Whey or Casein - Liver Fat Reduction and Metabolic Improvement by Fast vs. Slow Proteins
- Conditions
- Type2 DiabetesNAFLD
- Interventions
- Dietary Supplement: protein supplementDietary Supplement: placebo supplement
- Registration Number
- NCT04564391
- Lead Sponsor
- Charite University, Berlin, Germany
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 80
- healthy glucose levels or T2DM
- 40-79 years
- overweight/obesity
Main
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Whey protein group, 60g/day protein supplement Three weeks, daily supplementation with 60 g of whey protein pea protein group, 60g/day protein supplement Three weeks, daily supplementation with 60 g of pea protein placebo arm placebo supplement Three weeks, daily supplementation with placebo Casein protein group, 60 g/day protein supplement Three weeks, daily supplementation with 60 g of casein protein
- Primary Outcome Measures
Name Time Method change of glucagon concentration pg/ml (ELISA) in mixed-meal test 3 weeks change of glucagon concentration (pg/ml) in mixed-meal test
change of insulin concentration (mIU/ml) in mixed-meal test 3 weeks change of insulin concentration (mIU/ml) in mixed-meal test calculated as (disposition index)
change of fasting insulin sensitivity in mixed-meal test 3 weeks change of fasting insulin sensitivity in mixed-meal test (HOMA-IR)
Liver fat change after three weeks 3 weeks absolute liver fat reduction after three weeks (MR spectroscopy)
change of 2-hours glucose levels in mixed meal test 3 weeks change of 2-hours glucose levels in mixed meal test
change of dynamic insulin sensitivity in mixed-meal test 3 weeks change of dynamic insulin sensitivity in mixed-meal test (Matsuda)
- Secondary Outcome Measures
Name Time Method change of insulin secretion in consecutive mixed-meal test after an initial breakfast MMT 3 weeks change of insulin secretion in consecutive mixed-meal test after an initial breakfast MMT
change of urea concentration in serum(mmol/l) 2 weeks change of urea concentration in Serum (mmol/l)
Trial Locations
- Locations (1)
Charité Campus Benjamin Franklin
🇩🇪Berlin, Germany