Clinical trial NCT03068078: A Reduced-carbohydrate Diet High in Monounsaturated Fats in Type 2 Diabetes
Official title: A Reduced-carbohydrate Diet High in Monounsaturated Fats in Type 2 Diabetes: a Six-month Study of Changes in Metabolism, Liver- and Cardiovascular Function (ReDuCtion)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type2 Diabetes
Nonalcoholic Steatohepatitis
Non-Alcoholic Fatty Liver Disease
Atherosclerosis
Dyslipidemias
Lead sponsor: Odense University Hospital
Sponsor class: OTHER
Collaborators: name: Danish Diabetes Academy
name: Region of Southern Denmark
name: Odense Patient Data Explorative Network
name: Novo Nordisk A/S
name: University of Southern Denmark
First posted: 2017-03-01
Enrollment: 185
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Further studies are needed to establish the optimal diet for treating T2D.

The investigators wishes to investigate whether a low carbohydrate diet, high in monounsaturated fats (LCD) will affect cardiovascular function, metabolism and the liver.

135 participants with T2D, will be following either a LCD, or a regular diabetes diet (RDD) for 6 months. Measurements and investigations will be performed at baseline and after 6 months.

Detailed description: Type 2 diabetes (T2D) is an increasing global problem, especially in developing countries. T2D is associated with an increased risk of cardiovascular disease (CVD), where hyperglycemia is especially important for microvascular damage.

Previous studies in T2D on reduced carbohydrate intake has shown beneficial effects on glycemic control, indicated by reduction in HbA1c, fasting insulin and 2h-glucose (OGTT) values. However further studies are needed to establish the optimal diet for treating T2D.

The investigators wishes to investigate whether a low carbohydrate diet, high in monounsaturated fats will:

1. Improve glycemic control, dyslipidemia and metabolic markers in T2D despite unchanged anti-diabetic treatment.
2. Improve endothelial function assessed by flow-mediated vasodilation (FMD) in the brachial artery as well as microvascular damage assessed by retinal scan, urine albuminuria and minimal forearm vascular resistance (MFVR).
3. Improve Non-Alcoholic Fatty Liver Disease (NAFLD) assessed by \>2 points reduction in NAFLD Activity score with at least 1 point reduction in either lobular inflammation or hepatocellular ballooning, without worsening of fibrosis.
4. Improve quality of life
5. Improve gut dysbiosis

The study will be conducted through a 6 month randomized controlled trial with 135 participants with type 2 diabetes. 90 participants will be randomized to the intervention group, following a LCD, and 45 participants will be randomized to the control group (regular diet for diabetes, RDD). The below described measurements will be conducted before baseline and after 6 months, and the participants will fill out a QoL questionnaire at 0, 3 and 6 months.

Planned examinations are ultrasound assessment of flow-mediated vasodilation, Dual-energy X-ray absorptiometry (DEXA-scan), retina scan, liver biopsy, liver-scans, blood, urine, hair, saliva and feces. Accelerometers will be applied before, during and after the study to evaluate compliance in unchanged exercise pattern. Compliance with diet will be evaluated by a clinical dietitian and through food diaries.

Baseline histology from the first 50 participants suggest that the current inclusion criteria doesn't cover the full spectrum of NAFLD (NASH and fibrosis) as expected. Further 50 participants who will have had diabetes for more than 10 years and who will not fulfill inclusion criteria number 1 and 2 will be included. On this group of participants we will only perform liver-investigations and DEXA-scan. This group of participants, will not affect the timeschedule of the main study.

Eligibility criteria: Inclusion Criteria:

1. Duration of established T2D for more than six months and less than five years and HbA1c in compliance with T2D (above 48 mmol/mol), but without need for adjustment of antidiabetic treatment\*
2. Serum cholesterol below 4.5 mmol/l and LDL cholesterol below 2.5 mmol/l at inclusion\*\*
3. Age of 18 or above
4. Stable diabetic treatment three months prior to inclusion\*\*\*
5. Be able to read and understand Danish language
6. Signed written consent

   * based on the assumption that metabolic and cardiovascular changes are less likely to be reversible in patients with longstanding T2D. HbA1c and need for adjustment and if the patient is eligible for inclusion will be evaluated individually based on the patients current treatment and current HbA1c by the project responsible. If the patient has duration of diabetes \> 5 years but with current treatment ≤ 2 oral antidiabetic drugs and without insulin treatment, the patient will be accepted for enrolment.

     * To avoid changes in lipid-lowering treatment during follow-up total cholesterol should be below 4.5 mmol/l and LDL cholesterol below 2.5 mmol/l at inclusion. Higher levels may be accepted if the patient cannot tolerate lipid-lowering treatment \*\*\*Patients can be enrolled three months after medication change

Exclusion Criteria:

1. Low carbohydrate diet prior to inclusion
2. Hypoglycemic unawareness
3. Excessive weight loss within the last three months, defined as more than 10 kilograms
4. Current treatment with glucocorticoids (systemic)
5. Continuous treatment with steatosis-inducing drugs (e.g. carbamazepine)
6. Treatment with antibiotics up to 2 months before inclusion\*
7. Treatment with chemotherapy
8. Pregnancy or expected pregnancy within the next 6 months
9. Active alcohol overuse\*\*
10. Active cancer
11. Significant co morbidity including liver disease
12. Poor compliance \*Participants can be rescheduled to be included 2 months after use of antibiotics \*\* Prior alcohol overuse and eligibility will be evaluated individually

Primary outcomes:
measure: Glycemic control, dyslipidemia and metabolic markers
timeFrame: Change from baseline at 6 months
Secondary outcomes:
measure: Endothelial function
timeFrame: Change from baseline at 6 months
measure: Non-Alcoholic Fatty Liver Disease (NAFLD)
timeFrame: Change from baseline at 6 months
measure: Quality of life
timeFrame: Change from baseline at 6 months
measure: Gut dysbiosis
timeFrame: Change from baseline at 6 months
Other outcomes:
Locations:
city: Odense
country: Denmark
facility: Odense University Hospital
Study officials:
affiliation: Odense University Hospital
name: Henning Beck-Nielsen, Professor
role: PRINCIPAL_INVESTIGATOR
References: