Eng2

Jfuas No.1 June 2013

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Assessment of Liver Function in Sudanese patients with

Long Standing Type2 Diabetes Mellitus

Mustafa Abdalla Yahya1 and Dr. Bader Eldein Hassan Elabid2

1- Faculty of Education, University of El Fashir . Email:[email protected]

2- Faculty of Medical Laboratory Sciences, University of Scienceand Technology. Email: [email protected] .

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Abstract:

Abnormal liver function tests are not uncommonly encountered

in diabetes mellitus. The aim of this study was to assess liver function

in Sudanese diabetic patients and to determine their correlation with

the duration of diabetes. A case-control study was conducted during

the period from January 2011 to December 2012, to compare the

plasma levels of alanine transaminase, aspartate transaminase, alkaline

phosphatase, bilirubin, total protein, albumin and HbA1c of 200

Sudanese patients with long standing Type2 diabetes mellitus (as a

test group) those of 100 apparently healthy volunteers (as a control

group).Participants in this study were from Jaber Abu Elez diabetic

center in Khartoum state, Sudan. Age and sex of the test group were

matched with the control group. The plasma levels of ALT,AST, ALP,


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bilirubin, total protein, albumin and HbA1c were measured using a

semi automated methods. The means of the plasma levels of ALT,

AST,ALP,bilirubin and HbA1c% of the diabetic group were

significantly raised compared to the control group. The means of the

plasma levels of total protein and albumin of the diabetic group were

significantly reduced when compared to the control group. In the

diabetic group the plasma levels of ALT, AST, ALP and bilirubin

showed positive correlations with the duration of diabetes, whereas

the plasma levels of total protein and albumin showed negative

correlation with the duration of diabetes. From the results of this

study, it is concluded that: in Sudanese patients, type2 diabetes

mellitus is associated with high plasma levels of ALT, AST, ALP and

bilirubin and low levels of total protein and albumin. In addition, there

is positive correlations between the plasma levels of ALT, AST, ALP

and bilirubin with the duration of diabetes, and negative correlation

between the plasma levels of total protein and albumin with the

duration of diabetes.

Keywords: Liver Function Tests, Glycosylated haemoglobin,

Nonalcoholic fatty liver disease.

Introduction:

Diabetes mellitus is a group of metabolic disorders with one

common manifestation, hyperglycemia, caused by famial disease or

acquired deficiency in production of insulin by the pancreas, or by the

ineffectiveness of the insulin produced (Jennifer, 1997).


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In 2006 world health organization (WHO) reported, at least 171

million people worldwide were suffering from diabetes. Its incidence

is increasing rapidly, and it is estimated that by the year 2030, this

number will be doubled (Pefitti et al., 2007)

Diabetes mellitus is a disease with many complications that

represent the major cause of morbidity. Diabetes has two to four fold

greater risk of vascular disease occurrence as compared with non

diabetic diseases (Sone et al., 2002).

The liver plays a major role in regulation of carbohydrate

metabolism, as it uses glucose as a fuel, it has the capability to store

glucose as glycogen and also synthesize glucose from

noncarbohydrate sources. This key function of liver makes it

vulnerable to diseases in subjects with metabolic disorders,

particularly diabetes. In diabetes mellitus there is Increase activities of

liver enzymes, such as aspartate aminotransferase (AST), alkaline

aminotransferase (ALT) and γ- glutamyltranspeptidase (GGT) which

are indicators of hepatocellular injury (Levinthal et al., 1999 ).

Increased activity of these markers is associated with insulin

resistance, metabolic syndrome, and types 2 diabetes (Marchesini et al

2001 and Wannamethee et al., 2005). An association exists between

diabetes and liver injury. Liver pathology among diabetics is similar

to that of alcoholic liver disease, including fatty liver (steatosis),

steatohepatitis, fibrosis, and cirrhosis (Erbey et al., 2000). Elevated

serum activity of the two amino-transferases, aspartate

aminotransferase (AST) and alanine aminotransferase (ALT), is the


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most frequently measured indicator of liver disease and occurs in

diabetics more frequently than in the general population. The same

spectrum of liver injury and enzyme changes in diabetes has also been

described among overweight individuals without diabetes. Whether an

association of liver disease with diabetes is independent of

confounding factors, such as overweight and alcohol consumption is

unknown (7). Nearly 70 to 80% of the diabetic subjects have been

reported to have hepatic fat accumulation, referred to as nonalcoholic

fatty liver (NAFL). NAFL leads to nonalcoholic steatohepatitis

(NASH), a progressive fibrotic disease, which can result in cirrhosis

or liver related death (Wong et al., 2004).

