The Metabolic Impact of Intermittent Carbohydrate Restriction in Individuals With Type 2 Diabetes

Study Overview
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Brief Summary
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The primary aim of this randomized cross-over intervention study is to investigate the effect of four weeks of intermittent carbohydrate restriction (alternating between two days of normal dietary intake and two days of carbohydrate restriction to 70-90 grams) on 24-hour average sensor glucose in individuals with type 2 diabetes compared with a four-week control period with normal dietary intake.

Official Title
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The Metabolic Impact of Intermittent Carbohydrate Restriction in Individuals With Type 2 Diabetes

Conditions
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Diabetes Mellitus, Type 2, Overweight and Obesity, Non-Alcoholic Fatty Liver Disease, Metabolic Syndrome

Intervention / Treatment
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* Other: Dietary macronutrient composition


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women 35-75 years old BMI >27 kg/m2 Known type 2 diabetes in stable glucose lowering therapy (for three months) or with HbA1c >48 mmol/mol if no glucose lowering therapy Exclusion Criteria: Anemia (hemoglobin <8 mmol/L for men and <7 mmol/L for women) TSH outside reference range Treatment with insulin, sulfonylurea, or SGLT2-inhibitors Treatment with systemic corticosteroids HbA1c >70 mmol/mol eGFR <90 ml/min/1.73 m2 Contraindications for MR-scan: abdominal height exceed limitations of the MR-scanner, pacemaker or other electronic device implanted, implanted metal devices, severe claustrophobia Food allergies (including lactose and gluten intolerance) Vegetarian/vegan diet or following of specific dietary plans Alcohol consumptions >84/168 g/week (women/men) Strenuous activity level > 120 minutes per week Weight loss (>5 kg) within the last three months or previous bariatric surgery High risk of fibrosis of the liver (estimated by FIB4 score > 3.25)

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Dietary intervention
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intermittent carbohydrate restriction<br>Four weeks of intermittent carbohydrate restriction: a dietary regime alternating between two days of restricting carbohydrate intake to 70-90 grams, while energy intake is ad libitum, from fat- and protein-containing foods, and two days of non-restricted diet. | Other: Dietary macronutrient composition<br>* Intermittent carbohydrate restriction<br>|
| No Intervention: Control arm<br>Four weeks of free-living with no dietary restrictions. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 24-hour average sensor glucose | A patient-blinded continuous glucose monitoring (CGM) is worn during the last two weeks of both the intervention and control period. | 24-hour average sensor glucose is measured as the average of eight consecutive days (starting from two days post sensor mounting) from the intermittent carbohydrate restriction period and the corresponding days of the control period (i.e. days 17-24). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liver triacylglycerol content | Liver TG content will be measured by 1H-Magnetic Resonance Spectroscopy (MRS) on the day before and the day after the 4-week dietary intervention (i.e. day 0 and day 30) and on the day before and the day after the 4-week control period (i.e. day 0 and day 30). | day 30 adjusted for baseline | 
| Fasting plasma concentrations of triacylglycerols | Fasting plasma concentrations of triacylglycerols measured on the day before and the day after the 4-week dietary intervention (i.e. day 0 and day 30) and on the day before and the day after the 4-week control period (i.e. day 0 and day 30). | day 30 adjusted for baseline |