Personalized Fiber and Insulin Sensitivity

Study Overview
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Brief Summary
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In this project the investigators intend to study the therapeutic potential of a personalized fibre mixture in individuals at high risk of developing T2DM, and aim to address the following key objectives: To investigate whether a mixture of fermentable fibres, which differ in DP and side chains, will stimulate a broad range of SCFA-producing bacterial genera, resulting in enhanced chronic SCFA production throughout the whole colon with a large variation between individuals; To unravel whether providing personalized fibre mixtures, selected based on the individuals' initial microbiota and capacity for SCFA production is crucial to successfully improve host insulin sensitivity and metabolic health

Official Title
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Personalized Microbial Substrates to Prevent Type 2 Diabetes

Conditions
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Type 2 Diabetes, Insulin Resistance

Intervention / Treatment
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* Dietary Supplement: Fermentable oligosaccharide
* Dietary Supplement: Personalized fiber mixture


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Overweight/obese insulin resistant/prediabetic participants (age 30-70 y, BMI ≥ 28 kg/m2 < 40 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.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

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 |
| --- | --- |
| Active Comparator: isocaloric fermentable oligosaccaride<br>isocaloric fermentable oligosaccaride | Dietary Supplement: Fermentable oligosaccharide<br>* Supplementation period 12 weeks<br>|
| Experimental: Personalized fiber mixture<br>12 g for 2 weeks, followed by 24 g for 10 weeks | Dietary Supplement: Personalized fiber mixture<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 (m-value) 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 |
| --- | --- | --- |
| 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 | 
| circulating SCFA | The change in concentrations of circulating SCFA | Before and 12 week after the start of the intervention | 
| Faecal SCFA | The change in concentrations of faecal 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 assessing abundances of bacteria and diversity indices as assessed via 16s rRNA gene | Before and 12 week after the start of the intervention | 
| Circulating hormones such as insulin | The change in concentrations of circulating hormones in peripheral blood | Before and 12 week after the start of the intervention | 
| Circulating metabolites such as glucose | The change in concentrations of metabolites in peripheral blood | Before and 12 week after the start of the intervention | 
| body fat percentage | The change in body fat percentage as assessed using DEXA scans | Before and 12 week after the start of the intervention | 
| fat mass | The change in fat mass in kg as assessed using DEXA scans | Before and 12 week after the start of the intervention | 
| lean mass | The change in lean mass in kg as assessed using DEXA scans | Before and 12 week after the start of the intervention | 
| visceral fat | The change in visceral fat in gram as assessed using DEXA scans | Before and 12 week after the start of the intervention | 
| body weight | The change in body weight in kg using a weight scale | Before and 12 week after the start of the intervention |