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Gene - Diet Interactions (Genediet)

This study has been completed.
Sponsor:
Collaborator:
Kuopio University Hospital
Information provided by (Responsible Party):
Marjukka Kolehmainen, University of Eastern Finland
ClinicalTrials.gov Identifier:
NCT01274091
First received: January 10, 2011
Last updated: April 16, 2012
Last verified: April 2012
History of Changes
  Purpose

Interactions between genes and environment, i.e. our inherited responses to environmental changes, may be crucial in the development of the common diseases. The investigators were the first to identify PPARG gene as risk gene for type 2 diabetes. The role of the Pro12Ala polymorphism in diabetes risk has also been verified in meta-analysis. However, this effect on seems to depend on intervention and age. In this study the effects of diets high with saturated fatty acids (SAFA) and polyunsaturated fatty acids (PUFA) are compared in subjects carrying either Pro12Pro or Ala12Ala genotype of the PPARG gene.

Aim of the study:

To test if subjects with Pro12Pro and Ala12Ala genotypes respond differentially to a diet supplemented with high saturated (SAFA) or polyunsaturated fat (PUFA).

Hypotheses:

  1. Specific: Subjects with the Ala12Ala genotype will be more sensitive to dietary modification, and therefore respond more favorably to PUFA diet
  2. More general: Dietary instructions individually tailored according to the genotype would allow better treatment of obesity and diabetes

Condition Intervention
Insulin Sensitivity
 Other: PUFA-diet
Other: SAFA-diet

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Gene-diet Interactions

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by University of Eastern Finland:

Primary Outcome Measures:
  • insulin sensitivity [ Time Frame: week 0 ] [ Designated as safety issue: No ]
    insulin sensitivity measured by oral glucose tolerance test at the beginning of the first, randomised diet

  • insulin sensitivity [ Time Frame: week 8 ] [ Designated as safety issue: No ]
    insulin sensitivty measured by oral glucose tolerance test after the first diet

  • insulin sensitivity [ Time Frame: week 10 ] [ Designated as safety issue: No ]
    Insulin sensitivity measured by oral glucose tolerance test in the beginning of the second, randomised diet

  • insulin sensitivity [ Time Frame: week 18 ] [ Designated as safety issue: No ]
    insulin sensitivity measured by oral glucose tolerance test after the second diet


Secondary Outcome Measures:
  • peripheral blood mononuclear cell gene expression [ Time Frame: week 8 ] [ Designated as safety issue: No ]
  • peripheral blood mononuclear cell gene expression [ Time Frame: week 18 ] [ Designated as safety issue: No ]
  • serum lipids [ Time Frame: week 8 ] [ Designated as safety issue: No ]
    serum lipids, including serum lipidomics and fatty acid composition

  • serum lipids [ Time Frame: week 18 ] [ Designated as safety issue: No ]
    serum lipids, including serum lipidomics and fatty acid composition

  • inflammation [ Time Frame: week 8 ] [ Designated as safety issue: No ]
    inflammation measured as serum cytokines and adipose tissue inflammation

  • inflammation [ Time Frame: week 18 ] [ Designated as safety issue: No ]
    inflammation measured as serum cytokines and adipose tissue inflammation

  • energy expenditure [ Time Frame: week 8 ] [ Designated as safety issue: No ]
    energy expenditure and the rates of substrate oxidation

  • energy expenditure [ Time Frame: week 18 ] [ Designated as safety issue: No ]
    energy expenditure and the rates of substrate oxidation

  • insulin secretion [ Time Frame: week 8 ] [ Designated as safety issue: No ]
  • insulin secretion [ Time Frame: week 18 ] [ Designated as safety issue: No ]
  • adipose tissue gene expression [ Time Frame: week 8 ] [ Designated as safety issue: No ]
  • adipose tissue gene expression [ Time Frame: week 18 ] [ Designated as safety issue: No ]

Enrollment: 30
Study Start Date: August 2010
Study Completion Date: December 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: P/S-ratio 1.0

Diets will contain 30% of energy as fat, 18% as protein and 52% as carbohydrates:

polyunsaturated fatty acid diet (PUFA) will have P/S ratio 1.0.

