Abstract:

Iraqi J Pharm Sci, Vol.20(1) 2011 HbA1c and foot ulceration

Measurements of HbA1c for Patients with Diabetes

Mellitus and Foot Ulceration
Mohammed A.Taher

*,1
, Mayada M. Moustafa

*
, Aqeel S. Mahmood

*Department of Clinical Laboratory Sciences,College of Pharmacy,University of Baghdad,Baghdad, Iraq.

**Medical City , Baghdad Teaching Hospital, Baghdad, Iraq.

Abstract
People with diabetes can develop different foot problems. In the blood stream glucose reacts with

hemoglobin to make a glycosylated hemoglobin molecule called hemoglobin A1c or HbA1c, the more

glucose in the blood the more hemoglobin A1c will be present in the blood. The HbAlc test is currently

one of the best ways to check diabetes to be under control. The aim of study is to compare between the

blood investigations which includes the fasting blood sugar and HbAlC (glycosylated hemoglobin), and

to evaluate the benefit of HbAlc (measurement for diabetic patients with foot ulcer, to be a good

indicator for controlling blood glucose). Sixty patients with type2 diabetes mellitus from the outpatient

clinic of Baghdad Teaching Hospital, Medical City over the period from Nov. 2006 to Nov. 2008, were

included in the study. Follow up was done only to 30 patients with diabetic foot ulcer. Twenty

(66.66%) were males and 10(33.33%) were females their age range from (23-75) years (mean age of

52years), and 21 normal subjects as control. A (Glycohemoglobin HbAl-Test/fast lon-Exchange Resin

Separation Method) kit was used. The data finding that there is a greater association between HbAlc

level and foot ulceration healing. There is a relationship between the age of the patients and the HbAlc

level. The patients who used (Glibenclamide+Metformin) have the lower range of HbAlC, while those

who use (Metformin) have the higher level of HbAlc. HbAlc (glycosylated hemoglobin) is most

accurate test to determine actual reading over the past 2-3 months, and to evaluating the risk of

glycemic damage to the tissues. So, we recommend the HbAlc testing, but it can't be used to monitor

day-to-day blood glucose concentration because it's not influenced by fluctuation in blood

concentration.

Key words: Diabetic foot ulcer, HbAlc

الخالصة
ّىٓ اْ تتطٛر ٌد٠ُٙ اٌحاٌة اٌّزظي١ة اٌيٝ اابيابة بتمز يا ليٟ اٌميدَ ج ليٟ ِميزٜ اٌيدَ ش٠ يا ّاٌّصاب١ٓ بداء اٌسىزٞ ِٓ اٌ

ٚوٍّيا وأيك و١ّية اٌىٍٛويٛس HbA1cاٚ A1cاٌىٍٛوٛس تٍتصك با١ٌّٙٛغٍٛب١ٓ ٌتى٠ٛٓ وال٠ىٛس١ال٠تد ١ّ٘ٛغٍٛب١ٓ ٚتدعٝ ١ّ٘ٛغٍيٛب١ٓ

ٚا يد ِيٓ HbA1cٚ يد ليٟ ااٚٔية ااة١يزن بياْ ااسيتاأة باةتتيار ِسيتٜٛ اوثز ج ٌمد A1cلٟ اٌدَ اوثز وٍّا وأك و١ّة ا١ٌّٙٛغٍٛب١ٓ

اٌغا٠ة ِٓ ٘ذٖ اٌدراسة ٌٍّمارٔة بي١ٓ اٌطيزق اٌّتتاية ٚاٌّاتّيد ع١ٍٙيا ليٟ ٞ اٌٛالع تحك اٌس١طزن جالعً اٌطزق ٌٍتحمك ِٓ ِزض اٌسىز

