(OR10-03-25) Enhanced Starch Turnover in the Gut May Drive the Postprandial Glucose Response in People With Type 2 Diabetes

Objectives: Postprandial plasma glucose concentration is determined by the balance between total glucose appearance (TotalRa) (a result of both endogenous glucose production (EGP), and meal-derived glucose appearance (mealRa)); and glucose disposal (Rd). The relative contribution of these processes in type 2 diabetes (T2D) is unknown. We investigated the effect of a starch-rich meal on EGP, mealRa and glucose Rd.

Methods: Eight people with T2D (4M, 4F, age 53±13 y, BMI 30±6 kgm^-2) and eight healthy controls (6M, 2F, age 38±9 y, BMI 23±2 kgm^-2) were recruited.

A test meal was consumed, using potatoes grown in a closed-atmosphere ¹³C labelling chamber. This unique method produces universal, intrinsic, ¹³C labelling of the carbon in the starch molecules, enabling measurement of the impact processing has on starch availability and utilization.

After an overnight fast, the test meal, consisting of mashed potato (10 g [U¹³C]-intrinsically-labelled potato in 193 g non-labelled potato, giving 5 % enrichment) mixed with 25 g butter (total 36 g carbohydrate, 20 g fat), was consumed at 0 min. A variable [6,6-²H₂]glucose infusion, was delivered via forearm intravenous cannula, from -120 min to 360 min. Blood samples were taken from the contralateral arm for insulin and glucose concentration. MealRa, Rd and EGP were estimated by Bayes mathematical modelling.

Results: Plasma glucose concentration incremental area under the curve (IAUC, 0-180 min) was 523 % higher with T2D than control (p < 0.001). MealRa was 54 % higher in T2D than control (IAUC, 0-120 min, p=0.036). EGP was higher in T2D at baseline (12.9±2.4 versus 10.7±1.4 μmol/kg/min, p=0.046) but was suppressed to a greater extent (-10.7±1.6 versus ‑7.3±2.3 μmol/kg/min, p=0.004), and for longer, than control (time*group interaction, 0-360 min, p< 0.001). No differences were observed in insulin response or Rd.

Conclusions: After a starch meal, EGP suppression and tissue uptake was conserved inT2D. Surprisingly, a greater delivery into the systemic circulation from the gut was driving postprandial dysglycemia. Work is needed to determine whether this is due to differences in speed of gastric emptying, alterations in gut microbiome, or other mechanisms.

Funding Sources: Biotechnology and Biological Sciences Research Council, UK; Alliance for Potato Research and Education, US.