Abstract
Background Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a significant clinical concern, particularly in populations where hepatic complications manifest at relatively low body mass index (BMI) thresholds. While type 2 diabetes mellitus (T2DM) is often associated with the progression of hepatic damage, there is a limited amount of prospective, longitudinal data comparing the specific rate of fibrosis development between diabetic and non-diabetic individuals in the South Indian clinical setting. This study aimed to monitor biochemical and radiological markers over a 12-month period to quantify the impact of T2DM on the temporal progression of hepatic fibrosis. Methods This prospective, longitudinal cohort study was conducted at a tertiary care academic hospital in South India from January to December 2024. A total of 126 participants with ultrasound-confirmed MASLD and a controlled attenuation parameter (CAP) >248 dB/m were initially enrolled. Following an attrition of 28 participants (22.2%) due to failure of follow-up, a final per-protocol analysis was conducted on 98 participants, divided into Group A (T2DM; n=49) and Group B (non-T2DM; n=49). Follow-up assessments were performed at baseline (M0), midpoint (M6), and endpoint (M12) using a double-look imaging strategy. Hepatic fat and stiffness were quantified using transient elastography (FibroScan®) to measure CAP and liver stiffness measurement (LSM), supplemented by the calculated Fibrosis-4 (FIB-4) index. Results At baseline, the diabetic cohort in Group A exhibited a significantly higher metabolic burden, including a higher mean BMI (27.2 ± 3.1 vs 25.1 ± 2.4 kg/m(2); p=0.018) and higher hemoglobin A1C (HbA1c; 7.8 ± 1.2% vs 5.3 ± 0.3%; p<0.01) compared to Group B. Over the 12-month study period, Group A showed a linear and steady increase in mean LSM from 6.4 ± 1.6 kPa (7.1 ± 1.8 kPa at M6) to 7.8 ± 2.1 kPa (+1.4 kPa change; p<0.001), while Group B remained relatively stable (5.7 ± 1.3 to 5.9 ± 1.4 kPa; p=0.21). Additionally, 20.4% (n=10) of participants in Group A transitioned to a higher fibrosis stage, whereas only 4.1% (n=2) in Group B showed similar progression. Multivariable linear regression analysis confirmed that mean HbA1c remained a strong independent predictor of the increase in LSM (β = 0.45; p < 0.001) even after adjusting for baseline age and BMI. CAP scores indicating hepatic steatosis also worsened significantly in the diabetic cohort (292 ± 38 to 306 ± 42 dB/m; p=0.042). Conclusion The presence of T2DM accelerates the evolution of hepatic stiffness in South Indian MASLD patients, driving a substantial increase in fibrosis markers within a relatively short 12-month window. This progression underscores the unique metabolic vulnerability of the Indian population, where severe structural liver damage occurs at lower absolute body weights that already constitute clinical obesity (≥25 kg/m(2)) in this demographic. These findings emphasize the urgent need to integrate non-invasive screening tools such as FibroScan® and the FIB-4 index directly into primary diabetes care to facilitate early diagnosis and optimize the timing of specialized hepatology referrals.