Introduction
Recently, the American Diabetes Association (ADA) has recommended that all patients with diabetes should be screened for heart failure using NT-proBNP as a biomarker. The purpose of this study is to compare the levels of NT-proBNP in diabetics and non-diabetics in our pool of life insurance applicants.
Challenges and Methods
When considering levels of NT-proBNP in diabetics and non-diabetics, it is important to consider how diabetics and non-diabetics might not be alike in other ways. For example, diabetics tend to be older since diabetes incidence rises with age. Similarly, NT-proBNP levels rise with age. Therefore, if one were to compare all non-diabetics to all diabetics it is virtually a foregone conclusion that the NT-proBNP levels would be higher in diabetics. Sex difference may also be a confounder. Also, those with diabetes are more likely to have a history of heart disease than those without, and having heart disease is associated with a higher level of NT-proBNP. Fortunately, we can use a statistical technique of stratified sampling to account for differences in age, sex, and heart disease history. Basically, we take our long list of diabetics and match them randomly to non-diabetics of the same age, sex, and heart disease status. This way, we can compare the NT-proBNP levels of diabetics and non-diabetics who are alike in the other ways that we can measure. It is also important to consider those things that we cannot measure (because we do not have access to them). For example, we do not have access to the medication lists of our applicants. It is likely that diabetics take medications like ACE-inhibitors and beta-blockers at higher rates than non-diabetics, and these medications can lower NT-proBNP levels.
Finally, we must consider how to define “diabetic”. There is a question on the lab slip regarding a history of diabetes, and we also have hemoglobin A1c on our applicants. So, for the purposes of this study, the definition of diabetic will be anyone who has a history of diabetes or an A1c greater than 7.0%.
Because we have a stratified sample, we have equal age and sex distributions between the two groups, and they have an identical prevalence of heart disease. We can now compare the NT-proBNP levels of the two groups.
Results and Conclusion
As shown in the figure, there is a higher proportion of the highest category of NT-proBNP among diabetics compared to non-diabetics.
Figure 1
The percentage of diabetics with NT-proBNP between 300 and 1000 pg/mL is 4.5 compared to 3.5 for non-diabetics. The percentage of diabetics with NT-proBNP greater than 1000 pg/mL is 1.1 compared to 0.6 for non-diabetics. So, the risk of having a very elevated NT-proBNP level is nearly doubled in diabetics. It may, therefore, be reasonable to consider reflexing to NT-proBNP when applicants admit diabetes or have an elevated A1c.
## Criticisms
While our method of determining diabetic status is fairly comprehensive, it is not perfect, as some applicants may not admit diabetes and may still have low A1c levels and therefore be counted as non-diabetic in our data set. Also, NT-proBNP is affected by other factors, most notably kidney function and albumin level, as documented in a recent CRL publication in the Journal of Insurance Medicine. In the future, more detailed studies could be carried out to account for these factors. It may be helpful to consult this calculator which determines the expected distribution of NT-proBNP levels considering these other factors.
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About the Author
Dr. Steven J. Rigatti is a consulting medical director with Clinical Reference Laboratory, with 12 years’ experience in the life insurance industry. He is the current chair of the Mortality Committee of the American Academy of Life Insurance Medicine.