Cut Down on Carbohydrate Usage in the Diet of Type 2 Diabetes

NCT02764021 | Completed DMC

• 1 other identifier: H-15020386
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

Scientific evidence for the dietary treatment of type 2 diabetes (T2D) is insufficient. The study group hypothesizes that a lower carbohydrate content in the diabetic diet than the recommended 55 energy percentage (E%) will decrease the postprandial glucose excursion. This will reduce postprandial insulin concentration, which together with lower glucose concentration leads to less fat accumulation in the liver and muscle tissue, resulting in an improved insulin sensitivity which together with a reduced glucose load improves the glucose metabolism. This clinical study will examine in subjects with type 2 diabetes the effect of highly controlled dietary low carbohydrate intervention on metabolic pathways with respect to insulin action, pancreatic islet function, lipid metabolism, ectopic fat accumulation, incretin hormones, low grade inflammation in plasma and adipose tissue, novel measures of fatty acid metabolism, and heart rate variability, respectively. The studies exhibit the potential to reform dietary recommendation aiming to prevent and ameliorate type 2 diabetes.

Conditions

Type 2 Diabetes Mellitus

Keywords

HbA1c; Diabetes-Releated Complications; Diet, Low Carbohydrate; Carbohydrate-Restricted Diet; Diabetes Mellitus; Metabolic Disorder; Glucose Metabolism Disorders; Endocrine System Diseases

Outcome Measures

Primary Outcomes (1)

• Changes in glycated hemoglobin (HbA1c) at the end of 6 weeks of isoenergetic low carbohydrate diet compared to 6 weeks of the recommended antidiabetic control diet.

  Changes in HbA1c during a fully controlled dietary cross-over intervention from baseline to week 6 will be compared to changes in HbA1c from week 6 to week 12. Changes in HbA1c will be assessed from week 12 to week 36 during a prolonged period where the participants receive dietician guidance to reinforce coherence to the low carbohydrate diet. HbA1c will be assessed at a follow-up visit at week 42. In addition HbA1c will be meassured every 14 days during the first 12 weeks, and every 4 weeks during the 24 weeks prolonged period. HbA1c will be expressed in mmol/mol.

  42 weeks

Secondary Outcomes (20)

• Changes in heart rate variability (HRV) from baseline to week 6 will be compared to changes in HRV from week 6 to 12. Changes in HRV will be assessed from week 12 to 36.

  36 weeks

• Changes in diurnal blood pressure (DBP) from baseline to week 6 will be compared to changes in DBP from week 6 to 12. Changes in DBP will be assessed from week 12 to 36.

  36 weeks

• Changes in insulin sensitivity from baseline to week 6 will be compared to changes in insulin sensitivity from week 6 to 12. Changes in insulin sensitivity will be assessed from week 12 to 36.

  36 weeks

• Changes in beta-cell function from baseline to week 6 will be compared to changes in beta-cell function from week 6 to 12. Changes in beta-cell function will be assessed from week 12 to 36.

  36 weeks

• Changes in glucagon-like-petide-1 (GLP-1) at baseline to week 6 will be compared to changes in GLP-1 from week 6 to 12. Changes in GLP-1 will be assessed from week 12 to 36.

  36 weeks

Study Arms (2)

1.

EXPERIMENTAL

Subjects will be randomly assigned to initially receive 6 weeks of standard antidiabetic dietary treatment or 6 weeks of experimental carbohydrate-restricted dietary treatment, crossing over to the opposite diet from week 6 to 12.

Dietary Supplement: Carbohydrate-Restricted Diet

2.

ACTIVE COMPARATOR

Subjects will be randomly assigned to initially receive 6 weeks of standard antidiabetic dietary treatment or 6 weeks of experimental carbohydrate-restricted dietary treatment, crossing over to the opposite diet from week 6 to 12.

