How do Your Genes Affect Obesity and Diabetes


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Diet and Genetics

A popular area of research is to determine genetic causes of obesity, diabetes, heart disease, autoimmune disease, depression and any other illness or condition that is plaguing our society. Proposed genetic solutions will result in expensive and profit-driven procedures that do not solve the primary cause of the problem.

This area of research ignores the fact that often our genetic code does not determine health outcomes and it will not solve the problems of our society’s rapidly failing health.

Frequently the problem is not that complicated.

PPARG and ADRB2 Genes

Gardner and colleagues chose three genes: PPARG (PPAG-gamma), ADRB2 and FABP2. They claimed that variations in these genes result in a low-fat responsive genotype and a low-carbohydrate responsive genotype. 1

PPARG 2 is association with fat cell differentiation. Mutations in PPARG may be a cause of type 2 diabetes and hyptertension. 3

A variation of the ADRB2 4 gene is associated with a reduced ability to breakdown fatty acids, and in women, a reduced ability to oxidise fat. 5. The conclusion is that this variation of the ADRB2 gene “may be an important factor in the development or progression of obesity and obesity-related disorders”.

That conclusion is a hypothesis – it is not a rigorous conclusion. The study group consisted of 43 females and 65 males, who were very overweight. The BMI range was 26.1-48.4 kg/m. (BMI over 25 is overweight, over 30 is obese.) There was no control group so it is not possible to compare the incidence of these genetic variations in normal-weight subjects. Without a control group, valid comparisons cannot be made. Perhaps they were simply eating a very poor diet.

Another paper that was attempting to find a link with variations in the ADRB2 gene has concluded that the ADRB2 gene polymorphisms studied do not contribute in any important way to the risk of essential hypertension or heart attacks in subjects of European ancestry. 6

FABP2 Gene

FABP2 7 gene encodes a protein that is involved in long-chained fatty acid metabolism and transport. Some authors suggest that variations of this protein can have an effect on fatty acid assimilation resulting in an increase fat oxidation and a reduction in insulin resistance.

Pima people (The River People) are native Americans from New Mexico, central and southern Arizona and NW Mexico.

The Pima Indians of Arizona reportedly have the highest prevalence of type 2 diabetes of any population which afflicts more than half of the population over 35. 8

A group of overweight, non-diabetic participants from Arizona was examined for the presence of 3 FABP2 alleles. An allele is a different version of the same gene. The 3 alleles are referred to AA, AT and TT. Average weight for the three alleles were 99kg, 96kg and 103kg respectively.

Diets of their diet was not disclosed.

There was no significant correlation between the presence of the three alleles and the weight of the participants. However, the AT and TT alleles “may potentially be more deleterious in individuals who consume a diet high in saturated long-chain fatty acids, which is characteristic of the modern, ‘Westernized’ diet.”

Therefore, the variation in the FABP2 alleles is not associated with an increase in body weight but “may be” associated with greater health risks in those who are obese.

A similar conclusion is found in a 2007 paper that states, “Results from the current study suggest that, in sedentary middle-aged to older non-diabetic persons following a low-fat diet, FABP2 Thr54 (TT and AT) carriers have lower glucose tolerance and lower insulin action than do their Ala54-homozygous (AA) counterparts.” 9

Two Japanese studies did not find any association with FAPB2 gene in health outcomes.

The first paper stated there was “no evidence for the role of the common FABP2 A54T gene polymorphism in increased plasma levels of asymmetric dimethylarginine in patients with carotid stenosis.” 12

The conclusion is that in normal-weight individuals, the FABP2 gene does not affect health outcomes.

The DIETFITS Randomized Clinical Trial

The DIETFITS Randomized Clinical Trial 13 was to determine the effect of a “healthy” low-fat diet compared with a “healthy” low-carbohydrate diet on weight change and if genotype pattern or insulin secretion are related to the dietary effects on weight loss.

The only information given about the diets in the Gardner study is:

  • the amount of energy consumed
  • amount of carbohydrate
  • fat
  • protein
  • saturated fat
  • fibre

Some conclusions can be made from these figures but it is not sufficient to determine how healthy a diet is. What foods were they consuming?

ImportantA healthy diet is the result of everything that we eat.

CriteriaLow-Fat DietLow-Carb Diet
Energy Intake (kcal)17161697
Carbohydrate (%)4830
Fat (%)2945
Protein (%)2123
Protein (g)8593
Saturated Fat (%)915
Fibre (g)2319
Important19 adverse events “were evenly distributed across the 2 diet groups.” 7 events required hospitalisation. 11 of these events were related or possible related to the study. Not a great endorsement for either of the diets.

