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The respective effects of the level of glycogen stores and the size of the glucose load on the pathways of carbohydrate (CHO) metabolism were compared over the 5-hour period following glucose ingestion in normal human subjects. For this purpose, labeling of the oral glucose load with [3-(3)H]- and [U(14)C] glucose was combined with indirect calorimetry. In group I, 75 g glucose was given to subjects who had either been "fed" with intravenous (IV) glucose or fasted for 13, 24, or 36 hours, or 4 days. In fed versus 4-day-fasted subjects, net CHO storage averaged approximately 15 versus 63 g/5 h (P <.001). About 83% of the increase in fasted subjects was due to suppression of glycogen breakdown, with only minimal stimulation of glycogen synthesis from oral glucose. Over the whole range of nutritional conditions tested, a strong positive correlation existed between basal CHO oxidation and glycogen breakdown occurring during the oral glucose tolerance test (OGTT), suggesting that the initial degree of repletion of hepatic glycogen stores is a major determinant of postprandial glycogen turnover. In group II, OGTTs with 33 and 100 g glucose were compared in 13-hour-fasted subjects. Net storage rose from approximately -6 to approximately 37 g/5 h (P <.001) solely because of an increase in glycogen synthesis with no inhibition of glycogen turnover. Overall, these results show that the initial dietary state and the size of the glucose load modulate postprandial net CHO accumulation by different mechanisms., (Copyright 2003, Elsevier Science (USA). All rights reserved.)

To analyze the effects of metformin (M) on the kinetics and pathways of glucose utilization after glucose ingestion, nine non-insulin-dependent diabetes mellitus (NIDDM) patients underwent two 5-hour oral glucose tolerance tests (OGTTs) preceded in random order by a 3-week treatment with either M (850 mg twice per day) or placebo. Each test included intravenous infusion of 3-3H-glucose and labeling of the oral dose (75 g) with 1-14C-glucose, with measurements of glucose kinetics, glycolytic flux (3H2O production), and glucose oxidation (indirect calorimetry and expired 14CO2). Basal glycemia was decreased by M (6.6 v 8.2 mmol/L, P < .01) with no changes in insulin levels, with the hypoglycemic effect correlating strongly (P < .001) with a decrease in glucose production. Mean 0- to 5-hour postprandial glycemia was also decreased by the drug (9.9 v 12.2 mmol/L, P < .04), lactate concentration was increased (1.79 v 1.44 mmol/L, P < .01), and absolute insulin levels were increased, but not to a significant extent. The rates of appearance (Ra) of exogenous and endogenous glucose were not modified, and the hypoglycemic effect of M in the postprandial state was entirely related to an increase in systemic glucose disposal (85.1 v 77.5 g/5 h, P < .001). Carbohydrate oxidation was unchanged, and glycolytic flux and nonoxidative glycolysis were increased by approximately 13 g/5 h (P < .01), with the excess lactate produced probably being converted to glycogen in the liver. Whole-body glycogen synthesis through the direct pathway tended to be reduced (-8 g/5 h, P > .05). Thus, M decreases postprandial glycemia by increasing glucose disposal and stimulates lactate production. The data also suggest that the drug increases the proportions of glycogen deposited through the indirect rather than the direct pathway.

The relative contribution of liver and peripheral tissues to the postprandial glucose response has been examined in 19 obese non-insulin-dependent diabetes mellitus (NIDDM) patients and 11 matched nondiabetic control subjects during a 5-hour oral glucose tolerance test (OGTT) performed with a load of 75 g, corresponding to approximately 67 g/1.73 m2. A dual-tracer technique was used to measure exogenous and endogenous glucose fluxes separately. Glucose oxidation was measured by indirect calorimetry. Diabetic patients were subdivided into two subgroups designated as "mild" (n = 7) and "severe" (n = 12) NIDDM according to postabsorptive glucose concentration with a cut-off point of 140 mg/dL. In the basal state, glucose concentrations averaged 99, 117, and 194 mg/dL, respectively, in control subjects and in the two diabetic subgroups, but insulin concentrations were not significantly different between groups. In comparison to control subjects, the basal hyperglycemia of mildly diabetic patients was entirely caused by a reduced metabolic clearance rate (118 v 144 mL/min; P < .05), whereas in severely diabetic patients basal hyperglycemia resulted from a combination of increased hepatic glucose output (187 v 139 mg/min; P < .001) and decreased metabolic clearance rate (97 v 144 mL/min; P < .001). A similar situation prevailed during the initial 2 hours after glucose ingestion. In patients with mild NIDDM, glucose concentration increased by 121 +/- 10 mg/dL as compared with 36 +/- 7 mg/dL in control subjects (P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)