316-OR: Oral vs. Intravenous Glucose Administration Produce Opposing Microvascular Actions in Skeletal Muscle of Healthy People

Skeletal muscle microvascular blood flow (MBF) increases in response to an insulin infusion (hyperinsulinemic-euglycemic clamp) or the consumption of a mixed meal to augment glucose disposal. This microvascular action is impaired during insulin resistance. We recently demonstrated that an oral glucose challenge (50g glucose) acutely impairs skeletal muscle MBF in healthy people, compared to a mixed meal challenge, despite similar levels of hyperinsulinemia. We aimed to determine whether post-prandial hyperglycemia or gut-derived factors are the primary mediators of impaired MBF observed in response to orally ingested glucose. Seven healthy overnight-fasted subjects (sex 2M/5F, age 29±9 yrs, BMI 23.5±3.2 kg/m², blood glucose 4.5±0.3 mM, HbA1c 5.2±0.3%, total cholesterol 3.9±1.0 mM, triglycerides 0.8±0.3 mM) underwent an oral glucose tolerance test (OGTT, 75g glucose) and an intravenous glucose tolerance test (IVGTT- bypassing the gut) matched for similar blood glucose levels, on successive visits (<4 weeks apart: cross-over design). MBF was assessed in the vastus lateralis by contrast-enhanced ultrasound at baseline, 60 and 120 minutes post-OGTT and -IVGTT. Despite similar area under the glucose time curve (OGTT: 846.8±124.8, IVGTT: 845.9±121.1 mMx2hr, P=0.98), MBF was only stimulated with the IVGTT, at 60 min (Δ MBF: OGTT -0.3± 0.5; IVGTT 0.3± 0.3 Acoustic intensity/sec, P=0.02) and 120 min post- infusion (Δ MBF: OGTT -0.4± 0.3; IVGTT 0.2± 0.3 Acoustic intensity/sec, P<0.01). Therefore, the extent of post-prandial hyperglycemia per se does not acutely impact microvascular responses in skeletal muscle in healthy humans. These data support the role of gut-derived factor(s) in the impairment of MBF following orally ingested glucose. These findings have important physiological implications for the consumption of high glycemic index meals.