Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes.
Level 4 - case-series / case-control
Cross-sectional comparative physiological study across four participant groups
PubMed 11739435 · doi:10.1210/jcem.86.12.8075
What was done
Researchers compared insulin sensitivity, intramuscular lipid (IMCL) accumulation, and skeletal muscle oxidative capacity across four participant groups: 9 sedentary lean, 11 obese, 8 obese with type 2 diabetes mellitus, and 9 lean endurance-trained subjects (total n = 37). Insulin sensitivity (M) was measured using a hyperinsulinemic-euglycemic clamp (40 mU·m⁻²·min⁻¹). Percutaneous vastus lateralis biopsies were analyzed for IMCL area via Oil Red O staining and for oxidative capacity via succinate dehydrogenase (SDH) staining.
What was found
Insulin sensitivity (M, mg·min⁻¹·kg fat-free mass⁻¹) was significantly greater (P < 0.01) in lean (9.45 ± 0.59) and trained (10.26 ± 0.78) groups compared with obese (5.51 ± 0.61) and diabetic (1.15 ± 0.83) groups. IMCL content was approximately 2-fold higher in diabetic subjects (3.04 ± 0.39% area) and also higher in trained subjects (2.36 ± 0.37% area) compared to lean subjects (1.40 ± 0.28% area; P < 0.01). Muscle oxidative capacity was highest in trained subjects (50.0 ± 4.4 optical density units) compared with lean (36.1 ± 4.4), obese (29.7 ± 3.8), and diabetic (33.4 ± 4.7) subjects (P < 0.01). IMCL negatively correlated with insulin sensitivity when trained subjects were excluded (r = -0.57, P < 0.05), but the correlation was not significant when trained individuals were included. Oxidative capacity positively correlated with M among non-diabetic participants (r = 0.37, P < 0.05).
Why it matters
This paper describes the 'athlete's paradox,' demonstrating that elevated intramuscular lipid stores do not cause insulin resistance when accompanied by high skeletal muscle oxidative capacity.
Limits
The study is cross-sectional with small group sizes (8 to 11 participants per group), preventing causal conclusions. It relied on histochemical staining without differentiating specific lipid species such as diacylglycerols or ceramides.
Cited by
- supports Bret Goodpaster and David Kelley demonstrated that lean, highly insulin-sensitive endurance athletes have intramuscular triglyceride levels as high as obese individuals with type 2 diabetes.