European Journal of Cardiovascular Medicine

One of the leading causes of morbidity and mortality worldwide, diabetes mellitus poses a hazard to public health [1]. Over 90% of persons worldwide have type 2 diabetes (T2D), and approximately 1 in 11 has diabetes mellitus, according to the International Diabetes Federation (IDF). Approximately 80% of diabetic patients reside in low- and middle-income nations; South-East Asian nations are especially impacted [2]. Numerous liver conditions, including cirrhosis, hepatocellular carcinoma, and non-alcoholic fatty liver disease (NAFLD), have been linked to diabetes. These liver conditions are thought to be a major cause of death in people with type 2 diabetes mellitus [3]. Diabetes is frequently associated with elevated levels of blood aminotransferase, including γ-glutamyltransferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) [4]. The most specific indicators of hepatic damage are aspartate aminotransferase and alanine aminotransferase, which are found in the mitochondria and hepatocellular cytoplasm, respectively [5]. Increased ALT and AST are significantly linked to insulin resistance, type 2 diabetes, and metabolic syndrome, according to a recent study [6, 7].

Changes in liver enzyme levels, which are biological indicators that connect diabetes and liver disease, are present in NAFLD [8]. Using a calculated fibrosis-4 index (derived from age, ALT, AST, and platelets [PLTs]), adults with type 2 diabetes or prediabetes, especially those who are obese, should be screened/risk stratified for NAFLD with clinically significant fibrosis (moderate fibrosis to cirrhosis), as advised by the American Diabetes Association in 2023. In high-risk groups, such as those with obesity or type 2 diabetes mellitus (T2DM), clinicians fail to diagnose the potentially progressive form of NAFLD because they underestimate its prevalence and do not regularly use adequate screening measures. The lack of referrals and insufficient prescribing of drugs that have been shown to be effective in treating NASH exacerbate the under diagnosis [9]. The role of liver enzymes play in diabetes prediction has drawn more attention. In this sense, despite the fact that numerous researches have demonstrated a connection between diabetes and high liver enzymes, the findings is still erratic, and there aren't many studies on the subject [10]. Numerous studies have demonstrated a strong correlation between diabetes mellitus and elevated levels of blood liver enzymes, such as AST, ALT, and GGT [11]. While some research found that just ALT and GGT are risk factors for T2D, other studies found that ALT, AST, and GGT all raise the risk of T2D [12].

Aims and Objective: The objective is to investigate the relationship between liver enzyme levels and HbA1C levels in individuals with type 2 diabetes.

This was a case control study carried out in a tertiary care Indian hospital. The study enrolled 50 type 2 diabetes mellitus cases fulfilling the inclusion criteria and same number of aged matched control (nondiabetic).

Inclusion criteria

• Patients age ≥18 years with both gender
• Patients diagnosed with T2DM.
• Patients who provide written informed consent

Exclusion criteria

• Age <18 Years
• Patients of Type 1 diabetes, chronic inflammation, Autoimmune diseases, Malignancy
• Alcohol consumption ≥20 g/day in the past 3 month
• A history of either acute or chronic liver illness
• Hepatotoxic medication use
• Patients who not provide written informed consent

This study includes diabetic patients who are admitted as inpatients or examined in outpatient departments during the study period. At the time of admission, a pre-made proforma is used to gather information and obtain a thorough history. The American Diabetes Association's standards for diagnosing type 2 diabetes were followed. Every participant had their HbA1C levels and liver function tests measured. HbA1C levels are associated with liver enzymes

Statistical analysis: IBM SPSS statistics version 22 was used to perform the statistical analysis. For the explanatory and outcome variables, descriptive statistics were computed using the mean, standard deviation, frequency, and proportions for the quantitative variables and the proportions for the qualitative variables. A p value <0.05 was considered statistically significant

This was a case control study carried out in a tertiary care Indian hospital. The study enrolled 50 type 2 diabetes mellitus cases fulfilling the inclusion criteria and same number of aged matched control (nondiabetic).

