Type 2 diabetes is a chronic metabolic disorder characterized by high blood glucose levels due to insulin resistance and/or impaired insulin secretion.[1]The change in our lifestyle and increasing incidence of obesity has caused an increase  in the prevalence of T2DM in the past few decades[2].More younger patients are developing T2DM than before, which is causing an enormous burden on the healthcare[3].It is predicted that the total number of diabetics will increase to a total of 600 million globally by the year 2035[4].

The main pathogenesis in T2DM is insulin resistance. The liver plays a major role in maintaining glucose homeostasis [5]. Any damage to the liver in the form of oxidative stress or abnormal fat deposition can alter the glucose homeostasis causing chronic hyperglycaemia [6]. The roles of liver enzymes are diverse and have often been identified as biomarkers of liver injury [7].  

Studies have shown abnormalities in liver enzymes seen in diabetics [8], though the exact mechanism of these abnormalities remains unclear. The AST/ALT ratio was first introduced in the year 1957, [9] since then, it has been used to interpret diseases such as metabolic syndrome [10], NAFLD [11] and insulin resistance [12].

Therefore, the present study is undertaken to discover the prevalence of LFT abnormality in patients with diabetics in comparison to non-diabetics and find the predominance of LFT abnormalities among diabetics. We shall also determine the correlation of various liver biochemical abnormality with HbA1c, so that, it could offer new insight to clinicians in improving the disease outcome.

SOURCE OF DATA

Primary data- In Patients and out patients attending Medicine Department at G R Medical college, hospital and research centre.

Secondary data-Published articles, journals, books, case sheets and related websites will be used for planning of the study.

 METHOD OF COLLECTION OF DATA

Study Design- A Hospital based cross-sectional comparative study.

Study Period- Period of 1 year between March 2024 to February 2025.

 Sample size: 100 (50 – cases, 50 – controls)

• INCLUSION CRITERIA- Subjects above 18 years of age
• EXCLUSION CRITERIA- Alcohol use disorder, known liver disease or other comorbidities.

 HUMAN ETHICS

The study was approved by Institutional Ethical committee (IEC) G R Medical college, hospital and research centre.

 PERSONAL INFORMATION, SPECIMEN COLLECTION AND LABORATORY. 

Information on demographic including age, sex was collected after obtaining informed consent. 

Blood samples were collected by trained nurses. Venous blood samples were stored in a refrigerator at 4 °C prior to analysis in the hospital laboratory. LFT (Direct bilirubin, indirect bilirubin, AST, ALT, Alp, albumin), HbA1c were measured using blood sample collected from each participant in a hospital laboratory.

 STASTICAL ANALYSIS  

Data obtained from the study will be entered in Microsoft Excel sheets and analysed using IBM SPSS software version 20.0 (Trial version) and presented as descriptive statistics in the form of frequency, tables, figures and graphs. Results were expressed as mean ± SD. ANOVA test used for testing the significance between the groups. Correlation of parameters is done by Pearson’s correlation formula. A p value of <0.05 is considered statistically significant.

In our comparative study, Out of the100 study subjects, 50 subjects (cases) were diabetic patients who were diagnosed as per ADA criteria ^[13] and 50 subjects (controls) were healthy individuals.

TABLE 1 – SEX DISTRIBUTION CHART

Sex distribution between the cases and controls were similar with 21 males and 29 females in both the subgroups as depicted in Table 1.

 TABLE 2 – AGE DISTRIBUTION AMONG SUBGROUPS

The mean age of subjects in the cases subgroup was 59.2 +/- 12.9 years, whereas it was 50.28 +/- 14.6 years in the controls subgroup, with the maximum number of individuals belonging to the age group 41-60 years in both the groups as depicted in Table 2.

 TABLE 3- BASELINE CHARECTERISTICS OF SUBGROUPS

The distribution of age and sex in both the group were comparable which reduces the potential for confounding bias and increases the internal validity of the study.

The mean HbA1c of the case subgroup was 9.38% which was significantly higher (<0.000) as compared to control subgroup.

The activity of AST were comparable in both the group whereas, the activity of ALT and ALP were significantly higher in the cases sub group (<0.05) as shown in table 3.

TABLE 4- CORRELATION OF HbA1c AND LIVER PARAMETERS.

Table 4 represents the correlation between liver enzymes and HbA1c among all subjects. ALT, ALP showed a positive correlation to HbA1c, ALP correlation statistically significant whereas, AST and AST/ALT ratio showed a negative correlation. 

The present study was undertaken to understand the complex nature of how diabetes affects the liver and throw some light on the hepatic dysfunctions seen in diabetics.

In a study done in Shanghai, china. A comparative study conducted on 2046 study subject by Jie-Ying wan and Li-zhen Yang ^[14], showed ALT to have a strong positive correlation with HbA1c, which was similar to our study. In another study done by Sana Alam et al ^[15] done in New Delhi, a comparative study on 612 subjects, showed a significantly higher ALT and ALP among the diabetic population which was similar to our study though it showed a negative correlation of all liver enzymes with HbA1c.

In another retrospective cohort study done by Liden Chen et al ^[16], on a population of 15,291 participant, the results showed a negative correlation of AST/ALT ratio to HbA1c with a nonlinear relation between the two. The study went on to show that AST/ALT ratio was a cost effective way to assess insulin resistance, risk of development of NAFLD. A similar result was obtained in our study as well.

A study done by P.Deepa and Sasivathanam on AST/ALT ratio in metabolic syndrome ^[17] a case control study, showed a significantly lower AST/ALT ratio among subjects with metabolic syndrome and in our study AST/ALT ratio showed a negative correlation with HbA1c. We can infer that risk of development of metabolic syndrome is higher among patient with higher insulin resistance and poor glycaemic control.

LIMITATION OF THE STUDY.

This study is associated with a few limitations such as sample size, the study design being a cross sectional due to which it was hard to determine whether the hepatic abnormality preceded diabetes or vice versa. The present study did not use HOMA-IR or hyperglycaemiceuglycaemic glucose clamp technique to determine the insulin resistance in order to correlate with insulin resistance. The study could have further used imaging modality to correlate with liver pathology such as NAFLD. 

The present study shows a significantly higher ALT and ALP levels in T2DM patients and negative correlation of AST/ALT ratio with HbA1c showing that this ratio can be used as a cost effective method to assess insulin resistance.

The present study shows the prevalence of LFT abnormalities of patients with T2DM and the importance of monitoring the same, as early detection and management of liver parameter would help in reducing liver related morbidity in diabetic population.

The take home message is to advice LFT in all diabetic patients because of the high prevalence of LFT abnormalities in these patient.

 DECLARATIONS

Funding: Self

Conflict of interest: None

Ethical approval: Approved.

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