Adiposity, Skeletal Muscle Mass and Handgrip Strength in Relation to Hepatic Steatosis and Liver Fibrosis in Individuals with Type 2 Diabetes Mellitus: A Dual-Energy X-ray Absorptiometry and Transient Elastography Study

Technical Summary: Adiposity, Skeletal Muscle Mass, and Handgrip Strength in Relation to Hepatic Steatosis and Liver Fibrosis in Type 2 Diabetes

Problem Statement
Type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) share common pathophysiological roots, specifically adiposity and insulin resistance. While the progression of liver disease is traditionally linked to the stage of fibrosis, emerging evidence suggests that whole-body composition—the balance between adipose tissue and skeletal muscle—is a critical determinant of disease severity. Specifically, the "sarcopenic obesity" phenotype, characterized by the coexistence of excess fat and impaired skeletal muscle, is hypothesized to amplify metabolic risk, insulin resistance, and lipotoxicity. However, there is a paucity of data simultaneously profiling adiposity, DXA-derived muscle mass, and muscle function against elastography-defined steatosis and fibrosis, particularly within South Asian populations who exhibit a distinct "thin-fat" body composition with high visceral adiposity at relatively modest Body Mass Index (BMI) levels.

Methodology
This single-centre, cross-sectional study was conducted at a tertiary-care hospital in northern India between January 2023 and August 2024. The cohort consisted of 150 adults (80% male) aged 20–75 years with T2DM. Exclusion criteria included other chronic liver diseases, significant alcohol intake, cardiovascular disease, Type 1 diabetes, severe renal impairment, and pregnancy.

The study employed a multi-modal assessment approach:

• Body Composition: Whole-body Dual-Energy X-ray Absorptiometry (DXA) was used to quantify total body fat, total lean mass, appendicular lean mass, and visceral adipose tissue (VAT). The Appendicular Skeletal Muscle Mass Index (SMI) was calculated as appendicular lean mass divided by height squared, with low muscle mass defined against Asian Working Group for Sarcopenia (AWGS) 2019 thresholds.
• Muscle Function: Handgrip strength was measured via hydraulic dynamometry in both hands.
• Liver Assessment: Vibration-controlled transient elastography (FibroScan) was performed after a minimum four-hour fast. Hepatic steatosis was defined by a Controlled Attenuation Parameter (CAP) ≥ 238 dB/m, and liver fibrosis was assessed via Liver Stiffness Measurement (LSM), with thresholds of ≥ 8.0 kPa and ≥ 9.6 kPa indicating clinically relevant and advanced fibrosis, respectively.
• Serum Markers: Fibrosis scores (FIB-4, NAFLD fibrosis score, etc.) were calculated using standard formulae.
• Statistical Analysis: Associations were examined using Pearson or Spearman correlations, and differences across fibrosis strata were analyzed using ANOVA or Kruskal–Wallis tests.

Key Results

• Cohort Profile: The mean age was 53.6 years, with a mean BMI of 28.1 kg/m² (76% obese). The mean total body fat was 34.1%, and mean visceral adipose tissue was 769.6 g.
• Adiposity and Liver Disease: Total body fat showed a significant positive correlation with both hepatic steatosis (CAP, r = 0.420, p < 0.001) and liver fibrosis (LSM, r = 0.329, p < 0.001). Adiposity measures (BMI, waist circumference, total body fat) increased stepwise across LSM strata. For instance, total body fat rose from 33.2% in the LSM < 8 kPa group to 40.4% in the LSM > 12 kPa group.
• Muscle Mass vs. Function: Contrary to the expectation that low muscle mass drives fibrosis, height-indexed muscle mass (SMI) correlated positively with CAP (r = 0.295) and LSM (r = 0.243). The authors attribute this to the confounding effect of body size, where absolute and height-indexed lean mass rise alongside fat mass in obesity.
• The Quantity–Quality Dissociation: A critical finding emerged when stratifying by serum fibrosis risk (FIB-4). Participants with a higher FIB-4 score (≥ 1.3) were, on average, leaner (lower BMI and body fat) but exhibited significantly lower handgrip strength (24.8 kg vs. 28.3 kg in the right hand) compared to those with lower FIB-4 scores. This indicates a dissociation where muscle quantity may be preserved or increased with obesity, but muscle function declines with advancing fibrosis risk.

Key Contributions

1. Characterization of the Sarcopenic-Obesity Phenotype in T2DM: The study provides empirical evidence that in T2DM, the risk of liver fibrosis is associated with a complex interplay where increased adiposity drives steatosis and fibrosis, while muscle function deteriorates even as absolute muscle mass may remain high or increase.
2. Differentiation of Risk Stratification Tools: The paper highlights that elastography (LSM) and serum markers (FIB-4) identify distinct phenotypes. LSM correlates strongly with adiposity, whereas FIB-4 identifies an older, leaner, and functionally weaker subgroup. This suggests that relying on a single non-invasive marker may be insufficient for comprehensive risk stratification.
3. Limitations of Height-Indexed Muscle Mass: The findings underscore that height-based muscle indices (like SMI) can mask sarcopenia in obese populations because they do not account for the parallel increase in fat and lean mass. Functional measures (handgrip strength) are necessary to unmask the decline in muscle quality.

Significance and Claims
The authors conclude that in individuals with T2DM, greater total and visceral adiposity is closely associated with elastography-defined hepatic steatosis and fibrosis. However, absolute skeletal muscle mass increases with obesity, while muscle function (indexed by handgrip strength) declines with advancing fibrosis risk.

This "quantity–quality dissociation" supports the existence of a sarcopenic-obesity phenotype. The paper argues that liver risk stratification in diabetes should incorporate assessments of both adiposity and muscle function, rather than relying solely on BMI or muscle mass indices. The authors posit that interventions targeting the sarcopenic-obesity axis—such as structured resistance exercise and adequate protein intake—may simultaneously benefit glycaemic control and liver health, though they note that prospective studies are required to confirm the causal contribution of body composition to diabetic liver disease.

The study acknowledges limitations, including its cross-sectional design (precluding causal inference), single-centre nature, male predominance, and the use of grip strength as the sole measure of physical performance.