OBJECTIVE -We investigated whether alterations of glycolytic and oxidative enzyme capacity in skeletal muscle of patients with type 2 diabetes pertain to specific muscle fibers and are associated with changes in muscle fiber composition.RESEARCH DESIGN AND METHODS -Vastus lateralis muscle was obtained by percutaneous biopsy from 10 patients with type 2 diabetes and 15 age-and BMI-matched healthy volunteers. Using cytophotometry, muscle fiber composition and fiber type-specific glycolytic and oxidative enzyme activities were measured in slow oxidative, fast oxidative glycolytic, and fast glycolytic fibers.RESULTS -In the whole muscle, oxidative activity was decreased in patients with type 2 diabetes. The slow oxidative fiber fraction was reduced by 16%, whereas the fast glycolytic fiber fraction was increased by 49% in skeletal muscle from the diabetic patients. Both oxidative and glycolytic enzyme activities were significantly increased in fast glycolytic and fast oxidative glycolytic fibers of type 2 diabetic patients. However, the fiber-specific ratio of glycolytic enzyme activity relative to oxidative activity was not different between type 2 diabetic patients and the control subjects. The myofibrillic ATP activity was significantly lower in all fiber types of patients with type 2 diabetes and correlates with glucose infusion rate during the steady state of a euglycemic-hyperinsulinemic clamp and maximal aerobic capacity and negatively with HbA 1c values.CONCLUSIONS -Reduced oxidative enzyme activity in muscle of type 2 diabetic patients is most likely due to a reduction in slow oxidative fibers. Increased glycolytic and oxidative enzyme activities in individual muscle fibers are closely related to measures of long-term glycemic control and whole-body insulin sensitivity and could therefore represent a compensatory mechanism of the muscle in function of the altered glucose metabolism. Diabetes Care 29:895-900, 2006T ype 2 diabetes is characterized by severe insulin resistance of skeletal muscle associated with an impaired insulin-stimulated glucose disposal rate (1,2). Insulin resistance correlates with skeletal muscle fiber type distribution (3), a reduced percentage of slow oxidative type I fibers (4), and reduced oxidative enzyme capacity (5-7). Aging and physical inactivity, which are both associated with insulin resistance, also lead to diminished oxidative capacity of skeletal muscle (6). Simoneau and Kelley (6) showed that an increased ratio of glycolytic to oxidative enzymes contributes to insulin resistance in skeletal muscle of patients with type 2 diabetes. Interestingly, with singlefiber analysis, no differences have been found in the fiber type composition between lean, obese, and type 2 diabetic subjects (7). In this study, significant differences in oxidative but not in glycolytic enzyme activity and in the glycolytic-tooxidative ratio were reported for the comparison of lean and obese subjects and patients with type 2 diabetes (7). However, it is still not entirely understood whether metabolic...