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

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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; HbA1c: 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. identifier: NCT02472951.

Original languageEnglish
JournalClinical Nutrition ESPEN
Pages (from-to)46-52
Number of pages7
Publication statusPublished - 2020

    Research areas

  • Continuous glucose monitoring, Glycaemic variability, Low-carbohydrate diet, Type 2 diabetes

ID: 247491857