A Comparative Study of Plasma N-Terminal Pro- Brain Natriuretic Peptide to Assess Asymptomatic Cardiovascular Disease in Type 2 Diabetic Patients

Research Article

Austin J Endocrinol Diabetes. 2023; 10(1): 1098.

A Comparative Study of Plasma N-Terminal Pro- Brain Natriuretic Peptide to Assess Asymptomatic Cardiovascular Disease in Type 2 Diabetic Patients

Sudhir Bhandari1*; Govind Rankawat2; Abhishek Agarwal3; Vishal Gupta4

1Vice Chancellor RUHS Jaipur and Professor Emeritus, SMS Medical College, India

2Assistant Professor, Department of General Medicine, SMS Medical College, India

3Senior Professor, Department of General Medicine, SMS Medical College, India

4Professor, Department of General Medicine, SMS Medical College, India

*Corresponding author: Sudhir Bhandari Vice Chancellor RUHS Jaipur and Professor Emeritus, SMS Medical College, D 126-A, Bapu nagar, Krishna Marg, University Road, Jaipur 302015, India. Tel: 9829078844 Email: [email protected]

Received: April 01, 2023 Accepted: May 12, 2023 Published: May 19, 2023


Background: This study aimed to assess NT-pro BNP level in patients of T2DM without overt cardiovascular disease to determine presence of Asymptomatic Left Ventricular Dysfunction (ALVD) compared with matched control group.

Methods: This study conducted at SMS Hospital, Jaipur by selecting 60 patients of type 2 diabetes mellitus and 60 control of non-diabetic population. Information regarding demographic data, clinical symptoms, past medical history, laboratory parameters, NT pro-BNP and 2D Echocardiography collected from selected sample population for comparative analysis among both groups.

Results: Patients of T2DM have significantly higher value of NT pro-BNP, blood sugar and HbA1c with proportionally increased diastolic dysfunction as compared to matched non-diabetic population (P<0.05). Absolute value of NT pro-BNP in patients of T2DM is directly correlated with age, duration of diabetes, Blood pressure, blood sugar level, HbA1c level, creatinine, total cholesterol and urine protein (positive correlation coefficient with P-value<0.05). Left ventricular ejection fractions were found statistically similar among both groups.

Conclusion: Heart failure in patients with T2DM is a most crucial diabetic complication for diagnosis as well as management. Level of NT-pro BNP in blood stream is an important tool for early diagnosis of heart failure especially HFpEF. This study suggests that the secretion of NT-pro BNP is increased in patients with T2DM compared with control subject without overt heart disease. Therefore, measurement of NT-pro BNP paired might be a simple screening tool to identify patients with diabetes at risk for ventricular dysfunction requiring further examination with echocardiography.

Keywords: Diabetes mellitus; Diastolic dysfunction; Echocardiography; HFpEF; NT pro-BNP


Diabetes Mellitus (DM) is one of the most challenging public health problems in the 21st century. There is an urgency for greater action to improve diabetes outcomes and reduce the global burden of diabetes now affecting more than 425 million people, of which one-third are people older than 65 years. The estimates of children and adolescents below age 19 with type 1 diabetes have risen to over a million [1]. If nothing is done, the number of people with diabetes may rise to 693 million in 2045, although positively the incidence has started to drop in some high-income countries [2]. At the same time, a further 352 million people with impaired glucose tolerance are at high risk of developing diabetes. By the end of this year, 4 million deaths will happen as a result of diabetes and its complications [3].

Alongside other non-communicable diseases, diabetes is increasing most markedly in the cities of low and middle- income countries. The IDF South-East Asia and Western Pacific regions are at the epicenter of the diabetes crisis: China alone has 121 million people with diabetes and India has a total of 74 million populations with diabetes. African, Middle Eastern, Northern African and South-East Asian regions are expected to face the highest upsurge in the next 28 years. People from these regions develop the disease earlier, get sicker and die sooner than their counterparts in wealthier nations [4].

It is important to know about the awareness level of a disease condition in a population, which plays a vital role in future development, early detection and prevention of disease. Prevention is important because the burden of diabetes and its complications on health care and its economic implications are enormous, especially for a developing country like India. Patient education is always considered an essential element of DM management [5].

Diabetes Mellitus (DM) is a chronic metabolic disorder being characterized by increased blood sugar levels. It is like a termite that insidiously eats up one’s own body and, if not controlled, it cripples the body irreversibly. People get tagged with this incurable disease, if not detected and controlled in earlier stages. Over time, poor glycemic control can lead to multiple chronic complications like damage to eyes (leading to blindness), kidneys (leading to renal failure) and nerves (leading to numbness in the limbs, impotence and foot disorders/possibly amputation) as well as increased risk of heart diseases and stroke [6]. These complications contribute to the decreased quality of life for affected individuals and their families, with a devastating long-term effect on their financial and social wellbeing.

The management of DM largely depends on the affected person’s ability to pursue self-care in daily living. Proper management requires patients to be aware of the nature of the disease, its risk factors, treatment and complications. Thus, effective DM education, with consequent improvements in knowledge, attitudes and skills, leads to better control of the disease and reduce the incidence of complications. Various studies have been conducted in India to look for awareness among diabetics. The Indian Council of Medical Research (ICMR) conducted a study in four regions of India in which they found that only 43.2% of the overall study population had heard about a condition called diabetes [7]. Another study found that 17% of their participants had poor knowledge and more than half believe it to be a communicable disease. Having complete knowledge about the disease is like a small investment for the large benefit [8].

