assessment of muscle glycogen storage after mixed meals in normal and type 2 diabetic subjects. Am J Physiol Endocrinol Metab 284: E688-E694, 2003. First published December 3, 2002 10.1152/ajpendo.00471.2002To understand the day-to-day pathophysiology of impaired muscle glycogen storage in type 2 diabetes, glycogen concentrations were measured before and after the consumption of sequential mixed meals (breakfast: 190.5 g carbohydrate, 41.0 g fat, 28.8 g protein, 1,253 kcal; lunch: 203.3 g carbohydrate, 48.1 g fat, 44.0 g protein, 1,497.5 kcal) by use of natural abundance 13 C magnetic resonance spectroscopy. Subjects with diet-controlled type 2 diabetes (n ϭ 9) and ageand body mass index-matched nondiabetic controls (n ϭ 9) were studied. Mean fasting gastrocnemius glycogen concentration was significantly lower in the diabetic group (57.1 Ϯ 3.6 vs. 68.9 Ϯ 4.1 mmol/l; P Ͻ 0.05). After the first meal, mean glycogen concentration in the control group rose significantly from basal (97.1 Ϯ 7.0 mmol/l at 240 min; P ϭ 0.005). After the second meal, the high level of muscle glycogen concentration in the control group was maintained, with a further rise to 108.0 Ϯ 11.6 mmol/l by 480 min. In the diabetic group, the postprandial rise was markedly lower than that of the control group (65.9 Ϯ 5.2 mmol/l at 240 min, P Ͻ 0.005, and 70.8 Ϯ 6.7 mmol/l at 480 min, P ϭ 0.01) despite considerably greater serum insulin levels (752.0 Ϯ 109.0 vs. 372.3 Ϯ 78.2 pmol/l at 300 min, P ϭ 0.013). This was associated with a significantly greater postprandial hyperglycemia (10.8 Ϯ 1.3 vs. 5.3 Ϯ 0.2 mmol/l at 240 min, P Ͻ 0.005). Basal muscle glycogen concentration correlated inversely with fasting blood glucose (r ϭ Ϫ0.55, P Ͻ 0.02) and fasting serum insulin (r ϭ Ϫ0.57, P Ͻ 0.02). The increment in muscle glycogen correlated with initial increment in serum insulin only in the control group (r ϭ 0.87, P Ͻ 0.002). This study quantitates for the first time the subnormal basal muscle glycogen concentration and the inadequate glycogen storage after meals in type 2 diabetes. type 2 diabetes; magnetic resonance spectroscopy; insulin resistance MAINTENANCE OF GLUCOSE HOMEOSTASIS after meals depends on storage of glucose as glycogen in muscle and liver, suppression of hepatic glucose output, and increase in glucose oxidation. Previous work has quantitated the extent of glycogen storage in the liver and muscle of healthy young subjects and has demonstrated that, in both organs, the postprandial increase peaks around 5 h, declining thereafter (35, 36). In type 2 diabetes, glucose homeostasis fails, and marked postprandial hyperglycemia is typical. Because the normal stimulation of muscle glycogen storage is controlled principally by insulin, and because insulin action in muscle is decreased in type 2 diabetes, it may be hypothesized that this contributes to the postprandial hyperglycemia. The practical importance of this has been emphasized by data linking the extent of postprandial hyperglycemia with the vascular complications of diabetes (9, 12).Under c...