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

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.

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

Conditions4

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