Non-alcoholic Fatty liver Disease may range from simple steatosis to non-alcoholic steatohepatitis (NASH) and cirrhosis. At a time, it may progress to hepatocellular carcinoma. Globally, NAFLD has become the most common liver disorder, with a median prevalence of approximately 20 % in general population. 1

Prediabetes is a condition intermediate to normoglycemia and overt type 2 Diabetes mellitus (T2DM). It is defined by Impaired fasting glucose (IFG), Impaired glucose tolerance (IGT) or elevated HbA1c level between 5.7% to 6.4%. Prediabetics are at higher risk of developing overt diabetes and cardiovascular diseases. Insulin resistance is hallmark of prediabetes and is also a key pathological mechanism in NAFLD leading to fat accumulation in liver causing liver dysfunction and metabolic complications. 2

Several studies in the past have highlighted significant association between prediabetes and NAFLD. A study by Das et al have shown that prediabetes has significant positive association with NAFLD and highlighted the role of insulin resistance in its pathophysiology.3 Another study in eastern India also reported that 22.9% of NAFLD patient were prediabetic, further emphasizing the interrelation between these metabolic disorders.4

The prevalence of NAFLD is rising in India. India is a diverse country and its regional variation in prevalence of NAFLD is influenced by genetic, dietary, sociocultural and lifestyle factors. Very limited data is available on the burden of NAFLD among individual with prediabetes, particularly in the Rohilkhand region of Uttar Pradesh. Understanding the prevalence of NAFLD in this population will help us for early detection and timely intervention to prevent disease progression and associated complications. In this study, we aim to determine the prevalence of NAFLD in individuals with prediabetes in Rohilkhand region and analyse its association with other metabolic factors.

This was a cross-sectional study conducted between June 2024 to December 2024 at Rohilkhand Medical College and Hospital, Bareilly, a tertiary care teaching hospital in Rohilkhand region of Uttar Pradesh.

Individuals aged 18 years and above attending the outpatient department for routine health check-ups or minor ailments were screened for eligibility. Prediabetes was defined according to the American Diabetes Association (ADA).⁵ criteria: Impaired Fasting Glucose (IFG): Fasting Plasma Glucose (FPG) levels between 100 mg/dL and 125 mg/dL. Impaired Glucose Tolerance (IGT): 2-hour plasma glucose levels between 140 mg/dL and 199 mg/dL during a 75-gram Oral Glucose Tolerance Test (OGTT). Glycated Hemoglobin (HbA1c): Levels between 5.7% and 6.4%. Individuals meeting any of the above criteria were considered prediabetic.

Exclusion Criteria-

• History of significant alcohol consumption (defined as >20 grams/day for men and >10 grams/day for women).
• Known liver diseases such as viral hepatitis, autoimmune hepatitis, or drug-induced liver injury.
•  
• Critical illness or organ failure patients.

Sample size - Based on previous studies indicating a prevalence of NAFLD among prediabetic individuals ranging from 22.9% to 59%, a sample size of 200 prediabetic subjects was calculated to achieve a 95% confidence level with a 5% margin of error. ⁶

Methodology-

• After obtaining informed consent, participants underwent a comprehensive evaluation, including anthropometric measurement (Weight, Height, BMI, Waist and hip circumference), Blood Pressure measurement and Biochemical Investigations (FPG, HbA1c, Liver function test-Serum Aspartate Aminotransferase (AST), Alanine Aminotransferase (ALT), Gamma-Glutamyl Transferase (GGT), and Alkaline Phosphatase (ALP) and Lipid profile- Total cholesterol, Triglycerides, High-Density Lipoprotein (HDL), and Low-Density Lipoprotein (LDL).

Diagnosis of NAFLD: NAFLD was diagnosed using ultrasonography (USG), a non-invasive and widely accepted modality for detecting hepatic steatosis.^7,8 Grading of fatty liver was performed as follows:

• Grade 1 (Mild): Slight diffuse increase in hepatic echogenicity with normal visualization of the diaphragm and intrahepatic vessel borders.
• Grade 2 (Moderate): Moderate diffuse increase in hepatic echogenicity with slightly impaired visualization of intrahepatic vessels and diaphragm.
• Grade 3 (Severe): Marked increase in echogenicity with poor visualization of intrahepatic vessel borders, diaphragm, and posterior portion of the right lobe.

The ultrasonography was performed by experienced radiologists blinded to the participants' clinical and biochemical data.

Statistical Analysis

Data were analysed using Statistical Package for the Social Sciences (SPSS) version 25.0. Continuous variables were expressed as mean ± standard deviation, and categorical variables as frequencies and percentages. The prevalence of NAFLD was calculated, and comparisons between groups were made using the chi-square test for categorical variables and the independent t-test for continuous variables. A p-value of <0.05 was considered statistically significant.

The detailed comparison is shown in the table below:

Table 1. Comparison of Clinical and Biochemical Parameters between NAFLD and Non-NAFLD Groups

We have found high prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) among prediabetic individuals in the Rohilkhand region, with 39% of the 200 prediabetic subjects diagnosed with NAFLD. This finding is consistent with previous studies in India and globally, where NAFLD prevalence among prediabetics has ranged from 22.9% to 59%.^9,10,11.12 This study highlights the significant burden of NAFLD in this metabolically at-risk group i.e. Prediabetics and underscores the importance of targeted screening and early intervention.

