Article open access publication

Isocaloric substitution of carbohydrates with protein: the association with weight change and mortality among patients with type 2 diabetes

Cardiovascular Diabetology, Springer Nature, ISSN 1475-2840

Volume 14, 1, 2015

DOI:10.1186/s12933-015-0202-7, Dimensions: pub.1024776850, PMC: PMC4403776, PMID: 25896172,



  1. (1) University Medical Center Utrecht, grid.7692.a
  2. (2) University of Bonn, grid.10388.32
  3. (3) International Agency For Research On Cancer, grid.17703.32
  4. (4) Aarhus University, grid.7048.b, AU
  5. (5) The Arctic University of Norway, grid.10919.30
  6. (6) Institut Gustave Roussy, grid.14925.3b
  7. (7) German Cancer Research Center, grid.7497.d
  8. (8) University of Naples Federico II, grid.4691.a
  9. (9) Lund University, grid.4514.4
  10. (10) Istituto per lo Studio e la Prevenzione Oncologica, grid.417623.5
  11. (11) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  12. (12) Cancer Registry and Histopathology Unit, “Civic - M.P-Arezzo” Hospital, ASP, Ragusa, Italy
  13. (13) National Institute for Public Health and the Environment, grid.31147.30
  14. (14) Jefe Del Servicio De Epidemiologia, Prevencion Y Promocion De La Salud, Instituto de Salud Pública, Leyre 15, 31003, Pamplona, Spain
  15. (15) University of Turin, grid.7605.4
  16. (16) Public Health Division of Gipuzkoa, BioDonostia Research Institute, Health Department of Basque Region, San Sebastian, Spain
  17. (17) Umeå University, grid.12650.30
  18. (18) University of Gothenburg, grid.8761.8
  19. (19) Danish Cancer Society, grid.417390.8
  20. (20) Division of human nutrition, WU Agrotechnology & Food Sciences, P.O. Box 8129, 6700, Wageningen, EV, The Netherlands
  21. (21) German Institute of Human Nutrition, grid.418213.d


BACKGROUND: The health impact of dietary replacement of carbohydrates with protein for patients with type 2 diabetes is still debated. This study aimed to investigate the association between dietary substitution of carbohydrates with (animal and plant) protein and 5-year weight change, and all-cause and cardiovascular (CVD) mortality risk in patients with type 2 diabetes. METHODS: The study included 6,107 diabetes patients from 15 European cohorts. Patients with type 1 diabetes were excluded. At recruitment, validated country-specific food-frequency questionnaires were used to estimate dietary intake. Multivariable adjusted linear regression was used to examine the associations between dietary carbohydrate substitution with protein and 5-year weight change, and Cox regression to estimate hazard ratios (HRs) for (CVD) mortality. RESULTS: Annual weight loss of patients with type 2 diabetes was 0.17 (SD 1.24) kg. After a mean follow-up of 9.2 (SD 2.3)y, 787 (13%) participants had died, of which 266 (4%) deaths were due to CVD. Substitution of 10 gram dietary carbohydrate with total (ß = 187 [75;299]g) and animal (ß = 196 [137;254]g) protein was associated with mean 5-year weight gain. Substitution for plant protein was not significantly associated with weight change (β = 82 [-421;584]g). Substitution with plant protein was associated with lower all-cause mortality risk (HR = 0.79 [0.64;0.97]), whereas substitution with total or animal protein was not associated with (CVD) mortality risk. CONCLUSIONS: In diabetes patients, substitution with plant protein was beneficial with respect to weight change and all-cause mortality as opposed to substitution with animal protein. Therefore, future research is needed whether dietary guidelines should not actively promote substitution of carbohydrates by total protein, but rather focus on substitution of carbohydrates with plant protein.


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