Accepted Manuscript

The significance of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and

lymphocyte-monocyte ratio in predicting peripheral arterial disease, peripheral
neuropathy, osteomyelitis and amputation in diabetic foot infection

Tuna Demirdal, Pinar Sen

PII: S0168-8227(18)30602-8
DOI: https://doi.org/10.1016/j.diabres.2018.08.009
Reference: DIAB 7481

To appear in: Diabetes Research and Clinical Practice

Received Date: 12 April 2018

Revised Date: 10 July 2018
Accepted Date: 13 August 2018

Please cite this article as: T. Demirdal, P. Sen, The significance of neutrophil-lymphocyte ratio, platelet-lymphocyte
ratio and lymphocyte-monocyte ratio in predicting peripheral arterial disease, peripheral neuropathy, osteomyelitis
and amputation in diabetic foot infection, Diabetes Research and Clinical Practice (2018), doi: https://doi.org/
10.1016/j.diabres.2018.08.009

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Title: The significance of neutrophil-lymphocyte ratio, platelet-lymphocyte ratio and

lymphocyte-monocyte ratio in predicting peripheral arterial disease, peripheral neuropathy,

osteomyelitis and amputation in diabetic foot infection

Running Title: Diabetic foot infections

Tuna Demirdal1 ; Prof., Pinar Sen1; M.D.

1
:Izmir Katip Celebi University Ataturk Training and Research Hospital, Department of

Infectious Diseases and Clinical Microbiology

Corresponding Author:

Pinar Sen, M.D., Izmir Katip Celebi University Ataturk Training and Research Hospital,

Department of Infectious Diseases and Clinical Microbiology

E-mail: pinarozdemirsen@gmail.com

Adress: Izmir Katip Celebi University Ataturk Research and Training Hospital 35360,

Karabaglar/Izmir, Turkey.

Tel: +905058946042, Fax: +902322431530

Conflict of interest: None declared.

Acknowledgments: None declared.

Abstract

Aims: The aim of the study was to evaluate the value of neutrophil to lymphocyte

ratio(NLR), platelet to lymphocyte ratio(PLR) and lymphocyte to monocyte ratio(LMR) in

predicting peripheral arterial disease, peripheral neuropathy, osteomyelitis and need for

amputation in diabetic foot infection(DFI).

Methods: A total of 280 patients were analyzed retrospectively. The NLR,PLR and LMR

were evaluated statistically in DFI.

Results: A total of 280 patients were enrolled in the study. PLR was significantly higher in

osteomyelitis and NLR was found higher in peripheral arterial disease in DFI
(p=0.008,p=0.007). A PLR of >187.3 was calculated as the cut off value with 67.9%

sensitivity and 59.1% specificity in predicting osteomyelitis. A NLR of >6.5 was calculated as

the cut off with 53.3% sensitivity and 63% specificity in predicting peripheral arterial disease.

NLR, PLR and LMR had a predictive value in predicting amputation in DFI (p<0.001,

p<0.001,p=0.006). NLR and PLR were higher in patients who required amputation than in

patients who required debridement/drainage (p<0.001,p=0.002). NLR was significant in

determining amputation levels (minor or major)(p=0.013).

Conclusions: NLR can predict peripheral arterial disease and elevated PLR can predict

osteomyelitis in DFI. NLR, PLR and LMR are predictive of the need for amputation in DFI.

Key words: diabetes, foot, infection, lymphocyte, ratio

Introduction

Diabetic foot ulcers are an important problem with serious consequences for both patients and

health care systems. In diabetic patients, foot ulcer prevalence ranges from 4-10% and the

lifetime incidence may increase up to 25% (1). Longer diabetes duration, insulin use, poor

glycemic control, age, Charcot deformity, foot insensitivity, foot ischemia, history of

ulcer/amputation have been shown as risk factors for foot ulceration (2). Among these factors,

long-term complications of diabetes include vasculopathy and neuropathy are most strongly

associated with development of diabetic foot ulcers (2,3).

Infection is a common problem that affects more than half of diabetic foot ulcers and

osteomyelitis develops in 20% of moderate infections and 50-60% of severe infections (3).

