Brain Natriuretic Peptide as a Potential Marker of Diastolic Dysfunction in Type 2 Diabetes

In the January issue of Diabetes Care, Poirier et al. (1) reported on the prevalence of left ventricular diastolic dysfunction (LVDD), as determined by echocardiography in 46 middle-aged men with well-controlled type 2 diabetes. Remarkably, they found a prevalence of LVDD as high as 60%. Although this needs to be replicated with studies of much larger sample sizes, they nevertheless illustrated the importance of identifying pseudonormal patterns of ventricular filling, which have been underestimated by previous studies using Doppler assessment of transmitral flow velocity, to help diagnose early or subclinical LVDD (1). As elucidated by the excellent editorial of Gustafsson and Hildebrandt (2), the prognostic implication and possibility for intervention remain unknown and warrant further studies before early echographic screening in diabetic patients can be justified. We speculate that a potential marker of diastolic dysfunction in diabetic cardiomyopathy may help in the selection of high-risk diabetic patients for early cardiological assessment.

The natriuretic peptide family (including atrial, brain, and type C natriuertic peptide) plays a key role in the homeostasis of intravascular fluid balance and in the maintenance of cardiovascular hemodynamics (3). Originally isolated from porcine brain tissue (4), brain natriuretic peptide (BNP) is a vasodilator produced by cardiac myocytes in the ventricles and is degraded by neural endopeptidase. Along with atrial natriuretic peptide (ANP), BNP has effects on natriuresis, diuresis, and inhibition of the renin-angiotensin-aldosterone system, all of which contribute to the modulation and control of cardiovascular hemodynamics (5). There is growing evidence that BNP may be a marker of advanced heart failure (5,6). More importantly, it may also be a marker of early heart failure as manifested by isolated diastolic dysfunction (7) or diastolic dysfunction in association with hypertension (8). The underlying pathophysiology for elevated BNP levels in diastolic heart failure is not fully understood. However, it is likely that BNP production is increased as a compensatory response to diminish preload (vasodilatation) and postload (natriuresis and diuresis), thereby improving cardiac contractility. This is supported by the observation that infusion of BNP in patients with diastolic dysfunction improves hemodynamic response in isolated diastolic heart failure (9).

Although elevation of BNP in cardiac failure is not specific to disease states, BNP may be a useful tool in diabetic patients with microalbuminuria. This is supported by the study of Poirier et al. (1), in which there was a greater incidence of microalbuminuric patients in the group with abnormal ventricular relaxation pattern (15 of 28 [54%]) compared with the group with normal diastolic function (6 of 18 [33%]) (1). Furthermore, it has recently been shown by Yano et al. (10) that BNP is elevated in type 2 diabetic patients with microalbuminuria compared with those with normoalbuminuria. In their study, all microalbuminuric patients were normotensive, suggesting that any potential elevation of blood pressure commonly associated with microalbuminuria may have been compensated by the increased BNP level through its action on natriuresis and vasodilatation. Hence, it is at least physiologically plausible that increased circulating BNP concentrations in the presence of microalbuminuria may be a useful marker for early diastolic dysfunction in diabetic patients. Unlike ANP levels, which can be increased by acute hyperglycemia, circulating BNP concentrations have been shown to be unaffected by an elevated glucose level (11), making it more suitable for screening in diabetic patients. Further research will be required to determine the potential value of BNP in selecting microalbuminuric diabetic patients for further cardiological assessment.