The gender distribution in our study revealed a slightly higher prevalence of NAFLD in males (41.7%) compared to females (35%), which aligns with earlier reports suggesting a male preponderance. ^12,13 This may be attributed to differences in fat distribution, hormonal influences, and lifestyle factors. However, high prevalence among females also indicates that NAFLD is a significant concern across both sexes.

Obesity was strongly associated with NAFLD in our study. Among overweight or obese participants (BMI >27.5 kg/m²), 60% had NAFLD, compared to only 25% in those with lower BMI. This supports the established role of obesity, particularly central adiposity, in the pathogenesis of NAFLD.^13,14 Insulin resistance, a hallmark of prediabetes, is also a key pathophysiological mechanism leading to hepatic fat accumulation and liver dysfunction. ^9,12.14 Our findings further reinforce the need for weight management and metabolic control in prediabetic populations to reduce NAFLD risk.

Biochemical analysis revealed that patients with NAFLD had significantly higher HbA1c, fasting blood glucose, and elevated liver enzymes (ALT and AST) compared to those without NAFLD. These results are consistent with the pathophysiological link between insulin resistance, impaired glucose metabolism, and hepatic steatosis.^9,12,.14 Elevated liver enzymes further suggest ongoing hepatic injury or inflammation, which may predispose these individuals to progression from simple steatosis to non-alcoholic steatohepatitis (NASH) and advanced liver disease. ^9,14

The grading of NAFLD in this study showed that a substantial proportion of patients (59%) had moderate to severe fatty liver (grades 2 and 3). This is clinically important, as higher grades of steatosis are associated with increased risk of progression to fibrosis, cirrhosis, and hepatocellular carcinoma.^1,14. Early detection and intervention in prediabetic individuals with moderate to severe NAFLD could therefore have significant implications for preventing liver-related morbidity and mortality.

Table 2- Comparison of different studies on prevalence of NAFLD in prediabetes

Limitations

We have not performed liver biopsy therefore we may have missed early cases of NAFLD. This was a single centre study therefore the findings may not be generalizable to all Indian population.

Our study confirms that NAFLD is highly prevalent in prediabetes with strong associations between BMI, ALT, HbA1c, and NAFLD. These findings emphasize the need for early screening, lifestyle modifications, and tighter glycaemic control to prevent progression to NASH and Type 2 Diabetes Mellitus. Longitudinal studies are needed to further explore the impact of metabolic interventions on NAFLD outcomes in prediabetic individuals.

1. 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;64(1):73-84.
2. Tabák AG, Herder C, Rathmann W, Brunner EJ, Kivimäki M. Prediabetes: a high-risk state for diabetes development. The Lancet. 2012 Jun 16;379(9833):2279-90.
3. Das K, Das K, Mukherjee PS, Ghosh A, Ghosh S, Mridha AR, et al. Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease. Hepatology. 2010 May;51(5):1593-602.
4. Singh SP, Nayak S, Swain M, Rout N, Mallik RN, Agrawal O, et al. Prevalence of nonalcoholic fatty liver disease in coastal eastern India: A preliminary ultrasonographic survey. Trop Gastroenterol. 2004 Apr-Jun;25(2):76-9.
5. American Diabetes Association. "Standards of Medical Care in Diabetes—2024." Clinical Diabetes, vol 47, issue 1, January 2024. https://diabetesjournals.org/care/issue/47/Supplement_1.
6. Daniel WW, editor. 7th ed. New York: John Wiley & Sons; 1999. Biostatistics: a foundation for analysis in the health sciences.
7. Hernaez R, Lazo M, Bonekamp S, Kamel I, Brancati FL, Guallar E, Clark JM. Diagnostic accuracy and reliability of ultrasonography for the detection of fatty liver: a meta-analysis. Hepatology. 2011;54:1082–1090.
8. Dasarathy S, Dasarathy J, Khiyami A, Joseph R, Lopez R, McCullough AJ. Validity of real time ultrasound in the diagnosis of hepatic steatosis: a prospective study. J Hepatol. 2009;51:1061–1067.
9. Das K, et al. Prevalence of non-alcoholic fatty liver disease among diabetes and prediabetes patients. J Family Med Prim Care. 2023;12(2):410-415.
10. Duseja A, et al. Prevalence of Non-alcoholic Fatty Liver Disease in India: A Systematic Review and Meta-analysis. Indian J Gastroenterol. 2022;41(3):211-222.
11. Bouzid K, et al. Pre-diabetes and NAFLD; A study of an Algerian population sample. Metabolism Open. 2020;7:100014.
12. Younossi ZM, et al. The effect of diabetes and prediabetes on the prevalence and risk of nonalcoholic fatty liver disease. World J Gastroenterol. 2022;28(22):2468-2481.
13. European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), European Association for the Study of Obesity (EASO). EASL–EASD–EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016;64(6):1388-402.
14. Samuel VT, Shulman GI. The pathogenesis of insulin resistance: integrating signaling pathways and substrate flux. J Clin Invest. 2016;126(1):12-22.
15. Yadav D, Choudhary N, Dabas A, et al. Prevalence of NAFLD in prediabetes: A hospital-based study in India. J Clin Exp Hepatol. 2020;10(3):245-251.
16. Mishra P, Kumar R, Sharma R, et al. Association of prediabetes with NAFLD: Insights from a North Indian cohort. Int J Diabetes Dev Ctries. 2021;41(4):398-405.
17. Long MT, Zhang X, Xu H, et al. Prediabetes and NAFLD: Evidence from the Framingham Heart Study. Hepatology. 2019;69(2):558-569.