Nutraceutical Improvement of Glucose Metabolism, NAFLD and Insulin Resistance by Oat-fiber Supplementation in Type 2 Diabetes Mellitus Patients

Study Overview
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Brief Summary
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Cohort studies show an association between increased intake of insoluble (cereal) fiber and decreased risk for cardiovascular disease, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), cancer, infectious and inflammatory disorders. Intervention studies, specifically addressing non-fermentable carbohydrates instead of their food sources (whole grain, pulses, legumes) are still sparse. Whole grain trials reported beneficial effects, but cannot pinpoint these benefits on fiber, as minerals, vitamins, grain protein and food matrix contribute to the metabolic results. The antidiabetic effectiveness of cereal fiber might be explained by a) an increased secretion of incretins and other glucose-induced gastrointestinal hormones, b) an alteration of the gut microbiome, or c) a fermentation to short-chain fatty acids. Fermentable fibers (most of which are soluble) show these mechanisms, but lack strong diabetes-protective associations in cohort studies. In recent supplementation trials, insoluble, mostly non-fermentable fibers improved insulin resistance, glycemia and inflammation in patients with metabolic syndrome or prediabetes. Between 2022-2024, we want to assess the effectiveness of insoluble, poorly fermentable cereal fiber in a shorter Intervention period in patients with high responsiveness (insulin-naïve overt type 2 diabetes mellitus with insulin resistance and NAFLD), using a fiber drinking supplement. Our triple-blinded RCT compares the metabolic effects and mechanistic outcomes of isocaloric treatments with 15 grams of oat-fiber supplement per day (vs. placebo) in 92 patients, covering an intervention period of 12 weeks.

Detailed Description
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Cohort studies show an association between increased intake of insoluble (cereal) fiber and decreased risk for cardiovascular disease, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), cancer, infectious and inflammatory disorders. Intervention studies, specifically addressing non-fermentable carbohydrates instead of their food sources (whole grain, pulses, legumes) are still sparse. Whole grain trials reported beneficial effects, but cannot pinpoint these benefits on fiber, as minerals, vitamins, grain protein and food matrix contribute to the metabolic results. The antidiabetic effectiveness of cereal fiber might be explained by a) an increased secretion of incretins and other glucose-induced gastrointestinal hormones, b) an alteration of the gut microbiome, or c) a fermentation to short-chain fatty acids. Fermentable fibers (most of which are soluble) show these mechanisms, but lack strong diabetes-protective associations in cohort studies. In recent supplementation trials, insoluble, mostly non-fermentable fibers improved insulin resistance, glycemia and inflammation in patients with metabolic syndrome or prediabetes. Between 2022-2024, we want to assess the effectiveness of insoluble, poorly fermentable cereal fiber in a shorter Intervention period in patients with high responsiveness (insulin-naïve overt type 2 diabetes mellitus with insulin resistance and NAFLD), using an oat fiber drinking supplement. Our triple-blinded RCT compares the metabolic effects and mechanistic outcomes of isocaloric treatments with 15 grams of oat-fiber supplement per day (vs. placebo) in 92 patients, covering an intervention period of 12 weeks.

Official Title
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Nutraceutical Improvement of Glucose Metabolism, NAFLD and Insulin Resistance by Oat-fiber Supplementation in Type 2 Diabetes Mellitus Patients

Conditions
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Type 2 Diabetes, NAFLD

Intervention / Treatment
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* Dietary Supplement: Drinking powder supplement


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: type 2 diabetes mellitus HOMA-IR > 2.5 NAFLD (MR-S > 5,56 %) Exclusion Criteria: insulin treatment diabetes type 1, 3 or 4 severe cardiopulmonary, renal, inflammatory, gastrointestinal, psychiatric or endocrine disorder alcohol abuse or excess alcohol intake recent CVD event (< 3months) relevant liver disease other than NAFLD current cancer diagnosis or treatment allergy or incompatibility to the supplement

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: parallel-designed triple-blinded randomised placebo-controlled intervention study
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Supplementation with insoluble cereal fiber<br>Drinking powder supplement providing 7,5 grams of insoluble fiber per sachet, taken twice daily over a period of 12 weeks without any changes in dietary behavior, caloric intake or physical activity | Dietary Supplement: Drinking powder supplement<br>* Drinking powder supplement, to be taken twice daily over 12 weeks<br>|
| Placebo Comparator: Supplementation with placebo<br>Drinking powder supplement providing no insoluble fiber, but maltodextrin, taken twice daily over a period of 12 weeks without any changes in dietary behavior, caloric intake or physical activity | Dietary Supplement: Drinking powder supplement<br>* Drinking powder supplement, to be taken twice daily over 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in liver fat content (MRS) | change in liver fat content (MRS) | 12 weeks | 
| change in glucose tolerance (mixed-meal test) | change in glucose tolerance (mixed-meal test) | 12 weeks | 
| change in insulin resistance (Matsuda) | change in insulin resistance (Matsuda) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in fasting glucose | change in fasting glucose | 12 weeks | 
| change in HbA1c | change in HbA1c | 12 weeks | 
| change in inflammation parameters (CRP, leucocytes, IL-6, IL-1ß, IL-18, IL-10, IL-22 | change in inflammation parameters (CRP, leucocytes, IL-6, IL-1ß, IL-18, IL-10, IL-22 | 12 weeks | 
| change in incretins (GLP-1, GIP, PYY) | change in incretins (GLP-1, GIP, PYY) | 12 weeks | 
| change in FGF21 | change in FGF21 | 12 weeks | 
| change in IGF-1 and its binding proteins | change in IGF-1 and its binding proteins | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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insoluble cereal fiber, insulin resistance, glucose tolerance, inflammation, incretins