Whey or Casein - Liver Fat Reduction and Metabolic Improvement by Fast vs. Slow Proteins (MOCA)

Molke Oder Casein - Leberfettreduktion Und Stoffwechselverbesserung Durch Schnelle vs. Langsame Proteine (Whey or Casein - Liver Fat Reduction and Metabolic Improvement by Fast vs. Slow Proteins)

High-protein diets have been recently demonstrated to effectively reduce insulin resistance, derangements of the lipid profile and liver fat content in subjects with moderately and severely impaired glucose metabolism and non-alcoholic fatty liver disease (LeguAN, LEMBAS, DiNA-P, DiNA-D). The effects can be attributed to prolonged insulin secretion and improved second meal effect, higher energy expenditure by urea synthesis, suppression of glucagon or other mechanisms. Up to now, it is unclear, if proteins with slower or faster digestibility lead to differential results in these study designs. The proposed study will elucidate this question. The Investigators hypothesize, that slowly-digestible proteins induce a prolonged insulin plateau supporting the second-meal effect. The investigators also assume, that these dietary proteins lead to a markedly stronger short-term secretion of glucagon followed by desensitisation of this hormone release. Fast-digestible proteins, on the other hand, will presumably induce a smaller second-meal effect and do not inhibit a second rise of glucagon in a consecutive meal.

The investigators intend to study the effects of a 3-weeks high-protein diet in 80 subjects with NAFLD and T2DM on liver fat content (MR spectroscopy) and glucose metabolism. The investigators expect different results for slow protein (casein) and fast protein (whey), thus comparing both protein species. The two major clinical visits before and after the intervention period will include MRI spectroscopy, fasting blood sampling for later analysis, full anthropometric assessment, a mixed meal tolerance test and a set of behavioral tests, investigating decision making processes. In order to characterize the postprandial profiles (e.g. insulin, glucagon, amino acids) of the varying protein sources, preliminary meal tests are performed in overweight subjects with and without T2DM.

Study Overview

• Status: Recruiting
• Conditions: NAFLD; Type2 Diabetes
• Intervention / Treatment: Dietary supplement: protein supplement; Dietary supplement: placebo supplement

Detailed Description

High-protein diets have been recently demonstrated to effectively reduce insulin resistance, derangements of the lipid profile and liver fat content in subjects with moderately and severely impaired glucose metabolism and non-alcoholic fatty liver disease (LeguAN, LEMBAS, DiNA-P, DiNA-D). The effects can be attributed to prolonged insulin secretion and improved second meal effect, higher energy expenditure by urea synthesis, suppression of glucagon or other mechanisms. Up to now, it is unclear, if proteins with slower or faster digestibility lead to differential results in these study designs. The proposed study will elucidate this question. The investigators hypothesize, that slowly-digestible proteins induce a prolonged insulin plateau supporting the second-meal effect. They also assume, that these dietary proteins lead to a markedly stronger short-term secretion of glucagon followed by desensitisation of this hormone release. Fast-digestible proteins, on the other hand, will presumably induce a smaller second-meal effect and do not inhibit a second rise of glucagon in a consecutive meal.

The investigators intend to study the effects of a 3-weeks high-protein diet in 80 subjects with NAFLD and T2DM on liver fat content (MR spectroscopy) and glucose metabolism. The investigators expect different results for slow protein (casein) and fast protein (whey), thus comparing both protein species. The two major clinical visits before and after the intervention period will include MRI spectroscopy, fasting blood sampling for later analysis, full anthropometric assessment, a mixed meal tolerance test and a set of behavioral tests to investigate decision making processes.

In order to characterize the postprandial hormonal and amino acid profiles (e.g. insulin, glucagon, amino acids) of the varying protein sources, preliminary meal tests are performed. The first tests assess the protein dose-finding in 20 participants, 10 with T2DM and 10 without. On each day of the dose-finding assessment pre-trial one of the following dosages is used in a single oral protein tolerance test (5 g, 10 g and 30 g of whey or casein each).The second tests assess whether 30 g mixes of whey and casein in variable proportions induce different hormonal profiles of glucagon and insulin in comparison with 30 g pea protein, served as drinks together with a standardized breakfast. Therefore, 20 subjects, 10 with Metabolic Syndrome and T2DM and 10 with Metabolic Syndrome without T2DM undergo seven separate investigation days. The third preliminary tests assess the role of the product matrix/consistency in 6 participants with overweight/obesity. Participants consume commercially available milk products each 30 g protein content (approx. 80% Casein) but with different product consistency on three separate investigation days. Subjects without prior diabetes diagnosis additionally undergo an initial oral glucose tolerance test (OGTT) to ensure healthy glucose levels.

