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

Mads N Thomsen; Mads J Skytte; Arne Astrup; Carolyn F Deacon; Jens J Holst; Sten Madsbad; Thure Krarup; Steen B Haugaard; Amirsalar Samkani

doi:10.1016/j.clnesp.2020.07.002

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

Clin Nutr ESPEN. 2020 Oct:39:46-52. doi: 10.1016/j.clnesp.2020.07.002. Epub 2020 Aug 1.

Authors

Mads N Thomsen¹, Mads J Skytte², Arne Astrup³, Carolyn F Deacon⁴, Jens J Holst⁴, Sten Madsbad⁵, Thure Krarup², Steen B Haugaard⁶, Amirsalar Samkani²

Affiliations

¹ Dept. of Endocrinology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark. Electronic address: mads.norvin.thomsen@regionh.dk.
² Dept. of Endocrinology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark.
³ Dept. of Nutrition, Exercise and Sports, University of Copenhagen, Denmark.
⁴ Endocrinology Research Section, Dept. of Biomedical Sciences, University of Copenhagen, Denmark; Section for Translational Physiology, NNF Center for Basic Metabolic Research, University of Copenhagen, Denmark.
⁵ Dept. of Endocrinology, Copenhagen University Hospital Amager Hvidovre, Copenhagen, Denmark.
⁶ Dept. of Endocrinology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark; Dept. of Internal Medicine, Copenhagen University Hospital Amager Hvidovre, Copenhagen, Denmark.

PMID: 32859328
DOI: 10.1016/j.clnesp.2020.07.002

Abstract

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.

Keywords: Continuous glucose monitoring; Glycaemic variability; Low-carbohydrate diet; Type 2 diabetes.

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Blood Glucose
Blood Glucose Self-Monitoring
Diabetes Mellitus, Type 2* / drug therapy
Diet, High-Protein*
Humans
Metformin* / therapeutic use
Middle Aged

Substances

Blood Glucose
Metformin

Associated data

ClinicalTrials.gov/NCT02472951