Role of Adipose Tissue Compartments for Cardiovascular Risk in Diabetes Endotypes

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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.

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