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Salman et al (2020): function Tests in Type- 2 Nov 2020 Vol. 23 Issue 18 Study of in Diabetes Type- 2 patients in Ramadi City, Iraq

Maryam I. Salman1*,Rashied M. Rashied2,Hajir SH. Hamad1

1. Department of Biology,College of Science, University ofAnbar, Iraq 2. Department of Biotechnology, College of Science, University of Anbar, Iraq

*Corresponding author: [email protected](Salman)

Abstract

Diabetes mellitus is a group of metabolic disorders and major diverse disease around the world. Unusual liver function tests are oftenobserved in patients with diabetes mellitus, and are associated with sever complication.This study was conducted in the AL-Ramadi Teaching hospital between June 2017 and June 2018, with the participation of 100 type -2 diabetic patients and 100 age- matched healthy subjects in order to detect the liverfunction tests abnormality in type-2 diabetic patients. Parameters like , serum total , (ALP), serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) were used.The results showed thatliver function testparameters including, ALP, AST and ALT were significantly elevated in type -2 diabetic patients when compared to healthy subjects (p <0.001), serum albumin was significantly lower in type- 2 diabetic patients (p <0.001), while serum bilirubin was not significantly different between the two groups p value was0.917.Despite of the differences were statically significant, the means of all the parameters in this study were within the normal range. 46% of the patients had at leastone or moreabnormal liver function test.

Key words: Liver function tests, Diabetes mellitus, Serum albumin, Alkaline phosphatase (ALP)

How to cite this article: Salman MI, Rashied RM, Hamad HS (2020): Study of liver functiontests in diabetes type-2 patients in Ramadi city, Iraq, Western Iraq, Ann Trop Med & Public Health; 23(S18): SP231824. DOI: http://doi.org/10.36295/ASRO.2020.231824

Abbreviations: DM: Diabetes Mellitus; FBS: Fasting Blood Sugar; BMI: Body Mass Index; ALT: Alanine Aminotransferase; AST: Aspartate Aminotransferase; ALP: Alkaline Phosphatase; TB: Total Bilirubin; LFTs: Liver Function Tests.

Introduction

Diabetes mellitus (DM) refers to a group of metabolic disorders characterized by plus disorder in carbohydrate, lipid, and protein due to defects in secretion, insulin action or both (1). InIraq it has been reported that the number of cases of diabetes to be estimated about 3.5 million in 2013. The total number of diabetics is expected to increase from 171 million in 2000 to 366 million in 2030(2). Type- 2 diabetes is present in the scope of 85-95% of all diabetics’ cases within high-income countries (3). Most patients with diabetes are prune to increase risk of nephropathy, neuropathy, retinopathy, heart disease and stroke; however only a few understand that their diabetes is also raising their risk of having both liver diseases and liver cancer. The liver is a vital organ in metabolism plays a central and critical role in regulation of carbohydrates metabolism and maintaining homeostasis, it has the ability to store glucose as glycogen and to synthesize glucose from non carbohydrate sources this role makes the liver more sensitive to disease in subject with metabolic disease like DM(4). In hyperglycemia, intracellular glycogen accumulates in hepatocytes in response to increase glycogen synthesis.This causealiver injury where there is a mild increase in aminotransferase (5). Liver related diseases recognized in diabetes include elevated aminotransferase, fatty liver diseases, , liver carcinoma and liver failure (6). Several studies from around the world indicate altered liver biochemical findings in diabetic patients but such studies from Iraqi people are rare so the aim of this study is to examine and compare various liver parameters between type 2 diabetic patients and non diabetic subjects attending the Al-Ramadi teaching hospital in the city of Ramadi, Iraq.

Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.231824

Salman et al (2020): Liver function Tests in Diabetes Type- 2 Nov 2020 Vol. 23 Issue 18

Materials and Methods:

A prospective study was performed on 100 T2DM patients and 100 aged- matched healthy subjects visiting Al-Ramadi TeachingHospital from June 2017 to June 2018.Demographic parameters such as age, height, weight and body mass index (BMI) were recorded for all the patients.

