Role of Adipose Tissue Compartments for Cardiovascular Risk in Diabetes Endotypes

Area of Science:

• Metabolic Syndrome
• Cardiovascular Disease
• Diabetes Research

Background:

• Severe insulin-resistant diabetes (SIRD) is a distinct endotype associated with metabolic dysfunction-associated steatotic liver disease and increased cardiovascular risk.
• Understanding the lipid distribution in SIRD is crucial for risk stratification and targeted interventions.

Purpose of the Study:

• To investigate whether skeletal muscle or adipose tissue lipids are elevated in the severe insulin-resistant diabetes (SIRD) endotype.
• To determine the association between lipid accumulation in different tissues and cardiovascular risk in diabetes.

Main Methods:

• Utilized data from 420 participants in the German Diabetes Study (GDS).
• Employed 1H-magnetic resonance spectroscopy to quantify intramyocellular lipids (IMCLs), intrahepatic lipids (IHLs), and visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes.
• Assigned participants to diabetes clusters using a validated algorithm.

Main Results:

• SIRD endotype exhibited significantly higher intrahepatic lipids (IHLs) and both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes compared to other endotypes, even after adjusting for BMI.
• No significant differences in intramyocellular lipids (IMCLs) were observed across diabetes endotypes.
• VAT volume and IHLs demonstrated a positive correlation with cardiovascular risk scores (Framingham).

Conclusions:

• The SIRD endotype is characterized by increased intrahepatic and adipose tissue lipid accumulation, rather than skeletal muscle lipid accumulation.
• Adipose tissue volume and intrahepatic lipids are significant contributors to cardiovascular risk in individuals with severe insulin resistance.
• These findings highlight the importance of body fat distribution in the metabolic and cardiovascular complications associated with SIRD.