The risk of amputation in the presence of osteomyelitis in diabetic foot infections (DFI) is

significantly higher than isolated soft tissue infections (3,4). Early diagnosis and appropriate

treatment of osteomyelitis are crucial for the prevention of lower extremity amputation in DFI

(4). However, despite advanced imaging techniques and laboratory tests, it may be difficult to

diagnose and treat osteomyelitis. Because histological and bone culture studies, which are the
most appropriate methods in the diagnosis of osteomyelitis, are difficult, invasive and time-

consuming, and long-term antimicrobial therapy and/or surgical intervention are needed for

treatment (5).

Chronic inflammation is implicated in the pathogenesis of diabetes and the development of

diabetic complications (6). White blood cell (WBC) count, C-reactive protein (CRP) and

erythrocyte sedimentation rate (ESR) are routinely used laboratory markers of inflammation.

Recently, it has been pointed out that the changes in the rate of circulating leukocytes are

simple, rapid and novel promising inflammation parameter in many diseases (7,8).

Early detection of vasculopathy, neuropathy and osteomyelitis is essential for early diagnosis

of high-risk diabetic foot and timely treatment. Early recognition of need for amputation is

also crucial in terms of limiting amputation level and decreasing mortality. Despite the close

association between inflammation and diabetes, the role of leukocyte subtypes in DFI was

analyzed in a limited number of studies. To our knowledge, this is the first study to

investigate the distribution of circulating neutrophil, lymphocyte, monocyte and platelet

parameters in DFI in terms of complications and clinical course in a single study. In the

present study, we aimed to evaluate the value of neutrophil to lymphocyte ratio (NLR),

platelet to lymphocyte ratio (PLR) and lymphocyte to monocyte ratio (LMR) in predicting

peripheral arterial disease, peripheral neuropathy, osteomyelitis and need for amputation in

DFI.

Subjects, Materials and methods

Patients

A total of 280 consecutive patients who were hospitalized in our Infectious Disease Clinic

were analyzed retrospectively from February 2010 through March 2016 at the Katip Celebi

University Ataturk Training and Research Hospital, Izmir, Turkey. The study protocol was
approved by our local ethics committee. Patients were enrolled the study if they were diabetic

and hospitalized for DFI. The exclusion criteria were age less than 18 years, pregnancy,

malignancy, autoimmune disorder, underlying haematological disease, glucocorticoid use,

other foci of infection and previous antibiotic use. The data of the patients including

demographics, type of diabetes, disease duration, clinical findings (presence of chronic ulcer,

osteomyelitis, peripheral vasculopathy or neuropathy), laboratory parameters, results of

microbiological cultures, treatment type (medical, debridement/drainage, minor or major

amputation), history of previous debridement/amputation and treatment outcome were

obtained from medical records. Treatment outcome was defined as complete recovery,

development of chronic ulcer or reoperation requirement.

Assessment of clinical features

DFI was defined on the basis of the clinical signs of inflammation such as warmth,

tenderness, redness, pain or swelling. In addition, purulent or nonpurulent secretions and foul

odor were also regarded as sign of infection (5). Diagnosis of osteomyelitis was based on

clinical, laboratory and imaging findings. Peripheral arterial disease was diagnosed by a

vascular surgeon from faint/nonpalpable distal pulses and confirmed by imaging methods.

Peripheral neuropathy was diagnosed by a neurologist and was defined as loss of sensation,

foot deformity, tingling sensation and/or decreased vibratory sensation in either foot of

patients. Minor amputation was defined as partial foot amputation involving infected tissue

and bone with the preservation of ankle joint (9). Proximal amputation including ankle joint

was defined as major amputation (9).

Laboratory analysis

Infection markers such as WBC, ESR, CRP and procalcitonin (PCT) were examined as

laboratory tests. Wound swab samples, deep tissue samples and blood samples were analyzed

microbiologically. All laboratory studies were analyzed according to the standard procedures
of our laboratory department. Venous blood samples were obtained simultaneously to

determine the level of biomarkers on the first day after admission before receiving

antimicrobial therapy. The NLR, PLR and LMR were calculated using neutrophil,

lymphocyte, monocyte and platelet levels in the complete blood count measurement. NLR,

PLR and LMR values were analyzed statistically in terms of predicting peripheral arterial

disease, peripheral neuropathy, osteomyelitis and need for amputation in DFI.

