TY - JOUR

T1 - Effect of Calorie-Unrestricted Low-Carbohydrate, High-Fat Diet Versus High-Carbohydrate, Low-Fat Diet on Type 2 Diabetes and Nonalcoholic Fatty Liver Disease

T2 - A Randomized Controlled Trial

AU - Hansen, Camilla Dalby

AU - Gram-Kampmann, Eva-Marie

AU - Hansen, Johanne Kragh

AU - Hugger, Mie Balle

AU - Madsen, Bjørn Stæhr

AU - Jensen, Jane Møller

AU - Olesen, Sara

AU - Torp, Nikolaj

AU - Rasmussen, Ditlev Nytoft

AU - Kjærgaard, Maria

AU - Johansen, Stine

AU - Lindvig, Katrine Prier

AU - Andersen, Peter

AU - Thorhauge, Katrine Holtz

AU - Brønd, Jan Christian

AU - Hermann, Pernille

AU - Beck-Nielsen, Henning

AU - Detlefsen, Sönke

AU - Hansen, Torben

AU - Højlund, Kurt

AU - Thiele, Maja Sofie

AU - Israelsen, Mads

AU - Krag, Aleksander

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Female

KW - Humans

KW - Male

KW - Middle Aged

KW - Blood Glucose/metabolism

KW - Cholesterol, HDL

KW - Cholesterol, LDL

KW - Diabetes Mellitus, Type 2

KW - Diet, Carbohydrate-Restricted

KW - Diet, Fat-Restricted

KW - Diet, High-Fat

KW - Glycated Hemoglobin

KW - Non-alcoholic Fatty Liver Disease

KW - Weight Loss

KW - Aged

U2 - 10.7326/M22-1787

DO - 10.7326/M22-1787

M3 - Journal article

C2 - 36508737

VL - 176

SP - 10

EP - 21

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

SN - 0003-4819

IS - 1

ER -