Role of Adipose Tissue Compartments for Cardiovascular Risk in Diabetes Endotypes

OBJECTIVE The severe insulin-resistant diabetes (SIRD) endotype is associated with metabolic dysfunction-associated steatotic liver disease and higher cardiovascular risk. We investigated whether skeletal muscle or adipose tissue lipids are elevated in SIRD. RESEARCH DESIGN AND METHODS Participants (N = 420) of the German Diabetes Study (GDS) were assigned to diabetes clusters using a validated algorithm. 1H-magnetic resonance methods were used to quantify intramyocellular lipids (IMCLs), intrahepatic lipids (IHLs), and visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes. RESULTS Aside from elevated IHLs (P < 0.01), SIRD showed higher VAT and SAT than other endotypes after adjustment for BMI (all P < 0.05) but not for multiple comparisons. All endotypes featured comparable IMCLs. VAT volume and IHLs correlated with cardiovascular risk scores (Framingham r = 0.661 and 0.548, respectively, P < 0.05). Polygenic risk scores for VAT were associated with higher cardiovascular risk. CONCLUSIONS SIRD features higher IHLs and nominally higher VAT volume, which likely contribute to increased cardiovascular risk, highlighting implications for tailored prevention and treatment.