Statistical analysis

Statistical analyses were performed using the SPSS software version 24. The variables were

investigated using the Kolmogorov-Smirnov test. Descriptive analyses were presented using

means and standard deviations for normally distributed variables. Student’s t-test was used to

compare these parameters. The Chi-square test was used for the comparison of independent

groups. The receiver operating characteristic curves (ROC) analyzes, sensitivity and

specificity values were calculated by using MedCalc version 14 (MedCalc Software). P value

<0.05 was considered statistically significant.

Results

Study Population

A total of 280 patients were enrolled in the study including 198 (70.7%) men and 82 (29.3%)

women. The mean age was 59.5±11.1 years. Ten (3.6%) of the patients were type 1 diabetes

and 260 (96.4%) of them were type 2 diabetes and mean duration of diabetes was 13.6±9.5

years. The time from foot ulcer development to hospital admission was 10.6±5.3 days. The

proportion of oral antidiabetic drug users was 17.7% and the proportion of insulin users was

71.9% while the proportion of patients who did not receive any antidiabetic treatment was

10.4%. The causes of the DFI were as follows; ischemic ulcer (51.6%), trauma (23.9%),

neuropathic ulcer (7.5%), toenail fungus (6.3%), burn injury (3.8%), post surgical infection

(3.8%), ingrown toenails (0.6%) and idiopathic (2.5%). Of these patients, 47.1% had right
foot wound, 44.5% had left foot wound and 8.4% had bilateral wounds. Anatomical

distribution of the foot lesions was as follows; fingertips and/or toes (33.7%), heel (11.4%),

midfoot (33.7%), hallux (1.3%) and multiple regions (19.9%). Among all patients, 53.6% had

chronic foot ulcers, 54.2% had osteomyelitis, 43.7% had peripheral arterial disease and 6.8%

had peripheral neuropathy. There were 24 (8.6%) patients with prior history of debridement

and 46 (16.4%) patients had a history of surgery. Treatment modalities included medical

treatment (96, 34.9%), debridement/drainage (70, 25.5%), minor amputation (43, 15.6%) and

major amputation (66, 24%). Two hundred seventy-five patients were evaluated for treatment

modality because 5 patients died before any effective treatment. Follow-up data was available

for 231 of the 280 patients; 123 patients completely recovered, 42 patients developed a

chronic foot ulcer and 66 patients required reoperation. The overall mortality rate was found

2.8%.

Distribution of microorganisms

Blood cultures were positive in 3 patients and all isolates were Staphylococcus aureus

(S.aureus). Two patients had methicillin-susceptible S.aureus (MSSA) and 1 patient had

methicillin resistant S.aureus (MRSA) in blood cultures. Positive wound cultures were

yielded from 157 patients, 69.8% of them were Gram-negative and 29.6% of them were

Gram-positive bacteria. There was only one patient with fungal aetiology (0.6%). More than

one organism was isolated in 15 patients. Pseudomonas aeruginosa was the most frequently

isolated bacterium. Among the 22 S.aureus strains isolated from the wound culture, 17 strains

were MSSA and 5 strains were MRSA. Microorganisms isolated from soft tissue specimens

were shown in Table 1.

Laboratory Findings

The mean values of laboratory values on admission were as follows; blood glucose levels

251.8±128.1 mg/dl, HbA1c 9.4±2.3%, haemoglobin 11.1±1.9 g/dl, WBC 13586.4±6889.9

k/ul, neutrophil 11092±6730.7 k/ul, lymphocyte 1758.8±893.9 k/ul, monocyte 806.9±400.5

k/ul, platelet 377278.6±142179.5 k/ul, CRP 13.3±10.8 mg/dl, ESH 83.2±30.9 mm/h, PCT

2.7±12.4 ng/ml, NLR 8.4±7.9, PLR 261.7±162.6 and LMR 2.7±1.9.

