Evaluation of Liver Function in Type 2 Diabetic Patients during Clinical Trials in Kirkuk City
Fadheelah S Azeez1, Ali M Saadi2
1Assist Lecturer, Pathology Analysis Div., Hawija Technical Institute, Northern Technical University Kirkuk/Iraq.
2Lecturer, Animal Production Div., Mosul Technical Institute, Northern Technical University Mosul/Iraq.
*Corresponding Author E-mail:
ABSTRACT:
Disease of diabetes mellitus is a condition for uncontrolled metabolism with an abnormally high level of glucose in the blood. Type II diabetes is a heterogeneous multi-faceted group of metabolic conditions described by high levels of glucose in the blood due to poor insulin and/or insulin secretion. In patients with type 2 diabetes, abnormalities in functional liver tests are not uncommon. The objective of this study is to investigate deviations in liver function from a group of diabetics in the city of Kirkuk and identify the factors associated with these changes in chemistry. A various primary health care centers were included with a total of 30 patients between March 2016 and August 2017 in Kirkuk. The results found that although the values of Alanine aminotransferase ALT, Aspartate aminotransferase AST were within a typical range, but there was a high significant increase in both values of patients than that of healthy subjects, ALT and AST were known (46.66%) and (43.33%) respectively. Also, no association in both ALT and AST with the sex of patients of diabetes. In addition, there was a weak positive relationship between each ALT and AST with BMI (0.1066), (0.1207), respectively. In conclusion, abnormalities in the consequences of liver function are more common among diabetics. Elevation in ALT, AST is a marker of non-alcoholic fatty liver disease in diabetic patients. Accordingly, the ALT and AST test should be performed to examine the primary fatty liver, especially with diabetes, with a high BMI.
KEYWORDS: ALT, AST, BMI, Liver Function, Obesity, Type two Diabetes Mellitus.
1. INTRODUCTION:
In the past few decades, especially in developing countries, diabetes is the fourth leading cause of death. 2 Currently, diabetes affects about 240 million people worldwide, and by 2025 this number is expected to reach 380 million. Diabetes in this indicator creates an alarming situation that can have serious long-term consequences and is a problem for health stakeholders. Six Arab countries: Saudi Arabia, Kuwait, Qatar, Lebanon, Bahrain and the United Arab Emirates are among the largest countries in the world with the highest prevalence of type 2 diabetes (T2DM), which affected 32.8 million people in 2011, By 2030 will increase to 60 million. (Waqas et al. 2016).
Liver which plays an important role in regulating the metabolism of carbohydrates because it uses glucose as a fuel, has the ability to store glucose as glycogen, and also produce glucose from the non carbohydrate intermediates. This basic function of the liver makes it susceptible to diseases in people with metabolic disorders, especially diabetes. (Stefano et al. 2016).
Actually, the defeat of the direct effect of insulin to suppress the glycogen breakdown and formation of glucose in the liver of type 2 DM, is the main causes of hepatic glucose load. (Tsutomu 2017). Therefore, the weak glucose balance is one of the most common causes of death in the United States. (American Diabetes Association 2015). In Type II-DM hyperinsulinemia in a mixture of a large design of free fatty acids (FFA) and high blood sugar, to regulate the fat-hoarding factors dictation. Moreover, the pathways that reduce the FFA aggregation in the liver ie., along with FFA oxidation and liver fat flow by liver are compromised. Glucose output, FFA, and insulin lead to formation of Malonyl-CoA by the stimulation of the CoA-Carboxylase, which modifies acetyl-CoA malonyl -CoA. (Philip et al 2014).
Excess fatty acids exhaust the mitochondrial system of oxidation in the liver, which leads to the accumulation of fatty acids in the liver. (Philip et al 2014) All these mechanisms lead to non-alcoholic fatty liver disease (NAFLD) in patients with T2DM. (Razi et al. 2017). Numerous studies have shown the relationship between NAFLD and metabolic syndrome characteristics containing dyslipidemia and DM, stressing the link with insulin resistance as an important character of NAFLD. Many authors believe that NAFLD can be a hepatic component of T2DM as a metabolic syndrome. (Pedras 2016). NAFLD produces asymmetric deformities in the level of some liver enzymes, including alanine alanine (ALT) and alkaline phosphatase (ALP), aspartate alanine (AST). ( Balaji 2014) ALT is the most dependent on the accumulation of fat in the liver, so ALT is used as a marker for the NAFLD.(Arrelias 2015).
The global obesity epidemic has led to the fact that obesity has become the main cause of diabetes in pre-diabetes and type 2DM. (Jalal et al. 2017). In addition, non-alcoholic liver disease associated with obesity has reached epidemic proportions and has become the most common cause of chronic liver disease in the Western world. Furthermore, studies indicate that increased activity of liver enzymes is associated with metabolic syndrome and related clinical manifestations, including cardiovascular disease and type 2 diabetes. (Belay et al. 2014).
