1300-P: Visceral Adipose Tissue Volume Is Increased in Severe Insulin Resistant Diabetes

Introduction & Objective: The severe insulin resistant diabetes (SIRD) endotype associates with markedly higher risk of metabolic dysfunction associated steatotic liver disease (MASLD). However, it is not known if ectopic lipid deposition is also higher in skeletal muscle or adipose tissue compartments than in other endotypes.

Methods: Participants (n=697, known diabetes duration <1 y) of the prospective German Diabetes Study (GDS) underwent ¹H magnetic resonance spectroscopy for quantifying intramyocellular lipids (IMCL) in tibialis anterior muscle, intrahepatic lipids (IHL), visceral (VAT) and subcutaneous adipose tissue (SAT) volumes. The validated clustering algorithm used age, sex, BMI, HOMA-IR, HOMA-B, islet-directed autoantibodies.

Results: As expected, SIRD (n=40) had the highest IHL (11±5%) compared to mean IHL values of 2-6% in moderate obesity-related (MOD, n=215), moderate age-related (MARD, n=237) and severe autoimmune diabetes clusters (SAID, n=193; all p<0.01). Interestingly, SIRD presented with higher VAT than MOD, MARD and SAID (6089±2705 vs 3260±2310, 3056±1963, 1524±1401 cm³) even after adjustment for BMI (all p<0.05). Also, SAT was higher in SIRD than MARD (27879±6777 vs 17127±6218 cm³, p<0.05), while differences to other subtypes lost statistical significance upon correction for BMI. There were no differences in IMCL between subtypes. Overall, VAT correlated with cardiovascular risk (Framingham, r=0.661, p<0.05), whole-body insulin sensitivity derived from hyperinsulinemic euglycemic clamp (r=-0.537, p<0.05) and with beta cell function during intravenous glucose tolerance test (r=0.379, p<0.05). Within SIRD, VAT was further associated with fasting glycemia (r=0.121, p=0.05) and fasting insulin resistance (HOMA-IR; r=0.372, p<0.05).

Conclusion: The increases in IHL and VAT underline their key role in the pathophysiology and progression of severely insulin resistant diabetes and shall help to refine subtyping approaches for precision diabetology.