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 subjects with NAFLD (40 subjects without T2DM, 40 subjects with T2DM) on insulin resistance (mixed-meal tolerance tests; MMTT), second meal effect (second, consecutive MMTT on the same day) and liver fat content (MR spectroscopy) as well body-fat distribution (MR tomography). 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 also include fasting blood sampling for later analysis, full anthropometric assessment and a set of behavioral tests, investigating postprandial decision making processes. All clinical assessments will be conducted in Charité (Lead: A.F.H. Pfeiffer). Psychobehavioral tests (Prof. Park), assessment of body fat distribution including liver fat (Dr. Machann) and measurements of amino acid levels throughout the meal tests (Prof. Rohn) are secondary work packages.

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 examine the effects of a 3-weeks high-protein diet in subjects with NAFLD (40 subjects without T2DM, 40 subjects with T2DM) on insulin resistance (mixed-meal tolerance tests; MMTT), second meal effect (second, consecutive MMTT on the same day) and liver fat content (MR spectroscopy) as well body-fat distribution (MR tomography). 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 also include fasting blood sampling for later analysis, full anthropometric assessment and a set of behavioral tests, investigating postprandial decision making processes. In order to identify the suitable dosage for protein loads in the 3-weeks intervention trial, the study follows a dose-finding assessment in 40 subjects (20 subjects with Metabolic Syndrome and T2DM; 20 subjects with Metabolic Syndrome without T2DM), which undergo six separate investigation days. 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, 20 g and 30 g of whey or casein each). Subjects with NAFLD from this pre-study are eligible for the main trial. Additional test will assess whether mixes of whey and casein in variable proportions induce different hormonal profiles of glucagon and insulin. All clinical assessments will be conducted in the Dept. Endocrinology, Diabetes and Nutrition, Charité, Campus Benjamin Franklin (Lead: DIfE, A.F.H. Pfeiffer). Psychobehavioral tests (Prof. Park), assessment of body fat distribution including liver fat (Dr. Machann) and measurements of amino acid levels throughout the meal tests (Prof. Rohn) are secondary work packages.

drinks and food supplements are provided in neutral boxes and containers supplements cannot be identified by visual appearance, taste, texture or odour

protein supplement, twice daily, 2 x 30 g of protein, 3 weeks of intervention; blinded to patients and personnel

Placebo supplement, twice daily, 2 x 30 g of placebo, 3 weeks of intervention; blinded to patients and personnel

Subcohort 1 (n=40): Inclusion Criteria: healthy with NAFLD 18-79 years Exclusion Criteria: severe endocrine, gastrointestinal, metabolic, cardiovascular, pulmonary, inflammatory or psychiatric disorder active or recent relevant cancer Subcohort 2 (n=40): Inclusion Criteria: T2DM with NAFLD 18-79 years Exclusion Criteria: severe endocrine, gastrointestinal, metabolic, cardiovascular, pulmonary, inflammatory or psychiatric disorder active or recent relevant cancer