Fiber and Insulin Sensitivity

Study Overview
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Brief Summary
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Based on previous research of the investigators group, the investigators hypothesize that slowly fermentable fibers with a high degree of polymerization that increase SCFA specifically in the distal colon are expected to have higher potential for influencing host metabolism and metabolic health by improving adipose tissue function, preventing lipid overflow and hepatic as well as skeletal muscle fat accumulation thereby improving insulin sensitivity. The objective of this randomized clinical trial is to test, whether the a dietary fiber product containing different physiological acting fibers reverses peripheral and hepatic insulin resistance in overweight/obese insulin resistant participants.

Official Title
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Gut Microbial Substrate Switch to Improve Metabolic Health

Conditions
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Obesity, Insulin Resistance

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: Whole fiber product


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Overweight/obese insulin resistant/prediabetic participants (age 45-70 y, BMI ≥ 28 kg/m2 < 35 kg/m2) Exclusion criteria: Type 2 diabetes mellitus (defined as fasting plasma glucose ≥ 7.0 mmol/L and 2h glucose ≥ 11.1 mmol/L) Gastroenterological diseases or abdominal surgery; Cardiovascular diseases, cancer, liver or kidney malfunction, disease with a life expectancy shorter than 5 years; Abuse of products; alcohol and drugs, excessive nicotine use defined as >20 cigarettes per day; Plans to lose weight or following of a hypocaloric diet; Regular supplementation of pre- or probiotic products, use of pre- or probiotics 3 months prior to the start of the study; Intensive exercise training more than three hours a week; Use of any medication that influences glucose or fat metabolism and inflammation (i.e. NSAIDs); Regular use of laxation products; Use of antibiotics in the last three months (antibiotics use can alter substantially the gut microbiota composition). Follow a vegetarian diet. Metal objects such as implants present in the body (e.g. electronic implants, pacemakers, metal fragments in the eyes, skin or body) The use of permanent make-up (eyeliners, eyebrows) or tattoos on the head, shoulders, breast or neck Claustrophobia

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 70 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>isocaloric placebo | Dietary Supplement: Placebo<br>* Supplementation period 12 weeks<br>|
| Experimental: whole fiber product<br>15 g for 2 weeks, followed by 30 g for 10 weeks | Dietary Supplement: Whole fiber product<br>* Supplementation period 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peripheral insulin sensitivity | The change of peripheral insulin sensitivity as assessed by a hyperinsulinaemic-euglycemic clamp | Before and 12 week after the start of the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| hepatic and adipose tissue insulin sensitivity | The change in hepatic and adipose tissue insulin sensitivity as assessed by a hyperinsulinaemic-euglycemic clamp | Before and 12 week after the start of the intervention | 
| Energy expenditure (indirect calorimetry) | The change in energy expenditure as measured via ventilated hood system | Before and 12 week after the start of the intervention | 
| Substrate oxidation (indirect calorimetry) | The change in substrate oxidation as measured via ventilated hood system | Before and 12 week after the start of the intervention | 
| Faecal and circulating SCFA | The change in faecal and circulating SCFA | Before and 12 week after the start of the intervention | 
| Faecal microbiota composition and in vitro microbial activity testing | The change in faecal microbiota composition as assessed via 16s rRNA gene sequencing | Before and 12 week after the start of the intervention | 
| In vitro microbial activity testing | The change in fin vitro microbial activity testing as assessed using an in vitro model of the human colon | Before and 12 week after the start of the intervention | 
| Circulating hormones such as insulin | The change in circulating hormones in peripheral blood | Before and 12 week after the start of the intervention | 
| Circulating metabolites such as glucose | The change in metabolites in peripheral blood | Before and 12 week after the start of the intervention | 
| Circulating inflammatory markers such as TNF | The change in inflammatory markers in peripheral blood | Before and 12 week after the start of the intervention | 
| body weight | The change in body weight in kg | Before and 12 week after the start of the intervention | 
| body composition | The change in body compostion as assessed using DEXA scans | Before and 12 week after the start of the intervention | 
| liver fat content | The change in liver fat content as assessed by proton magnetic resonance spectrometry | Before and 12 week after the start of the intervention |