Protein, Fiber, and Metabolic Syndrome - The PROFIMET Study

Study Overview
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Brief Summary
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Randomized controlled single-blinded intervention study in 111 overweight and obese subjects with risk factors of developing type 2 diabetes, with the aim to investigate effects of isoenergetic high cereal fiber as compared with high protein diets over 6 and 18 weeks. Proof of principle study with analysis according to study protocol, investigating whether isoenergetic high cereal fiber and high protein diets with comparable fat contents, if adhered to and after exclusion of known confounders such as changes in body weight, intake of drugs with known effects on insulin sensitivity, or relevant changes in physical activity, indeed affect insulin sensitivity.

Detailed Description
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This is a randomized controlled single-blinded intervention study in 111 overweight and obese subjects with risk factors of developing type 2 diabetes, with the aim to investigate effects of isoenergetic high cereal fiber versus high protein diets over 6 and 18 weeks. We also investigate effects of a combined high-cereal-fiber/high-protein (mix) diet, and effects in a control group. All diets are based on foods from plants and whey products commonly assumed to be healthy. This trial is designed as a proof of principle study focusing on participants that are likely to adhere to the respective isoenergetic diets, in order to show whether high protein versus high cereal fiber diets indeed affect insulin sensitivity, as indicated by epidemiological observations. Study participants will receive intensive and regular nutritional advice in order to achieve the respective dietary targets. Dietary adherence of the participants will be supported by providing tailored dietary supplements in all four groups, twice daily over 18 weeks. Supplements are provided for twice daily consumption for all participants in all four dietary intervention groups, throughout the 18-wk intervention (each of the participants will be instructed to consume a total 252 portions of tailored supplements during the intervention, which will handed to the participants in sealed single portions at weeks 0, 3, 6 and 12, totalling 63 portions at each occasion). The packaging of the sealed portions for the 4 intervention arms do not indicate the type of dietary intervention for the participant, but are coded for identification by the supplier. Energy contents of the supplements are considered when calculating individual energy intake. Supplements have been specifically designed for this intervention study, in order to facilitate achieving dietary targets. A 6 week strictly controlled isoenergetic study period (regular group and individual sessions, daily food diaries/FFQs over the first 6 weeks with adaptation of food intake, if necessary, as indicated by direct analysis of FFQs and food protocols, and by weighing the participants; 3-day food protocols at weeks 0, 6, 12, and 18; various biomarkers of dietary adherence) will be followed by a further 12 week ad libitum period, with ongoing intake of the respective diet including the supplements, but no further dietary advice. The primary outcome measure is the detection of diet-induced changes in insulin sensitivity during weight maintaining isoenergetic conditions. Secondary outcomes are changes in factors that may explain potential diet-induced alterations of insulin sensitivity. During the 12-weeks ad libitum period we will further investigate potential effects of the respective diet on changes in body weight, body composition and biomarkers related to energy intake. Participants will be re-invited for anthropometric measurements and measurement of biomarkers in blood (18 weeks after completion of the study), as well as for taking a second muscle tissue biopsy (subset of participants that agreed to this procedure).

Official Title
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Effects of High Protein and High Cereal Fiber Diets on Insulin Sensitivity in Overweight and Obese Subjects With the Metabolic Syndrome - The PROFIMET Study

Conditions
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Overweight, Obesity, Metabolic Syndrome

Intervention / Treatment
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* Other: control diet, supported by dietary supplement twice daily
* Other: high cereal fiber diet, supported by dietary supplement twice daily
* Other: high protein diet, supported by dietary supplement twice daily
* Other: diet moderately high both in cereal fiber and protein, supported by dietary supplement twice daily


