Predictors of the outcome of Predictors of the outcome of diabetic foot ulcer at Assiut diabetic foot ulcer at Assiut

university hospitaluniversity hospital ByBy

Walaa Anwar Muhammad KhalifaWalaa Anwar Muhammad Khalifa

M.B.B.CHM.B.B.CHM.ScM.ScFaculty of medicineFaculty of medicine

Assiut UniversityAssiut University

Under supervision ofUnder supervision ofProf. Dr. Lobna Farag EltoonyProf. Dr. Lobna Farag Eltoony

Professor of internal medicine&head of endocrinology unitProfessor of internal medicine&head of endocrinology unitFaculty of medicineFaculty of medicineAssiut UniversityAssiut University

Dr. Mona Muhammad SolimanDr. Mona Muhammad SolimanLecturerLecturer of internal medicine of internal medicine

Faculty of medicineFaculty of medicineAssiut UniversityAssiut University

IntroductionIntroduction Diabetic foot ulcers are a common and much Diabetic foot ulcers are a common and much

feared complication of diabetes, with recent feared complication of diabetes, with recent studies suggesting that the lifetime risk of studies suggesting that the lifetime risk of developing foot ulcer in diabetic patients may be developing foot ulcer in diabetic patients may be as high as 25% (Singh et al.,2005).as high as 25% (Singh et al.,2005).

Up to 50% of older patients with type 2 diabetes Up to 50% of older patients with type 2 diabetes have one or more risk factors for foot ulceration. have one or more risk factors for foot ulceration.

A list of the principal risk factors that might A list of the principal risk factors that might result in foot ulcer development are result in foot ulcer development are demonstrated ( Abbott et al ., 2002.) demonstrated ( Abbott et al ., 2002.)

Risk factors of foot ulcerRisk factors of foot ulcer1-1- Previous amputation.Previous amputation.

2-2- Past history of foot ulceration.Past history of foot ulceration.

3-3- Peripheral neuropathy.Peripheral neuropathy.

4-4- Peripheral vascular disease.Peripheral vascular disease.

5-5- Foot deformityFoot deformity..

6-6- Visual impairment.Visual impairment.

7-7- Diabetic nephropathy.Diabetic nephropathy.

8-8- Poor glycemic controlPoor glycemic control..

9-9- Cigarette smokingCigarette smoking

The most common triad of causes that The most common triad of causes that

interact and result in foot ulceration has interact and result in foot ulceration has

been identified asbeen identified as neuropathy neuropathy,, deformity deformity

and and traumatrauma ( Boulton et al., 2004) ( Boulton et al., 2004)

• The risk of amputation is 15 to 40 times The risk of amputation is 15 to 40 times greater in a person with diabetes than in greater in a person with diabetes than in one who doesn't have the disease one who doesn't have the disease

( Nabuurs et al..2005).( Nabuurs et al..2005).

The population of diabetic patients who The population of diabetic patients who present with foot ulceration are present with foot ulceration are

heterogenous,there are characteristics that heterogenous,there are characteristics that may vary among patients, such as the may vary among patients, such as the presence of peripheral arterial disease presence of peripheral arterial disease

infection,andco-morbidities. infection,andco-morbidities. Peripheral arterial disease is considered Peripheral arterial disease is considered

an important predictor of outcomean important predictor of outcome (Prompers et al., 2007).(Prompers et al., 2007).

Therefore. Outcome data on these patients Therefore. Outcome data on these patients with diabetic foot ulcer are needed such a with diabetic foot ulcer are needed such a requirement is underlined by the fact that requirement is underlined by the fact that although diabetic foot ulcers are usually although diabetic foot ulcers are usually reported and analyzed as one clinical entity reported and analyzed as one clinical entity marked differences in patient, foot and marked differences in patient, foot and ulcer characteristics can exist between ulcer characteristics can exist between patientspatients. . These observations raise the These observations raise the question of wether predictors of outcome in question of wether predictors of outcome in patients may differ (Prompers et al., 2007).patients may differ (Prompers et al., 2007).

The aim of the studyThe aim of the study To assess the potential baseline clinical and To assess the potential baseline clinical and

laboratory characteristics that best predict poor laboratory characteristics that best predict poor outcome (non healing of the foot ulcer).outcome (non healing of the foot ulcer).

The main outcome of the study is complete The main outcome of the study is complete healing of the foot within the maximum follow healing of the foot within the maximum follow up period of 1 year.up period of 1 year.

Healing was defined as healing (intact skin) of Healing was defined as healing (intact skin) of the whole foot at two consecutive visits. the whole foot at two consecutive visits.

Patients & study designPatients & study design It is a prospective study in which 100 It is a prospective study in which 100

patients with diabetic foot ulcer will be patients with diabetic foot ulcer will be followed and managed for 1 year.followed and managed for 1 year.

About 50 patients are still under About 50 patients are still under research.research.

Patients includedPatients included were those presenting were those presenting for the first time with a new foot ulcer for the first time with a new foot ulcer within period of 12 months.within period of 12 months.