Further proof of the association of liver disease with diabetes

comes from the insulin resistance atherosclerosis study (IRAS), which

showed that liver function markers like the aspartate aminotrans-

ferase (AST) and alanine aminotransferase (ALT) are predictors of

incident diabetes (Hanley et al., 2004 ). Sudan, and most of Africa, is

believed to have one of the highest mortality rates for non infectious

disease.

One study indicated that 10% of adult patient deaths in hospitals

were caused by diabetes. The current prevalence of diabetes in Sudan

is unknown although the very initial study estimated the prevalence by

3.4%, and with no doubt the risk of morbidity due to this disease is

increasing, especially in the urban areas (Ahmed et al., 2001).

Therefore, a comprehensive study of diabetes mellitus and its impact

needs to be undertaken. The present study was aimed to evaluate the


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liver function in Sudanese patients with long standing type 2 diabetes

compared to non diabetic control group and to assess the impact of

diabetes on liver function in relation to duration of the disease.

MATERIALS AND METHODS

The current case-control study was conducted during the period

from January 2011 to November 2012 in Jaber Aboalez Diabetic

center in Khartoum to study the effect of long standing type 2 diabetes

mellitus on liver function test. A total of 200 sudanese patients

diagnosed as having type 2 diabetes mellitus for at least 10 years and

100 healthy individuals (control) were selected randomly to

participate in the study. The objective of the study were explained to

each individual under study after having his verbal consent to

participate in the study, data were collected by questionnaire then

clinical check was done by a medical practitioner to determine any

exclusion factor. Five ml of venous blood were then collected from

each participant under aseptic technique using disposable syringe. The

collected blood sample were divided into (3ml dispensed into heparin

container and the remaining 2ml into EDTA container). The blood

specimens were then centrifuged and the plasma separated into other

container and stored at -20°C in a deep freezer until tested. Plasma

were then tested for ALT, AST, ALP, Bilirubin, Total protein and

albumin using Roche diagnostic/Hitachi 902/Hitachi, Japan and using

the heparin specimen. While the EDTA blood was used to measure the

glaciated haemoglobin (HbA1c) using Nycard reader 11. Statistical

analsis of the results was done using SPSS. Data are presented as


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group (mean ± SD). T test was used for comparison of group and

linear regression and Pearson, correlation were used to assess

correlation between two variables. Statistical significance was set as

P 0.05. Permission to conduct the study was taken from the health

authorities in the study area.

RESULTS:

In the current study both the diabetic group and the control group

were matched for age and sex.Among the patients group 112 were

males representing 56% and 88 were females representing 44%, on

the other hand, 55% of the control group were males and 45% were

females .

Table(1) Demographic characteristic of the study and control group.

P.valueControl group

n=100

Test group

n=200Variable

0.250

0.010

0.060

0.000

59.06±11.99

38-84)(

67.45±14.04

46-96)(

157.48±15.11

137-184)(

24.07±2.94

18.5-28.9)(

60.33±7.88

(39-84)

72.02±9.37

(50-103)

159.81±1.15

(139-193)

27.15±4.02

(19-40)

Age (years )

Weight(Kg)

Height(Cm)

BMI(Kg/m²)

Table (1) shows the mean± Standard deviation, range in brackets and

probability (P).


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• t-test was used for comparison.

Table (2) Comparison between the plasma levels of ALT, AST, ALP and

bilirubin of the test group and the control group.


n=100

Test group

n=200Variable

0.002

0.003

0.005

0.011

18.85±5.39

(10-29)

16.70±4.49

(9-27)

44.27±15.20

(40-77)

0.61±0.32

(0.220.86)

39.70±10.60

(17-66)

37.41±11.27

(15-79)

82.90±34.35

(30-180)

1.10±0.43

(0.332.10)

P.ALT(U/L)

P. AST(U/L)

P.ALP(U/L)

P.bilirubin(mg/dl)

The above table shows significant increase in the means of the

plasma levels of ALT, AST, ALP and bilirubin of the diabetic group

when compared to the control group.