ٌسيىزٞ ليٟ اٌية اٌصي١اَ ِٚمارٔتيٗ باةتتيار ِسيتٜٛ اٌس١طزن عٍٝ ٔستة اٌسيىز ٌيدٜ اٌّزظيٝ اٌسيىزٞ ِيٓ إٌيٛن اٌثيأٟ خ ِثيً اةتتيار ا

30شخص ِصاب١ٓ بّزض اٌسىزٞ ِٓ إٌيٛن اٌثيأٟ ٚاسيتّز اٌدراسية عٍيٝ 60اٌىال٠ىٛس١ال٠تد ١ّ٘ٛغٍٛب١ٓ ج ا ز٠ك اٌدراسة عٍٝ

%( ج 33.33) 10( ٚاأيا 66.66%) 20سٕة ٚواْ عيد اٌيذوٛر 75-23شخص ُِٕٙ ِصاب بتمز ا لٟ اٌمدَ ٚبّادي عّزٞ ِٓ

شخص س١ٍُ غ١يز ِصياب بيداء اٌسيىزٞ ٌٚي١ه ٌد٠يٗ تمز يا )ِمّٛعية سي١طزن( ٚليد ٚ يدٔا ٔت١مية ٘يذٖ اٌدراسية بياْ 21بـ وّا استا١ٓ

ج وّيا ٚ يدٔا ٕ٘يان عاللية بي١ٓ عّيز ٚشيفاء تمز يا اٌميدَ HbA1cتف١يد بياْ ٕ٘يان عاللية وت١يزن بي١ٓ ِسيتٜٛ إٌتائج اٌّستحصيً ع١ٍٙيا

ٛس١ال٠تد ١ّ٘ٛغٍٛب١ٓ لٟ اٌدَ خ ويذٌه ٚ يدٔا ِيٓ ةيالي ٘يذٖ اٌدراسية بياْ اٌّزظيٝ اٌّاياٌم١ٓ بّمّٛعية اا ٠ٚية اٌّز٠ط ٚٔستة اٌىال٠ى

اٌّخفعيية ٌٍسييىز )١ِتفييٛر١ِٓ ي و١ٍت١ٕىالِا٠ييد( لييد أخفييط ِسييتٜٛ اٌىال٠ىٛسيي١ال٠تد ١ّ٘ٛغٍييٛب١ٓ اوثييز ِييٓ ِمّٛعيية اٌّزظييٝ اٌييذ٠ٓ

٠ىٛس١ال٠تد ١ّ٘ٛغٍٛب١ٓ اعٍٝ ج تستٕتج اٌدراسة باْ اٌىال٠ىٛس١ال٠تد ١ّ٘ٛغٍٛب١ٓ ٘يٛ استاٍّٛا )ا١ٌّتفٛر١ِٓ( لمط ١ث واْ ِستٜٛ اٌىال

اشٙز سابمة ٌٚتمد٠ز اٌخطٛرن اٌتٟ ٠تازض ٌٙا اٌّصياب ج ٌيذٌه ٔٛبيٟ باسيتاّاي 3 – 2ابح اةتتار ٌتا١١ٓ اٌم١ّة اٌحم١م١ة ٌٍسىز بّدن

جّة اٌسىز اٌّتغ١زن ١ِٛ٠ااط١ٕا ل١اةتتار اٌىال٠ىٛس١ال٠تد ١ّ٘ٛغٍٛب١ٓ تٝ ٚاْ واْ ا٠

Introduction
People with diabetes can develop

different foot problems
[1,2]

. Foot problems

most often occur when there is neuropathy,

poor blood flow , or changes in the shape of

feet toes
[2-4]

, Ulcers occur most often on the

ball of the foot or in the bottom of the big toe.