Inclusion criteria: Patients with confirmed T2DM diagnosed as per the criteria set by American Diabetes Association (ADA) in 2016.Fasting plasma glucose (FPG) ≥ 126 mg/dl, or random or two hour post prandial plasma glucose (PPG) of ≥ 200 mg/dl were included in the present study.

Exclusion Criteria: People who were confirmedto have B and C virus illness (HBsAg positive plus HCV antibody positive) were eliminated from this study. The diabetic in the midst of the past of alcohol drinking, hepatotoxic medication, anti-tuberculoses medication, not willing to participate in study,having liver and/or biliary diseases andpregnant females with were also excluded.

Blood collection: Ten ml of venous blood were taken from every diabetic and healthy subjects via a disposable plastic syringe. The blood was teeming in a test tube and after that centrifuged following it clotted. The serum was reserved at -40C̊ in the refrigerator until applied. Fasting blood sugar (FBS) and parameters deciding liver function such us serum albumin, Total bilirubin, serum alkaline phosphatase (ALP), serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) were estimated by a multi chemical fully automated chemistry analyzer using different reagent kits from Randox (France).

Statistics: Mean and standard deviations were calculated. All the statistical analysis was performed using SPSS ver. 20.0. Student´s t-test was used to analyze the differences parameters between both groups.. P value <0.001was considered as significant.

Result: The study includes 200 participated subjects aged 40-65 years in the AL-Ramadi Teaching Hospital. Of whom 108 were male and 92 were female. The mean age of the participants was 56±12.The number of type 2 diabetic patients andthat of the control group was 100 people.

The results showed an increased level of ALT (15%), AST (13%), ALP (9%), total bilirubin ( 3% ) and decreased level of albumin ( 6%) in the diabetic population ( Table 1).

Table 1: Mean value of biochemical variables among Diabetic group (N=100)

NO. of patients outside the Variables Means±SD normal range (%)

ALT (IU/L) 29.82 ± 4.03 15

AST(IU/L) 24.54 ± 2.3 13

ALP (lU/L) 74.54 ± 3.21 9

Albumin (gm%) 40.61 ± 0.62 6

TB(mg/dl) 0.892 ± 0.042 3

ALT, AST and ALP were significantly higher in diabetic population when compared to control ( p<0.001 ). Whereas albumin was significantly decreased in diabetic patients ( p<0.001 ). However, no significant difference in bilirubin level was observed between the two groups ( p<0.917 ) (Table 2 and Figures 1-5).

Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.231824

Salman et al (2020): Liver function Tests in Diabetes Type- 2 Nov 2020 Vol. 23 Issue 18

Table:2 Comparison of liver function tests between diabetics and controls (N=200)

Variables Control Patients P value

FBS (mg/dl) 83.140 ± 0.847 249.30 ± 7.270 <0.001

ALT (IU/L) 18.8 ± 2.5 29.82 ± 4.03 <0.001

AST (IU/L) 17.4 ± 3.4 24.54 ± 2.3 <0.001

ALP (IU/L) 50.43 ± 3.42 74.54 ± 3.21 <0.001

Albumin (gm%) 45.01 ± 0.887 40.61 ± 0.62 <0.001

TB(mg/dl) 0.892 ± 0.042 0.742± 0.035 0.917

BMI 28.4± 0.322 28.64± 0.72 0.833

35 30 29.82 ALT (U/L) AST (U/L) 24.54 30 25 25 18.8 20 17.4 20 15 15 10 10 5 5 0 0 Patients Control Patients Control

Patients Control Patients Control

Figure 1: Comparison of ALT in diabeticPatients Figure 2: Comparison of AST in diabetic Patients and controland control

46 80 74.54 ALP (U/L) Albumin%(gm) 45.01 70 45 44 60 50.43 50 43 40 42 30 41 40.61 20 40 10 39 0 38 Patients Control Patients Control

