Indicates equal contribution
To assess the diurnal patterns of postprandial glucose tolerance and insulin sensitivity, 19 type 2 diabetes [8F; 60±11 yrs.; BMI: 32±5 kg/m2] and 19 anthropometrically matched non-diabetic (ND) subjects [11 F; 53±12 yrs.; BMI: 29±5 kg/m2] were studied during breakfast (B), lunch (L), and dinner (D) with identical mixed meals (75 gm carbs) on three consecutive days in a randomized Latin square design. Three stable isotopes of glucose were utilized to estimate meal fluxes and mathematical models used for estimating indices of insulin action and beta cell function. Post meal glucose excursions were higher at D vs B and D vs L in type 2 diabetes (p<0.05) while in ND they were higher at D vs. B (p=0.025) and L vs B (P=0.04). Insulin iAUC was highest at B as compared to L and D in type 2 diabetes while there were no differences observed in ND. Disposition Index (DI) was higher at B than at L (p<0.01) and D (p<0.001) in ND subjects while DI was low with unchanging pattern across B-L-D in type 2 diabetes. Furthermore, between meal differences in beta cell responsivity to glucose (φ) and insulin sensitivity (SI) were concurrent with changes in DI within groups. Fasting and post meal glucose, insulin, C-peptide concentrations, along with estimates of endogenous glucose production (EGP), rate of glucose disappearance (Rd), SI, Φ, hepatic extraction of insulin (HE), insulin secretion rate, extracted insulin and DI were altered in type 2 diabetes compared to ND (P < 0.011 for all).The data shows diurnal pattern of postprandial glucose tolerance in overweight otherwise glucose tolerant ND individuals differs from overweight type 2 diabetes. The results not only provide valuable insight into management strategies for better glycemic control in people with type 2 diabetes but also improved understanding of daytime glucose metabolism in overweight individuals without impaired glucose tolerance or overt diabetes.