Neglecting ulcers can result in infections,

which in turn may lead to loss of a limb
[5]

Diabetic patients are at higher risk and they

show 2 - 4 times more likely to have heart

disease or suffer a stroke than people without

diabetes
[5-7]

. In the blood stream glucose reacts

to the hemoglobin to make a hemoglobin

molecule called hemoglobin A1c (HbA1c), the

more glucose in the blood , the more

hemoglobin A1c will be formed in the

blood
[6,7]

. About 90% of hemoglobin is

hemoglobin A
[7]

1Corresponding author E- mail : mayada_aga@yahoo.com

Received : 9/5/2010

Accepted : 3/1/2011

http://en.wikipedia.org/wiki/HbA1c#cite_note-1
http://en.wikipedia.org/wiki/HbA1c#cite_note-1
http://en.wikipedia.org/wiki/HbA1c#cite_note-1
http://en.wikipedia.org/wiki/HbA1c#cite_note-1
http://en.wikipedia.org/wiki/HbA1c#cite_note-1
http://www.medicinenet.com/script/main/art.asp?articlekey=3690
http://www.medicinenet.com/script/main/art.asp?articlekey=3690

Iraqi J Pharm Sci, Vol.20(1) 2011 HbA1c and foot ulceration

Although one chemical component accounts

for 92% of hemoglobin A, approximately 8%

of hemoglobin A is made up of minor

components that are chemically slightly

different. These minor components include

hemoglobin A1c, A1b, A1a1, and A1a2.

Hemoglobin A1c is a minor component of

hemoglobin to which glucose is bound. Thus

it's referred to as glycosylated or glucosylated

hemoglobin
[8-10]

.The HbA1c test is currently

one of the best ways to check diabetes is under

control. The HbA1c level changes slowly, over

10 week, so it can be used as a ((quality

control)) test
[11-13]

. Hemoglobin A1c was first

separated from other forms of hemoglobin by

Huisman and Meyering in 1958 using a

chromatographic column.
[12]

It was first

characterized as a glycoprotein by Bookchin

and Gallop in 1968.
[13]

Its increase in diabetes

was first described in 1969 by Samuel Rahbar

and coworkers the reactions leading to its

formation were characterized by Bunn and his

co-workers in 1975.
[14, 15]

The use of

hemoglobin A1c for monitoring the degree of

control of glucose metabolism in diabetic

patients was proposed in 1976 by Anthony

Cerami, Ronald Koenig and coworkers
[16]

. In

the normal 120-day life span of the red blood

cell, glucose molecules react with hemoglobin,

forming glycosylated hemoglobin. In

individuals with poorly controlled diabetes, the

quantities of these glycosylated hemoglobins

are much higher than in healthy people
[16,

17]
.Once a hemoglobin molecule is

glycosylated, it remains that way. A buildup of

glycosylated hemoglobin within the red cell

therefore reflects the average level of glucose

to which the cell has been exposed during its

life cycle
[18, 19]

. Measuring glycosylated

hemoglobin assesses the effectiveness of

therapy by monitoring long-term serum

glucose regulation. The HbA1c level is

proportional to average blood glucose

concentration over the previous four weeks to

three months
[20]

. Some researchers state that

the major proportion of its value is related to a

rather shorter period of two to four weeks.
[7]

The 2010 American Diabetes Association

Standards of Medical Care in Diabetes added

the A1c ≥ 6.5% as another criterion for the

diagnosis of the diabetes
[21]

. There were

numbers of laboratories techniques used to

measure glycosylated hemoglobin
[22]

 high-performance liquid chromatography
(HPLC).

 Immunoassay.

Patients and methods
Patients with type 2 diabetes mellitus

with foot ulcers seen in the outpatient clinic of

Baghdad Teaching Hospital, Medical City over

the period from Nov. 2006 to Nov. 2008. A

total number of 30 patients with diabetic foot

ulcer and 21 normal subjects.. The age of

patients range from 23-75 years (mean age 52),

as shown in table (1) and occupation of the

patients, in table (2). Diagnosis of the presence

of foot ulcers was made by a specialist

physician through physical examination and x-

ray examination.