Most studies of liver enzymes associated with metabolic syndrome and type 2 diabetes are associated mainly with middle-aged and elderly people. (Stefano et al. 2016). The relationship between diabetes and liver injury is established. Sickness of the liver among diabetics is the same as for alcoholic liver disease, including fatty liver, hepatitis, liver cirrhosis. ( Pinho 2015). High serum level of AST and ALT is the most common indication for the measurement of liver disease and is more common in patients with diabetes than in the general population. (Santos 2015).
Several studies have shown that high level of blood sugar levels can lead to oxidation and glycation reactions. Glycation products then begin to undergo rearrangement in molecules and oxidation reactions (Glycoxidation) and eventually become stable so-called advanced glycation end products (AGEs). The modification of proteins AGE can modify or reduce functional or structural features that can lead to tissue damage, as seen in DM. As well as, oxidative stress can be one of the factors that can affect liver enzymes ALT, AST and ALP. (Durdi et al. 2018).
A similar set of liver damage and changes in the enzyme in diabetes are also described among people who are overweight without diabetes, it is not known whether the liver disease associated with diabetes, the factors confusing, such as alcohol consumption and excess weight. It is reported that 70-80% of patients with diabetes observed accumulation of hepatic fat, called non-alcoholic fatty liver NAFL. ( Perfect et al. 2017), leading to non-alcoholic steatohepatitis NASH, a progressive disease that can lead to liver cirrhosis or liver related death.( Prapaipan et al. 2017).
In the 1980s, non-alcoholic fatty liver was first recorded in obese women with diabetes. Recently, there has been increasing interest in increasing the prevalence of diabetes, and as shown, is a predisposing factor for insulin resistance and hyperinsulinemia. (Juliana V and Laercio J 2018). The main evidence of the study of liver disease association with diabetes is insulin resistance and arteriosclerosis IRAS, which showed that liver function markers such as AST and ALT are the predictions of diabetes. ( Mehmet et al. 2017). Currently, there are not many therapeutic options for non-alcoholic fatty liver, with the exception of modifications the obesity using hypo caloric diets and exercise and control of blood sugar levels with a diet, insulin or oral hypoglycemic agents. (Foster et al. 2013).
The study is currently aim to evaluate the liver function of type 2 diabetics in the long term compared with the non-diabetic group.
2. MATERIALS AND METHODS:
In Kirkuk/Iraq cross sectional study conducted on 30 patients with type 2 diabetes with long-term diabetes whose fasting glucose in plasma (FPG) ≥126 mg/dl and 20 healthy were included in the control group. In this study, patients with diabetes who had the disease for at least five years screened for liver function except patients with a history of liver disease or heavy or debilitating diseases such as cancer and malignant anemia (hemoglobin <10 g / dl), patients with clinical and subclinical hypothyroidism are excluded, also the patients who have no history of taking cortisone, tamoxifen and amiodarone.
Blood collection:
In this study, each volunteer collected 5 ml of venous blood using a disposable plastic syringe. Blood was poured into a flat container and then removed after coagulation. The serum was kept at -20 ° C in a sterile condition until use. ALT, AST and glucose were evaluated and analyzed using Roche diagnostic / Hitachi 902 (Hitachi, Japan)
Statistics:
Unpaired t-test was used to compare controls and patients. P less than 0.05 concerned significant. All results expressed as mean ± S.D.
3. RESULTS:
For this study, 30 patients with type 2 diabetes were selected with a duration of more than 5 years and 20 subjects as control group. The median age was 51 ± 2.81 years, ranging from 40 to 60 years in patients with diabetes and 50 ± 5.68 years ranging between 40-60 years of the control group. Among the patients group, 12 patients were men, represent 40%, and 18 patients were women, represent 60%.]
Twelve patients (40%) had a BMI of less than 25 kg/m2, four patients (13.33%) had a BMI of 25 to 30 kg / m2 and 14 patients (46.66%). BMI> 30 kg / m2 as it shown in table 1.
Table 1. Clinical and demographic features of diabetic patients and normal controls
|
Features |
Patients (n = 50) |
Control (n = 30) |
|
Average age (yrs) |
51±2.81 |
50±5.68 |
|
Standard (BMI < 25) |
12 |
7 |
|
Overweight (BMI > 25) |
4 |
9 |
|
Obesity (BMI > 30) |
14 |
4 |
Both means of ALT and AST had no correlation with gender of the diabetes patients as it is clear in table 2.
