The rise in blood glucose after lunch is less if breakfast has been eaten. The metabolic basis of this second-meal phenomenon remains uncertain. We hypothesized that storage of ingested glucose as glycogen could be responsible during the post-meal suppression of plasma NEFAs (non-esterified fatty acids; 'free' fatty acids). In the present study we determined the metabolic basis of the second-meal phenomenon. Healthy subjects were studied on two separate days, with breakfast and without breakfast in a random order. We studied metabolic changes after a standardized test lunch labelled with 3 g of 13C-labelled (99%) glucose. Changes in post-prandial muscle glycogen storage were measured using 13C magnetic resonance spectroscopy. The rise in plasma glucose after lunch was significantly less if breakfast had been taken (0.9+/-0.3 compared with 3.2+/-0.3 mmol/l, with and without breakfast respectively; P<0.001), despite comparable insulin responses. Pre-lunch NEFAs were suppressed after breakfast (0.13+/-0.03 compared with 0.51+/-0.04 mmol/l) and levels correlated positively with the maximum glucose rise after lunch (r=0.62, P=0.001). The increase in muscle glycogen signal was greater 5 h after lunch on the breakfast day (103+/-21 compared with 48+/-12 units; P<0.007) and correlated negatively with plasma NEFA concentrations before lunch (r=-0.48, P<0.05). The second-meal effect is associated with priming of muscle glycogen synthesis consequent upon sustained suppression of plasma NEFA concentrations.

The measurement of tissue lipid and glycogen contents and the establishment of normal levels of variability are important when assessing changes caused by pathology or treatment. We measured hepatic and skeletal muscle lipid and glycogen levels using (1)H and (13)C MRS at 3 T in groups of subjects with and without type 2 diabetes. Within-visit reproducibility, due to repositioning and instrument errors was determined from repeat measurements made over 1 h. Natural variability was assessed from separate measurements made on three occasions over 1 month. Hepatic lipid content was greater in subjects with diabetes relative to healthy subjects (p = 0.03), whereas levels of hepatic and skeletal muscle glycogen, and of intra- and extra-myocellular lipid, were similar. The single-session reproducibility values (coefficient of variation, CV) for hepatic lipid content were 12% and 7% in groups of subjects with and without diabetes, respectively. The variability of hepatic lipid content over 1 month was greater than the reproducibility, with CV = 22% (p = 0.08) and CV = 44% (p = 0.004) in subjects with and without diabetes, respectively. Similarly, levels of variation in basal hepatic glycogen concentrations (subjects with diabetes, CV = 38%; healthy volunteers, CV = 35%) were significantly larger than single-session reproducibility values (CV = 17%, p = 0.02 and CV = 13%, p = 0.05, respectively), indicating substantial biological changes in basal concentrations over 1 month. There was a decreasing correlation in measurements of both hepatic lipid and glycogen content with increasing time between scans. Levels of variability in intra- and extra-myocellular lipid in the soleus muscle, and glycogen concentrations in the gastrocnemius muscle, tended to be larger than expected from single-session reproducibility, although these did not reach significance.

In subjects with T2DM, a mixed meal challenge is associated with a significant elevation in the serum levels of ALT, HA and P3NP without significant changes in LFC. These markers should be performed in the fasted state.

Aims/hypothesis We compared in vivo changes in liver glycogen concentration during exercise between patients with type 1 diabetes and healthy volunteers. MethodsWe studied seven men with type 1 diabetes (mean ± SEM diabetes duration 10±2 years, age 33±3 years, BMI 24±1 kg/m 2 , HbA 1c 8.1±0.2% and VO 2 peak 43±2 ml [kg lean body mass] −1 min −1 ) and five non-diabetic controls (mean ± SEM age 30±3 years, BMI 22±1 kg/m 2 , HbA 1c 5.4±0.1% and VO 2 peak 52±4 ml [kg lean body mass] −1 min −1 , before and after a standardised breakfast and after three bouts (EX1, EX2, EX3) of 40 min of cycling at 60% VO 2 peak. 13 C Magnetic resonance spectroscopy of liver glycogen was acquired in a 3.0 T magnet using a surface coil. Whole-body substrate oxidation was determined using indirect calorimetry.Results Blood glucose and serum insulin concentrations were significantly higher (p<0.05) in the fasting state, during the postprandial period and during EX1 and EX2 in subjects with type 1 diabetes compared with controls. Serum insulin concentration was still different between groups during EX3 (p<0.05), but blood glucose concentration was similar. There was no difference between groups in liver glycogen concentration before or after the three bouts of exercise, despite the relative hyperinsulinaemia in type 1 diabetes. There were also no differences in substrate oxidation rates between groups. Conclusions/interpretation In patients with type 1 diabetes, hyperinsulinaemic and hyperglycaemic conditions during moderate exercise did not suppress hepatic glycogen concentrations. These findings do not support the hypothesis that exercise-induced hypoglycaemia in patients with type 1 diabetes is due to suppression of hepatic glycogen mobilisation.