For every case, the following had been done,

1. Patient medical history recorded.
2. Full physical examination, a complete

blood picture and renal function test.

3. Lab. Investigations:
a. Fasting blood sugar: was measured in

serum obtained for all subjects blood by a

commercial kit obtained from Biomaghreb,

using the enzymatic method
(23)

b. HbAlC (glycosylated hemoglobin): Method
of measurement was followed according to

the instructions mentioned in

glycohemoglobin HbA1-test kit which

obtained from Wiesbaden-Germany using

blood specimens and EDTA as

anticoagulant
(24) .

4. Request form was given to all patients
which include the details of age, sex,

occupation, symptoms, site of ulcers, table

(3).

5. All 30 patients with diabetic foot ulcer
were put on therapy with oral

hypoglycemic drugs for 3months (we

measured their fasting blood sugar and

HbAlC before and after the therapy). These

drugs, metformin [500mg, 2/day]

Glibenclamide [5mg, 2/day] and

combination of Glibenclamide 5mg

(2/day)+ Metformin 500mg (2/day)
(25)

table (5).

6. The relationship of patients age and
(HbAlC and FBS) were determined, table

(7).

7. A control groups: The control group was
represented by 21 apparently healthy

persons and their FBS (fasting blood sugar)

and HbAlC were measured, table(4).

8. Data were expressed as mean ± standard
deviation and differences between means

were analyzed by paired student's t-test. P

value less than 0.05 were considered

significantly different.

http://www.medicinenet.com/script/main/art.asp?articlekey=3608
http://en.wikipedia.org/wiki/HbA1c#cite_note-1
http://en.wikipedia.org/wiki/HbA1c#cite_note-1
http://en.wikipedia.org/wiki/Chromatography
http://en.wikipedia.org/wiki/HbA1c#cite_note-1
http://en.wikipedia.org/wiki/Glycoprotein
http://en.wikipedia.org/wiki/HbA1c#cite_note-pmid4874776-2
http://en.wikipedia.org/wiki/Samuel_Rahbar
http://en.wikipedia.org/wiki/HbA1c#cite_note-pmid1201013-4
http://en.wikipedia.org/wiki/Anthony_Cerami
http://en.wikipedia.org/wiki/Anthony_Cerami
http://en.wikipedia.org/wiki/HbA1c#cite_note-pmid934240-5
http://en.wikipedia.org/wiki/Red_blood_cell
http://en.wikipedia.org/wiki/Red_blood_cell
http://en.wikipedia.org/wiki/Glycation
http://en.wikipedia.org/wiki/Diabetes
http://en.wikipedia.org/wiki/HbA1c#cite_note-1
http://en.wikipedia.org/wiki/HbA1c#cite_note-1
http://en.wikipedia.org/wiki/Biological_life_cycle
http://en.wikipedia.org/wiki/Biological_life_cycle
http://en.wikipedia.org/wiki/HbA1c#cite_note-1
http://en.wikipedia.org/wiki/HbA1c#cite_note-6
http://en.wikipedia.org/wiki/American_Diabetes_Association
http://en.wikipedia.org/wiki/HbA1c#cite_note-6
http://en.wikipedia.org/wiki/HbA1c#cite_note-1
http://en.wikipedia.org/wiki/High-performance_liquid_chromatography
http://en.wikipedia.org/wiki/Immunoassay

