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It remains unclear if a low-carbohydrate, high-fat diet is a possible treatment strategy for type 2 diabetes. This randomized clinical trial examines whether a low-carbohydrate, high-fat diet without a recommendation to restrict calories is more effective than a high-carbohydrate, low-fat diet at improving glycemic control, metabolic markers, and nonalcoholic fatty liver disease.
Background:
It remains unclear if a low-carbohydrate, high-fat (LCHF) diet is a possible treatment strategy for type 2 diabetes mellitus (T2DM), and the effect on nonalcoholic fatty liver disease (NAFLD) has not been investigated.
Objective:
To investigate the effect of a calorie-unrestricted LCHF diet, with no intention of weight loss, on T2DM and NAFLD compared with a high-carbohydrate, low-fat (HCLF) diet.
Design:
6-month randomized controlled trial with a 3-month follow-up. (ClinicalTrials.gov: NCT03068078)
Setting:
Odense University Hospital in Denmark from November 2016 until June 2020.
Participants:
165 participants with T2DM.
Intervention:
Two calorie-unrestricted diets: LCHF diet with 50 to 60 energy percent (E%) fat, less than 20E% carbohydrates, and 25E% to 30E% proteins and HCLF diet with 50E% to 60E% carbohydrates, 20E% to 30E% fats, and 20E% to 25E% proteins.
Measurements:
Glycemic control, serum lipid levels, metabolic markers, and liver biopsies to assess NAFLD.
Results:
The mean age was 56 years (SD, 10), and 58% were women. Compared with the HCLF diet, participants on the LCHF diet had greater improvements in hemoglobin A1c (mean difference in change, −6.1 mmol/mol [95% CI, −9.2 to −3.0 mmol/mol] or −0.59% [CI, −0.87% to −0.30%]) and lost more weight (mean difference in change, −3.8 kg [CI, −6.2 to −1.4 kg]). Both groups had higher high-density lipoprotein cholesterol and lower triglycerides at 6 months. Changes in low-density lipoprotein cholesterol were less favorable in the LCHF diet group than in the HCLF diet group (mean difference in change, 0.37 mmol/L [CI, 0.17 to 0.58 mmol/L] or 14.3 mg/dL [CI, 6.6 to 22.4 mg/dL]). No statistically significant between-group changes were detected in the assessment of NAFLD. Changes were not sustained at the 9-month follow-up.
Limitation:
Open-label trial, self-reported adherence, unintended weight loss, and lack of adjustment for multiple comparisons.
Conclusion:
Persons with T2DM on a 6-month, calorie-unrestricted, LCHF diet had greater clinically meaningful improvements in glycemic control and weight compared with those on an HCLF diet, but the changes were not sustained 3 months after intervention.
Primary Funding Source:
Novo Nordisk Foundation.
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Affiliations:
Department of Gastroenterology and Hepatology, Odense University Hospital, and Institute of Clinical Research, University of Southern Denmark, Odense, Denmark (C.D.H., M.B.H., N.T., M.K., S.J., K.H.T., M.S.T.)
Steno Diabetes Center Odense, Odense University Hospital, Odense, Denmark (E.M.G., H.B., K.H.)
Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark (J.K.H., B.S.M., J.M.J., S.O., D.N.R., P.A., M.I.)
Department of Gastroenterology and Hepatology, Odense University Hospital, and Institute of Clinical Research, University of Southern Denmark, Odense SV, Denmark (K.P.L.)
Department of Sport Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark (J.C.B.)
Department of Medical Endocrinology, Odense University Hospital, Odense, Denmark (P.H.)
Institute of Clinical Research, University of Southern Denmark, and Department of Pathology, Odense University Hospital, Odense, Denmark (S.D.)
Novo Nordisk Foundation, Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark (T.H.)
Department of Gastroenterology and Hepatology, Odense University Hospital, and Institute of Clinical Research, University of Southern Denmark, Odense C, Denmark (A.K.)
Acknowledgment: The authors thank all participants in this study. Furthermore, the authors thank Louise Just, Vibeke Nielsen, Ida Spedtsberg, and the entire staff at Odense Liver Research Centre; Trine Møller, Minna Ingham, Charlotte Damby Jensen, Line Dan Jensen, Kirsten Dalhøj, and all the staff at Department of Gastroenterology and Hepatology; Anette Tyrsted and Lea Grip from the Department of Clinical Biochemistry and Pharmacology at Odense University Hospital; and the Department of Open Patient Data Explorative Network.
Financial Support: By the Novo Nordisk Foundation (NNF16OC0021038), Region of Southern Denmark, University of Southern Denmark, Odense University Hospital, Danish Diabetes Academy, A.P. Møller Foundation, and Overlæge Johan Boserup and Lise Boderups Legat.
Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M22-1787.
Data Sharing Statement: The following data will be made available with publication: deidentified participant data. (Interested researchers may contact Dr. Hansen at camilla.
Corresponding Author: Aleksander Krag, MD, PhD, Odense Liver Research Centre, Department of Gastroenterology and Hepatology, Odense University Hospital, Kloevervaenget 10, Entrance 112, 5000 Odense C, Denmark; e-mail, aleksander.
Author Contributions: Conception and design: H. Beck-Nielsen, E.M. Gram-Kampmann, C.D. Hansen, T. Hansen, J.M. Jensen, A. Krag.
Analysis and interpretation of the data: H. Beck-Nielsen, J.C. Brønd, C.D. Hansen, T. Hansen, K. Højlund, M. Israelsen, A. Krag, M.S. Thiele.
Drafting of the article: H. Beck-Nielsen, J.C. Brønd, C.D. Hansen, K. Højlund, M. Israelsen, J.M. Jensen, S. Johansen, A. Krag, K.H. Thorhauge.
Critical revision of the article for important intellectual content: H. Beck-Nielsen, S. Detlefsen, C.D. Hansen, J.K. Hansen, T. Hansen, P. Hermann, K. Højlund, M. Israelsen, J.M. Jensen, S. Johansen, M. Kjaergaard, A. Krag, B.S. Madsen, M.S. Thiele, N. Torp.
Final approval of the article: P. Andersen, H. Beck-Nielsen, J.C. Brønd, S. Detlefsen, E. Gram-Kampmann, C.D. Hansen, J.K. Hansen, T. Hansen, P. Hermann, K. Højlund, M.B. Hugger, M. Israelsen, J.M. Jensen, S. Johansen, M. Kjaergaard, A. Krag, K.P. Lindvig, B.S. Madsen, S. Olesen, D.N. Rasmussen, M. Thiele, K.H. Thorhauge, N. Torp.
Provision of study materials or patients: H. Beck-Nielsen, S. Detlefsen, E. Gram-Kampmann, M.B. Hugger, A. Krag, S. Olesen.
Obtaining of funding: H. Beck-Nielsen, E. Gram-Kampmann, C.D. Hansen, T. Hansen, A. Krag.
Administrative, technical, or logistic support: P. Andersen, H. Beck-Nielsen, C.D. Hansen, J.K. Hansen, P. Hermann, K. Højlund, M.B. Hugger, J.M. Jensen, A. Krag, K.P. Lindvig, S. Olesen.
Collection and assembly of data: S. Detlefsen, E. Gram-Kampmann, C.D. Hansen, J.K. Hansen, M.B. Hugger, M. Israelsen, J.M. Jensen, M. Kjaergaard, K.P. Lindvig, B.S. Madsen, S. Olesen, N. Torp.
This article was published at Annals.org on 13 December 2022.
