NT-proBNP and Diabetes: Risks of Misdiagnosis in Heart Failure

NT-proBNP and diabetes are closely linked, and this interplay can alter test interpretation in heart-failure diagnosis. N-terminal pro B-type natriuretic peptide (NT-proBNP) is a biomarker widely used to assess heart failure (HF) and other cardiovascular conditions. It is the inactive fragment released when the heart produces brain natriuretic peptide (BNP), a hormone involved in fluid balance and blood pressure regulation.

Key takeaways (TL;DR): NT-proBNP and diabetes can distort biomarker interpretation via CKD; combine NT-proBNP with kidney function and imaging to reduce misdiagnosis.

NT-proBNP levels are often elevated in cases of heart failure, making it an important diagnostic tool in the management of heart-related conditions. However, research shows that diabetes and high blood sugar levels may influence NT-proBNP readings, leading to potential misdiagnosis, underdiagnosis, and complications in patients with diabetes and cardiovascular disease.

This article explores the relationship between NT-proBNP and high blood sugar levels in diabetes, the risks for patients, and the implications for clinical practice.

NT-proBNP and Diabetes: What the Biomarker Shows—and Where It Misleads

NT-proBNP is a biomarker used to aid in the diagnosis and monitoring of heart failure. When the heart is under stress, such as in the case of HF or myocardial infarction, it releases BNP. NT-proBNP is a more stable and easier-to-measure marker than BNP itself, which makes it a convenient and reliable indicator for assessing cardiac function.

Elevated levels of NT-proBNP correlate with disease severity, and testing is also used in atrial fibrillation, acute coronary syndrome, and pulmonary hypertension. Importantly, NT-proBNP levels may be influenced by age, sex, kidney function, and—as recent studies confirm—diabetes.

How Diabetes Influences NT-proBNP Levels

The flow below summarises how NT-proBNP and diabetes interact through kidney disease, elevating NT-proBNP and increasing misdiagnosis risk.

UK/EU context: In NHS pathways (NICE NG106), natriuretic peptide testing is combined with echocardiography; in people with diabetes—especially with CKD—interpret NT-proBNP cautiously and consider HFpEF.

The Role of High Blood Sugar

Diabetes, particularly when poorly controlled, is a major risk factor for cardiovascular disease. Patients with diabetes often present with higher NT-proBNP levels than non-diabetic individuals. Elevated blood glucose may increase cardiac stress even in the absence of overt HF, partially explaining these elevated values.

The Impact of Diabetic Kidney Disease (CKD)

Chronic kidney disease (CKD), a common complication of diabetes, further increases NT-proBNP due to impaired clearance. This can make NT-proBNP appear high even without cardiac pathology. Studies such as Pivetta et al. (2016) show that patients with diabetes and CKD present misleadingly elevated NT-proBNP readings, complicating diagnosis.

NT-proBNP Misdiagnosis and Underdiagnosis Risks in Diabetes

False Positives from Kidney Disease

Diabetic patients with renal dysfunction often show elevated NT-proBNP despite no clinical evidence of HF. This can result in unnecessary HF treatment or diagnostic imaging, increasing both patient burden and healthcare costs. This is a common pitfall when interpreting NT-proBNP and diabetes alongside reduced renal clearance.

False Negatives in Diabetic Patients with HF

Conversely, some diabetic patients with HF may not exhibit elevated NT-proBNP due to complex metabolic interactions. This underdiagnosis risks delaying treatment, worsening outcomes, and increasing hospitalisations.

Clinical Implications for Heart Failure Diagnosis in Diabetic Patients

The interplay between diabetes, NT-proBNP, and CKD underscores the risk of both over- and under-treatment. Misdiagnosis can expose patients to inappropriate therapies such as diuretics, while underdiagnosis delays life-saving interventions.

Healthcare providers must interpret NT-proBNP within a holistic context, factoring in:

• blood sugar levels,
• kidney function,
• comorbidities (hypertension, obesity), and
• clinical presentation.

Why Healthcare Providers Must Use a Holistic Approach

Relying solely on NT-proBNP testing in diabetic patients is risky; NT-proBNP and diabetes require a holistic read that includes kidney function and imaging. A combined approach—including clinical assessment, kidney function testing, and advanced diagnostics—improves accuracy.

New technologies such as Cardio-HART offer echocardiography-equivalent insights in primary care, complementing NT-proBNP and reducing misinterpretation.

Future Directions and Research Needs

More research is needed to:

• clarify the link between diabetes and NT-proBNP fluctuations,
• refine diagnostic thresholds in diabetic populations, and
• integrate device-based tools with biomarker testing for better accuracy.

NICE guideline NG106 on chronic heart failure also highlights the importance of additional diagnostic tools to support NT-proBNP interpretation.

NT-proBNP in Heart Failure Diagnosis: Challenges, Clinical Effectiveness, and the Need for More Accurate Tools

NT-proBNP in Heart Failure Diagnosis: Clinical Delay, Biomarker Limits, and the Need for Diagnostic Reinvention

Conclusion: Balancing NT-proBNP with Clinical Context

The relationship between NT-proBNP and diabetes is complex. While NT-proBNP remains a valuable biomarker, elevated levels in diabetes may reflect metabolic or renal factors rather than heart failure alone.

To avoid misdiagnosis or underdiagnosis, clinicians should interpret NT-proBNP alongside other clinical findings. As diabetes prevalence rises, combining biomarkers with innovative diagnostics will be critical to ensuring timely, accurate, and patient-centred heart failure care.