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

NCT04564391 | Recruiting

• 1 other identifier: MOCA
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Type2 Diabetes; NAFLD

Keywords

NAFLD; type 2 diabetes; whey protein; casein; second meal effect; pea protein

Outcome Measures

Primary Outcomes (6)

• Liver fat change after three weeks

  absolute liver fat reduction after three weeks (MR spectroscopy)

  3 weeks

• change of 2-hours glucose levels in mixed meal test

  change of 2-hours glucose levels in mixed meal test

  3 weeks

• change of glucagon concentration pg/ml (ELISA) in mixed-meal test

  change of glucagon concentration (pg/ml) in mixed-meal test

  3 weeks

• 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

• change of dynamic insulin sensitivity in mixed-meal test

  change of dynamic insulin sensitivity in mixed-meal test (Matsuda)

  3 weeks

• change of fasting insulin sensitivity in mixed-meal test

  change of fasting insulin sensitivity in mixed-meal test (HOMA-IR)

  3 weeks

Secondary Outcomes (2)

• change of insulin secretion in consecutive mixed-meal test after an initial breakfast MMT

  3 weeks

• change of urea concentration in serum(mmol/l)

  2 weeks

Other Outcomes (2)

• change in fasting amino acid concentration in blood

  3 weeks

• change in uric Acid concentration in Serum (µmol/l)

  3 weeks

Study Arms (4)

Whey protein group, 60g/day

ACTIVE COMPARATOR

Three weeks, daily supplementation with 60 g of whey protein

Dietary Supplement: protein supplement

Casein protein group, 60 g/day

ACTIVE COMPARATOR

Three weeks, daily supplementation with 60 g of casein protein

Dietary Supplement: protein supplement

pea protein group, 60g/day

ACTIVE COMPARATOR

Three weeks, daily supplementation with 60 g of pea protein

Dietary Supplement: protein supplement

placebo arm

PLACEBO COMPARATOR

Three weeks, daily supplementation with placebo

Dietary Supplement: placebo supplement

Interventions

protein supplement DIETARY_SUPPLEMENT

protein supplement, daily 60 g of protein, 3 weeks of intervention; blinded to patients

Casein protein group, 60 g/day; Whey protein group, 60g/day; pea protein group, 60g/day

placebo supplement DIETARY_SUPPLEMENT

Placebo supplement, daily intake of placebo, 3 weeks of intervention; blinded to patients

placebo arm

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• healthy glucose levels or T2DM
• years
• overweight/obesity

You may not qualify if:

• 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):
• T2DM
• with NAFLD
• years
• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• Technische Universität Berlin: collaborator
• University Hospital Tuebingen: collaborator
• German Institute of Human Nutrition: collaborator

Study Sites (1)

Charité Campus Benjamin Franklin

Berlin, 12203, Germany

RECRUITING

Related Publications (1)

• Zhang J, Schafer SM, Kabisch S, Csanalosi M, Schuppelius B, Kemper M, Markova M, Meyer NMT, Pivovarova-Ramich O, Keyhani-Nejad F, Rohn S, Pfeiffer AFH. Implication of sugar, protein and incretins in excessive glucagon secretion in type 2 diabetes after mixed meals. Clin Nutr. 2023 Apr;42(4):467-476. doi: 10.1016/j.clnu.2023.02.011. Epub 2023 Feb 21.

  PMID: 36857956 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Andreas FH Pfeiffer, Prof. Dr.

  Charité Universitätsmedizinh Berlin

  STUDY DIRECTOR

Central Study Contacts

Stefan Kabisch, M.D.

CONTACT

+4930 450; Stefan.kabisch@charite.de

Andreas FH Pfeiffer, Prof. Dr.

CONTACT

+4930 450; afhp@charite.de

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: For the preliminary meal tests all drinks and food supplements are provided in neutral bottles and cannot be identified by visual appearance, taste, texture or odour. Masking applied to participants, care providers, investigators and outcomes assessors. For the interventional study provided drinks and food supplements were masked best possible for the participants.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head Dept. Endocrinology, Diabetes and Nutrition

Model Details: parallel-designed randomised controlled trial

Study Record Dates

• First Submitted: July 21, 2020
• First Posted: September 25, 2020
• Study Start: September 21, 2020
• Primary Completion: December 31, 2024
• Study Completion: June 30, 2025
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)