Mechanism and Effects of Glucose Absorption during an Oral Glucose Tolerance Test Among Females and Males

Background: Several epidemiological studies revealed sex-specific differences during oral glucose tolerance tests (OGTTs), such as higher prevalence of glucose intolerance (i.e. increased glucose at the end of the OGTT) in females, which was not yet explained. Thus, we aimed to analyze sex-related distinctions on OGTT glucose metabolism, including gut absorption, in healthy humans. Methods: Females (n = 48) and males (n = 26) with comparable age (females, 45 +/- 1 yr; males, 44 +/- 2 yr) and body mass index (both, 25 +/- 1 kg/m(2)) but different height (females, 166 +/- 1 cm; males, 180 +/- 2 cm; P < 0.000001), all normally glucose tolerant, as tested by frequently sampled, 3-h (75-g) OGTTs, underwent hyperinsulinemic [40 mU/(min . m(2))] isoglycemic clamp tests with simultaneous measurement of endogenous glucose (D-[6,6-(2)H(2)] glucose) production (EGP). EGP and glucose disappearance during OGTT were calculated from logarithmic relationships with clamp test insulin concentrations. After reliable model validation by double-tracer technique (r = 0.732; P < 0.007), we calculated and modeled gut glucose absorption (ABS). Results: Females showed lower (P < 0.05) fasting EGP [1.4 +/- 0.1 mg/(kg . min)] than males [1.7 +/- 0.1 mg/(kg . min)] but comparable whole-body insulin sensitivity in clamp tests [females, 8.1 +/- 0.4 mg/(kg . min); males, 8.3 +/- 0.6 mg/(kg . min)]. Plasma glucose OGTT concentrations were higher (P < 0.04) from 30-40 min in males but from 120-180 min in females. Glucose absorption rates were 21-46% increased in the initial 40 min in males but in females by 27-40% in the third hour (P < 0.05). Gut glucose half-life was markedly higher in females (79 +/- 2 min) than in males (65 +/- 3 min, P < 0.0001) and negatively related to body height (r = -0.481; P < 0.0001). Conclusions: This study in healthy, glucose-tolerant humans shows for the first time different ABS rates during OGTT in women and men and a negative relationship between body height and gut glucose half-life. Prolonged ABS in females might therefore contribute to higher plasma glucose concentrations at the end of OGTT. (J Clin Endocrinol Metab 96: 515-524, 2011)