The Acute Effect of Low-carb Diet on the Plasma Fatty Acid Composition in Type 2 Diabetes

The Acute Effect of a Low-carbohydrate Meal on the Plasma Fatty Acid Composition in Patients With Type 2 Diabetes

The investigators wishes to investigate the acute effect of a low carbohydrate meal on the plasma fatty acid (FA) composition compared with a control meal in a cross-over study of patients with type 2 diabetes (T2D).

In two trial days 12 participants with T2D will either have a low carbohydrate meal or control meal, measurements will be performed at baseline and continuously over 5 hours.

Study Overview

• Status: Recruiting
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Dietary supplement: Low carbohydrate

Detailed Description

Type 2 diabetes (T2D) is the most common metabolic disorder worldwide, and with an increasing prevalence T2D has become a major healthcare burden.

Low carbohydrate diet (LCD) has become increasingly popular as a method of improving glycemic control in patients with type 2 diabetes. However, the higher content of especially saturated fat in LCD has raised concerns about harmful effects.

A previous study has shown increase in non esterified fatty acids after a low carbohydrate meal, but it still needs to be investigated how a low carbohydrate meal affects the plasma FA composition.

The aim of this project is to investigate the hypothesis that a single low carbohydrate meal results in an improved plasma FA composition in patients with T2D and that this, at least in part, corresponds to the changes observed after 6 months LCD.

The study will be conducted as a cross-over trial with 12 participants with T2D. The participants will randomly be assigned to either start with the low carbohydrate meal or a control meal with a 2 weeks washout period.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kurt Højlund, MD; Phone Number: +45 25320648; Email: kurt.hoejlund@rsyd.dk
• Study Contact Backup: Name: Julie Rasmussen; Email: juras17@student.sdu.dk

Study Locations

• Denmark
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
    • Contact: Kurt Højlund, MD; Phone Number: +45 25320648; Email: kurt.hoejlund@rsyd.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Duration of established type 2 diabetes for more than six months and less than five years, but duration of type 2 diabetes for up to 10 years if the current treatment consists of ≤ 2 oral antidiabetic drugs without insulin.
2. HbA1c in compliance with type 2 diabetes (above 48 mmol/mol), with or without use of glucose-lowering pharmacotherapy, but without need for adjustment of antidiabetic treatment.
3. Stable antidiabetic treatment three months prior to inclusion.
4. Well treated dyslipidemia (LDL cholesterol < 2.5 mmol/l and total cholesterol < 4.5 mmol/l at inclusion) with or without statins.
5. BMI ≥ 25.
6. Age ≥ 18 years.
7. All participants have to understand oral and written Danish.
8. All participants have to sign an informed consent after oral and written information on experimental design.

Exclusion Criteria:

1. Significant comorbidity, including liver disease.
2. A history of cancer < 5 years or current chemotherapy.
3. Other severe co-morbidity that could interfere with study compliance or safety (e.g. previous gastrointestinal operations, liver disease, history of eating disorder, current alcohol overuse or hypoglycemic unawareness).
4. Current treatment with glucocorticoids (systemic).
5. Continuous treatment with steatosis-inducing drugs.
6. Treatment with antibiotics during the last two months before inclusion.
7. Low-carbohydrate diet prior to inclusion, or other restrictive diet.
8. Weight-loss > 10 kg over the last three months before inclusion.
9. Pregnancy or expected pregnancy within the next 6 months.
10. Elevated blood pressure (180/110) with or without antihypertensives.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low carbohydrate; The intervention meal is a low-carbohydrate meal composed of 15 E% carbohydrates, 20 E% protein and 65 E% fat	Dietary supplement: Low carbohydrate; Participants will have a low carbohydrate meal; Other Names: LCD
No Intervention: Control meal; The control meal is a regular diabetes meal according to the official Danish dietary guidelines composed of 50 E% carbohydrates, 20 E% protein and 30 E% fat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma fatty acid composition	Quantified as weight percentage (wt%) of total plasma phospholipid FA	5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma glucose		5 hours
Serum insulin		5 hours
Plasma ketones		5 hours
Plasma free fatty acid		5 hours
Total cholesterol		5 hours
LDL cholesterol		5 hours
HDL cholesterol		5 hours
Triglycerides		5 hours
Other lipoprotein fractions		5 hours
Glucagon Like Peptide 1 (GLP1)		5 hours
Glucose-Dependent Insulinotropic Polypeptide (GIP)		5 hours
Cholecystokinin (CCK)		5 hours
Peptide YY (PYY)		5 hours
Ghrelin		5 hours
Subjective appetite	Visual analog scale - mm. 0 mm - 100 mm. 0 mm = none and 100 mm = very strong	5 hours

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: Aalborg University Hospital
• Investigators: Principal Investigator: Kurt Højlund, MD, Odense University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 25, 2022
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: August 10, 2022
• First Submitted That Met QC Criteria: August 10, 2022
• First Posted (Actual): August 12, 2022

Study Record Updates

• Last Update Posted (Actual): September 7, 2022
• Last Update Submitted That Met QC Criteria: September 1, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: Cardiovascular disease; Low carbohydrate diet; LCD; Plasma FA composition; Free fatty acids
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: S-20220003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No