Intramyocellular Triglyceride Content During the Early Course of Type 1 and Type 2 Diabetes Mellitus

Intramyocellular lipid content (IMCL) is elevated in insulin-resistant humans, but its changes over time and relationships with comorbidities remain unclear. We examined IMCL during the initial course of diabetes and its associations with complications. Participants of the German Diabetes Study (GDS) with recent-onset type 1 (n=132) or type 2 diabetes (n=139) and glucose-tolerant controls (n=128) underwent 1H-magnetic resonance spectroscopy to measure IMCL and muscle volume, whole-body insulin sensitivity (hyperinsulinemic-euglycemic clamps; M-value) and cycling spiroergometry (VO2max). Subgroups underwent the same measurements after 5 years. At baseline, IMCL was ~30% higher in type 2 diabetes than in other groups independently of age, sex, BMI and muscle volume. In type 2 diabetes, M-value was ~36% and ~62% lower compared to type 1 diabetes and controls, respectively. After 5 years, M-value decreased by ~29% in type 1 and ~13% in type 2 diabetes, whereas IMCL remained unchanged. The correlation of IMCL and M-value in type 2 diabetes at baseline was modulated by VO2max. IMCL also associated with microalbuminuria, Framingham risk score for cardiovascular disease and cardiac autonomic neuropathy. Changes in IMCL within 5 years after diagnosis do not mirror progression of insulin resistance in type 2 diabetes but associate with early diabetes-related complications.