Effect of Calorie-Unrestricted Low-Carbohydrate, High-Fat Diet Versus High-Carbohydrate, Low-Fat Diet on Type 2 Diabetes and Nonalcoholic Fatty Liver Disease
Camilla Dalby Hansen, Eva-Marie Gram-Kampmann, Johanne Kragh Hansen, Mie Balle Hugger, Bjørn Stæhr Madsen, Jane Møller Jensen, Sara Olesen, Nikolaj Torp, Ditlev Nytoft Rasmussen, Maria Kjærgaard, Stine Johansen, Katrine Prier Lindvig, Peter Andersen, Katrine Holtz Thorhauge, Jan Christian Brønd, Anne Pernille Hermann, Henning Beck‐Nielsen, Sönke Detlefsen, Torben Hansen, Kurt Højlund, Maja Thiele, Mads Israelsen, Aleksander Krag
Abstract
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: (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.