Excluded patientsExcluded patients 1- Patients who had been treated for an 1- Patients who had been treated for an

ulcer on the ipsilateral foot during the ulcer on the ipsilateral foot during the previous 12 months. previous 12 months.

2- Patients with sever end organ 2- Patients with sever end organ failure.failure.

3- Patients with gangrenous foot. eg, 3- Patients with gangrenous foot. eg, gas gangrene.gas gangrene.

MethodMethod Data collected prospectively of patients Data collected prospectively of patients

referred to a foot care clinic referred to a foot care clinic recorded recorded Data include. Data include.

Demographics,detailed history and complete Demographics,detailed history and complete physical examinationphysical examination

Data on co- morbidities including ( retinopathy Data on co- morbidities including ( retinopathy nephropathy, hypertension and ischemic heart nephropathy, hypertension and ischemic heart disease) .disease) .

Data on foot examinationData on foot examination include. include.

(foot inspection, Pedal pulse, (foot inspection, Pedal pulse, ABI measurement and joint ABI measurement and joint examination).examination).

Data on ulcer characteristics.Data on ulcer characteristics. ulcers were classified ulcers were classified

according toaccording to1-PEDIS system.1-PEDIS system. ( perfusion, extent, depth, ( perfusion, extent, depth,

infection and sensation ) infection and sensation ) ..

22 - -Meggitt- wagner classification of foot ulcers

Grade0Grade0:Pre- or post- ulcerative lesion :Pre- or post- ulcerative lesion completely epithelializedcompletely epithelialized

Grade1Grade1:Superficial, full thickness:Superficial, full thickness ulcer limited ulcer limited to the dermis, not extending to the subcutisto the dermis, not extending to the subcutis

Grade 2Grade 2:Ulcer of the skin extending through the :Ulcer of the skin extending through the subcutis with exposed tendon or bone and subcutis with exposed tendon or bone and without osteomyelitis or abscesswithout osteomyelitis or abscess

Grade 3Grade 3:Deep ulcers with osteomyelitis or :Deep ulcers with osteomyelitis or abscess formationabscess formation

GradeGrade 44:Localized gangrene of the toes or the :Localized gangrene of the toes or the forefoot forefoot

GradeGrade 55:Foot with extensive gangrene:Foot with extensive gangrene

3- The university of Texas classification 1998

StageStageGradeGrade

00112233

AAPre- or post- Pre- or post- ulcerative ulcerative lesion lesion completely completely epithelailizd epithelailizd

Superficial Superficial wound not wound not involving involving tendon, tendon, capsule or capsule or bone bone

Wound Wound penetrating penetrating to tendon or to tendon or capsule capsule

Wound Wound penetrating penetrating to bone or to bone or joint joint

BBWith With infectioninfection

With With infection infection

With With infectioninfection

With With infectioninfection

CCWith With ischemiaischemia

With With ischemiaischemia

With With ischemiaischemia

With With ischemiaischemia

DDWith With infectioninfectionand and ischemiaischemia

With With infectioninfectionand and ischemiaischemia

With With infectioninfectionand and ischemiaischemia

With With infectioninfectionand ischemiaand ischemia

Laboratory data includeLaboratory data include

Complete blood picture, liver Complete blood picture, liver function, urea and creatinine ,24 function, urea and creatinine ,24 hrs proteins in urine, creatinine hrs proteins in urine, creatinine clearance, lipogram and (Hb A1c)clearance, lipogram and (Hb A1c)

. .

Management of diabetic foot ulcerManagement of diabetic foot ulcer

All Patients were treated According to protocols based All Patients were treated According to protocols based on the international consensus on the diabetic foot on the international consensus on the diabetic foot which include offloading ,diagnosis and treatment of which include offloading ,diagnosis and treatment of infection, assessment of vascular status and regular infection, assessment of vascular status and regular wound debridement . wound debridement .

Results of 50 patients:In 50 patients: 34 (68%) females ,the mean age 50.76 ± 13.35.

Diagram (2) :shows results of patient characteristics

non-smokers

past history of amputation

insulin therapy

neuropathic symptom

s

0

10

20

30

40

50

no.

of c

a ses

Diagram(3):shows results of Diagram(3):shows results of foot inspectionfoot inspection

VariableVariableHealedHealed(n= 31)(n= 31)

UnhealedUnhealed(n= 19)(n= 19)

TotalTotal(n= 50)(n= 50)P-valueP-value

Age:47.39 ± 11.4247.39 ± 11.4256.26 ± 16.7656.26 ± 16.7650.76 ± 13.3550.76 ± 13.350.0210.021

Sex:

0.0140.014 Males n%6(37.5%)6(37.5%)10(62.5%)10(62.5%)1616

Females n%25(73.6%)25(73.6%)9(26.4%)9(26.4%)3434

Smoking (n%)2(20.0%)2(20.0%)8(80.0%)8(80.0%)10100.0070.007

BMI31.64 ± 3.8831.64 ± 3.8829.21 ± 5.6029.21 ± 5.6030.72 ± 4.7130.72 ± 4.71NSNS

Diabetes duration:

0.0010.001 < 10 years22(84.6%)22(84.6%)4(15.4%)4(15.4%)2626

≥ 10years9(37.5%)9(37.5%)15(62.5%)15(62.5%)2424

Insulin use (n%)25(61.0%)25(61.0%)16(39.0%)16(39.0%)4141NSNS

Retinopathy (n%)10(50%)10(50%)10(50%)10(50%)2020NSNS

Hypertension10(47.6%)10(47.6%)11(53.4%)11(53.4%)2121NSNS

Ischemic heart disease6(42.9%)6(42.9%)8(57.1%)8(57.1%)1414NSNS

Nephropathy6(35.3%)6(35.3%)11(64.7%)11(64.7%)17170.0050.005

Table(1)Baseline characteristics of patients with healed and unhealed ulcers

VariableHealed( n=31)Unhealed n=19TotalP-value Sever neuropathy(n %4(30.7%)9(69.3%)130.018ABI0.93±0.050.75±0.090.86±0.80.000Colour change (n%)1(10%)9(90.0%)100.001Superficial infection8(53.3%)7(46.7%)15NSDeep infection2(20%)8(80%)100.007Ulcer site:

For foot10(32.2%)3(15.8%)13NSMid foot4(12.9%)4(21%)8NSHind foot6(19.3%)7(36.8%)13NSToes8(25.8%)4(21%)12NSDorsum3(9.6%)1(5.2%)4NS

Ulcer extent0.009 1-5cm23(76.7%)7(23.3%)30

>5cm8(40.0%)12(60.0%)20Ulcer duration

0.001 <1 week15(88.3%)2(11.7%)171 week-3months13(68.4%)6(31.6%)19>3 months3(21.4%)11(78.6%)14

Table(2)Baseline characteristics of ulcer examination and relation to healing

VariableHealedUnhealed Totalp. value Ulcer depth (n%)

0.005Grade.116(88.9%)2(11.1%)18Grade.213(54.2%)11(45.8%)24Grade.32(25.0%)6(75.0%)8

Texas class. (n%)1A+2A21(84%)4(16%)250.0012D+3D1(10.0%)9(90.0%)100.001

Wagner class. (n%):

0.001Grade 116(88.9%)2(11.1%)18Grade 213(59.1%)9(40.9%)22Grade 32(20%)8(80%)10

Base line characteristics of ulcer examination and relation to healing (cont.)

Table (3) aboratory data and relation to healing VariableUnHealed n=19Healed n=31P-value

Urea mmol/L8.09 ± 2.636.68 ± 1.94NS

S.Creatinine umol/L206.63 ± 165.5093.36 ± 36.600.001

Cr.Clearance ml/min56.25 ± 32.0792.53 ± 27.180.000

24 hr protein in urine mg/l442.42 ± 226.22229.71 ± 149.420.000

WBCS k/ul11.39 ± 3.907.33 ± 2.040.000

Hgb gm/dl10.11 ± 1.7311.62 ± 1.080.004

Platelets k/ul247.00 ± 28.93235.10 ± 27.07NS

Hb A1c H%12.88 ± 2.038.06 ± 0.990.008

Serum albumin g/l26.28 ± 5.8730.69 ± 4.370.004

Bilirubin umol/l11.31 ± 3.0510.97 ± 2.61NS

ALT Iu/l20.31 ± 4.8115.72 ± 6.20NS

AST Iu/l18.03 ± 6.4616.65 ± 5.95NS

S. Cholest mg/dl228.47 ± 67.16189.39 ± 45.350.010

TG mg/dl162.56 ± 40.69139.42 ± 87.640.000

HDLmg/dl37.49 ± 8.0743.15 ± 8.600.000

LDLmg/dl113.42 ± 29.7895.92 ± 16.140.048

Predictor variablePredictor variableOutcome: Outcome: unhealingunhealing

Sig.Sig.OROR95.0%C.I.95.0%C.I.

Duration of diabetes: > 10 yrsDuration of diabetes: > 10 yrs0.008*0.008*2.162.161.02-2.611.02-2.61

Male sexMale sex0.024*0.024*1.111.111.03-2.861.03-2.86

Sever p.neuropathySever p.neuropathy0.012*0.012*1.131.130.89-1.460.89-1.46

Texas grade 2D, 3DTexas grade 2D, 3D0.004*0.004*1.241.241.15-3.241.15-3.24

Wagner grade-3Wagner grade-30.005*0.005*1.181.181.09-2.981.09-2.98

>3 months Ulcer duration>3 months Ulcer duration0.013*0.013*1.121.121.33-2.851.33-2.85

ABI< 0.8ABI< 0.80.006*0.006*1.161.161.05-2.681.05-2.68

Table (4)Multivariate regression analysis of predictor variables towards unhealing.

Case (1)Case (1)

Case (2)Case (2)

Case (3)Case (3)

Case 4

Case 5

Case 6

Unhealed cases Unhealed cases

Conclusion In conclusion, the major findings from this

study are, male sex, duration of diabetes ≥10years, sever pripheral neuropathy, ulcer duration>3month,Wagner grade3,Texas grade2D,3D and limb ischemia as ABI<0.8 independently predict poor outcome (unhealing) of diabetic foot ulcer .

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