Rethinking metabolic risk in primary biliary cholangitis: The prognostic impact of lean type 2 diabetes mellitus

Table 1 Metabolic determinants of disease progression in primary biliary cholangitis

Factor	Mechanism	Clinical impact in PBC	Ref.
Type 2 diabetes mellitus	Insulin resistance, chronic inflammation, profibrogenic signaling	Fibrosis progression ↑, mortality ↑	[17,25]
Lean type 2 diabetes mellitus	β-cell dysfunction, metabolic dysregulation independent of adiposity	Underrecognized high-risk phenotype, mortality ↑	[11]
Obesity/high BMI	Visceral adiposity, adipokine imbalance, systemic inflammation	Steatosis, altered biochemical profile, variable fibrosis impact ↑	[14]
MASLD overlap	Lipotoxicity, oxidative stress, mitochondrial dysfunction	Response to UDCA ↓, liver-related complications ↑	[7]
Visceral adiposity	Cytokine release, insulin resistance	Cardiometabolic risk, fibrosis progression ↑	[47]
Sarcopenia/Low BMI	Reduced muscle mass, frailty, metabolic dysregulation	Associated with worse outcomes, potential reverse causality	[20,21]
Dyslipidemia in PBC	Altered bile acid metabolism, lipid abnormalities	High prevalence but variable CV risk impact	[48]
Adipose tissue dysfunction	Cytokines, endocrine signaling	Promotes inflammation and fibrogenesis	[18]

BMI: Body mass index; MASLD: Metabolic dysfunction-associated steatotic liver disease; PBC: Primary biliary cholangitis; UDCA: Ursodeoxycholic acid; CV: Cardiovascular.