Weight reduction and the impaired plasma-derived free fatty acid oxidation in type 2 diabetic subjects

J Clin Endocrinol Metab. 2001 Apr;86(4):1638-44. doi: 10.1210/jcem.86.4.7397.


In a previous study the oxidation of plasma free fatty acids (FFA) under baseline conditions and during exercise was lower in type 2 diabetic subjects compared with weight-matched controls. The present study intended to investigate the effect of weight reduction (very low calorie diet) on plasma FFA oxidation in seven type 2 diabetic male subjects (body fat, 37.4 +/- 1.2%; age, 51.3 +/- 3.4 yr; plasma glucose, 7.45 +/- 0.48 mmol/L). Subjects underwent a 10-week diet period. Body composition and substrate utilization during rest and during bicycle exercise (50% of maximum aerobic capacity) were determined before and after the diet (during weight-stable conditions). FFA metabolism was studied by means of the tracer [U-(13)C]palmitate. Rates of oxidation of plasma FFA were corrected with an acetate recovery factor. Additionally, activities of mitochondrial enzymes and cytosolic fatty acid-binding protein were determined in biopsies from the vastus lateralis muscle before and after the diet. The very low calorie diet resulted in a weight loss of 15.3 kg (110.8 +/- 7.4 vs. 95.5 +/- 5.8 kg; P < 0.01). The basal rates of appearance and disappearance of FFA decreased as a result of diet. The rates of appearance and disappearance of FFA during exercise were not different before and after diet. The oxidation of plasma-derived fatty acids tended to decrease after diet during baseline conditions (P = 0.10), whereas the plasma FFA oxidation during exercise was not different before and after the diet (14.1 +/- 1.9 vs. 14.8 +/- 1.8 micromol/kg fat-free mass.min). Skeletal muscle cytosolic fatty acid-binding protein and the activities of muscle oxidative enzymes did not significantly change as a result of weight loss. In conclusion, considerable weight reduction did not significantly improve plasma-derived FFA oxidation under baseline conditions and during exercise, suggesting that this impairment reflects a primary defect leading to the development of type 2 diabetes mellitus rather than resulting from the type 2 diabetic state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arteries
  • Body Composition
  • Calorimetry, Indirect
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / pathology*
  • Fatty Acids, Nonesterified / blood
  • Fatty Acids, Nonesterified / metabolism*
  • Hormones / blood
  • Humans
  • Insulin / physiology
  • Male
  • Middle Aged
  • Muscle, Skeletal / pathology
  • Osmolar Concentration
  • Oxidation-Reduction
  • Oxygen Consumption
  • Weight Loss*


  • Fatty Acids, Nonesterified
  • Hormones
  • Insulin