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
Name: PUFA-diet
Description: 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.Type: OtherP/S-ratio 1.0
Name: SAFA-diet
Description: 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.Type: OtherP/S-ration 0.3
Description: insulin sensitivity measured by oral glucose tolerance test at the beginning of the first, randomised diet
Measure: insulin sensitivity Time: week 0Description: insulin sensitivty measured by oral glucose tolerance test after the first diet
Measure: insulin sensitivity Time: week 8Description: Insulin sensitivity measured by oral glucose tolerance test in the beginning of the second, randomised diet
Measure: insulin sensitivity Time: week 10Description: insulin sensitivity measured by oral glucose tolerance test after the second diet
Measure: insulin sensitivity Time: week 18Description: serum lipids, including serum lipidomics and fatty acid composition
Measure: serum lipids Time: week 8Description: serum lipids, including serum lipidomics and fatty acid composition
Measure: serum lipids Time: week 18Description: inflammation measured as serum cytokines and adipose tissue inflammation
Measure: inflammation Time: week 8Description: inflammation measured as serum cytokines and adipose tissue inflammation
Measure: inflammation Time: week 18Description: energy expenditure and the rates of substrate oxidation
Measure: energy expenditure Time: week 8Description: energy expenditure and the rates of substrate oxidation
Measure: energy expenditure Time: week 18Allocation: Randomized
Crossover Assignment
There is one SNP
The role of the Pro12Ala polymorphism in diabetes risk has also been verified in meta-analysis. --- Pro12Ala ---
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 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 Insulin Sensitivity Hypersensitivity Insulin Resistance Obesity and type 2 diabetes are increasing in all western countries, including Finland. --- Pro12Ala ---
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 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 Insulin Sensitivity Hypersensitivity Insulin Resistance Obesity and type 2 diabetes are increasing in all western countries, including Finland. --- Pro12Ala --- --- Pro12Ala ---
The role of the Pro12Ala polymorphism in diabetes risk has also been verified in meta-analysis. --- Pro12Ala ---
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. --- Pro12Ala ---
However, an important conclusive proof that subjects selected based on their Pro12Ala genotype would respond differently to specifically tailored diet modification is still needed. --- Pro12Ala ---