Prolonged Glycemic Adaptation Following Transition From a Low- to High-Carbohydrate Diet: A Randomized Controlled Feeding Trial

Objective: Consuming ≥150 g/d carbohydrate is recommended for 3 days before an oral glucose tolerance test (OGTT) for diabetes diagnosis. To evaluate this recommendation, time courses of glycemic changes following transition from a very-low-carbohydrate (VLC) to high-carbohydrate (HC) diet were assessed by continuous glucose monitoring (CGM).

Research Design and Methods: After achieving 15±3% weight loss on the run-in VLC diet, participants (18-50 years; BMI: ≥27 kg/m²) were randomly assigned for 10 weeks to 3 isoenergetic diets: VLC (5% carbohydrate, 77% fat), HC-Starch (57%, 25%; with 20% refined grains), or HC-Sugar (57%, 25%; with 20% sugar). CGM was done throughout the trial (n=64) and OGTT at start and end (n=41). All food was prepared in a metabolic kitchen and consumed under observation.

Results: Glucose metrics continued to decline after week 1 in HC-Starch and HC‑Sugar (p<0.05), but not VLC. From weeks 2-5, fasting and 2-hr glucose (mmol/L per week) decreased in HC-Starch (fasting: -0.10, p=0.001; 2-hr: -0.10, p=0.04). From weeks 6-9, 2-hr glucose decreased in HC-Starch (-0.07, p=0.01), and fasting and 2-hr glucose decreased in HC‑Sugar (fasting: -0.09, p=0.001; 2-hr: -0.09, p=0.003). The number of participants with abnormal glucose tolerance by OGTT remained 10 (of 16) in VLC at start and end but decreased from 17 to 9 (of 25) in both HC groups.

Conclusions: Physiological adaptation from a low- to high-carbohydrate diet may require many weeks, with implications for the accuracy of diabetes tests, interpretation of macronutrient trials, and risks of periodic planned deviations from a VLC diet.