Higher Endogenous Glucose Production during OGTT vs Isoglycemic Intravenous Glucose Infusion

CONTEXT: Oral glucose ingestion elicits a larger insulin response and delayed suppression of glucagon compared to isoglycemic intravenous (iv) glucose infusion (IIGI).

OBJECTIVE: We studied whether these differences translate into effects on endogenous glucose production (EGP) and glucose disposal in patients with type 2 diabetes and non-diabetic control subjects.

DESIGN: Single-blinded, randomized, crossover study.

SETTING: The study was conducted at a specialized research unit.

PARTICIPANTS: Ten patients with type 2 diabetes (age [mean ± SD] 57.1 ± 6.7 years; body mass index (BMI) 29.0 ± 4.3 kg/m(2); HbA1c 53.8 ± 11.0 mmol/mol; duration of diabetes 9.2 ± 5.0 years) and 10 matched non-diabetic control subjects (age 56.0±10.7 years; BMI 29.8 ± 2.9 kg/m(2); HbA1c 33.8 ± 5.5 mmol/mol) Interventions: Three experimental days: 75 g-oral glucose tolerance test (OGTT), IIGI and IIGI+glucagon (IIGI with a concomitant iv glucagon infusion (0.8 ng/kg/min from 0 to 25 min) designed to mimic portal glucagon concentrations during OGTT in the type 2 diabetic group).

MAIN OUTCOME MEASURES: Glucose kinetics assessed by the double-tracer technique.

RESULTS: Glucose rate of disappearance was higher during the OGTT vs IIGIs in the control group, but similar on all days in the diabetic group. Surprisingly, in both groups, EGP was more suppressed during IIGI than during OGTT and exogenous glucagon infusion during IIGI did not restore EGP to the levels observed during OGTT.

CONCLUSION: EGP was less suppressed during OGTT than during IIGI in both patients with type 2 diabetes and in non-diabetic control subjects. Based on the present experimental design it was not possible to attribute this difference to the delayed glucagon suppression observed in the initial phase of the OGTT.