Introduction  

NAFLD is a continuation of the process of insulin resistance [1]. The diagnosis of NAFLD is based on the results of anamnesis and clinical examination, liver function tests, radiological image and histopathological examination. Abnormal liver function tests are often the main reason why NAFLD patients are referred to a hepatologist. Elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) are the most common laboratory abnormalities. In the early phase of steatosis, ALT levels are usually higher than AST. Elevated bilirubin values, decreased albumin and prolonged plasma prothrombin time indicate advanced liver disease and liver failure has occurred [2, 3].

Liver function tests (LFT) are often used in clinical practice to screen for liver disease, monitor the progress of previously known diseases, and monitor the effects of drugs that have the potential to be hepatotoxic. Common liver function tests include: ALT, AST, alkaline phosphatase, bilirubin, albumin and prothrombin time. ALT and AST provide an overview of the concentration of intracellular liver enzymes that enter the circulation and act as markers of liver cell/hepatocyte injury. Alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), and bilirubin are markers of biliary system function and cholestasis [4]. Albumin and prothrombin time are reflection of liver synthesis function. ALT and AST are normally < 30-40 units/L. An increase in aminotransferases of more than 8 times the upper limit of normal indicates acute hepatitis, ischemic hepatitis, or drug or toxin-related liver injury. Meanwhile, transaminases that increase slightly but over a long time are often found in patients with diabetes mellitus [4, 5].

The theory behind the improvement in liver function test results in diabetic patients is that the liver plays a role in maintaining normal blood glucose levels during fasting and after meals. Loss of insulin effect in the liver can lead to glycogenolysis and increased hepatic glucose production. Abnormalities in triglyceride stores and lipolysis in insulin-sensitive tissues such as the liver are early manifestations of conditions associated with insulin resistance, and they appear earlier than fasting hyperglycemia [6]. However, the precise role of genetic, environmental and metabolic factors and the sequence of events that lead to insulin resistance remains unclear [6].

In experiments conducted on animals, it was found that chronic hyperinsulinemia is a predisposing factor to the occurrence of insulin resistance in the liver. It is characterized by the failure of insulin to signal an increase in insulin 2^nd receptor substrate. There is also an upregulation of SREBP-1c (sterol regulatory element binding-protein-1c) which causes lipogenesis. Lipogenesis occurs mainly in the liver causing an increase in intracellular triglycerides and leading to fatty liver. It can also increase the synthesis of VLDL secretion. Therefore it can be concluded that the condition of hyperinsulinemia can be directly correlated with insulin resistance in the liver and this is related to fatty liver [7].

The condition of excess free fatty acids found in insulin resistance is known to have a toxic effect on hepatocytes. Possible mechanisms for this are cell membrane damage at high concentrations of free fatty acids, mitochondrial dysfunction, toxin formation, and activation and inhibition of important metabolic regulatory steps [8]. Another possibility that can lead to increased levels of transaminases in insulin resistance states includes oxidative stress caused by reactive lipid peroxidation and inflammatory cells which have recently been involved [9]. The state of insulin resistance is also characterized by the emergence of proinflammatory cytokines such as TNF-α (tumor necrosis factor-alpha) which can also play a role in the hepatocellular injury. In a preeliminary study it was found that an increase in the TNF-α promoter was found in patients with NASH (nonalcoholic steatohepatitis) [10]. The above theories are theories that link the elevation of transaminitis with hepatocyte injury. A hypothesis can also be drawn that states that an increase in ALT, which is a gluconeogenic enzyme whose gene transcription can be suppressed by insulin, may indicate a disturbance in insulin signaling, not just hepatocellular injury [11].

Materials and Methods

Study design

This study was an observational analytic study with a cross-sectional approach. Data collection was carried out in October 2022 at Tugurejo Hospital, Semarang City, Central Java Province, Indonesia.  The study was conducted on the medical records of patients diagnosed with NAFLD from 2020 -2021 using the total sampling method. The research data is secondary data obtained from the patient's medical records including age, sex, body mass index, presence or absence of DM comorbidities, random blood sugar laboratory results, fasting blood sugar, lipid profile, liver enzyme profile including ALT and AST.

Statistical analysis

Data analysis was carried out by looking at parameters that differed significantly in groups of patients with type 2 diabetes mellitus and non-diabetes using the T-Independent test if the data were normally distributed and the MannWhitney test if the data were not normally distributed. Prognostic factors were analyzed using univariate analysis using the kai-square test (X2 test) and multivariate analysis using logistic regression analysis to obtain relative risk values (RR).

Ethical considerations

The study protocol was approved by the Clinical Research Ethics Committee of Medical Faculty, University of Muhammadiyah Semarang (approval date: 23.11.2022, approval number: 066/EC/KEPK-FK/UNIMUS/2022) The study was conducted in accordance with the 1975 Declaration of Helsinki, as revised in 2013.

Results and Discussion

Abbreviations: SD: Standart Deviation; N:number of participants

This study included 107 male and female participants. Their characteristics are presented in (Table 1). Subject gender was divided into 41 male subjects and 66 female subjects, with an average age of 51.6 years old.  The research data was taken from patient medical records including BMI, Blood Sugar Level, Fasting Blood Sugar, Total Cholesterol, Triglyceride, Cholesterol-LDL, Cholesterol-HDL, AST and ALT.

Abbreviations : OR: Odd Ratio; CI: Confidence Interval

* Significant (p <0.05)

Table 2 shows that participants were grouped into 54 patients who had NAFLD and 53 patients who were Non-NAFLD. For the chi-square test analysis, subjects were regrouped into 30 DM patients with NAFLD and 26 DM patients without NAFLD (total patients with DM = 56 patients). Non-DM patients with NAFLD were 24 patients, Non-DM and Non-NAFLD patients were 27 patients (total Non-DM patients = 52 patients.  The results of the chi square test using Continuity Correction obtained a p-value = 0.632, because the p-value > 0.05, it can be concluded that there is no significant relationship between the incidence of T2DM and NAFLD.

* Significant (p <0.05); ^¥ Continuity Corrections; ^‡ Mann Whitney

From the analysis test results it is known that only BMI and TG have significant differences based on NAFLD as shown in Table 3. The test results also showed that increased levels of the transaminase enzyme did not have a significant effect on the occurrence of NAFLD. To find out the factors that have a strong influence, from the results of the bivariate test with a p-value <0.25, a logistic regression multivariate test was performed.

Abbreviations : RR: Relative Risk; CI: Confidence Interval

* Significant (p < 0.05)

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