The primary goal was to determine which diet had the better weight loss outcome and if this was associated with a genotype pattern.

  • Both diets are very low in energy intake. The chances are that the subjects were hungry and miserable. The completion rates for both diets was only 74%. People are going to lose weight if energy intake is restricted regardless of the type of diet.
  • The “low-fat” diet is contains 29% of calories from fat. This is not a low-fat diet. The average American consumes 33% of fats from calories. A whole-food, plant-based diet (no added fats) has 10-15% of calories from fat.
  • Based on nitrogen balance studies, the Recommended Dietary Intake (RDI) for protein is 0.84 g/(kg · day) for males and 0.75 g/(kg · day). Based on reference weight of 76 kg for males and 61 kg for females, the DRI for protein is 64 g of protein for males and 45 g for females. Both diets were far in excess of these amounts.
  • These amounts are easily consumed when protein is approximately 10%-12% of the daily energy intakes.
  • Note that human breast milk is 6% protein – the lowest amount of any mammal that has been recorded. Yet this meets the needs of a baby for the first 6 months of life when the need for protein is at its greatest.
  • Note that the RDI is not how much protein is required, but the amount required to meet or exceed the requirements of 98% of the population. 14
  • Any protein consumed above requirements are not utilised and need to eliminated from the body, placing additional load on the kidneys.
  • The recommended amount of fibre is 25 g. Both groups failed to meet even this low level this level. Optimal amount of fibre is much higher.
  • High levels of anti-oxidants are associated with good health. It is impossible on the figures shown to consume a significant level of anti-oxidants.

The conclusion of this study was:

In this 12-month weight loss diet study, there was no significant difference in weight change between a healthy low-fat diet vs a healthy low-carbohydrate diet, and neither genotype pattern nor baseline insulin secretion was associated with the dietary effects on weight loss. In the context of these 2 common weight loss diet approaches, neither of the 2 hypothesized predisposing factors was helpful in identifying which diet was better for whom.

Other studies have shown that variants of 25 genes have been linked with type 2 diabetes in human populations. Of these 25 genes, only 6 15 have shown significant associations in a limited number of studies. There is no universal agreement as to what genes are associated with type 2 diabetes and obesity.

Japanese and Hawaiian Migration Studies

During 1955 and 1956, Ancel and Margaret Keys, along with Brian Bronte-Stewart from Oxford, Noburo Kimuro and Akira Kusukawa from Japan, and Nils Larsen from Honolulu were involved in a study involving Japanese men living in Japan, Hawaii and Los Angeles

They studied Japanese living in Fukuoka, on the southern most island of Kyushu, Americans living on the air base in Fukuoka, Japanese men in Hawaii and Los Angeles.

Heart attacks were non-existent in Fuuoka, despite Japanese having a high smoking rate. Levels of cancer, high blood pressure and stroke were relatively high. One factor was the high level of sodium in the diet. This was due to salt being used to preserve food, particularity in the north and the use of mono sodium glutamate (MSG) in soy sauce.

Below is a table showing the consumption of fats in the diet of Japanese and the serum cholesterol levels.

Place% Fat
Los Angeles40212.75.5

Below is a table showing the percentage of calories from fats from various food sources for different populations of Japanese and Caucasians.

Meat, eggs and dairy products3.320.228.133.728.0
Fish and other marine animals5.
Vegetable sources2.810.210.26.713.9

This supports the idea that genetics plays an insignificant role in heart disease. When Japanese move and change their diets to reflect their new location, their cholesterol level changes as does the exposure to heart disease – it is not due to their genetics.

Except for the rare condition of familiar hypercholesterolaemia (FH), genetics does not play a significant role in heart disease. FH is caused by a defect of a single gene. The cells are unable to produce a protein than allows LDL cholesterol to be removed from the body. This results in a significant build up of cholesterol in the blood. Children as young as 6 may suffer heart attacks as a result. It is much more prevalent in places such as Norway and north-west India where marriage between cousins was more prevalent.

Seven-day Adventist’s Studies

A strong commitment to health has been a part of Adventist’s tradition since its founding in the 1840s. There has been three large Adventist cohort studies in the United States and Canada. These studies have generated hundreds of papers, which give a valuable insight to diet and the implication for our health.

