up to 50% of patients (1,2). Type 2 diabetes is considered by many to be a cardiovascular disease (CVD) (3).

Plasma levels of the NH₂-terminal fragment of the brain natriuretic peptide (NT-proBNP) have recently gained extreme importance as markers of myocardial dysfunction in type 2 diabetes. Excessive secretion of NT-proBNP is independently associated with coronary artery disease and overt nephropathy (4) in addition to microalbuminuria (5). Moreover, NT-proBNP levels appear as a new independent predictor of excess secretion overall and of cardiovascular mortality in asymptomatic type 1 diabetic patients with microalbuminuria (6).

Data regarding the association between DPN and NT-proBNP levels are scarce. Noteworthy, only an abstract has reported a significant relationship between NT-proBNP levels and the presence of DPN in type 1 diabetes (7). Therefore, in a cross-sectional pilot study, we assessed the hypothetical relationships between NT-proBNP levels, CVD, and DPN in a group of type 2 diabetic patients (n = 104 [66 male and 38 female subjects]) randomly selected from the North Catalonia Diabetes Study.

The prevalence of microvascular disease was evaluated according to guidelines of the American Diabetes Association (8). DPN was diagnosed by clinical neurological examination and electrodiagnostic studies that were previously described (9). Presence of CVD (i.e., coronary heart disease, stroke, and/or peripheral vascular disease) was assessed by review of medical records. Serum NT-proBNP was measured using an immunocheminoluminometric assay (Elecsys; Roche Diagnostics, Indianapolis, IN).

Patients were treated with oral agents and/or biguanides (79%) or insulin (21%). They were aged 63.5 ± 7.6 years and had diabetes duration averaging 10.2 ± 1.2 years. CVD and DPN prevalence were 22.0 and 23.1%, respectively. Those with either CVD or DPN disclosed significantly higher logNT-proBNP values (P < 0.0005). LogNT-proBNP levels correlated with DPN (r = 0.346, P < 0.0005), even after correction for CVD (r = 0.289, P = 0.010). Clinical neurological examination and sural nerve motor and sensitive conduction velocities disclosed a significant relationship (r = 0.882, P < 0.0005).

In summary, we report that a novel and significant relationship between DPN and NT-proBNP levels appears independently of previous CVD. Increased NT-proBNP levels would presumably indicate the presence of repetitive microhypoxic insults to nerve fibers’ arterial supply independently of the presence of macrovascular disease. Further prospective studies with DPN-affected individuals are warranted.