European Journal of Cardiovascular Medicine

Being the second most populated nation in the world, India also happens to have the seventh-largest landmass. Recent years have seen a dramatic increase in the prevalence of non-alcoholic fatty liver disease (NAFLD), which is mostly attributable to factors including the obesity and type 2 diabetes mellitus (T2DM) epidemics, the convenience of calorie-dense meals, and the prevalence of sedentary lifestyles. Non-alcoholic fatty liver diseasexincorporates non-alcoholic steatohepatitis (NASH). Since the majority of NAFLD patients do not experience any symptoms, the actual incidence is likely underreported. In people with type 2 diabetes mellitus, the prevalence of non-alcoholic fatty liver disease ranges from 34%xto 94% worldwide.[1] It is unclear how common NASH is among those with type 2 diabetes because there are no symptoms. Although liver biopsies are the exclusive way to diagnose NAFLD, they are not performed frequently until medically necessary. India has a little body of research on the frequency of (NAFLD) in type 2 diabetes patients, but no controlled attenuation parameter (CAP) study has focused on the Indian state of West Bengal. Because of the country's size and cultural diversity, it's not easy to generalise findings from one area of India to another.[2] Alcohol consumption history, liver enzyme values (ALT, SGOT, GGT), imaging evidence of hepatic steatosis, and the presence of steatosisxcombined with inflammationxor fibrosis on liver biopsy can all be used to diagnose NAFLD.[3] Comparing ultrasound to computerised tomography and magnetic resonance imaging (MRI), twoxnoninvasive imaging modalities, ultrasonography is both more sensitive and less expensive. NAFLD has-been linked to obesity, hypertension, and dyslipidaemia, type 2xdiabetes is the most significant metabolic issue involved in this syndrome.[4] Because insulin resistance occurs in type 2 diabetes, whether it is present alone or in conjunction with metabolic syndrome, it has been found to be highly related with non-alcoholic fatty liver disease (NAFLD).[5] In addition, reports indicate that the presence of both type 2 diabetes and non-alcoholic fatty liver disease is associated with an increased risk of mortality, including mortality from cardiovascular disease and liver disease.[6] In Asian countries, these factors and co-factors are becoming more common. This might be because Asians are genetically more likely to experience insulin resistance even in the absence of severe obesity, because their body composition differs from Caucasians in relation to the distribution and quantity of body fat.[7] Nevertheless, there is a lack of comprehensive data from India on this topic, as regular screening and monitoring of diabetics is not prevalent in NAFLD. So, most people with NAFLD don't get treatment. Disease load on the Indian population is likely to rise due to a lack of knowledge about NAFLD and its consequences, as well as related illnesses and risks. To investigate nonalcoholic fatty liver disease in people with type 2 diabetes. The purpose of this study is to investigate the relationship between glycemic control (FBS) and diabetes duration with ALT/SGPT levels.

Study Setting and Duration: For eighteen months beginning in July 2022 and ending in December 2023, researchers from Katihar Medical College and Hospital in Katihar carried out this cross-sectional study.

Study Population: The participants in the trial were people with type 2 diabetes who were seen by the general medicine doctors at Katihar Medical College and Hospital, either as outpatients or inpatients.

Study Design: A cross-sectional study design was utilised in the investigation.

Sample Size: According to the inclusion and exclusion criteria, one hundred cases were chosen to participate in the study.

Informed Consent: Ethical compliance was ensured by informing all patients about the study specifics and obtaining signed informed consent before participation.

Inclusion Criteria

• People whose doctors have confirmed a diagnosis of type 2 diabetes mellitus according to WHO standards.

Exclusion Criteria

• Previous history of icterus.
• History of alcohol consumption.
• Medications like glitazones, acarbose, tamoxifen, amiodarone, diltiazem, steroids, and statins are known to impact liver function tests (LFTs).
• State of having tested positive for hepatitis B surface antigen (HbsAg).