All clinical assessments will be conducted in the Dept. Endocrinology, Diabetes and Nutrition, Charité, Campus Benjamin Franklin (Lead: Charité, A.F.H. Pfeiffer). Psychobehavioral tests (DIfE, Prof. Park), assessment of body fat distribution including liver fat (University Hospital Tuebingen, Dr. Machann) and measurements of amino acid levels throughout the meal tests (Technische Universität Berlin, Prof. Rohn) are secondary work packages.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Stefan Kabisch, M.D.; Phone Number: 514429 +4930 450; Email: Stefan.kabisch@charite.de
• Study Contact Backup: Name: Andreas FH Pfeiffer, Prof. Dr.; Phone Number: 514422 +4930 450; Email: afhp@charite.de

Study Locations

• Germany
  • Berlin, Germany, 12203
    • Recruiting
    • Charite Campus Benjamin Franklin
    • Contact: Andreas FH Pfeiffer, Prof. Dr. med.; Phone Number: 030 450 514 422; Email: Afhp@charite.de
    • Contact: Stefan Kabisch, M.D.; Phone Number: 514429 +4930 450; Email: Nina.Meyer@charite.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Subcohort 1 (n=46):

Inclusion Criteria:

• healthy glucose levels or T2DM
• 40-79 years
• overweight/obesity

Main Exclusion Criteria:

• type 1 diabetes, prediabetes
• currently receiving treatment with insulin
• lactose intolerance, or food intolerance/allergy to any of the study products
• severe endocrine, gastrointestinal, metabolic, cardiovascular, pulmonary, inflammatory or psychiatric disorder
• active or recent relevant cancer
• intake of glucocorticoids or other medication that influences glucose metabolism
• pregnancy, breastfeeding

Subcohort 2 (n=80):

Inclusion Criteria:

• T2DM
• with NAFLD
• 18-79 years

Main Exclusion Criteria:

• type 1 diabetes, prediabetes
• currently receiving treatment with insulin
• lactose intolerance, or food intolerance/allergy to any of the study products
• severe endocrine, gastrointestinal, metabolic, cardiovascular, pulmonary, inflammatory or psychiatric disorder
• active or recent relevant cancer
• intake of glucocorticoids or other medication that influences glucose metabolism
• pregnancy, breastfeeding
• claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Whey protein group, 60g/day; Three weeks, daily supplementation with 60 g of whey protein	Dietary supplement: protein supplement; protein supplement, daily 60 g of protein, 3 weeks of intervention; blinded to patients
Active Comparator: Casein protein group, 60 g/day; Three weeks, daily supplementation with 60 g of casein protein	Dietary supplement: protein supplement; protein supplement, daily 60 g of protein, 3 weeks of intervention; blinded to patients
Active Comparator: pea protein group, 60g/day; Three weeks, daily supplementation with 60 g of pea protein	Dietary supplement: protein supplement; protein supplement, daily 60 g of protein, 3 weeks of intervention; blinded to patients
Placebo Comparator: placebo arm; Three weeks, daily supplementation with placebo	Dietary supplement: placebo supplement; Placebo supplement, daily intake of placebo, 3 weeks of intervention; blinded to patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Liver fat change after three weeks	absolute liver fat reduction after three weeks (MR spectroscopy)	3 weeks
change of 2-hours glucose levels in mixed meal test	change of 2-hours glucose levels in mixed meal test	3 weeks
change of glucagon concentration pg/ml (ELISA) in mixed-meal test	change of glucagon concentration (pg/ml) in mixed-meal test	3 weeks
change of insulin concentration (mIU/ml) in mixed-meal test	change of insulin concentration (mIU/ml) in mixed-meal test calculated as (disposition index)	3 weeks
change of dynamic insulin sensitivity in mixed-meal test	change of dynamic insulin sensitivity in mixed-meal test (Matsuda)	3 weeks
change of fasting insulin sensitivity in mixed-meal test	change of fasting insulin sensitivity in mixed-meal test (HOMA-IR)	3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change of insulin secretion in consecutive mixed-meal test after an initial breakfast MMT	change of insulin secretion in consecutive mixed-meal test after an initial breakfast MMT	3 weeks
change of urea concentration in serum(mmol/l)	change of urea concentration in Serum (mmol/l)	2 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in fasting amino acid concentration in blood	change in fasting amino acid concentrations determined by LC-MS in blood	3 weeks
change in uric Acid concentration in Serum (µmol/l)	change in uric Acid concentration in Serum (µmol/l)	3 weeks

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Collaborators: University Hospital Tuebingen; Technische Universität Berlin; German Institute of Human Nutrition
• Investigators: Study Director: Andreas FH Pfeiffer, Prof. Dr., Charité Universitätsmedizinh Berlin

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): June 30, 2025

Study Registration Dates

• First Submitted: July 21, 2020
• First Submitted That Met QC Criteria: September 21, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: type 2 diabetes; NAFLD; whey protein; casein; second meal effect; pea protein
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2
• Other Study ID Numbers: MOCA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No