Table (3) Comparison between the plasma levels of total protein ,albumin,

and HbA1c% of the test group and the control group.


n=100

Test group

n=200Variable

0.006

0.004

0.003

8.36±2.21

(8-8.5)

4.49±0.14

(4-4.5)

5.33±0.36

(4-6.5)

7.45±0.02

(6.90-8)

3.46±0.01

(2.60-4)

8.28±0.16

(5-14)

P.total protein(g/dL)

P.albumin(g/dL)

HbA1c%

Table3 shows a significant difference between the means of the

plasma levels of total protein of the test group and the control group.

The mean of the test group is significantly reduced. The same table


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also shows a significant decrease of the mean of the plasma levels of

albumin of the test group when compared to the control group.

Table 3 also shows a significant difference between the means

of the blood levels of total HbA1c% of the test group and the control

group. The mean of the test group is significantly raised.

Figures 1,2,3 and 4 shows significant positive correlations

between the plasma levels of ALT, AST, ALP and bilirubin with

duration of diabetes, whereas there are significant negative

correlations between the plasma level of total protein and albumin

with duration of diabetes as shown in figures 5and 6 .

Fig(1) The relationship between the plasma levels of ALT and the duration

of diabetes.

(r = 0.217 , p = 0.002 )


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Fig(2) The relationship between the plasma levels of AST

and the duration of diabetes.

(r = 0.367 , p = 0.000 )

Fig(3) The relationship between the plasma levels of ALP and the duration

of diabetes.

(r = 0.253 , p = 0.000 )


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Fig (4) The relationship between the plasma levels of bilirubin and theduration of diabetes.(r = 0.208, p = 0.003)

Fig(5) The relationship between the plasma levels of T.protein and theduration of diabetes.(r = 0.546, p = 0.000)


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Fig (6) The relationship between the plasma levels of albumin and the

duration of diabetes.

(r = 0.239, p = 0.001)

Discussion:

Type2 diabetic patients have been reported to be associated with

higher incidence of abnormal liver function tests (LFTs) compared to

individuals without diabetes. Elevated ALT being the most common

abnormality (Harris, 2005). In our study the results showed a

significant difference between the mean of the plasma activity of ALT

and AST of the test group compared with that of the control group.

The means of the test group for both ALT and AST were both

significantly raised. These results agree with a study done by Mckenze

who found elevation in plasma ALT and AST activities in patients

with diabetes mellitus type2 (Mckenzie, 2006 ), as a result of

progressive liver cell damage as a consequence of long standing. Our

study also showed significant increase in the mean of the plasma

activity of ALP of the test group compared with the control group.

This may be due to the effect of long standing diabetes mellitus on


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bone causing diabetic bone disease. This result agrees with a study

done by Maxwell et al who found that there was an elevation in

plasma ALP activity in patients with diabetes mellitus type 2

(Maxwell, 1986). The present result disagreed with a study done by

Tibi who reported that there was no significant difference between the

diabetic and the control group in the plasma levels of ALP (Tibi,

1988) .

The present study showed a significant difference between the

mean of plasma levels of bilirubin of the test group compared with

that of the control group. The mean of the test group is significantly

elevated as shown in table 2. This result is in agreement with a study

done by Han et al (15) who studied the liver function tests of 81

diabetic patients in whom 4.9% were found to have high bilirubin

(Han et al ., 2012 ).

Also the study showed a significant difference between the

means of the plasma level of total protein and albumin of the test

group when compared with that of the control group. These results in

agreement with a study done by Idris et al, who studied the liver

function of 50 sudanese diabetic patients and reported that plasma

total protein and albumin were significantly reduced among diabetic

sudanese compared to healthy controls. However the mean values

were within the reference range ( Idris et al ., 2011) . The current

study also showed positive correlations between glycemic control

(HbA1c%) and duration of diabetes with ALT and AST. These results

agree with Jayarama et al. Who reported positive correlations between


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FBS,PPBS,the duration of type2 diabetes and ALT levels among the

cases (Jayarama et al., 2012).

Generally the liver enzymes in diabetic patients with type 2 are

due to physiological alternative pathway that leads diabetic patients to

consume fatty acids as energy instead of glucose, this leads to increase

activity of the liver enzymes (Harris, 2005).

In conclusion, values of liver function test for ALT, AST, ALP

and bilirubin in patients with type 2 diabetes mellitus are significantly

higher than that of healthy controls; moreover, diabetic patients have

lower concentration of plasma total protein and albumins in

comparison to healthy controls. In long standing diabetes there is a

possibility of underlying fatty liver, which might need further

evaluation and early intervention to prevent progression into cirrhosis

and chronic liver disease.

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