Discussion
Diabetic foot ulcers are one of the most serious complications of
diabetes mellitus that can result in amputation. Diabetic foot ulcers
usually progress with infection, and early diagnosis and effective
treatment is very important in preventing amputation.4For this reason, previous studies have emphasized biomarkers that show
both the severity of infection and the amputation rate, and which can be
used in early diagnosis.21 Among these biomarkers,
CRP, WBC, procalcitonin and ESR levels related to infection were
especially emphasized22, 23, and HbA1c levels were
examined with regard to the amputation rate.24 These
parameters can provide an evaluation of diabetic foot ulcers in terms of
infection and diabetes, while IMA can allow these patients to be
evaluated from a different angle. IMA is a molecule formed by the
modification of albumin as a result of ischemic damage. The popularity
of IMA has been increasing recently and its association with ischemic
injury-related diseases has been demonstrated.
In this present study, we aimed to determine the predictive value of IMA
in diabetic foot ulcer patients and compare them to CRP results, as well
as reviewing the relationship of IMA levels with diabetic foot ulcers
according to the Wagner classification. We found that the levels of IMA
in the diabetic foot patient group was significantly higher than those
of the healthy control group. In previous studies, IMA levels have been
considered in patients with diabetes and in patients with diabetes
complications. Piwowar et al. reported that IMA levels in patients with
type 2 diabetes were higher than the healthy control
group.13 In addition, IMA levels in diabetic
nephropathy25 and diabetic
retinopathy26 have been reported to be higher than the
corresponding control group. Gunduz et al. reported that IMA levels of
lower extremity ischemia patients and a healthy control group were
compared and IMA levels of the patient group were significantly
higher.27 Muhtaroğlu et al. examined IMA levels in
diabetic foot patients and reported that they were higher than the
healthy control group.28 The results from our study
support the results of Muhtaroğlu et al. When we investigated the CRP
result, the CRP level in the diabetic foot patient group was
significantly higher than the healthy control groupSimilar results were
reported in previous studies.21-23. These results show
that IMA also plays an important role in the pathogenesis of diabetic
foot patients.
In our study, we investigated the IMA levels in subgroups created
according to the Wagner classification, and this is the first study that
reports IMA levels in diabetic foot patients in terms of the Wagner
classification. We found the highest IMA levels in Wagner grade 5. There
was no significant difference between Wagner grade 1, 2 and 3 in terms
of IMA levels. The level of IMA in Wagner grade 4 was significantly
higher than those of Wagner grade 1, 2 and 3. We are unable to discuss
these results in detail since IMA levels in diabetic foot patients,
which were previously classified according to the Wagner classification,
were not examined. The highest CRP levels were determined in grade 5 in
subgroups created according to the Wagner classification, but there was
no statistically significant difference between grades 4 and 5. Also,
there was no statistically significant difference between grade 1 and 2
in terms of CRP. Grade 3 CRP levels were found to be significantly
higher than grade 1 and 2, and significantly lower than grade 4 and 5.
Raheem et al. divided diabetic foot patients into subgroups according to
the Wagner classification and examined their CRP levels. They reported
that there was no statistically significant difference between grade 1
and 2 and that the highest CRP levels were detected in grade
5.29 Hadavand et al. compared only the CRP levels of
class III and IV and found that the CRP levels of class IV were
statistically significantly higher than the class
III.22 Jeandrot et al. created subgroups using a
different method of diabetic foot classification and examined their CRP
values. While determining the highest CRP value in grade 4 in their
studies, they reported that there was no statistically significant
difference between the grade 1 and healthy control
groups.23 According to our results, both IMA levels
and CRP levels are closely related to the Wagner classification, which
evaluates according to the severity of infection, osteomyelitis, and
necrosis. In our study, we classified the diabetic foot patients
according to the presence of osteomyelitis and examined the IMA and CRP
levels. We found that IMA and CRP levels were significantly higher in
diabetic foot patients with osteomyelitis than in patients without
osteomyelitis. These results support that IMA is related to the severity
of infection in diabetic foot patients.
In our study, ROC analysis was performed to show the predictive value of
IMA and CRP in subgroups created according to the Wagner classification.
When the ROC curves are examined, it can be seen that the predictive
value of CRP is higher than IMA in the distinction between grades other
than grade 4-5. In distinguishing between Wagner grades 4 and 5, IMA
AUC, sensitivity and specificity values were higher than those of CRP.
According to our knowledge, there is no study examining the predictive
value of IMA in the Wagner classification: this assessment was made for
the first time in our study. Studies investigating the predictive value
of CRP in distinguishing the classification, severity and presence of
osteomyelitis have been conducted. Hadavand et al. reported that CRP has
high sensitivity and specificity, especially in determining the presence
of osteomyelitis in diabetic foot patients.22 However,
it should not be forgotten that CRP is an acute phase reactant and
naturally increases in many infection-related diseases. In other words,
CRP levels can also increase in a different complication, not associated
with the diabetic foot. Jeandrot et al. examined the predictive value of
CRP and procalcitonin in the separation of non-infected (grade 1) and
infected (grade 2) patients, reporting that there was no significant
difference between CRP and procalcitonin in terms of predictive value
and that the combination of CRP and procalcitonin gave much better
results.9 IMA was more specific and sensitive than CRP
in the distinction of grade 4 and grade 5 in patients with diabetic foot
ulcers . This may be due to the development of endothelium-induced
ischemia in tissues. Therefore, in these patients, besides blood,
glucose level regulation, control of HbA1c levels and detection of
infectious agents, ischemic conditions may also be considered.
There are some limitations in our study. One of these limitations is
that the duration of diabetes in patients is unknown, so we could not
clarify whether the duration of diabetes has an effect on IMA levels.
Another limitation is that the sample size of our control group is
relatively low. In advanced studies, the effects of diabetes duration on
IMA levels can be examined by creating larger sample sizes.
In conclusion, our data showed that IMA may play a role in the
pathogenesis of diabetic foot ulcers. In addition, it has been
determined that IMA levels have high sensitivity and specificity in
distinguishing Wagner grade 4 and 5 diabetic foot ulcers, especially
when the infection is severe. Therefore, it may be clinically useful to
examine IMA levels in the classification, progression and management of
diabetic foot ulcers.