Dietary Supplement: Standard Antidiabetic Diet

Interventions

Carbohydrate-Restricted Diet DIETARY_SUPPLEMENT

Macronutritional composition: Carbohydrate 30 E%, Protein 30 E%, Fat 40 E%

1.

Standard Antidiabetic Diet DIETARY_SUPPLEMENT

Macronutritional composition: Carbohydrate 50 E%, Protein 13 E%, Fat 17 E%

2.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent signed before any study-specific procedure
• Type 2 diabetes with glycated hemoglobin (HbA1c) between 48 mmol/mol and 97 mmol/mol with or without oral antidiabetic medicine
• Age \> 18 years, men and women
• Hemoglobin \> 7 mmol/L for men and \> 6 mmol/L for women
• Estimated glomerular filtration rate (eGFR) \> 30 mL/min/1.73 m2

You may not qualify if:

• Critical illness
• Systemic corticosteriod treatment e.g. prednisolone
• Reported or journalized severe food allergy or intolerance
• Reported or journalized severe gut disease e.g. Crohn's disease, Coeliac disease etc.
• Reported or journalized alcohol dependence syndrome
• Injectable diabetes medication
• Repeated fasting plasma glucose \> 13.3 mmol/l
• Urine albumin / creatinine ratio \> 300 mg/g
• Lactation, Pregnancy or planning of pregnancy during the study
• Inability, physically or mentally, to comply with the procedures required by the study protocol, as evaluated by the principal investigator
• Blood donation \< 1 month prior to the study and during the study

Sponsors & Collaborators

• Bispebjerg Hospital: lead
• University of Copenhagen: collaborator
• University of Aarhus: collaborator

Study Sites (1)

Bispebjerg Hospital

Copenhagen, Copenhagen NV, 2400, Denmark

Location

Related Publications (3)

• Thomsen MN, Skytte MJ, Samkani A, Weber P, Fenger M, Frystyk J, Hansen E, Holst JJ, Madsbad S, Magkos F, Thomsen HS, Walzem RL, Haugaard SB, Krarup T. Replacing dietary carbohydrate with protein and fat improves lipoprotein subclass profile and liver fat in type 2 diabetes independent of body weight: evidence from 2 randomized controlled trials. Am J Clin Nutr. 2025 Feb;121(2):224-231. doi: 10.1016/j.ajcnut.2024.11.030. Epub 2024 Nov 29.

  PMID: 39617302 DERIVED

• Alzahrani AH, Skytte MJ, Samkani A, Thomsen MN, Astrup A, Ritz C, Chabanova E, Frystyk J, Holst JJ, Thomsen HS, Madsbad S, Haugaard SB, Krarup T, Larsen TM, Magkos F. Body weight and metabolic risk factors in patients with type 2 diabetes on a self-selected high-protein low-carbohydrate diet. Eur J Nutr. 2021 Dec;60(8):4473-4482. doi: 10.1007/s00394-021-02605-0. Epub 2021 Jun 8.

  PMID: 34101004 DERIVED

• Skytte MJ, Samkani A, Petersen AD, Thomsen MN, Astrup A, Chabanova E, Frystyk J, Holst JJ, Thomsen HS, Madsbad S, Larsen TM, Haugaard SB, Krarup T. A carbohydrate-reduced high-protein diet improves HbA1c and liver fat content in weight stable participants with type 2 diabetes: a randomised controlled trial. Diabetologia. 2019 Nov;62(11):2066-2078. doi: 10.1007/s00125-019-4956-4. Epub 2019 Jul 23.

  PMID: 31338545 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus; Metabolic Diseases; Glucose Metabolism Disorders; Endocrine System Diseases

Interventions

Diet, Carbohydrate-Restricted

Condition Hierarchy (Ancestors)

Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• Thure Krarup, MD, DMSc

  Bispebjerg Hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Open Label
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD student

Study Record Dates

• First Submitted: April 26, 2016
• First Posted: May 6, 2016
• Study Start: April 1, 2016
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: March 2, 2018

Record last verified: 2018-03

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)