Glucose Metabolism as a Key Driver in Metabolic-Related Liver Diseases

An NHANES analysis finds glycemic markers—fasting glucose, HbA1c and insulin-resistance indices—track more closely with hepatic steatosis and liver stiffness than many conventional lipid measures, prompting a shift in liver-risk assessment toward glycemic dysfunction.

By emphasizing glycemic dysfunction rather than a primarily lipid-centered view, the study reframes how clinicians can think about metabolic-related liver disease. Routine workflows still prioritize lipid panels and cardiovascular risk, but these data suggest fasting glucose and measures of dysglycemia may better identify patients at elevated hepatic risk and deserve parallel attention in hepatology and primary care.

Using NHANES 2017–2020 data and vibration-controlled transient elastography outputs (CAP for steatosis; LSM for fibrosis), the investigators analyzed a weighted sample of 9,698 adults and reported that GLU, HbA1c and HOMA-IR–based insulin resistance were among the strongest positive correlates of both CAP and LSM compared with most conventional lipid indices. The authors reported positive associations for TG, GLU and HbA1c with CAP and LSM; adjusted coefficients cited include HbA1c (CAP B≈17.04; LSM B≈0.684) and glucose (CAP B≈0.527; LSM B≈0.018), with key comparisons reaching P<0.001. Subgroup and tree-based analyses identified high-risk phenotypes—for example, participants with insulin ≥14.705 µU/mL and glucose ≥5.861 mmol/L had the highest mean CAP, while those with insulin 17.1–28.205 µU/mL, HbA1c ≥6.15% and glucose ≥7.861 mmol/L had the highest mean LSM—underscoring that insulin resistance plus dysglycemia compounds hepatic risk relative to dyslipidemia-only profiles.

These results support prioritizing routine fasting glucose and HbA1c measurement and considering insulin-resistance assessment (HOMA-IR or equivalent) when evaluating patients with metabolic syndrome, prediabetes, type 2 diabetes or unexplained transaminase elevation or imaging steatosis. Integrating glucose-based markers into liver-risk workflows can better refine which patients warrant noninvasive fibrosis assessment (FibroScan) and which need earlier metabolic intervention. Early glycemic control and insulin-sensitizing strategies may more effectively target prevention of progression from steatosis to fibrosis, while dyslipidemia remains an important comorbidity and treatment focus.