The mean value of PLR was significantly higher in patients with osteomyelitis (p=0.008). On

the contrary, NLR and LMR had no diagnostic value in predicting osteomyelitis (p=0.121,

p=0.617) (Table 2). The area under the receiver operating characteristic (ROC) curve (AUC)

value for PLR was 0.611 (95% confidence interval (CI), 0.519-0.703) with the cut off point of

187.3 in predicting osteomyelitis. Applying ROC curve at the cut off point of 187.3, PLR

yielded 67.9% sensitivity and 59.1% specificity (Table 3) (Figure 1).

Mean NLR value was found higher in peripheral arterial disease in DFI (p=0.007). However,

no significant difference was found in terms of PLR and LMR values in the prediction of

arterial disease (p=0.052, p=0.191) (Table 2). The significant cut-off value of NLR was

determined as 6.5 and AUC was 0.588 (95% CI, 0.516-0.660) in distinguishing arterial

disease (Table 3) (Figure 1).

The initial values of NLR, PLR and LMR in amputated patients were significantly different

from medically treated patients (Table 2). Both NLR and PLR values were higher in

amputated patients (11.2±9.4 and 310.9±200.9) compared with medically treated patients

(6.6±6.8 and 218±120.1) (p<0.001, p<0.001). On the contrary, LMR value was found

statistically lower in amputated group than medically treated group (2.3±2 and 3.1±2,

p=0.006). Mean NLR and PLR values of amputated patients (11.2±9.4 and 310.9±200.9) was

higher than those treated with debridement/drainage (6±3.4 and 232.5±86.2) (p<0.001,

p=0.002). Additionally, NLR value of patients undergoing major amputation was different

significantly than those who undergoing minor amputation (12.9±9.8 and 8.5±8.1, p=0.013).

ROC curve analyses and AUC values according to the amputation status were given in Table

3 and Figure 1.
NLR, PLR and LMR values were insignificant in predicting peripheral neuropathy and

treatment outcome in patients with DFI (Table 2).

Discussion

The present study represents the first study to investigate the values of NLR, PLR and LMR

in predicting osteomyelitis, peripheral vascular disease, peripheral neuropathy, and need for

amputation in DFI. There are several main findings of our study. First, elevated NLR was

found in patients with peripheral arterial disease and in patients who require amputation.

Among patients who need amputation, NLR value was also found higher in patients who need

major amputation. Second, increased PLR was found in patients with diabetic foot

osteomyelitis and in patients undergoing amputation. But unlike NLR, PLR was not

significant in patients who need major amputation. Third, LMR was useful only in

distinguishing amputated patients from medically treated patients. Furthermore, unlike NLR

and PLR, lower levels of LMR were associated with risk of amputation. And fourth, NLR,

PLR and LMR values were insignificant in predicting peripheral neuropathy and treatment

outcome in patients with DFI.

Urgent aggressive debridement to remove dead tissues, appropriate antimicrobial therapy,

improvement of metabolic control, determination and treatment of predisposing factors such

as peripheral vascular disease and neuropathy are necessary for wound healing and limb

salvage (3). Therefore, early detection of peripheral vasculopathy, peripheral neuropathy and

osteomyelitis as well as timely surgical interventions are essential factors for early diagnosis

and timely treatment of high-risk diabetic foot.

The pathopysiological conditions including inflammation, endothelial dysfunction and

procoagulant imbalance play an important role in the development of both diabetes and

diabetes-related complications (10). The interplay between metabolic and inflammatory

disorders in diabetic patients cause tissue damage and ultimately nephropathy, retinopathy,
neuropathy, microangiopathy and macrovascular complications occur in the majority of

diabetic patients (10,11). Some investigations have indicated that changes in circulating

inflammatory biomarkers that play a role in this pathopysiological process may offer new

perspectives on the early diagnosis and targeted therapy in diabetes and its complications

(6,8,12,13).

