Morphemetric documentation of abnormal intramyocellular fat storage and reduced glycogen in obese patients with Type II diabetes

Aims/hypothesis. Insulin resistance of skeletal muscle has been associated with increased lipid availability. This study aimed to estimate volume frac tions of intramyocellular triglyceride droplets and glycogen granules In sk eletal muscle using electron microscopy and furthermore, relate these findi ngs to insulin sensitivity and the level of circulating lipids. Methods. We compared 11 obese patients with Type II (non-insulin-dependent) diabetes mellitus and 11 obese normoglycaemic subjects matched for age and sex. Glucose metabolism was determined using the euglycaemic hyperinsulina emic clamp technique (40 mU.m(-2).min(-1)) coupled with indirect calorimetr y and tritiated glucose. On the second day, using an automatic procedure, a fasting muscle biopsy was carried out and processed for electron microscop y. Volume fractions of intramyocellular structures were estimated by pointc ounting on photographic pictures in a blinded manner. Results. Insulin-stimulated total glucose disposal rate was lower in the Ty pe II diabetic subjects compared with the obese normoglycaemic subjects (4. 96 +/- 049 vs 10.35 +/-0.89 mg.min(-1) kg ffm(-1), p < 0.001) as was glucos e storage (2.03<plus/minus>0.50 vs 6.59 +/-0.83,p < 0.001). The electron mi croscopy study revealed that the diabetic subjects had higher intramyocellu lar amounts of triglyceride (1.430<plus/minus>0.21 vs 0.39 +/-0.07%, p < 0. 001) and lower amounts of glycogen (3.53<plus/minus>0.33 vs 6.44 +/-0.54%, p < 0.001), Mitochondrial volume was identical indicating equal aerobic cap acity. The fractional intramyocellular lipid volume was found to be positiv ely associated with fasting NEFA (r=0.63, p = < 0.05 and r = 0.79, p = < 0. 05) and triglyceride (r = 0.74, p = 0.01 and r = 0.62, p < 0.05) in the obe se diabetic and normoglycaemic cohorts respectively. Intramyocellular lipid content was negatively correlated to insulin sensitivity (r = -0.71, p < 0 .02) in the obese diabetic group whereas no significant association was fou nd in the obese normoglycaemic group. Conclusion/interpretation. This study shows that fat accumulates intramyoce llulary while glycogen stores are simultaneously reduced in obese subjects with Type II (non-insulin-dependent) diabetes mellitus. Quantitatively, a m ajor component of the excessive lipid accumulation could be secondary in or igin, related to the diabetic state in itself, although a contribution from ;the altered insulin action cascade of obesity and diabetes cannot be exclu ded. In both groups significant positive relations were found between circu lating and intramyocellular lipid.