Glucose concentrations 60 minutes after an oral glucose tolerance test (OGTT) ≥155 mg/dL (8.6 mmol/L) identify an increased risk of progression to type 2 diabetes even in those with normal glucose tolerance (NGT). Recent data suggests that these differences can be explained by increased intestinal glucose absorption due to increased expression of the sodium/glucose cotransporter 1 (SGLT1) in the intestine. To examine the contribution of meal appearance to postprandial glucose concentrations we studied 36 subjects with NGT using a 75g OGTT, and a labelled mixed meal. Insulin secretion and action, endogenous glucose production (EGP), meal-derived glucose appearance (Meal Ra) and glucose disappearance (Rd) were subsequently calculated. Participants were grouped according to 60 minute glucose into HI (≥155 mg/dl) or LO (<155mg/dl). No differences in age (47±3 vs. 50±2 years, LO vs. HI respectively, p=0.59) or BMI (28±1 vs. 28±1 Kg/M2, p=0.95) were observed. Fasting (11.9±0.6 vs. 12.6±0.6 μmol/kg/min, p=0.44) and nadir (2.0±0.8 vs. 3.3±0.3 μmol/kg/min, p=0.21) EGP did not differ. Similarly, peak (86±10 vs. 92±6 μmol/kg/min, p=0.59) and integrated (9.8±1.3 vs. 10.6±1.1 mmol per 6 hour, p=0.69) Meal Ra did not differ between groups. On the other hand, when β-cell responsivity (ϕ) was expressed as a function of insulin action (Si), the resulting Disposition Index (DI) was lower in the HI group (1862±409 vs. 893±103 10-14 dl/kg/min2 per pmol/l, p=0.01). When analyzed as a continuous variable, 60 minute glucose was inversely related to DI (r = -0.37, p=0.02) but did not correlate with peak (r=0.03, p=0.96) and integrated (r=0.02, p=0.91) Meal Ra. Taken together, these data indicate that increased 60 minute glucose concentrations, even in subjects with NGT, are explained by decreased β-cell function not by an increased systemic rate of appearance of meal-derived glucose.


J. Adams: None. G. Treiber: None. M.D. Hurtado: None. M.C. Laurenti: Other Relationship; Self; GlySens Incorporated. C. Dalla Man: None. C. Cobelli: Research Support; Self; Sanofi-Aventis. Advisory Panel; Self; Novo Nordisk Inc.. R.A. Rizza: None. A. Vella: Research Support; Self; Novo Nordisk Inc., XOMA Corporation. Advisory Panel; Self; VTV Therapeutics, Bayer AG.

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