The systemic inflammatory process leads to changes in neutrophil, lymphocyte, monocyte and

platelet levels (8). There are many studies indicating that NLR, PLR and LMR may predict

systemic inflammation and these markers may be useful in many diseases (6-8). Despite the

close association between inflammation and diabetes, the value of these biomarkers in DFI

has not been well studied. Abnormal immune functions of leukocytes appear due to impaired

glucose metabolism in diabetes (14). Defective neutrophil function has been determined as a

major factor for the development of infection in diabetes (14). Endothelial damage, which is

reported to cause worse outcome in diabetic wounds, is caused by the effects of inflammatory

mediators released from neutrophils (15). Moreover, these inflammatory mediators induce

thrombocytosis by stimulating megakaryocytes (16). Therefore, it has been suggested that

increased level of platelet is indicative of prothrombotic activity and ongoing inflammatory

condition (17). Lymphocyte levels are also influenced by inflammatory states. Lymphocytes

represent a modulatory effect on controlling inflammation and lymphocytopenia occurs due to

accelerated apoptosis of lymphocytes during systemic inflammation (16,18). Additionally

studies have stated that, in diabetic patients, hyperglycemia causes an increase in reactive

oxygen species and lymphocyte levels may decrease as a result of oxidative DNA damage in

lymphocytes (19). The high NLR, high PLR and low LMR detected in our study may be

attributed to an opposite effect of inflammation on lymphocyte counts.

The combined effect of peripheral arterial disease and neuropathy are among the most

common reasons of diabetic foot ulcers and DFI (2,3). Although the contribution of
inflammatory process to the pathogenesis of diabetic neuropathy has not yet been fully

elucidated, the role of systemic inflammation is widely recognized in the development and

progression of atherosclerosis which is closely related to peripheral arterial disease (3,5,6).

Neutrophil counts increases in atherosclerotic plaque, which plays proinflamatory role and

leads to adhesion and transmigration of platelet and monocytes through the vessel wall (20).

Gary et al. demonstrated that elevated NLR with a cut off 3.95, elevated PLR with a cut off

150 and decreased LMR with a cut off 3.1 were associated with a high risk for critical limb

ischemia in peripheral arterial disease (20,21). In another study, NLR was correlated with the

severity of peripheral arterial disease (22). However in these studies diabetic and non-diabetic

patients were assessed together. Furthermore, all patients had peripheral arterial disease and

no diagnostic evaluation was performed in terms of peripheral arterial disease. According to

best of our knowledge, this is the first report to evaluate the value of NLR, PLR and LMR in

predicting peripheral arterial disease in diabetic patients. We found that only NLR>6.5 was

associated with peripheral arterial disease in patients with DFI. Although PLR and LMR are

not found useful in predicting peripheral arterial disease, we conclude that PLR and LMR,

which are indicated to be useful in determining vascular endpoint such as critical limb

ischemia and myocardial infarction (20), may be beneficial to predict severity of peripheral

arterial disease in DFI. In addition, since all 3 inflammatory markers examined in our study

were found insignificant in discriminating peripheral neuropathy, we suggest that the

contribution of other pathological processes may be greater than inflammation in the

pathogenesis of diabetic neuropathy.

Some immunological defects including lymphocyte and macrophage dysfunction have been

reported in chronic osteomyelitis (23). Among NLR, PLR and LMR, we observed that only

NLR was evaluated in terms of osteomyelitis in a few study. Yapıcı et al. demonstrated that

NLR was significantly higher in patients with osteomyelitis than in patients without
osteomyelitis in DFI (12.3±8.6 and 6.0±3.7, p= 0.004) (12). However, cut-off, sensitivity and

specificity values of NLR were not reported in this study. Ong et al. also reported that NLR

was higher in diabetic patients with osteomyelitis than in those with noninfected ulcer

(3.51±2.42 and 7.59±8.19, p= 0.0229) (24). In this study, the cut off value for NLR was 3.5

with 35.6% sensitivity and 71.4% specificity in discriminating infection in diabetic foot.

Additionally, Schattner et al. reported that thrombocytosis is a new promising laboratory

finding in discriminating osteomyelitis in chronic leg ulcers (25). In our study, only PLR was

predictive of osteomyelitis in DFI. We anticipate that cytokine-induced reactive

thrombocytosis secondary to infection leads to an increase in PLR, thus PLR may be a useful

biomarker in predicting osteomyelitis in DFI. However, it is necessary to eliminate other

causes of thrombocytosis to obtain reliable results in predicting osteomyelitis. Additionally,

normal or low levels of PLR may not be used to rule out osteomyelitis. There is a need for

prospective extensive research in this regard.