Data from the AHS-2 study shows that Adventists smoke much less frequently than the general American population (males – 1.2%, females – 1.0%) and drink less alcohol (6.6% drink alcohol). Diet is also significantly different. 16

The consumption of meat is much less than the standard American diet, even for those who consume meat. There is a much greater prevalence of people consuming vegan and vegetarian  diets.

The AHS-1 study showed 30-year-old Adventist males lives 7.3 years longer than the average 30-year-old white Californian male and with females living 4.4 years longer than the average Californian white female. For vegetarians, it is 9.5 years longer for men and 6.1 years longer for women. 17

Much publicity is given to the longevity of the people of Japan and Okinawa (an archipelago that stretches from southern Japan to Taiwan). However, the population with the longest lifespan and the highest levels of health on the planet is the vegan Californian Seventh-day Adventists 18

There is more than sufficient evidence indicating that whole-food, plant-based diets, based on whole grains, fruit, vegetables and legumes, are not only optimal for our health but are also the best for the environment and for the animals we share the earth with.

Such diets will be low in fats, saturated fats, sugars and high in complex carbohydrates, fibre and antioxidants.

There is no need or benefit in over-complicating our current health issues by searching for complicated and expensive genetic solutions that at present offer only theoretical solutions to problems that frequently have a much simpler solution.

Related articles


  1. Gardner, C. D. et al. (2018) Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion: The DIETFITS Randomized Clinical Trial. Journal of American Medical Association. 319 (7), 667.
  2. peroxisome proliferator activated receptor-gamma
  3. Yen, C.-J. et al. (1997) Molecular scanning of the human peroxisome proliferator activated receptor γ (hPPARγ) gene in diabetic Caucasians: identification of a Pro12Ala PPARγ2 missense mutation. Biochemical and biophysical research communications. 241 (2), 270–274.
  4. adrenoceptor beta 2
  5. Jocken, J. W. E. et al. (2007) Association of a beta-2 adrenoceptor (ADRB2) gene variant with a blunted in vivo lipolysis and fat oxidation. International Journal of Obesity. 31 (5), 813–819.
  6. Herrmann, S.-M. et al. (2002) Polymorphisms of the β2-adrenoceptor (ADRB2) gene and essential hypertension: the ECTIM and PEGASE studies. Journal of hypertension. 20 (2), 229–235.
  7. Fatty acid-binding protein 2
  8. Baier, L. J. et al. (1995) An amino acid substitution in the human intestinal fatty acid binding protein is associated with increased fatty acid binding, increased fat oxidation, and insulin resistance. Journal of Clinical Investigation. 95 (3), 1281–1287.
  9. Weiss, E. P. et al. (2007) FABP2 Ala54Thr genotype is associated with glucoregulatory function and lipid oxidation after a high-fat meal in sedentary nondiabetic men and women. The American Journal of Clinical Nutrition. 85 (1), 102–108.
  10. Wanby, P. et al. (2007) Increased plasma levels of asymmetric dimethylarginine in patients with carotid stenosis: no evidence for the role of the common FABP2 A54T gene polymorphism. Acta neurologica scandinavica. 115 (2), 90–96. 10

    The second paper stated “Our data suggested that Ala54Thr polymorphism of the FABP2 gene is not a major contributing factor for obesity and obesity with dyslipidemia in Japanese children.” 11Endo, K. et al. (2001) No association found between the Ala54Thr polymorphism of FABP2 gene and obesity and obesity with dyslipidemia in Japanese schoolchildren. Journal of atherosclerosis and thrombosis. 8 (3), 80–83.

  11. Gardner, C. D. et al. (2018) Effect of Low-Fat vs Low-Carbohydrate Diet on 12-Month Weight Loss in Overweight Adults and the Association With Genotype Pattern or Insulin Secretion: The DIETFITS Randomized Clinical Trial. JAMA. 319 (7), 667.
  12. This amount is two standard deviations above the mean.
  13. sulfonylurea receptor, glucagon receptor, glucokinase, potassium inward rectifier channel Kir6.2, peroxisome proliferator activated receptor-gamma, and GLUT1 glucose transporter
  14. Le, L. & Sabate, J. (2014) Beyond Meatless, the Health Effects of Vegan Diets: Findings from the Adventist Cohorts. Nutrients.  6 (6), 2131–2147.
  15. Buettner, D. (2012) The Blue Zones. Second Ed. Washington DC: National Geographic.
  16. Fraser, G. E. & Shavlik, D. J. (2001) Ten Years of Life – Is It a Matter of Choice? Archives of Internal Medicine. 161 (13), 1645–1652.

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