Weight loss improves β-cell function independently of dietary carbohydrate restriction in people with type 2 diabetes: A 6-week randomized controlled trial

Abstract

Background: Carbohydrate restriction may benefit β-cell function and glucose metabolism in type 2 diabetes (T2D) but also leads to weight loss which in itself is beneficial.

Methods: In order to determine the additional effect of carbohydrate restriction in addition to a fixed body weight loss, we randomly assigned 72 adults with T2D and obesity (mean ± SD HbA1c 7.4 ± 0.7%, BMI 33 ± 5 kg/m2) to a carbohydrate-reduced high-protein diet (CRHP; energy percent from carbohydrate/protein/fat: 30/30/40) or an isocaloric conventional diabetes diet (CD; 50/17/33) for 6 weeks. All foods were provided free of charge and total energy intake was tailored individually, so both groups lost 6% of baseline body weight.

Results: Despite significantly greater reductions in HbA1c (mean [95% CI] -1.9 [-3.5, -0.3] mmol/mol) after 6 weeks, the CRHP diet neither improved glucose tolerance, β-cell response to glucose, insulin sensitivity, during a 4-h oral glucose tolerance test, nor basal proinsulin secretion when compared to the CD diet, but increased C-peptide concentration and insulin secretion rate (area under the curve [AUC] and peak) significantly more (~10%, P ≤ 0.03 for all). Furthermore, compared with the CD diet, the CRHP diet borderline increased basal glucagon concentration (16 [-0.1, 34]%, P = 0.05), but decreased glucagon net AUC (-2.0 [-3.4, -0.6] mmol/L ×240 min, P < 0.01), decreased basal triglyceride and total AUC (~20%, P < 0.01 for both), and increased gastric inhibitory polypeptide total AUC (14%, P = 0.01).

Conclusion: A moderately carbohydrate-restricted diet for 6 weeks decreased HbA1c but did not improve β-cell function or glucose tolerance beyond the effects of weight loss when compared with a conventional diabetes diet in people with T2D.

Clinical trials registration: www.Clinicaltrials.gov, Identifier: NCT02472951.

Keywords: carbohydrate restriction; insulin sensitivity; low-grade inflammation; type 2 diabetes; weight loss; β-cell function.

Conflict of interest statement

Author AA is a member of the advisory board/consultant for Gelesis (USA), Groupe Éthique et Santé (France), and Weight Watchers (USA) as well as co-owner of the University of Copenhagen spin-off Flax-Slim ApS and co-inventor on a pending provisional patent application for the use of biomarkers to predict responses to weight loss diets and other related patents and patent applications that are all owned by the University of Copenhagen in accordance with Danish law. He has also co-authored several diets and cookery books, including books on personalized diets. He is not a proponent of any particular diet (e.g., veganism, Atkins diet, gluten-free diet, high animal protein diet, or dietary supplements). Author JH is a member of advisory boards for Novo Nordisk. Author TL is an advisor for the “Sense” diet program. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Thomsen, Skytte, Samkani, Astrup, Fenger, Frystyk, Hartmann, Holst, Larsen, Madsbad, Magkos, Rehfeld, Haugaard and Krarup.

Figures

Figure 1

Concentrations of plasma glucose (A), serum insulin (B), serum C-peptide (C), insulin secretion rate (ISR) (D), serum triglyceride (E), and serum non-esterified fatty acids (NEFAs) (F) during an OGTT at baseline and after 6 weeks of a CD or CRHP diet. Inserted plots represent net AUC in the units stated x 240 min. Data are presented as mean (±SEM) following log-transformation, except for net AUCs; **P < 0.01; ***P < 0.001.

Figure 2

Changes in the composite index (ISIcomp) (A), metabolic clearance rate of insulin (MCRi) (B), β-cell responsiveness to glucose (Btotal) (C), and disposition index (Di) (D) derived from an OGTT at baseline and after 6 weeks of a CD or CRHP diet. Data are presented as median (25th, 75th) with individual changes. No differences between diets were evident from linear mixed model analysis: P = 0.47, P = 0.77, P = 0.65, and P = 0.99 for (A–D), respectively. Estimates are in units: L2 x mg−1 × μU−1 ×10−4 (ISIcomp), L × min−1 (MCRi), L x kg−1 × min−1 ×10−9 (Btotal), and L3 × g−2 x min−1 × μU−1 ×10−1 (Di).

Figure 3

Plasma concentrations of glucagon (A), GLP-1 (B), and GIP (C) during an OGTT at baseline and after 6 weeks of a CD or CRHP diet. Inserted plots represent net AUC in the units stated x 240 min. Data are presented as mean (±SEM) following log-transformation, except for net AUCs; *P < 0.05.

Figure 4

Plasma concentrations of CCK (A) and gastrin (B) during an OGTT at baseline and after 6 weeks of a CD or CRHP diet. Inserted plots represent net AUC in the units stated x 240 min. Data are presented as mean (±SEM) following log-transformation, except for net AUCs; *P < 0.05.