Gene - Diet Interactions
Condition: Insulin Sensitivity
MeSH terms: Insulin Resistance; Hypersensitivity
Study type: Interventional

Summary: 
      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
    

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.
    

Intervention name(s): PUFA-diet; SAFA-diet
Intervention type(s): Other; Other
Intervention description(s): 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.; 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.
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Gene-diet interaction; PPARgamma gene; Pro12Ala; Fatty acids; Dietary modification; Insulin sensitivity; Glucose metabolism