Cut Down on Carbohydrate Usage in the Diet of Type 2 Diabetes. The Hypo-energetic Study

NCT03814694 | Completed

• 1 other identifier: CUTDM-HYPO
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Scientific evidence for the dietary treatment of type 2 diabetes (T2D) is insufficient, which is why the investigators aim to reform dietary recommendation to the overweight or obese patient with type 2 diabetes. This clinical study will examine the effect of a highly controlled hypo-energetic carbohydrate-reduced high-protein (CRHP) diet intervention under caloric restriction-induced body weight loss as a treatment modality in T2D. The investigators hypothesize that this intervention compared to the conventional diabetes (CD) diet with similar loss in body weight improves metabolic control and cardiovascular risk profile in T2D by:

• Reducing diurnal and postprandial glycaemia, thereby facilitating a significant reduction in HbA1c
• Reducing ectopic lipid deposits in liver, muscle and pancreas
• Improving lipid profile towards a less atherogenic profile
• Improving metabolic actions of insulin, through increased sensitivity and β-cell function
• Reducing diurnal blood pressure with no adverse effect on heart rate variability

Conditions

Diabetes Mellitus, Type 2; Overweight and Obesity

Keywords

Weight Loss; Diet, Carbohydrate-Restricted; Diet, High-Protein; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Metabolic Syndrome

Outcome Measures

Primary Outcomes (1)

• Change in glycated hemoglobin (HbA1c) during 6 weeks of hypo-energetic CRHP diet compared with hypo-energetic CD diet.

  The change in HbA1c will be assessed during 6 weeks of fully provisioned hypo-energetic CRHP diet compared with hypo-energetic CD diet, while achieving concurrent body weight loss of 5-7 percent in both groups. Levels of HbA1c will be measured at baseline, week 2, 4, 5 and 6. HbA1c will be expressed in mmol/mol.

  6 weeks

Secondary Outcomes (2)

• Change in hepatic fat content after 6 weeks of hypo-energetic CRHP diet compared with hypo-energetic CD diet.

  6 weeks

• Change in fasting plasma triglycerides during 6 weeks of hypo-energetic CRHP diet compared with hypo-energetic CD diet.

  6 weeks

Other Outcomes (36)

• Change in fat content subcutaneously, viscerally and ectopically in pancreas and skeletal muscle after 6 weeks of hypo-energetic CRHP diet compared with hypo-energetic CD diet.

  6 weeks

• Change in lean body mass (LBM) after 6 weeks of hypo-energetic CRHP diet compared with hypo-energetic CD diet.

  6 weeks

• Change in fat mass (FM) after 6 weeks of hypo-energetic CRHP diet compared with hypo-energetic CD diet.

  6 weeks

Study Arms (2)

CRHP Diet

EXPERIMENTAL

Hypo-energetic carbohydrate-reduced high-protein (CRHP) dietary intervention with a controlled 5-7% loss in body weight.

Dietary Supplement: CRHP Diet

CD Diet

ACTIVE COMPARATOR

Hypo-energetic conventional diabetes (CD) dietary intervention with a controlled 5-7% loss in body weight.

Dietary Supplement: CD Diet

Interventions

CRHP Diet DIETARY_SUPPLEMENT

Dietary macronutrient composition of 30 E% from carbohydrate, 30 E% from protein and 40 E% from fat

CRHP Diet

CD Diet DIETARY_SUPPLEMENT

Dietary macronutrient composition of 50 E% from carbohydrate, 17 E% from protein and 33 E% from fat

CD Diet

Eligibility Criteria

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

You may qualify if:

• Type 2 diabetes with HbA1c between 48 mmol/mol and 97 mmol/mol with or without metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors
• Overweight or obesity with BMI ≥ 25 kg/m2 and desired weight loss
• Non-smokers for \> 1 year
• Willingness to abstain from alcohol for 6 weeks
• 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 as evaluated by the principal investigator
• Systemic corticosteroid 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, including insulin and GLP-1 analogues
• Sulfonylureas (SUs) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors, unless discontinuation is possible, in which case a 2-month wash-out is mandatory
• 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
• Presently participating in other clinical trials

Sponsors & Collaborators

• Bispebjerg Hospital: lead
• University of Copenhagen: collaborator
• University of Aarhus: collaborator
• The Danish Dairy Research Foundation, Denmark: collaborator
• Arla Foods: 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

• Jensen NJ, Wodschow HZ, Skytte MJ, Samkani A, Astrup A, Frystyk J, Hartmann B, Holst JJ, Larsen TM, Madsbad S, Magkos F, Miskowiak KW, Haugaard SB, Krarup T, Rungby J, Thomsen MN. Weight-loss induced by carbohydrate restriction does not negatively affect health-related quality of life and cognition in people with type 2 diabetes: A randomised controlled trial. Clin Nutr. 2022 Jul;41(7):1605-1612. doi: 10.1016/j.clnu.2022.05.005. Epub 2022 May 18.

  PMID: 35679680 DERIVED

• Thomsen MN, Skytte MJ, Samkani A, Carl MH, Weber P, Astrup A, Chabanova E, Fenger M, Frystyk J, Hartmann B, Holst JJ, Larsen TM, Madsbad S, Magkos F, Thomsen HS, Haugaard SB, Krarup T. Dietary carbohydrate restriction augments weight loss-induced improvements in glycaemic control and liver fat in individuals with type 2 diabetes: a randomised controlled trial. Diabetologia. 2022 Mar;65(3):506-517. doi: 10.1007/s00125-021-05628-8. Epub 2022 Jan 7.

  PMID: 34993571 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Overweight; Obesity; Weight Loss; Insulin Resistance; Non-alcoholic Fatty Liver Disease; Metabolic Syndrome

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes; Hyperinsulinism; Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• Steen B Haugaard, Professor

  Dept. of Endocrinology, Copenhagen University Hospital Bispebjerg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 8, 2019
• First Posted: January 24, 2019
• Study Start: January 29, 2019
• Primary Completion: July 22, 2020
• Study Completion: December 30, 2020
• Last Updated: January 27, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)