Clinical trial NCT04564391: Whey or Casein - Liver Fat Reduction and Metabolic Improvement by Fast vs. Slow Proteins
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type2 Diabetes
NAFLD
Keywords: NAFLD
type 2 diabetes
whey protein
casein
second meal effect
pea protein
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: Technische Universität Berlin
name: University Hospital Tuebingen
name: German Institute of Human Nutrition
First posted: 2020-09-25
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: parallel-designed randomised controlled trial
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Liver fat change after three weeks
timeFrame: 3 weeks
measure: change of 2-hours glucose levels in mixed meal test
timeFrame: 3 weeks
measure: change of glucagon concentration pg/ml (ELISA) in mixed-meal test
timeFrame: 3 weeks
measure: change of insulin concentration (mIU/ml) in mixed-meal test
timeFrame: 3 weeks
measure: change of dynamic insulin sensitivity in mixed-meal test
timeFrame: 3 weeks
measure: change of fasting insulin sensitivity in mixed-meal test
timeFrame: 3 weeks
Secondary outcomes:
measure: change of insulin secretion in consecutive mixed-meal test after an initial breakfast MMT
timeFrame: 3 weeks
measure: change of urea concentration in serum(mmol/l)
timeFrame: 2 weeks
Other outcomes:
measure: change in fasting amino acid concentration in blood
timeFrame: 3 weeks
measure: change in uric Acid concentration in Serum (µmol/l)
timeFrame: 3 weeks
Locations:
city: Berlin
country: Germany
facility: Charité Campus Benjamin Franklin
Study officials:
affiliation: Charité Universitätsmedizinh Berlin
name: Andreas FH Pfeiffer, Prof. Dr.
role: STUDY_DIRECTOR
References: