1595-P: Differential Effects of Carbohydrate Overfeeding on Postprandial Glucose Metabolism in Individuals with Low Compared with Normal Birthweight

Introduction & Objective: Individuals born with low birthweight (LBW) are at elevated risk of developing type 2 diabetes (T2D). We studied postprandial (pp) glucose metabolism during a mixed meal-test in healthy LBW compared with normal birthweight (NBW) men before and after carbohydrate overfeeding (CO).

Methods: Twenty-two non-obese, middle-aged LBW men (BW 2797±175g) and 21 age- and BMI-matched NBW controls (BW 3807±176g) were included. Glucose kinetics were assessed by [U-¹³C]Glucose (meal) and [6,6-D₂]Glucose continuous forearm venous infusion during a 5-hour liquid mixed meal-test before and after 4-week CO (+25% energy). Data were analyzed assessing change in pp area under the curve (AUC). Subgroup analysis was performed for five cases of screen-detected non-alcoholic fatty liver disease (NAFLD) among LBW men measured by magnetic resonance spectroscopy.

Results: CO resulted in increased weight (P<0.0001) and liver fat content (P=0.009) in both groups. LBW men responded to CO with an increase in pp insulin AUC (P=0.04), with no differences in pp glucose AUC, compared with NBW men. In response to CO, the pp total glucose rate of appearance (Ra) decreased paradoxically by 4.5% in the LBW group (with and without NAFLD), whereas it increased by 6.3% in the NBW group (P=0.03). This, in turn, was explained by a decrease of oral glucose Ra (P=0.01), and not endogenous (hepatic) Ra, in the LBW group. In response to CO, the pp glucose disposal rate (reflecting insulin action) decreased by 26% in the LBW group, whereas it increased by 40% in the NBW group (P=0.08).

Conclusion: LBW compared with NBW subjects respond to CO with increased plasma insulin levels, peripheral insulin resistance, and a decline in postprandial Ra of ingested glucose in the main circulation possibly caused by an increased hepatic retention of ingested glucose contributing to increased hepatic lipogenesis, fat storage and NAFLD risk in LBW subjects.