NAFLD, Type 2 Diabetes
Conditions
Keywords
insoluble cereal fiber, insulin resistance, glucose tolerance, inflammation, incretins
Brief summary
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
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.
Interventions
Drinking powder supplement, to be taken twice daily over 12 weeks
Sponsors
Study design
Masking description
blinding applies to participants, study personnel and statistician
Intervention model description
parallel-designed triple-blinded randomised placebo-controlled intervention study
Eligibility
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| change in liver fat content (MRS) | 12 weeks | change in liver fat content (MRS) |
| change in glucose tolerance (mixed-meal test) | 12 weeks | change in glucose tolerance (mixed-meal test) |
| change in insulin resistance (Matsuda) | 12 weeks | change in insulin resistance (Matsuda) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| change in IGF-1 and its binding proteins | 12 weeks | change in IGF-1 and its binding proteins |
| change in fasting glucose | 12 weeks | change in fasting glucose |
| change in HbA1c | 12 weeks | change in HbA1c |
| change in inflammation parameters (CRP, leucocytes, IL-6, IL-1ß, IL-18, IL-10, IL-22 | 12 weeks | change in inflammation parameters (CRP, leucocytes, IL-6, IL-1ß, IL-18, IL-10, IL-22 |
| change in incretins (GLP-1, GIP, PYY) | 12 weeks | change in incretins (GLP-1, GIP, PYY) |
| change in FGF21 | 12 weeks | change in FGF21 |
Other
| Measure | Time frame | Description |
|---|---|---|
| change in fasting serum amino acid pattern | 12 weeks | change in fasting serum amino acid pattern |
| change in secondary GI peptide hormons (GLP-2, PP, ghrelin, CCK) | 12 weeks | change in secondary GI peptide hormons (GLP-2, PP, ghrelin, CCK) |
| change in faecal excretion of BCAA metabolites | 12 weeks | change in faecal excretion of BCAA metabolites |
Countries
Germany