Patients Control Patients Control

Figure 3: Comparison of ALP in diabetic Patients Figure 4: Comparison of albumin in diabetic Patients and

control and control Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.231824

Salman et al (2020): Liver function Tests in Diabetes Type- 2 Nov 2020 Vol. 23 Issue 18

1 0.892 TB (mg /dl) 0.8 0.742 0.6 0.4 0.2 0 Patients Control Patients Control

Figure 5: Comparison of TB in diabeticPatients and control

Discussion: many studies around the globe show liver function abnormalities in individuals with mellitus (7,8,9,10). Bora et al in the district of Punjab inIndia deliberate the LFTs of 320 diabetic patients where 71.25% persons had a defect within at least one LFTs, 46.8% had elevated ALT and 48.5% had elevated ALP levels(1). A Study conducted by Ghimire et al. in Nepal (11) reported a high prevalence of LFTs abnormalities of about 62.3% in 162 type 2 diabetic patients 57% , 46% and 7% for ALT, AST and ALP respectively. The present studyshowed that 46% of diabetic patients have at least one abnormal liver function test, 15%have increased ALT, 13% have increased AST and 9% have increased ALP.Similarity, study conducted by Idris et al from Sudan(12)wherever 50 diabetic patients plus 30 usual control persons were examined for their liver function, reported high prevalence of LFTs abnormalities of about 12% for ALT and AST. Ni et al.(13) performed a study on 81 type 2 diabetic patients in Malaysia reported that about 18%, 12% and 5% have abnormal liver function tests in ALT, AST and ALP respectively. Wang et al. (14) conducted a study on 571 Type 2 diabetic cases and 571 matched controls, the study reported that ALT was significantly associated with increased risk of type 2 diabetes in Chinese population. The causeof the elevation of these enzymes could be due to potent hepatotoxic effect of fatty acids on the hepatocytesasthey areformed in excess amount as a result of chronic and relative (15).Mechanisms for this may include aggregation of free fatty acids, cell membrane disturbance at high concentration, mitochondrial dysfunction, toxin formation and oxidative stress which initiate an increase in proinflammatory cytokines such us Tissue Necrotic Factor (16).The present study data showed a statistically significant increase in ALT, AST and ALP with a significant decrease in albumin in diabetic group with the control (p≤ 0.001).Idris et al. also noticed a significant decrease in albumin level compared with the control (12).Blood plasma proteins are the first to acquire modified as they are directly exposed to elevated glucose concentration.Serum albumin is one of most abundant plasma proteins and is greatly glycated in diabetes(17), in diabetes albumin synthesis and secretion is decreased due to insulin deficiency, insulin has effect on the synthesis average of albumin in liver (18). In vivo in rats hepatocytes cultures insulin enlarged albumin gene transcription and mRNA synthesis within a dose-dependent way (19). On the other hand, plasma albumin concentration has been noticed to be inversely concerning with glycosylated haemoglobin (HbAlc) levels revealing a great proportion of weakly controlled diabetes in patients with lower plasma albumin concentrations (20). There is no significant difference in the bilirubin levelsoftype 2 diabetics and control participants in this study (p value was 0.917).This result was supported by a study done by Gohel et al. in Gujarat (21) on a total of 200 patients which also shows that there is no significant difference in bilirubin in diabetics and non-diabetics with p-value 0.7564, While it is not agree with the study of Luxmi et al (22) which shows that the value of total bilirubin concentration was significantly lower in contrast to that of the control group( p value 0.001).

Conclusion: Derangements in liver function are broadly concurrent with type- 2 diabetes in Ramadi. Screening for liver dysfunction in diabetics is required for preventing further complications associated with liver.

References:

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Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.231824

Salman et al (2020): Liver function Tests in Diabetes Type- 2 Nov 2020 Vol. 23 Issue 18

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Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.231824