The leading etiological cause of nontraumatic lower limb amputation is diabetes (26). In

recent publications, elevated NLR and PLR were reported to be associated with risk of

amputation (26-28). In a study conducted by Tasoglu et al., preoperative NLR≥5.2 was found

to be independent predictive factor for amputation in acute limb ischemia (27). In another

study, increased NLR and PLR were associated with extremity amputation in acute arterial

occlusions (28). However, diabetes-related lower extremity amputation was not assessed in

these studies. Only one other study, need for amputation was evaluated in patients with DFI

and NLR was found to be a predictor of amputation (12). But, cut off value for predicting

amputation was not determined in this study. We demonstrated that all three inflammatory

biomarkers had a predictive value in predicting amputation in DFI. In addition, our findings

take this one step further. We observed that NLR and PLR were also significantly higher in

patients who required amputation than in patients who required debridement/drainage.

Furthermore, NLR was found to have a predictive value in determining amputation levels in

DFI.

There are some limitations in our study. The current study is a retrospective and single-center

study. In addition, the stabilities of NLR, PLR and LMR for each patient were not assessed

over time. Moreover, prognostic values of these biomarkers were not evaluated in this study.

Further prospective, large randomized controlled studies should be performed to confirm

these results and NLR, PLR and LMR may also be investigated for their prognostic influence

in DFI.

Conclusion

On the basis of our study, NLR can predict peripheral arterial disease and elevated PLR can

predict osteomyelitis in DFI. NLR, PLR and LMR are predictive of the need for surgical

intervention in DFI. We conclude that these inflammatory biomarkers are simple, broadly

available and cost-effective promising parameters in DFI.

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Table 1. Causative microorganisms isolated from soft tissue specimens

Microorganisms Number (n) Percent (%)

Pseudomonas aeruginosa 33 19.2

Escherichia coli 31 18

Staphylococcus aureus 22 12.8

Enterococcus 15 8.7

Streptococcus 13 7.6

Klebsiella pneumoniae 13 7.6

Proteus mirabilis 12 6.9

Acinetobacter baumanii 10 5.8

Enterobacter 6 3.5

Citrobacter 6 3.5

Morganella morganii 4 2.3

Serratia marcescens 3 1.7

Gemella morbillorum 1 0.6

Pasteurella pneumotropica 1 0.6

Achromobacter 1 0.6

Candida albicans 1 0.6

 Table 2. NLR, PLR and LMR values according to clinical status, treatment type and treatment

outcome

Parameters NLR p PLR p LMR p

Yes 7.9±7.5 261±161.9 2.9±1.9
Osteomyelitis 0.121 0.008 0.617
No 6.2±5.6 200.9±85.4 2.8±1.7
Peripheral Yes 9.9±9.3 287.4±175.7 2.5±1.8
arterial 0.007 0.052 0.191
No 7.1±6.1 247±147.5 2.8±1.8
disease
Yes 9.8±11.5 285.8±207.4 3.1±2.9
Peripheral
0.158 0.117 0.797
neuropathy No 6.6±5.8 222.7±96.2 2.9±1.8

Treatment type
Amputation 11.2±9.4 310.9±200.9 2.3±2
<0.001 <0.001 0.006
Medical 6.6±6.8 218±120.1 3.1±2
Amputation 11.2±9.4 310.9±200.9 2.3±2
Debridement/ <0.001 0.002 0.093
Amputation 6±3.4 232.5±86.2 2.8±1.7
drainage
status
Major
12.9±9.8 340.8±209.4 2.3±2.3
Amputation
0.013 0.053 0.719
Minor
8.5±8.1 264.9±179.9 2.4±1.6
Amputation
Treatment outcome
Yes 8.6±8.4 256.8±143.8 2.7±2.4
Re-operation 0.305 0.591 0.468
No 7.5±6.8 244.9±155 2.9±1.9
Chronic Yes 6.3±5.7 238.1±138.4 3.2±2
0.143 0.630 0.223
wound No 8.1±7.5 250.6±154.7 2.8±2
 Complete Yes 7.9±7.1 247.3±160.8 2.8±1.8
0.840 0.910 0.783
recovery No 7.7±7.5 249.5±141.4 2.9±2.2
NLR: neutrophil to lymphocyte ratio, PLR: Platelet to lymphocyte ratio, LMR: Lymphocyte

