Protein, Fiber, and Metabolic Syndrome - The PROFIMET Study

Obesity Clinical Trial

— PROFIMET  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00579657
• Other study ID #: mow_PROFIMET
• Secondary ID: BMBF Profimet 03
• Status: Completed
• Phase: N/A
• First received: December 21, 2007
• Last updated: March 6, 2016
• Start date: August 2007
• Est. completion date: July 2013

Study information

• Verified date: March 2016
• Source: German Institute of Human Nutrition
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: July 2013
• Est. primary completion date: March 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 24 Years to 70 Years

Eligibility

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)

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Metabolic Syndrome
• Metabolic Syndrome X
• Obesity
• Overweight
• Syndrome

Intervention

Other:
• control diet, supported by dietary supplement twice daily
control diet, see above
• high cereal fiber diet, supported by dietary supplement twice daily
high cereal fiber diet, see above
• high protein diet, supported by dietary supplement twice daily
high protein diet, see above
• diet moderately high both in cereal fiber and protein, supported by dietary supplement twice daily
MIX diet, see above

Locations

Country	Name	City	State
Germany	Deutsches Diabetes Zentrum; Heinrich Heine University	Düsseldorf
Germany	Diagnostic and Interventional Radiology, Klinikum Ernst von Bergmann, Academic Teaching Hospital, Charité University Medicine Berlin	Potsdam
Germany	Eberhard-Karls University Tübingen, Section on Experimental Radiology, Department of Diagnostic and Interventional Radiology	Tübingen
United Kingdom	University Hospitals Coventry and Warwickshire NHS Trust	Coventry	Warwickshire

Sponsors (8)

Lead Sponsor	Collaborator
German Institute of Human Nutrition	Charite University, Berlin, Germany, Coventry University, German Federal Ministry of Education and Research, Heinrich-Heine University, Duesseldorf, Medical University of Vienna, University Hospital Tuebingen, University Hospitals Coventry and Warwickshire NHS Trust

Countries where clinical trial is conducted

Germany,  United Kingdom, 

References & Publications (12)

Cuthbertson DJ, Weickert MO, Lythgoe D, Sprung VS, Dobson R, Shoajee-Moradie F, Umpleby M, Pfeiffer AF, Thomas EL, Bell JD, Jones H, Kemp GJ. External validation of the fatty liver index and lipid accumulation product indices, using 1H-magnetic resonance — View Citation

Gögebakan O, Kohl A, Osterhoff MA, van Baak MA, Jebb SA, Papadaki A, Martinez JA, Handjieva-Darlenska T, Hlavaty P, Weickert MO, Holst C, Saris WH, Astrup A, Pfeiffer AF; DiOGenes. Effects of weight loss and long-term weight maintenance with diets varying in protein and glycemic index on cardiovascular risk factors: the diet, obesity, and genes (DiOGenes) study: a randomized, controlled trial. Circulation. 2011 Dec 20;124(25):2829-38. doi: 10.1161/CIRCULATIONAHA.111.033274. Epub 2011 Nov 21. — View Citation

Hattersley JG, Möhlig M, Roden M, Arafat AM, Loeffelholz CV, Nowotny P, Machann J, Hierholzer J, Osterhoff M, Khan M, Pfeiffer AF, Weickert MO. Quantifying the improvement of surrogate indices of hepatic insulin resistance using complex measurement techni — View Citation

Hattersley JG, Pfeiffer AF, Roden M, Petzke KJ, Hoffmann D, Rudovich NN, Randeva HS, Vatish M, Osterhoff M, Goegebakan Ö, Hornemann S, Nowotny P, Machann J, Hierholzer J, von Loeffelholz C, Möhlig M, Arafat AM, Weickert MO. Modulation of amino acid metabo — View Citation

Isken F, Klaus S, Osterhoff M, Pfeiffer AF, Weickert MO. Effects of long-term soluble vs. insoluble dietary fiber intake on high-fat diet-induced obesity in C57BL/6J mice. J Nutr Biochem. 2010 Apr;21(4):278-84. doi: 10.1016/j.jnutbio.2008.12.012. Epub 2009 Apr 14. — View Citation

Weickert MO, Arafat AM, Blaut M, Alpert C, Becker N, Leupelt V, Rudovich N, Möhlig M, Pfeiffer AF. Changes in dominant groups of the gut microbiota do not explain cereal-fiber induced improvement of whole-body insulin sensitivity. Nutr Metab (Lond). 2011 — View Citation

Weickert MO, Mohlig M, Koebnick C, Holst JJ, Namsolleck P, Ristow M, Osterhoff M, Rochlitz H, Rudovich N, Spranger J, Pfeiffer AF. Impact of cereal fibre on glucose-regulating factors. Diabetologia. 2005 Nov;48(11):2343-53. Epub 2005 Sep 20. — View Citation

Weickert MO, Möhlig M, Schöfl C, Arafat AM, Otto B, Viehoff H, Koebnick C, Kohl A, Spranger J, Pfeiffer AF. Cereal fiber improves whole-body insulin sensitivity in overweight and obese women. Diabetes Care. 2006 Apr;29(4):775-80. — View Citation

Weickert MO, Pfeiffer AF. Low-glycemic index vs high-cereal fiber diet in type 2 diabetes. JAMA. 2009 Apr 15;301(15):1538; author reply 1538-9. doi: 10.1001/jama.2009.483. — View Citation

Weickert MO, Pfeiffer AF. Metabolic effects of dietary fiber consumption and prevention of diabetes. J Nutr. 2008 Mar;138(3):439-42. Review. — View Citation

Weickert MO, Roden M, Isken F, Hoffmann D, Nowotny P, Osterhoff M, Blaut M, Alpert C, Gögebakan O, Bumke-Vogt C, Mueller F, Machann J, Barber TM, Petzke KJ, Hierholzer J, Hornemann S, Kruse M, Illner AK, Kohl A, Loeffelholz CV, Arafat AM, Möhlig M, Pfeiff — View Citation

Weickert MO. What dietary modification best improves insulin sensitivity and why? Clin Endocrinol (Oxf). 2012 Oct;77(4):508-12. doi: 10.1111/j.1365-2265.2012.04450.x. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	development of indices for the prediction of insulin resistance (liver, whole-body)		baseline, validation after 6 -18 weeks	No
Secondary	development for indices for the prediction of fat mass (liver, abdominal)		baseline, validation after 6 -18 weeks	No

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