Another major weapon in the management of diabetes is treatment adherence. The World Health Organization (WHO) defined adherence as “the extent to which a person’s behavior – taking medication, following a diet and/or executing lifestyle changes, corresponds with agreed recommendations from a health care provider” [9]. It has been indicated through various studies that despite the extensive therapy options available for various stages of type 2 diabetes, less than 50% of patients achieve the glycemic goals recommended by the American Diabetes Association (ADA) [10,11].

As diabetes is concerned, the knowledge, attitude and practice are dependent on socioeconomic background, habits and cultural beliefs. Proper knowledge of diabetes mellitus can prevent the occurrence of chronic complications associated with DM, which significantly influence the quality of life of patients with diabetes [12]. Diabetes and heart failure are closely related, When the two diseases are considered individually, heart failure has a much poorer prognosis than diabetes mellitus; therefore, heart failure has to be a priority for treatment in patients presenting with the two conditions [13]. It has been estimated that the proportion of CHF patients with known T2DM is 20–35 % [14].

As cardiac dysfunction increases, the synthesis and release of cardiac natriuretic peptides gradually rise in concert with the other neurohormonal responses observed in heart failure. Therefore, it has been proposed that increased B-type Natriuretic Peptide (BNP) and/or N-terminal pro-BNP (NT-pro BNP) be used as a marker for symptomatic ventricular dysfunction. In addition, irrespective of the degree of left ventricular dysfunction, blood BNP or NT- pro BNP levels are elevated in patients with many cardiac disorders, including previous myocardial infarction, cardiomyopathy, valvular heart disease, hypertensive heart disease, and atrial fibrillation [15].

The Framingham study demonstrated that subjects with higher plasma BNP levels exhibited an increased incidence of Congestive Heart Failure (CHF) [16]. It is therefore, possible that BNP or NT-pro BNP levels may serve as a useful marker of cardiovascular risk in the screening of the general population [17]. However, recent reports have shown that in the general population, the plasma BNP or NT-pro BNP level is affected by many extracardiac factors including age, obesity, and genetics [18,19]. Non-invasive cardiac imaging like 2D Echocardiogram and MRI of the heart is essential for diagnosis, evaluation and management of heart failure, but these are time- consuming and less acceptable. However, circulating NT-pro BNP is highly sensitive for Heart Failure with preserved and depressed ejection fraction in the asymptomatic patients. Therefore, elevated NT-pro BNP level may serve as an important diagnostic marker for Heart Failure in patients of T2DM if found to be useful.


Study Design

This is observational cross-sectional and comparative study, conducted at S.M.S. Medical College and attached Hospital, Jaipur, India from April 2019 to May 2020. This study was approved by the Institutional Ethics Committee. In this study 60 patients of T2DM selected as cases after application of exclusion criteria (patients of severe illness, past history of cardiovascular disorder, chronic lung disease and chronic kidney disease were excluded from this study) and 60 non-diabetic subjects selected as control. The study group underwent detail demographic analysis, clinical manifestation, medical history, treatment history, laboratory investigation especially HbA1c, hemogram, fasting and post-prandial sugar, renal function, urine routine and microscopic examination, NT-pro BNP, ultrasonography abdomen for renal size and 2D-echocardiogram. The data obtained were collected, tabulated, compiled, interpreted and analyzed. Both of these Groups were matched for age, gender and presence of other comorbidities.

Data Collection

All patients of T2DM (HbA1c ≥6.5%) as a cases and healthy subjects of without diabetes mellitus (HbA1c ≤5.5%) selected as control. Selected groups undergo detailed medical history to exclude confounding factors especially past history of cardiovascular disorder, chronic lung disease and chronic kidney disease. Demographic data obtained in the form age, sex, geographic distribution with clinical manifestations and duration of T2DM and other associated comorbidities. Vitals of both groups including systolic and diastolic blood pressure, heart rate and temperature were measured by standard protocol. In blood investigations haemoglobin, Total leukocyte count, Platelet count, fasting and postprandial blood sugar (2 hour after meal), HbA1c, NT pro- BNP, kidney function test, liver function test, total cholesterol and triglyceride were measured in both groups. NT-pro BNP was analyzed using a competitive enzyme immunosorbent assay designed to measure the immunoreactive NT-pro BNP (Biomedica Laboratories, Vienna, Austria). Blood samples were drawn in EDTA tube, immediately placed on ice, and promptly centrifuged at 4°C. NT-pro BNP measurements were done using an ELISA: a two steps sandwich assay with streptavidin coated microtiter plates. This assay does not require sample extraction and there is no detectable cross reactivity with ANP, NT-pro ANP, BNP, or urodilatin. Urine for routine and microscopy and electrocardiograph was examined in both groups. 2D Echocardiography with especial focus on diastolic dysfunction and left ventricular ejection fraction was performed in both groups. Transthoracic echocardiography was performed using a Philips IE 33 machine (Phillips Medical Systems, Best, and The Netherlands). All patients were examined with conventional 2-D and Doppler modalities, combined with color tissue Doppler imaging. Data were stored on compact discs and analyzed off-line with commercially available software (EchoPAC software) by an experienced investigator, with no other relation to the present study and blinded to all other information. The case and control selection were mentioned in (Figure 1).

Statistical analysis

The descriptive statistics for quantitative data was expressed as mean and standard deviation and qualitative data was expressed as proportions. The parameters were compared among different Groups using chi-square and z-score test for significant differences. The level of significance was assigned at a p-value less than 0.05.


A total of 60 patients of T2DM (Group A) and 60 subjects (Group B) of control group selected for study at SMS Medical College and attached group of Hospital, Jaipur, Rajasthan. All necessary data were collected, evaluated, interpreted and correlated within both groups to assess different manifestations of T2DM. Value of NT-pro BNP in patients of T2DM also correlated with various demographic, clinical and laboratory parameters.

Demographic Data (Table 1)