Data Collection: Utilising a systematic proforma, we gathered demographic information (age, sex, duration of diabetes), clinical parameters, and pertinent.

Medical history: The individuals' liver health was evaluated by the use of liver function tests. Additional imaging studies such as ultrasound was employed as necessary to evaluate the presence and extent of NAFLD.

NAFLD (Non-Alcoholic Fatty Liver Disease was diagnosed based on ultrasonography findings, specifically:

• Presence of "fatty liver" characterized by a diffuse increase in echogenicity
• Liver size greater than 16cm in the longitudinal plane, exceeding the upper limit of normal

Statistical Analysis: For statistical analysis, data were initially entered into a Microsoft Excel spreadsheet and then analyzed using SPSS (version 27.0; SPSS Inc., Chicago, IL, USA) and GraphPad Prism (version 5). Numerical variables were summarized using means and standard deviations, while categorical variables were described with counts and percentages. Two-sample t-tests, which compare the means of independent or unpaired samples, were used to assess differences between groups. Paired t-tests, which account for the correlation between paired observations, offer greater power than unpaired tests. Chi-square tests (χ² tests) were employed to evaluate hypotheses where the sampling distribution of the test statistic follows a chi-squared distribution under the null hypothesis; Pearson's chi-squared test is often referred to simply as the chi-squared test. For comparisons of unpaired proportions, either the chi-square test or Fisher’s exact test was used, depending on the context. To perform t-tests, the relevant formulae for test statistics, which either exactly follow or closely approximate a t-distribution under the null hypothesis, were applied, with specific degrees of freedom indicated for each test. P-values were determined from Student's t-distribution tables. A p-value ≤ 0.05 was considered statistically significant, leading to the rejection of the null hypothesis in favour of the alternative hypothesis

Table 1: Mean Levels of Liver Enzymes

Table 2: Correlation between NAFLD cases and ALT

Table 3: Correlation between NLFD cases and BMI

Table 4: Correlation between NLFD cases and Cholesterol Level

Figure1: Sex Distribution

Figure 2: Duration of Diabetes Mellitus

The study's participants were mostly female (59.0% of the sample) and slightly male (41.0%), according to the sex distribution. displays the average liver enzyme levels among the research participants. The average blood AST level was 33.21±14.48 U/L, the average ALT level was 36.64±9.94 U/L, and the average AST: ALT ratio was 0.88±0.18 U/L. On average, the GGT level was 32.91 ±9.17 U/L while the ALP level was 103.70±33.89 U/L. Total protein was 7.16±0.52 mg/dl and total bilirubin was 0.81±0.18 mg/dl, on average. Alanine aminotransferase (ALT) levels are correlated with non-alcoholic fatty liver disease (NAFLD) patients. Out of the 74 patients whose ALT levels were less than 44 U/L, 40 were found to have NAFLD and 34 were found to have no such condition. On the other hand, out of 26 individuals whose ALT levels were higher than 44 U/L, 20 did not have NAFLD and 6 did. A statistically significant association between increased ALT levels and the existence of NAFLD was indicated by a value of 4.19265 and a P value of 0.04, as determined by the Chi-square test. The correlation between NAFLD incidence and body mass index in a hundred individuals. In the group of 60 individuals who tested positive for NAFLD, 41 had a BMI of 24.9 or lower, while 19 had a BMI more than 25.0. Just four individuals in the NAFLD negative group had a body mass index (BMI) more than 25.0, while thirty-six had a BMI of 24.9 or lower. There is a substantially strong correlation between greater BMI and the existence of NAFLD was indicated by the Chi-square test, which yielded a value of 6.36175 with a P value of 0.011.The link between NAFLD cases and cholesterol levels. Out of the 60 people who tested positive for NAFLD, 30 had cholesterol levels below 150 mg/dl, 17 had levels between 150 and 199 mg/dl, and 13 had values of 200 mg/dl or more. Among the 40 people who tested negative for NAFLD, 33 had levels below 150 mg/dl, 6 had levels between 150 and 199 mg/dl, and 1 had levels of 200 mg/dl or more. A statistically significant link between increased cholesterol levels and the existence of NAFLD was indicated by the Chi- square test, which generated a value of 12.17650 with a P value of 0.002. Among those who took part in the study, 48.0% have had Diabetes Mellitus for 6 to 10 years, which is approximately half of the total duration. Those who have had diabetes for 11–15 years make up the next largest group at 31.0%. Only a minority, 21.0%, have been living with the illness for less than five years.

