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

Type2 Diabetes Clinical Trial

— MOCA  

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04564391
• Other study ID #: MOCA
• Status: Recruiting
• Phase: N/A
• Start date: September 21, 2020
• Est. completion date: June 30, 2025

Study information

• Verified date: March 2024
• Source: Charite University, Berlin, Germany
• Contact: Stefan Kabisch, M.D.
• Phone: +4930 450
• Email: Stefan.kabisch[@]charite.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: June 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 79 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• NAFLD
• Type2 Diabetes

Intervention

Dietary Supplement:
• protein supplement
protein supplement, daily 60 g of protein, 3 weeks of intervention; blinded to patients
• placebo supplement
Placebo supplement, daily intake of placebo, 3 weeks of intervention; blinded to patients

Locations

Country	Name	City	State
Germany	Charité Campus Benjamin Franklin	Berlin

Sponsors (4)

Lead Sponsor	Collaborator
Charite University, Berlin, Germany	German Institute of Human Nutrition, Technische Universität Berlin, University Hospital Tuebingen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	change in fasting amino acid concentration in blood	change in fasting amino acid concentrations determined by LC-MS in blood	3 weeks
Other	change in uric Acid concentration in Serum (µmol/l)	change in uric Acid concentration in Serum (µmol/l)	3 weeks
Primary	Liver fat change after three weeks	absolute liver fat reduction after three weeks (MR spectroscopy)	3 weeks
Primary	change of 2-hours glucose levels in mixed meal test	change of 2-hours glucose levels in mixed meal test	3 weeks
Primary	change of glucagon concentration pg/ml (ELISA) in mixed-meal test	change of glucagon concentration (pg/ml) in mixed-meal test	3 weeks
Primary	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
Primary	change of dynamic insulin sensitivity in mixed-meal test	change of dynamic insulin sensitivity in mixed-meal test (Matsuda)	3 weeks
Primary	change of fasting insulin sensitivity in mixed-meal test	change of fasting insulin sensitivity in mixed-meal test (HOMA-IR)	3 weeks
Secondary	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
Secondary	change of urea concentration in serum(mmol/l)	change of urea concentration in Serum (mmol/l)	2 weeks