Effect of Calorie-Unrestricted Low-Carbohydrate, High-Fat Diet Versus High-Carbohydrate, Low-Fat Diet on Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial

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; Pernille Hermann; Henning Beck-Nielsen; Sönke Detlefsen; Torben Hansen; Kurt Højlund; Maja Sofie Thiele; Mads Israelsen; Aleksander Krag

doi:10.7326/M22-1787

Effect of Calorie-Unrestricted Low-Carbohydrate, High-Fat Diet Versus High-Carbohydrate, Low-Fat Diet on Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial

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, Pernille Hermann, Henning Beck-Nielsen, Sönke Detlefsen, Torben Hansen, Kurt HøjlundMaja Sofie Thiele, Mads Israelsen, Aleksander Krag

Research output: Contribution to journal › Journal article › Research › peer-review

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: 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 A 1c (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.

Original language	English
Journal	Annals of Internal Medicine
Volume	176
Issue number	1
Pages (from-to)	10-21
ISSN	0003-4819
DOIs	https://doi.org/10.7326/M22-1787
Publication status	Published - Jan 2023

Keywords

Aged
Blood Glucose/metabolism
Cholesterol, HDL
Cholesterol, LDL
Diabetes Mellitus, Type 2
Diet, Carbohydrate-Restricted
Diet, Fat-Restricted
Diet, High-Fat
Female
Glycated Hemoglobin
Humans
Male
Middle Aged
Non-alcoholic Fatty Liver Disease
Weight Loss

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1 Ph.D. thesis

Prevalence of non-alcoholic fatty liver disease and assessment of a low-carbohydrate high-fat diet as a dietary treatment option
Dalby Hansen, C., 23. May 2023, Syddansk Universitet. Det Sundhedsvidenskabelige Fakultet. 157 p.
Research output: Thesis › Ph.D. thesis

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Hansen, C. D., Gram-Kampmann, E.-M., Hansen, J. K., Hugger, M. B., Madsen, B. S., Jensen, J. M., Olesen, S., Torp, N., Rasmussen, D. N., Kjærgaard, M., Johansen, S., Lindvig, K. P., Andersen, P., Thorhauge, K. H., Brønd, J. C., Hermann, P., Beck-Nielsen, H., Detlefsen, S., Hansen, T., ... Krag, A. (2023). Effect of Calorie-Unrestricted Low-Carbohydrate, High-Fat Diet Versus High-Carbohydrate, Low-Fat Diet on Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial. Annals of Internal Medicine, 176(1), 10-21. https://doi.org/10.7326/M22-1787

@article{53503bee9de64f3e95b410aecab55910,

title = "Effect of Calorie-Unrestricted Low-Carbohydrate, High-Fat Diet Versus High-Carbohydrate, Low-Fat Diet on Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial",

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: 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 A 1c (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.",

keywords = "Aged, Blood Glucose/metabolism, Cholesterol, HDL, Cholesterol, LDL, Diabetes Mellitus, Type 2, Diet, Carbohydrate-Restricted, Diet, Fat-Restricted, Diet, High-Fat, Female, Glycated Hemoglobin, Humans, Male, Middle Aged, Non-alcoholic Fatty Liver Disease, Weight Loss",

author = "Hansen, {Camilla Dalby} and Eva-Marie Gram-Kampmann and Hansen, {Johanne Kragh} and Hugger, {Mie Balle} and Madsen, {Bj{\o}rn St{\ae}hr} and Jensen, {Jane M{\o}ller} and Sara Olesen and Nikolaj Torp and Rasmussen, {Ditlev Nytoft} and Maria Kj{\ae}rgaard and Stine Johansen and Lindvig, {Katrine Prier} and Peter Andersen and Thorhauge, {Katrine Holtz} and Br{\o}nd, {Jan Christian} and Pernille Hermann and Henning Beck-Nielsen and S{\"o}nke Detlefsen and Torben Hansen and Kurt H{\o}jlund and Thiele, {Maja Sofie} and Mads Israelsen and Aleksander Krag",

year = "2023",

month = jan,

doi = "10.7326/M22-1787",

language = "English",

volume = "176",

pages = "10--21",

journal = "Annals of Internal Medicine",

issn = "0003-4819",

publisher = "American College of Physicians",

number = "1",

}

Hansen, CD, Gram-Kampmann, E-M, Hansen, JK, Hugger, MB, Madsen, BS, Jensen, JM, Olesen, S, Torp, N, Rasmussen, DN, Kjærgaard, M , Johansen, S , Lindvig, KP , Andersen, P , Thorhauge, KH , Brønd, JC , Hermann, P , Beck-Nielsen, H , Detlefsen, S, Hansen, T, Højlund, K , Thiele, MS , Israelsen, M & Krag, A 2023, 'Effect of Calorie-Unrestricted Low-Carbohydrate, High-Fat Diet Versus High-Carbohydrate, Low-Fat Diet on Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial', Annals of Internal Medicine, vol. 176, no. 1, pp. 10-21. https://doi.org/10.7326/M22-1787

Effect of Calorie-Unrestricted Low-Carbohydrate, High-Fat Diet Versus High-Carbohydrate, Low-Fat Diet on Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial. / Hansen, Camilla Dalby; Gram-Kampmann, Eva-Marie; Hansen, Johanne Kragh et al.
In: Annals of Internal Medicine, Vol. 176, No. 1, 01.2023, p. 10-21.

Research output: Contribution to journal › Journal article › Research › peer-review

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 - 2023/1

Y1 - 2023/1

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 A 1c (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 A 1c (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 - 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 - Female

KW - Glycated Hemoglobin

KW - Humans

KW - Male

KW - Middle Aged

KW - Non-alcoholic Fatty Liver Disease

KW - Weight Loss

U2 - 10.7326/M22-1787

DO - 10.7326/M22-1787

M3 - Journal article

C2 - 36508737

SN - 0003-4819

VL - 176

SP - 10

EP - 21

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

IS - 1

ER -

Effect of Calorie-Unrestricted Low-Carbohydrate, High-Fat Diet Versus High-Carbohydrate, Low-Fat Diet on Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial

Abstract

Keywords

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Prevalence of non-alcoholic fatty liver disease and assessment of a low-carbohydrate high-fat diet as a dietary treatment option

Cite this