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Page 10 of 14 Jagpal et al. Vessel Plus 2018;2:24 I http://dx.doi.org/10.20517/2574-1209.2018.27
[42]
on transplant patients focused on kidney transplantation. Lindholm et al. (1995) demonstrated that PTDM
increased the risk of CVD in transplant recipients. The relationship between PTDM and CVD is a concern
in heart transplant patients, as these patients are already at risk of CAV. As previously mentioned, CAV is an
accelerated form of coronary artery disease, it is also a major cause of death in patients surviving over a year
[43]
after heart transplantation .

[44]
A study by Kato et al. (2004) looked at the relationship between glucose intolerance and CVD in 151
heart transplant recipients. The researchers used HbA1c as an indicator of glucose metabolism and found
that increased HbA1c levels were associated with occurrence of CVD and could play a pivotal role in
[44]
its pathogenesis . A limitation of this study and many others in this area is the lack of information
surrounding the outcome of CVD in this population of patients. While it is important for clinicians
to recognise the link between PTDM and CVD, the management and consequences of this need to be
addressed.

Individuals with prediabetes are also at risk of CVD. Elevated fasting glucose among this group results
[45]
from both impaired insulin action and secretion . A meta-analysis comprising 1,611,399 individuals
[46]
conducted by Huang et al. (2016) found that prediabetes was associated with increased risk of composite
cardiovascular events which all lead to mortality. They also observed increased risk occurring when fasting
glucose was as low as 5.6 mmol/L.

In this study, it has been shown that patients on tacrolimus were prediabetic throughout the duration of the
trial, with levels considerably higher than 5.6 mmol/L. It is therefore essential to not only focus on a blood
test for diagnosis of diabetes but also any symptoms a patient may be experiencing. However, the study
[46]
published by Huang et al. consisted of data that was not specific to the transplant field. It is therefore
difficult to generalise Huang’s results to the current study’s population of patients. There is scope for research
in this area as data regarding the cardiovascular implications of prediabetes in heart transplant patients is
lacking.

Limitations of the study
Retrospective studies are prone to limitations which can affect the reliability of any results and conclusions
produced. This study is prone to selection bias as data used was collected from patient files, as a result there
was no participation selection.

The data for this study was collected from patient files where information was transplant specific. Therefore,
data that could influence the risk of diabetes was not measured, such as family history of diabetes and
ethnicity. Ideally, HbA1c would be collected at different time points after transplantation. However, there
was only one measurement available for both cohorts and so it is difficult to compare the results of the mean
fasting glucose and HbA1c.

The use of a steroid in immunosuppressive maintenance therapy is a significant confounding factor in
this study. As mentioned previously, a common side effect of steroid use is hyperglycaemia. Patients were
followed up for a 12-month period, so fluctuating fasting glucose levels seen may be a result of steroid use.
As steroids are removed from the regimen at 6 months, following up patients for a longer period could
eliminate this cofounding variable.

As well as a short follow up, this was a single centre study consisting of 52 patients. These factors can create
lack of external validity as results are difficult to generalise. Nonetheless, because the study was carried out
in one unit, all patients received similar care, similar selection for surgery, drug regimens and follow-up.
These factors give validity to the findings of this study.