. Real-time assessment of postprandial fat storage in liver and skeletal muscle in health and type 2 diabetes.

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...

The extent and time course of suppression of endogenous glucose production (EGP) in type 2 diabetes after a mixed meal have been determined using a new tracer methodology. Groups of age-, sex-, and weight-matched normal controls (n = 8) and diet-controlled type 2 diabetic subjects (n = 8) were studied after ingesting a standard mixed meal (550 kcal; 67% carbohydrate, 19% fat, 14% protein). There was an early insulin increment in both groups such that, by 20 min, plasma insulin levels were 266 +/- 54 and 190 +/- 53 pmol/l, respectively. EGP was similar basally [2.55 +/- 0.12 mg x kg(-1) x min(-1) in control subjects vs. 2.92 +/- 0.16 mg x kg(-1) x min(-1) in the patients (P = 0.09)]. After glucose ingestion, EGP declined rapidly in both groups to approximately 50% of basal within 30 min of the meal. Despite the initial rapid decrease, the EGP was significantly greater in the diabetic group at 60 min (1.75 +/- 0.12 vs. 1.05 +/- 0.14 mg x kg(-1) x min(-1); P < 0.01) and did not reach nadir until 210 min (0.96 +/- 0.17 mg x kg(-1) x min(-1)). Between 60 and 240 min, EGP was 47% higher in the diabetic group (0.89 +/- 0.09 vs. 1.31 +/- 0.13 mg x kg(-1) x min(-1), P < 0.02). These data quantitate the initial rapid suppression of EGP after a mixed meal in type 2 diabetes and the contribution of continuing excess glucose production to subsequent hyperglycemia.

Forty-one patients who had undergone bone marrow transplantation were examined. Nineteen (63%) of the 30 who had received fractionated total body irradiation (TBI) had cataracts in comparison with only 1 (9%) of the 11 non-irradiated patients. No significant differences in steroid therapy were demonstrated between these groups of patients. Dry eyes were observed in eight irradiated patients, seven of whom had preceding graft-versushost disease. Superficial punctate staining of the bulbar conjunctiva was observed in 25 (83%) of the irradiated group and, in milder form, in five (45%) of the non-irradiated group, Our data suggest that the incidence of cataract following fractionated TBI is influenced not only by the total dose of radiation but also by its rate of administration (defined by midline tissue dose rate and fractionation schedule). In addition dry eyes and conjunctival staining may be exacerbated by TBI, though other aspects ofconditioning may also be implicated.