Plasma glucose thresholds for counterregulation after an oral glucose load

Glucose counterregulation (GCR) plays an important role in the transition between exogenous and endogenous glucose delivery after an oral glucose load. This response is initiated when plasma glucose concentrations are decreased below threshold levels, previously defined in studies of insulin-induced hypoglycemia. In this study, we tested the plasma glucose thresholds for activation of the GCR response under more physiologic circumstances, ie, after glucose ingestion. We studied 20 normal subjects for 300 minutes after 75 g of oral glucose. Between 150 and 300 minutes, blood samples and symptom scores were obtained at 10-minute intervals. After oral glucose, individual glucose nadirs were observed over a wide time range (160 to 290 minutes). Mean glucose concentrations decreased from 5.3 ± 0.2 mmol/L at 30 minutes before the nadir (−30 minutes) to 3.8 ± 0.2 mmol/L at the nadir (0 minutes). Mean plasma epinephrine concentrations increased from 210 ± 35 pmol/L, were significantly elevated at −10 minutes (P < .05), and peaked at +20 minutes (1,008 ± 184 pmol/L, P < .001). Mean plasma glucagon concentrations were significantly increased over baseline (100%) at +10 minutes (P < .001) and peaked at +30 minutes (122% ± 7%, P < .001). Seven subjects (out of 15 tested) developed symptoms. Quantitative evaluation revealed a peak in the mean symptom score at +20 minutes, an increase from 0.4 ± 0.3 to 2.6 ± 0.1 arbitrary units (P < .06). Plasma glucose thresholds for epinephrine, glucagon, and appearance of symptoms were estimated to be 4.2 ± 0.2, 3.8 ± 0.2, and between 2.9 and 3.3 mmol/L, respectively, similar to those found during studies of insulin-induced hypoglycemia. We conclude that the levels and hierarchy of plasma glucose thresholds for GCR are maintained during the late phase after an oral glucose load. Also, even in normal subjects, mild symptoms may occur and peak together with epinephrine after the gluose nadir.