The clinical effects of a carbohydrate-reduced high-protein diet on glycaemic variability in metformin-treated patients with type 2 diabetes mellitus: A randomised controlled study

Background & aims: High glycaemic variability (GV) is associated with late complications in type 2 diabetes (T2D). We hypothesised that a carbohydrate-reduced high-protein (CRHP) diet would reduce GV acutely in patients with T2D compared with a conventional diabetes (CD) diet. Methods: In this controlled, randomised crossover study, 16 patients with metformin-treated T2D (median (IQR) age: 64.0 (58.8-68.0) years; HbA(1c): 47 (43-57) mmol/mol; duration of T2D: 5.5 (2.8-10.3) years) were assigned to an energy-matched CRHP diet and CD diet (31E%/54E% carbohydrate, 29E %/16E% protein and 40E%/30E% fat, respectively) for two separate 48-h intervention periods. Interstitial continuous glucose monitoring (CGM) was performed to assess accepted measures of glycaemic variability, i.e. standard deviation (SD) around the sensor glucose level; coefficient of variation in percent (CV); mean amplitude of glucose excursions (MAGE); continuous overlapping net glycaemic action (CONGA1, CONGA4) of observations 1 and 4 h apart; and mean absolute glucose (MAG) change. Results: All indices of glycaemic variability (mean +/- SD) were significantly reduced during CRHP diet compared with CD diet; including SD (1.0 +/- 0.3 (CRHP) vs 1.6 +/- 0.5 mmol/L (CD)), CV (12.3 +/- 3.8 vs 19.3 +/- 5.5%), MAGE (2.3 +/- 0.9 vs 4.2 +/- 1.3 mmol/L), CONGA1 (0.8 +/- 0.3 vs 1.5 +/- 0.4 mmol/L), CONGA4 (1.4 +/- 0.5 vs 2.5 +/- 0.8 mmol/L), and MAG change (0.9 +/- 0.3 vs 1.4 +/- 0.4 mmol/L/h) (p < 0.001 for all). Compared with the CD diet, the CRHP diet improved the diurnal glucose profile by reducing 24-h mean sensor glucose (7.7 +/- 1.6 vs 8.6 +/- 2.0 mmol/L). Conclusions: In T2D patients treated with diet and metformin, two days of iso-energetic replacement of dietary carbohydrates by protein and fat reduced all indices of glycaemic variability by 36%-45% when compared with a conventional diabetes diet. These data may support reduction of carbohydrates as dietary advice for T2D patients. Clinicaltrials.gov identifier: NCT02472951. (c) 2020 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.