 Other: PUFA-diet
Diets will contain 30% of energy as fat, 18% as protein and 52% as carbohydrates: polyunsaturated fatty acid diet (PUFA) will have P/S ratio 1.0.
Experimental: P/S-ration 0.3
Diets will contain 30% of energy as fat, 18% as protein and 52% as carbohydrates:. Saturated fatty acid diet (SAFA) will polyunsaturated/saturated (P/S) ratio of 0.3.
 Other: SAFA-diet
Diets will contain 30% of energy as fat, 18% as protein and 52% as carbohydrates: Saturated fatty acid diet (SAFA) will polyunsaturated/saturated (P/S) ratio of 0.3.

Detailed Description:

Obesity and type 2 diabetes are increasing in all western countries, including Finland. Recent genome wide analyses have found > 30 genes that contribute to either condition.. However, none of these genes explain >5% of the disease risk and altogether they explain < 10% of the total disease risk in cross-sectional studies. Therefore, diet and physical activity are still the major determinants of the risk, as demonstrated by our earlier intervention studies in order to find out the effect of different dietary modifications on glucose and lipid metabolism. More importantly, interactions between genes and environment, i.e. our inherited responses to environmental changes, may be crucial in the development of the common diseases. Unfortunately, gene-environment interaction can only be effectively investigated in intervention studies that are more expensive than cross-sectional population screenings. This leads to a lower sample size and reduced power to detect effects of minor alleles. Despite these limitations the investigators have been able to demonstrate gene-intervention interactions for several genes, including PPARG, in the Finnish Diabetes Prevention study. There is an urgent need for studies investigating effects of tailored diets in individuals selected based on their genotype. This will be the next essential step leading to improved dietary treatments guided by genetic information.

The investigators were the first to identify PPARG gene as risk gene for type 2 diabetes. The role of the Pro12Ala polymorphism in diabetes risk has also been verified in meta-analysis. However, this effect on seems to depend on intervention and age. Based on these findings the investigators created in collaboration with Johan Auwerx an Pro12Ala animal model that demonstrated a differential effect of dietary fat composition depending on the genotype. However, an important conclusive proof that subjects selected based on their Pro12Ala genotype would respond differently to specifically tailored diet modification is still needed.

In this study the effects of diets high with saturated fatty acids (SAFA) and polyunsaturated fatty acids (PUFA) are compared in subjects carrying either Pro12Pro or Ala12Ala genotype of the PPARG gene. As a primary endpoint the investigators expect insulin sensitivity to alter differently depending on the genotype. Additionally, a detailed characterization of energy, glucose and lipid metabolism will be performed. Because PPARG gene plays a central role in adipogenesis one of the aims of this study is to find new pathways, genes and gene clusters that are regulated by PPARG in humans.

  Eligibility

Ages Eligible for Study:   40 Years to 65 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • BMI >20kg/m2 <29kg/m2
  • Pro12Pro and Ala12Ala genotypes of PPARG Pro12Ala polymorphism
  • participation to METSIM-study (METabolic Syndrome in Men, currently >10000 men included from the population living in Kuopio, principal investigator Markku Laakso)
  • normoglycemia

Exclusion Criteria:

  • type 2 diabetes
  • other chronic diseases
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01274091

Locations
Finland
University of Eastern Finland
Kuopio, Finland, FIN-70211
Sponsors and Collaborators
Marjukka Kolehmainen
Kuopio University Hospital
Investigators
Principal Investigator: Jussi Pihlajamäki, Professor University of Eastern Finland, Kuopio University Hospital
Study Director: Ursula S Schwab, Clinical Lect, adjunct prof University of Eastern Finland
Study Chair: Matti Uusitupa, Professor Professor
  More Information

No publications provided

Responsible Party: Marjukka Kolehmainen, Senior scientist, University of Eastern Finland
ClinicalTrials.gov Identifier: NCT01274091     History of Changes
Other Study ID Numbers: 28//2010
Study First Received: January 10, 2011
Last Updated: April 16, 2012
Health Authority: Finland: Ethics Committee

Keywords provided by University of Eastern Finland:
Gene-diet interaction
PPARgamma gene
Pro12Ala
Fatty acids
 Dietary modification
Insulin sensitivity
Glucose metabolism

Additional relevant MeSH terms:
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on October 18, 2012