Evidence for spatial heterogeneity in insulin-and exercise-induced increases in glucose uptake: Studies in normal subjects and patients with type 1 diabetes

It is unknown whether resistance to insulin- or exercise-stimulated glucose uptake reflects a spatially uniform or nonuniform decrease in glucose upta ke within skeletal muscle. We compared the distributions of muscle glucose uptake and blood flow in eight patients with type 1 diabetes (age 24 +/- 1 yr, body mass index 22.0 +/- 0.8 kg/m(2)) and seven age- and weight-matched normal subjects using positron emission tomography, [F-18]-fluoro-deoxy-gl ucose, and [O-15]-water. Both groups were studied during euglycemic hyperin sulinemia and one-legged exercise. Heterogeneity was evaluated by calculati ng relative dispersion (SD divided by mean * 100%) of glucose uptake (RDg) and flow (RDf) in all pixels within a region of interest in femoral muscle. At rest insulin-stimulated glucose uptake was significantly lower in the t ype 1 diabetic patients (42 +/- 7 mu mol/kg per min) than in the normal sub jects (78 +/- 9 mu mol/kg per min, P < 0.001), while muscle blood flows wer e similar (26 +/- 1 vs. 31 +/- 3 ml/kg muscle per min, respectively). The e xercise-induced increment in glucose uptake but not in blood flow was also significantly lower in the type 1 diabetic patients than in the normal subj ects. Heterogeneity of glucose uptake but not of blood flow was greater in the insulin-resistant type 1 diabetic patients both at rest (RD 31 +/- 1 vs . 25 +/- 2%, patients with type 1 diabetes vs. normal subjects, P < 0.05) a nd during exercise, compared with normal subjects (27 +/- 1 vs. 21 +/- 2%, respectively, P < 0.05). Exercise increased both glucose uptake and blood f low several-fold and significantly decreased both RDg and RDf. Heterogeneit y of RDg, was inversely associated with total glucose uptake (r = -0.54, P < 0.001, pooled data) and was highest in the most insulin-resistant patient s. We concluded that both glucose uptake and blood flow are characterized b y heterogeneity in human skeletal muscle, whose magnitude is inversely prop ortional to respective mean values: This implies that an increase in glucos e uptake in human skeletal muscle is not a phenomenon, by which each unit i ncreases its glucose uptake by a fixed amount but rather a spatially hetero geneous process.