Inclusion criteria

• Patients age ≥18 years with both gender
• Patients diagnosed with T2DM.
• Patients who provide written informed consent

Exclusion criteria

• Age <18 Years
• Patients of Type 1 diabetes, chronic inflammation, Autoimmune diseases, Malignancy
• Alcohol consumption ≥20 g/day in the past 3 month
• A history of either acute or chronic liver illness
• Hepatotoxic medication use
• Patients who not provide written informed consent

This study includes diabetic patients who are admitted as inpatients or examined in outpatient departments during the study period. At the time of admission, a pre-made proforma is used to gather information and obtain a thorough history. The American Diabetes Association's standards for diagnosing type 2 diabetes were followed. Every participant had their HbA1C levels and liver function tests measured. HbA1C levels are associated with liver enzymes

Statistical analysis: IBM SPSS statistics version 22 was used to perform the statistical analysis. For the explanatory and outcome variables, descriptive statistics were computed using the mean, standard deviation, frequency, and proportions for the quantitative variables and the proportions for the qualitative variables. A p value <0.05 was considered statistically significant

A total of 100 participants (50 type 2 diabetes mellitus cases and 50 non diabetic controls) were enrolled and analysed in this study. Majority of the participants were males (64% in cases & 60% in control). The mean age among cases was 53.5 ± 9.3 and mean age among control was 49.8 ± 5.6. Most of them educated up to Primary school (cases 38% & control 40%) and Merchant by occupation (cases 48% & control 40%) [Table 1].

Table 1: Socio-demographic characteristics of study participants (N = 100)

Mean duration of diabetes was 7.86±5.38 years, mean HbA1c was 8.48±3.25, mean FBS was 169.54±91.35 and mean PPBS was 242.27±133.59 mg/dl [Table 2].

Table 2: Baseline characteristics of diabetic participants

Liver enzymes (AST, ALT, ALP, & GGT) were statistically significantly raised in diabetic patients as compared to non-diabetic control (p>0.05), also significant difference between mean age, BMI and RBS between diabetic and non-diabetic group (p>0.05).

Table 3: Correlation of laboratory parameters between non diabetic and diabetic participants

We investigate the association of liver enzymes abnormalities in patients with uncontrolled type 2 diabetes mellitus.

In the present study, the mean age of the diabetes and the control group were 53.5 ± 9.3 and 49.8 ± 5.6 years, respectively, there was statistically significant difference (p<0.05) statistically. Similar results were obtained by Jha et al [13] and Alam S, et al [14] reported that the average age of T2DM patients were 46.4±13.6 and 56.91±11.00 years, respectively.

In our study, majority of the participants were males in both cases and control group, no statistically significant difference (p>0.05), in agreement with the Shibabaw et al [15] and Mandal et al [16].

We have found that participants with type 2 diabetes mellitus had a higher prevalence of abnormal LFTs than participants without T2DM; our results were comparable with the other numerous research conducted by Islam S, et al [17], Xu L, et al [18] and Tohidi M, et al [19], reported that the prevalence of liver enzymes (ALT, AST, ALP and GGT) above upper normal upper limit was significantly higher in subjects having diabetes This could be due to the liver is more prone to inflammation in diabetic cases, which changes how the liver functions and causes changes in liver biomarkers.

We can understand that liver enzymes are not the only markers of liver dysfunction, which also have a predictive value to assess the severity of diabetes. Insulin resistance is a typical feature of T2DM, which shows that abnormality in glucose homeostasis by the liver. Glycation is the most common complication of T2DM that results oxidative stress in tissue [20].

The average HbA1C in our study is 8.48±3.25, and the average duration of diabetes is 7.86±5.38. The average FBS and PPBS were 169.54±91.35 and 242.27±133.59, respectively, our findings correlated with the data of Avinash, et al [21].

We have found that all liver enzymes like ALT, AST, ALP and GGT were significantly elevated and associated with the type 2 diabetes mellitus, in concordant with the many others research [22-24].

Our study evaluated the presence of elevated levels of liver marker enzymes among T2DM participants. This may be due to increases in glycogen/insulin effect on liver cells. The increase of glycogenolysis (breakdown of stored glycogen) and gluconeogenesis (glucose production from non-carbohydrate precursors) becomes the primary metabolic pathway.

A study performed by Nguyen QM, et al [25] reported that the elevated AST enzyme as marker for in diabetes risk assessment.

In a study done by Kariyawasan et al [26], patients with HbA1C >7 liver enzymes and lipid profile were deranged. Pearson’s correlation revealed a positive co-relation between HbA1C and VLDL and a negative correlation between bilirubin and HbA1C. Positive correlation between HbA1C, ALP, TG, and VLDL indicates progression of disease and probability of cardiovascular complications. The negative correlation between HbA1C and bilirubin indicates good control and may be useful in monitoring control

The primary emphasis of our research is the significance of keeping an eye on liver function tests in patients with uncontrolled type 2 diabetes. We have found a significant correlation between liver function test abnormality and type 2 diabetes mellitus. Liver enzymes like AST, ALT, ALP and GGT were significantly raised in Type 2 diabetes patients. All have a negative connection with HbA1C, Future research is needed to determine the causes of hepatic dysfunction in diabetics and investigate how liver abnormalities affect glycemic status.

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