Nonalcoholic fatty liver disease (NAFLD) incidence and characteristics were investigated in this cross-sectional research of 100 people with type 2 diabetes mellitus.

Our data shows that middle-aged people with type 2 diabetes are more likely to develop NAFLD; specifically, 41–50 year olds make up 39.3% of all cases, followed by 51–60 year olds at 31.3%. The greatest prevalence of NAFLD was observed in people's 50s, which is in agreement with the results of Ruhl and Everhart (2009).[8]

Despite previous research suggesting a male predominance, such as that of Lazo et al. (2013), our findings reveal that the prevalence of NAFLD is higher in females (59.0%) than in males (41.0%).[9]

Environmental and lifestyle factors that contribute to NAFLD may be similar across geographic areas, since the NAFLD distribution was nearly equal between individuals in urban areas (52.7% of them) and those in rural areas (47.3%). Contrary to Le et al. (2016), who discovered a greater frequency of NAFLD in urban regions, this is consistent with Bellentani et al. (2004)[10,11].

In line with the findings of Younossi et al. (2016), who noted that adults with diabetes had an increased chance of developing severe liver disease, this study highlights the significant impact of non-alcoholic fatty liver disease (NAFLD) on diabetes patients, as it was detected in 60% of the participants.[12]

Our participants were mostly within the healthy weight range of 23.0 to 24.9 kg/m², with lower percentages of overweight (13.3%) and obese (10.0%). This goes against the grain because larger research, such as Hossain et al. (2007), typically find that diabetic communities have greater rates of overweight and obesity.[13]

Both the AST and ALT levels were within normal ranges, with the ALT level being significantly higher at 36.64 U/L. Even within normal ranges, ALT levels may indicate underlying liver pathology, according to studies such as Prati et al. (2002).[14]

Four in ten (48.0%) had diabetes for six to ten years, and thirty-one percent for eleven to fifteen years. The prevalence and severity of NAFLD are found to be correlated with the duration of diabetes, according to Targher et al. (2007).[15]

Our study's participants' total cholesterol distribution sheds light on the lipid management of type 2 diabetes mellitus, which is an intriguing area of research. The American Heart Association recommends a total cholesterol level belo150 mg/dl to reduce cardiovascular risk, and 63.3% of the individuals achieved this.[16].

Our study found that over half of the participants struggle with glycaemic management, as 52.0% had fasting blood sugar levels below 126 mg/dl and 48.0% were beyond this threshold. Fasting blood sugar levels varied significantly, with an average of 185.24 ± 61.29 mg/dl. This is in line with what Selvin et al. (2023) found, which is that NAFLD and other comorbidities of type 2 diabetes are associated with inadequate glycaemic management.[17].

While 26.0% of T2DM patients had increased ALT levels suggesting possible liver damage or NAFLD, 74.0% had ALT levels < 44 U/L. The findings of Sattar et al. (2004), who discovered that elevated ALT predicts hepatic fat storage and inflammation, lend credence to the frequent association between elevated ALT and liver damage and metabolic syndrome in type 2 diabetes.[18]

The correlation between ALT levels and the duration of diabetes was found to be statistically significant (p=0.0126) in this study. Diabetes was present for an average of 6-10 years in patients with ALT levels ≤ 44 U/L (42 participants), while individuals with higher ALT levels were more prone to have had the condition for 11-15 years. These findings corroborate those of other studies showing that NAFLD and elevated liver enzymes are more common in diabetic patients with longer illness durations. (Targher et al., 2007).[15]

