Intestinal glucose absorption is a key determinant of 1-hour postload plasma glucose levels in nondiabetic subjects

Context: One-hour postload hyperglycemia, defined as 1-hour plasma glucose (1hPG) 155 mg/dL during an oral glucose tolerance test (OGTT), has been proposed as an independent predictor of type 2 diabetes. Recent evidence suggests that 1-hour hyperglycemia can be explained by enhanced duodenal glucose absorption, which in turn may increase the rate of appearance of oral glucose in the systemic circulation (RaO). However, the impact of RaO on 1hPG and 1-hour glucose excursions (incremental area under the curve calculated through the first hour after glucose ingestion; glucose iAUC1h) is still unknown. Objective: We quantified the relative contribution of postload RaO to 1hPG and glucose iAUC1h with respect to other major glucose homeostatic mechanisms in nondiabetic participants. Participants and Methods: Model-derived b-cell function, insulin clearance, glucose metabolic fluxes, and peripheral and hepatic insulin sensitivity were measured during a 75-g OGTT by a double tracer method in 23 nondiabetic volunteers. Results: Early insulin secretion, whole-body insulin sensitivity, and plasma glucose disposal were significantly impaired in participants with 1hPG 155 mg/dL (n = 11), who also showed nominally greater RaO (19%; P = 0.10). In multivariable models, postload RaO showed an independent effect on both 1hPG and glucose iAUC1h (partial r2 = 0.26 and 0.48, respectively; P, 0.003). The relative contribution of RaO to 1hPG (23%) and glucose iAUC1h (30%) was similar to that of early insulin secretion and peripheral insulin sensitivity and greater than that of hepatic insulin sensitivity. Conclusions: Our data highlight the primary role of RaO as a major determinant of 1-hour postprandial glucose excursions in nondiabetic participants.