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Waist > 80 cm (females) or > 94 cm (males) BMI > 25 kg/m² IFG, IGT, or insulin resistance; and/or dyslipidemia; and/or high blood pressure Willingness to comply with one of the randomly assigned diets over the study period Exclusion Criteria: Diabetes type 1 and type 2 Pregnancy Allergies including food allergies Metal implants Chronic disease of heart, kidney, or liver Relevant deviation of body weight during isoenergetic 6-weeks period (+/- 3 kg) Intake of drugs with known impact on whole-body insulin sensitivity during the study (e.g. cortisone, ASS, antibiotics) Missing data about primary outcome measures (Clamp data, data about dietary intake from food diaries or 3-day food protocols) Significant deviation from dietary targets during the monitored 6 weeks isoenergetic period (e.g. significant deviation from 30% target for dietary fat in all groups, intake of a low protein or low fiber diet in the high protein or high fiber groups, respectively)

Ages Eligible for Study
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Minimum Age: 24 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Intervention: 'control diet, supported by dietary supplement twice daily' control diet [carbohydrates 55(50 - 60)% , protein 15(10 - 20)% protein; fat ca. 30% of energy content; dietary fiber < 15 g/1000 kcal and day; intensive dietary advice plus supplement (2 x basic supplement daily)] | Other: control diet, supported by dietary supplement twice daily<br>* control diet, see above<br>|
| Experimental: 2<br>Intervention: 'high cereal fiber diet, supported by dietary supplement twice daily'. high cereal fiber diet [carbohydrates 55(50 - 60)% , protein 15(10 - 20)% protein; fat ca. 30% of energy content; dietary fiber > 20 g/1000 kcal and day; intensive dietary advice plus supplement (2 x basic supplement including 2 x 15 g cereal fiber daily)] | Other: high cereal fiber diet, supported by dietary supplement twice daily<br>* high cereal fiber diet, see above<br>|
| Experimental: 3<br>Intervention: 'high protein diet, supported by dietary supplement twice daily' high protein diet [carbohydrates 40 - 45% , protein > 25 - 30%; fat ca. 30% of energy content; dietary fiber < 15 g/1000 kcal and day; intensive dietary advice plus supplement (2 x basic supplement including 2 x 25 g whey and plant protein daily)] | Other: high protein diet, supported by dietary supplement twice daily<br>* high protein diet, see above<br>|
| Experimental: 4<br>Intervention: diet moderately high both in cereal fiber and protein, supported by dietary supplement twice daily. high cereal fiber/high protein (MIX) moderately high cereal fiber/high protein diet (carbohydrates 45- 50)% , protein 20 - 25%; fat ca. 30% of energy content; dietary fiber 15 - 20 g/1000 kcal and day; intensive dietary advice plus supplement (2 x basic supplement including 2 x 15 g cereal fiber and 2 x 25 g whey and plant protein daily) | Other: diet moderately high both in cereal fiber and protein, supported by dietary supplement twice daily<br>* MIX diet, see above<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in insulin sensitivity | whole-body insulin sensitivity measured with euglycemic hyperinsulinemic clamp; hepatic insulin sensitivity measured with stable isotope techniques (DD-glucose) during the clamps; relation with secondary outcome measures | 6 weeks | 
| change in insulin sensitivity | whole-body insulin sensitivity measured with euglycemic hyperinsulinemic clamp; hepatic insulin sensitivity measured with stable isotope techniques (DD-glucose) during the clamps; relation with secondary outcome measures | 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| factors that may contribute explaining changes in primary outcome measures | body fat composition (MRI and ADP), liver fat (H1-spectroscopy); hormones, adipokines, inflammatory and metabolic markers; insulin signaling pathways in adipose tissue (gene expression and protein level); changes in gut microbiota; bile acids; metabolite profiles; amino acid composition in diet and circulating blood. Relation of secondary outcome measures with primary outcome measures. | 0, 6, 18 weeks | 
| biomarkers indicating dietary adherence | urinary nitrogen/creatine ratio and fecal BCAA as markers for protein intake; fecal SCFA and breath hydrogen levels as markers for fermentable fiber intake; HDL cholesterol as marker for carbohydrate intake | 0, 6, 18 weeks | 
| development of indices for the prediction of insulin resistance (liver, whole-body) |  | baseline, validation after 6 -18 weeks | 
| development for indices for the prediction of fat mass (liver, abdominal) |  | baseline, validation after 6 -18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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parameters of metabolic syndrome