Correlation between NAFLD cases and ALT:

Twenty of the twenty-six people in our study who had ALT levels above 44 U/L were also diagnosed with NAFLD, demonstrating a strong relationship between the two variables. Contrarily, NAFLD was present in all but six of the subjects with increased ALT. A total of 40 out of 74 individuals with ALT levels < 44 U/L were found to have NAFLD. These results are in line with previous research showing that increased ALT is frequently associated with NAFLD and its severity (e.g., JM C et al., 2003).[19] Although elevated ALT indicates hepatocellular injury from inflammation and hepatic steatosis, it is not a very accurate diagnostic tool for NAFLD.

Assessment.

Our study found a strong connection between NAFLD and fasting blood glucose levels; 35 out of 60 NAFLD patients had fasting glucose levels higher than 126 mg/dl. When compared to this, 29 out of 40 individuals who did not have NAFLD exhibited fasting glucose levels below the cutoff. High fasting glucose levels were associated with NAFLD in the statistical analysis, as shown by the high chi-square value of 11.22462 and p-value of 0.0008. Our results align with those of Marchesini G et al. (2001) and others who have linked hyperglycemia and insulin resistance to the development and progression of NAFLD.[20]

There was no statistically significant correlation between the length of time a person had diabetes and the prevalence of NAFLD in our study. The distribution of diabetes duration among those with NAFLD was similar to that of the non-NAFLD group: 12 persons with 0-5 years of diabetes, 27 with 6-10 years, and 21 with 11-15 years. The duration of diabetes does not seem to have a significant impact on the development of NAFLD, according to the Chi- square analysis (1.12687, p=0.569). This contradicts earlier research, such as that of Targher et al. (2007), which indicated a more robust association between the severity of NAFLD and the length of time that a person has had diabetes.[15] It is possible that other variables, such as metabolic regulation and lifestyle, are more important in the development of NAFLD than the duration of diabetes alone.

The occurrence of NAFLD was significantly correlated with BMI. Nineteen people with NAFLD had a body mass index (BMI) of 25.0 or above, whereas just four people in the control group did not have NAFLD. There is a considerable association between NAFLD and a higher body mass index, as confirmed by the Chi-square test (6.36175, p=0.011).

Additional research is required to establish whether there is a linkage between NAFLD and higher cholesterol levels, especially LDL, in our population. As pointed out by Chalasani et al. (2018),[21] hyperlipidaemia is prevalent in metabolic syndrome and promotes hepatic lipid buildup and inflammation. The number 140 to better understand the metabolic variables impacting NAFLD, it may be helpful to analyse the lipid profile in this group.

Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition, affecting 60% of the population, with the highest incidence in those aged 41-50 and predominantly female. Factors such as higher BMI and elevated Alanine Aminotransferase levels are strongly linked to NAFLD. The risk of NAFLD in diabetics is significantly influenced by obesity and liver enzyme levels. NAFLD is a complex disorder that requires comprehensive screening and management strategies. There are no significant associations between NAFLD and age, sex, total cholesterol, or fasting blood sugar levels. Regular testing is recommended for diabetic patients, especially those with higher BMI and ALT levels, and targeted therapies for weight and metabolism control are advised to reduce the risk and severity of NAFLD.

