Effects of oral glucose on systemic glucose metabolism during hyperinsulinemic hypoglycemia in normal man

The widespread use of oral glucose in the treatment of hypoglycemia is main ly empirically based, and little is known about the time lag and subsequent magnitude of effects following its administration. To define the systemic impact and time course of effects following oral glucose during hypoglycemi a, we investigated 7 healthy young men twice. On both occasions, a 6-hour h yperinsulinemic (1.5 mU/kg/min)-hypoglycemic clamp was performed to ensure similar plasma glucose profiles during a stepwise decrease toward a nadir l ess than 50 mg/100 mL after 3 hours. On the first occasion, subjects ingest ed 40 g glucose and 4 g 3-ortho-methylglucose ([3-OMG] to trace glucose abs orption) dissolved in 400 mL tap water after 3.5 hours. The second examinat ion was identical except for the omission of 40 g oral glucose, and glucose levels were clamped at hypoglycemic concentrations similar to those record ed on the first examination. Plasma glucose curves were superimposable, and all participants reached a nadir less than 50 mg/100 mt. Similar increases in growth hormone (GH) and glucagon were observed in both situations. The glucose infusion rates (GIRs) were lower after oral glucose, with the diffe rence starting after 5 to 10 minutes, being statistically significant after 20 minutes, and reaching a maximum of 8.5 +/- 1.6 mg/kg/min after 40 minut es. Circulating 3-OMG increased after 20 minutes. In both situations, infus ion of insulin resulted in insulin levels of approximately 150 muU/mL and a suppression of C-peptide levels from 2.0 to 1.1 nmol/L (P < .01). After gl ucose ingestion, both serum C-peptide and glucagon-like peptide-1 (GLP-1) i ncreased (C-peptide from 1.1 +/- 0.05 to 1.4 +/- nmol/L and GLP-1 from 3.2 +/- 0.8 to 18.1 +/- 3.3 pmol/L), in contrast to the situation without oral glucose (P < .05). Isotopically determined glucose turnover was similar In conclusion, our data suggest that oral glucose affects systemic glucose met abolism rapidly after 5 to 10 minutes. Quantitatively, the immediate impact is relatively small, with the gross impact observed after approximately 40 minutes. Future studies aiming to identify therapeutic oral agents with pr ompt effect seem warranted. Copyright (C) 2000 by W.B. Saunders Company.