Iraqi J Pharm Sci, Vol.20(1) 2011 HbA1c and foot ulceration

Results
The percentages of diabetic foot ulcer

were greater over 70 years old and less under

30 years old, table (1). While table (2), Shows

the more effected diabetic patients with foot

ulcer were laborers and employees and less

were students. The biggest sites of foot ulcer

were on the bottom of the big toe and less at

the ball of the foot, table (3).Table (4), shows

significant difference between FBS & HbA1c

for diabetic foot ulcer patients and control

group. In table (5), Patients who used

metformin or Glibenclamide and the

combination of them (Glibenclamide +

Metformin) the mean±value HbAlC decreased

significantly after treatment p<0.05. FBSof

patients who used Metformin or Glibenclamide

and combination of them (Glibenclamid

+Metformine) the mean± value of FBS

decreased significantly compared with the

mean value before treatment ,and table (6),

shows patients who used combination of

(Glibenclamide+Metformin) have higher

percentage (53.84%) of healing than patients

treated with Glibenclamide 30.0% or

Metformin 28.57% .Table (7), Shows the

highest level of HbAlC and FBS over 70 years

old patients with foot ulcer and the lowest level

of HbA1c and FBS under 30 years old. Fig.(1)

Show the significant +ve correlation between

age and HbA1c% r=0.82, p< 0.01.

Fig. (2): Show that age of the patients is

proportional to FBS were r=0.8, p< 0.01.

For people without diabetes Mellitus, the

normal range for the HbA1c≤6.2%. (70%) of

patients whom have HbA1c level less than

(9.79%) did not complain from any

complications. And (30%) of patients with

high HbA1c (9.79-11.07%) shows that they

suffered from some of the following

complications:

a. Retinopathy (impairment of vision,
exudation and retinal hemorrhage).

b. Neuropathy (pain, numbness, and loss
of sensation).

c. Nephropathy (pleural effusions, ascites,
subcutaneous oedema in legs, high

blood urea levels, high serum creatinine

levels and albuminuria).

d. Gastropathy .

Table 1 : Age distribution

N = 30

Table 2 : The occupation of the patients

Occupation Percent

Farmer 15 %

Housewife 24.5 %

Laborers and employees 32.5 %

Student 3.5 %

Retired 24.5 %

Total 100 %

N = 30

Table 3 : The site of foot ulcers distribution.

Site Number of

patients

Percent

Ball of the foot 12 40%

Bottom of the big

toe
18 60%

Total 30 100%

N = 30

Table 4: Fasting blood sugar and

glycosylated hemoglobin in control subjects

and diabetic foot ulcer. Before starting

treatment.

Control

(n=21)

Diabetic foot

ulcer

(n=30)

FBS

(mg/dL)
83 ± 5.04 a 243.83 ± 7.10 b

HBA1c % 3.41 ± 0.17 a 9.25 ± 0.21 b

Data are expressed as mean ± SD.

n=number of patients.

Non-identical superscripts (a,b) represent

significant difference, P<0.001).

Age group Percentage of diabetic foot

ulcer

Less than 30 5.5 %

30-39 8.5 %

40-49 7.5 %

50-59 24.5 %

60-69 21.5 %

70-75 32.5%

Total 100 %

Iraqi J Pharm Sci, Vol.20(1) 2011 HbA1c and foot ulceration

Table 5 : HbA1c and FBS levels for patients with diabetic foot ulcer after and before treatment

HbA1c % FBS

Before After Before After

Metformin

(n=7)
9.06 ± 0.2 a 6.64 ± 0.08 a* 238.85 ± 8.08 a 138.98±5.01 a*

Glibenclamide

(n=10)
9.64 ± 0.32 a 6.65 ± 0.06 b* 248.08 ± 7.10 a 134.00±5.54 b*

Metformin +

Glibenclamide

(n=13)

9.05 ± 0.12 a 6.31 ± 0.07 c* 244.56 ± 6.13 a 124.6 ± 3.94 c*

Data are expressed as mean ± SD.

n=number of patients.

*P<0.05 with respect to pre-treatment value.

Non-identical superscripts (a,b,c) represent significant difference among groups, P<0.05).

Table 6 : Percentage of healing after treatment for diabetic foot ulcer patients.

Treatment
Patient

No.
Dose

Healing

cases

Percentage of

healing

Metformin 7 500mg (2/day) 2 28.57%

Glibenclamide 10 5mg (2/day) 3 30.0%

Glibenclamide + Metformin 13
5mg (2/day) +

500mg (2/day)
7 53.84%

Table 7 : Distribution of mean HbA1c and

FBS among the patients with foot ulcer.