Table 2. Correlation between ALT, AST and gender
|
Gender |
ALT |
AST |
||
|
Mean±SD |
p-value |
Mean±SD |
p-value |
|
|
Male |
48.2±13.55 |
NS |
47±12.86 |
NS |
|
Female |
46.25±8.63 |
48.25±8.24 |
||
Current study revealed that all of ALT, AST and serum glucose were assessed in type two diabetic patients and healthy group. As it offered in Table 3 and figure 1, mean values of ALT and AST were significantly greater in type two diabetic patients than in healthy group (P ≤ 0.0001) also, the mean value of serum glucose was evidently greater in diabetic patients than in healthy group (P ≤ 0.0001) (Table 3).
Table 3. Biochemistry in diabetic patients and healthy group
|
Parameters |
Patients |
Control |
P value |
|
ALT U/L* |
47.68 ± 11.4 |
22.85±7.60 |
0.0001 |
|
AST U/L* |
47.51±9.99 |
22.9±7.48 |
0.0001 |
|
Glucose mg/dl* |
247±70.49 |
94.65±17.98 |
0.0001 |
*Values represent Mean ± SD
Figure 1. values of ALT and AST of patients and healthy subjects
ALT, AST (P)=patients, ALT, AST(H)=Healthy subjects
Regarding correlation between ALT and BMI, our study revealed that the value of R is 0.1066 which is considered technically positive correlation (figure 2).
Figure 2. Correlation between ALT and BMI among diabetes patients (n = 30)
Also this study found that the value of R regarding correlation between AST and BMI is 0.1207 which considered technically positive correlation (figure 3).
Figure 3. Correlation between AST and BMI among diabetes patients (n = 30)
4. DISCUSSION:
Type II diabetes accounts for about 80% of diabetes mellitus cases. Diabetes is the main cause of morbidity and deaths worldwide. It is estimated that about 1% of the population with diabetes. Disease in the developed world 10% annually, especially the second type of diabetes, because of the increase in the incidence of obesity and depression activity level. Diabetes is expected to continue as well a serious health problem due to serious complications, special kidney disease of the end stage, heart aortic disease, gangrene lower limbs and blindness in adults. (Petta et al. 2016).
In our study, in general, 15 patients 50% had abnormal liver enzymes. 14 patients, 46.66% had elevated ALT levels, 13 patients 43.33% had raised AST, our results were consistent with (Agarawa J 2015), a study examined the liver function tests in 100 diabetics without chronic liver disease and have shown a significant elevation in both ALT and AST values in type 2 diabetic patients as compared to the controls (P<0.05) . Also, our results are consistent with Belay Z. (Belay et al. 2014).
A study conducted by Raiza Philip (2014) observed a significant increase in the level of ALT, AST and GGT, the increase in the liver enzymes clearly indicated the onset of type 2 diabetes. (Raiza et al. 2014).
According to a study conducted by Byrne C et al when interviewed 50 diabetic patients with diabetes and 30 controls, ALT, AST, GGT, total protein and albumin were significantly higher in diabetics than in controls, although the average values were within the normal range. ( Byrne C et al. 2015).
Liver weakness can be explained by many factors in diabetics, the most common cause of which is non-alcoholic fatty liver disease, and is associated with insulin resistance and metabolic syndrome in diabetes. In recent years, studies have linked the infection of hepatitis C virus in patients with diabetes, which caused a disorder of stroke, However, the intake of this relatively small drug may enhance the abnormal results of liver function. (Asselah T et al. 2016).
We observed that ALT was correlated positively with BMI, so that finding was in accordance with a study of Noura et al 2014. (Noura A et al. 2014) and many other studies (Ballestri, S et al. 2016). The underlying cause of NAFLD pathogenesis appears to be insulin resistance, resulting in fat decomposition and excess deposition of fat on the liver and create together affects inflammation, oxidative stress and lead to increase liver enzymes. (Raiza et al 2014).
In patients with diabetes, elevated liver enzymes can be steatohepatitis sign. However, there is no evidence of a statistically significant positive relationship between liver tissue and biochemical disorder. Advanced stage of NASH and fibrosis may occur in diabetics although if there are nonsignificant changes in liver function.
(Zhang Y et al. 2015).
5. CONCLUSION:
1. Liver function indicators for patients with type 2 diabetes were markedly higher than controls.
2. Because of high serum liver enzymes in type 2 diabetes patients, liver function tests is highly recommended to do.
3. More research on liver function should be done in diabetics in Iraq.
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Received on 25.01.2019 Modified on 18.02.2019
Accepted on 12.03.2019 © RJPT All right reserved
Research J. Pharm. and Tech. 2019; 12(4):1659-1663.
DOI: 10.5958/0974-360X.2019.00278.6