1. Angulo P. Nonalcoholic fatty liver disease. New England Journal of Medicine. 2002 Apr 18;346(16):1221-31.
2. Sinha A, Bankura B. Prevalence of nonalcoholic fatty liver disease in type 2 diabetes mellitus patients from the Eastern region of India. Diabetes Epidemiology and Management. 2023 Oct 1; 12:100161.
3. Dasarathy S, Dasarathy J, et al. Validity of real time ultrasound in the diagnosis of hepatic steatosis: a prospective study. J Hepatol. 2009;51(6):1061–1067.
4. Hassan K, Bhalla V, et al. Nonalcoholic fatty liver disease: A comprehensive review of a growing epidemic. World J Gastroenterol. 2014;20(34):12082.
5. Bhat G, Baba CS, et al. Insulin resistance and metabolic syndrome in nonobese Indian patients with non-alcoholic fatty liver disease. Trop Gastroenterol. 2013;34(1):18–24.
6. Targher G, Bertolini L, Poli F, Rodella S, Scala L, Tessari R, Zenari L, Falezza G. Nonalcoholic fatty liver disease and risk of future cardiovascular events among type 2 diabetic patients. Diabetes. 2005 Dec 1;54(12):3541-6.
7. Yoon K-H, Lee J-H, et al. Epidemic obesity and type 2 diabetes in Asia. The Lancet. 2006;368(9548):1681–1688.
8. Ruhl CE, Everhart JE. Determinants of the association of overweight with elevated serum alanine aminotransferase activity in the United States. Gastroenterology. 2003 Jan 1;124(1):71-9.
9. Lazo M, Hernaez R, Eberhardt MS, Bonekamp S, Kamel I, Guallar E, Koteish A, Brancati FL, Clark JM. Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988–1994. American journal of epidemiology. 2013 Jul 1;178(1):38-45.
10. Le MH, Devaki P, Ha NB, Jun DW, Te HS, Cheung RC, Nguyen MH. Prevalence of non-alcoholic fatty liver disease and risk factors for advanced fibrosis and mortality in the United States. PloS one. 2017 Mar 27;12(3):e0173499.
11. Bellentani S, Saccoccio G, Masutti F, Crocè LS, Brandi G, Sasso F, Cristanini G, Tiribelli C. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Annals of internal medicine. 2000 Jan 18;132(2):112-7.
12. Younossi ZM, Koenig AB, Abdelatif D, Fazel Y, Henry L, Wymer M. Global epidemiology of nonalcoholic fatty liver disease—meta‐analytic assessment of prevalence, incidence, and outcomes. Hepatology. 2016 Jul 1;64(1):73-84.
13. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world—a growing challenge. New England journal of medicine. 2007 Jan 18;356(3):213-5.
14. Prati D, Taioli E, Zanella A, Torre ED, Butelli S, Del Vecchio E, Vianello L, Zanuso F, Mozzi F, Milani S, Conte D. Updated definitions of healthy ranges for serum alanine aminotransferase levels. Annals of internal medicine. 2002 Jul 2;137(1):1-0.
15. Targher G, Bertolini L, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among type 2 diabetic patients. Diabetes Care. 2007;30(5):1212–1218
16. Grundy SM, Cleeman JI, Merz CN, Brewer Jr HB, Clark LT, Hunninghake DB, Pasternak RC, Smith Jr SC, Stone NJ. Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. Circulation. 2004 Jul 13;110(2):227-39.
17. Selvin E, Steffes MW, Zhu H, Matsushita K, Wagenknecht L, Pankow J, Coresh J, Brancati FL. Glycated hemoglobin, diabetes, and cardiovascular risk in nondiabetic adults. New England Journal of Medicine. 2023 Mar 4;362(9):800-11.
18. Sattar N, Scherbakova O, Ford I, O’Reilly DS, Stanley A, Forrest E, MacFarlane PW, Packard CJ, Cobbe SM, Shepherd J. Elevated alanine aminotransferase predicts new-onset type 2 diabetes independently of classical risk factors, metabolic syndrome, and C-reactive protein in the west of Scotland coronary prevention study. Diabetes. 2004 Nov 1;53(11):2855-60.
19. JM C. The Prevalence and Etiology of Elevated Aminotransferase Levels in the United States. Am J Gastroenterol. 2003;98(5):955-6.
20. Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M, McCullough AJ, Natale S, Forlani G, Melchionda N. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes. 2001 Aug 1;50(8):1844-50.
21. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non‐alcoholic fatty liver disease: Practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology. 2012 Jun;55(6):2005-23.