Age group HbA1c% FBS (mg/dl)

<30 8.18 ± 0.12 205 ± 5.25

30-39 8.56 ± 0.13 218.66 ± 6.67

40-49 9.79 ± 0.29 275.5 ± 13.07

50-59 10.99 ± 0.29 345.75 ± 18.46

60-69 11.01 ± 0.27 344.4 ± 19.39

>70 11.07 ± 0.64 354.5 ± 41.07

Figure 1 : The relationship between HbA1c

and Age.

Figure 2: The relationship between FBS and

Age.

Discussion and conclusion
The present study reflecting the

recommended tests and examinations, to assess

the diabetic care
(26,27)

. Diabetes is most

commonly associated with many micro and

macrovascular abnormalities. One of these

serious complications is the foot ulcer

development in patients with poor glucose

level control. HbA1c is the a useful indicator

of how well the blood glucose level has been

controlled in the recent past and may be used

to monitor the effects of diet,excrcise and drug

therapy on blood glucose in diabetic patients

..Most patients in this study (60%) have ulcer

in bottom of the big toe, while 40% have ulcer

0 10 20 30 40 50 60 70 80

H
b

A
1
c
%

Age (year)

"r=0.82, P<0.01"

100

150

200

250

300

350

400

450

500

0 20 40 60 80

F
B

S
(

m
g

/d
L

)

Age (year)

"r=0.8, P<0.01"

Iraqi J Pharm Sci, Vol.20(1) 2011 HbA1c and foot ulceration

in ball of foot. This may be due to the low rate

of blood circulation in these two sites, table (3)

(16)
. The groups of the patients were treated

with either Metformin, Glibenclamide or a

combination of (Glibenclamide + Metformin)

showed no significant difference among them

in respect to HbA1c and FBS before treatment.

The mean value of the HbAlc and FBS after

treatment in all groups decreased significantly

P<0.05, table (5). However, combination

therapy (Glibenclamide+Metformin) showed

high percentage of healing than other patients

who were on the Metformin or Glibenclamide

alone. So this combination was the best

treatment to control the HbA1c thus controlling

the glucose level table(6), hence faster healing

of foot ulcers. In this study we found that the

older patients have higher HbAlc and FBS

levels. That means older patients were with

less compliance than younger patients, table

(7). fig. (1), fig. (2). The higher HbA1c level

was detected in ages higher than 70 years old,

table (1)
(28)

, indicating bad glycemic control.

More percent of the patients were those with

occupation as laborers and employees. This

may be due to their hard work with defective

circulation due to their diabetes, table (2). In

July,2009, an international expert committee

published a report that made the case for using

the hemoglobin Alc assay to diagnose type2

diabetics
(29)

. Moreover as of January 2010, the

American Diabetes Association included Alc

as an appropriate diagnostic test
(21)

. It has been

reported that high HbA1c levels increase the

development and progression of eye, kidney

and nerve complications in diabetes mellitus

poor glucose control also increases the risk of

short-term complications of surgery such as

poor wound healing
(30-32)

. In our study patients

with high HbA1c levels (9.79-11.07%)

suffered from eye, nerve or kidney

complications, while patients with HbA1c level

less than (9.79%) did not suffer from

complications. Since HbA1c is not influenced

by daily fluctuations in blood glucose

concentration. We recommended that people

with diabetes should keep their HbA1c level

less than (6.63%) by following diet and drug

instructions, diabetes out of control could

result in complications .Patients with diabetes

mellitus should make HbA1c test every three

months to determine whether their blood

glucose have reached the target level of the

control. Patients who have glucose level under

good control may be able to wait longer

between the blood tests, but it's recommended

to be checked at least 2 times a year
(33)

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