to monocyte ratio

Table 3. NLR, PLR and LMR values in predicting osteomyelitis, peripheral arterial disease,

peripheral neuropathy and need for amputation in diabetic foot infections.

Variables AUC p value Cut Sensitivity Specificity +LR -LR +PV -PV

off* (%)** (%)** (%) (%)

Osteomyelitis

NLR 0.556 0.244 >6.9 39.7 (28.8-51.5) 77.3 (65.3-86.7) 1.7 0.8 67.4 52

PLR 0.611 0.018 >187.3 67.9 (56.4-78.1) 59.1 (46.3-71) 1.7 0.5 66.2 60.9

LMR 0.513 0.793 ≥3.8 28.2 (18.6-39.5) 81.8 (70.4-90.2) 1.6 0.9 64.7 49.1

Peripheral arterial disease

NLR 0.588 0.016 >6.5 53.3 (43.4-63) 63 (54.4-71.1) 1.4 0.7 52.8 63.5

PLR 0.568 0.069 >317.5 33.6 (24.8-43.4) 80.4 (72.8-86.7) 1.7 0.8 57.1 61

LMR 0.569 0.065 ≤1.6 42.9 (33.5-52.9) 73.7 (65.5-80.9) 1.6 0.8 56.1 62.3

Peripheral neuropathy

NLR 0.532 0.712 >8.4 42.1 (20.3-66.5) 76.9 (60.7-88.9) 1.8 0.7 47.1 73.2

PLR 0.528 0.765 >394.6 31.6 (12.6-56.6) 94.9 (82.7-99.4) 6.2 0.7 75 74

LMR 0.560 0.484 ≤2.3 63.2 (38.4-83.7) 57.9 (40.8-73.7) 1.5 0.6 42.9 75.9

Amputation

NLR 0.674 <0.0001 >8.2 53.2 (43.4-62.8) 77.1 (70-83.3) 2.3 0.6 60.4 71.5

PLR 0.634 0.0002 >337.8 35.8 (26.8-45.5) 89.8 (84.1-93.9) 3.5 0.7 69.6 68
LMR 0.656 <0.0001 ≤2.1 65.1 (55.4-74) 66.7 (58.9-73.8) 1.9 0.5 56.3 74.3

NLR: neutrophil to lymphocyte ratio, PLR: Platelet to lymphocyte ratio, LMR: Lymphocyte

to monocyte ratio, AUC: Area under the receiver operating characteristic curve, LR:

Likelihood ratio, PV: Predictive value

*Youden index was used in determining cut off value

** Presented with 95% confidence interval

Figure l. Receiver operating characteristic curves (ROC) analysis for various cutoff levels of

NLR, PLR and LMR in differentiating peripheral arterial disease (1-a, 1-b, 1-c), peripheral

neuropathy (2-a, 2-b, 2-c), osteomyelitis (3-a, 3-b, 3-c) and need for amputation (4-a, 4-b, 4-c)

in diabetic foot infection

NLR: neutrophil to lymphocyte ratio, PLR: Platelet to lymphocyte ratio, LMR: Lymphocyte

to monocyte ratio
Highlights

 Elevated NLR was found in patients with peripheral arterial disease and in patients

who require amputation.

 Increased PLR was found in patients with diabetic foot osteomyelitis and in patients

undergoing amputation.

 LMR was useful only in distinguishing amputated patients from medically treated

patients.

 NLR, PLR and LMR were predictive of the need for surgical intervention in DFI.

 NLR, PLR and LMR values were insignificant in predicting peripheral neuropathy and

treatment outcome in patients with DFI.