Type-2 diabetes affects about 9% of the US population and millions other world-wide. In those over age 65, one in four people has type-2 diabetes. While the overall numbers are a bit staggering, it is interesting to note that the peak for new cases was in the ’90s with a decrease in cases from 2005-2017.[ref]

Diabetes is thought to be caused partly by environment and partly due to genetics. Genetic susceptibility has been linked to a number of different genes, but one that stands out as being particularly relevant to almost all populations is the TCF7L2 gene.

The TCF7L2 (transcription factor 7-like 2) gene is involved in the regulation of blood glucose level with insulin by affecting the expression of pro-glucagon.  Variants in TCFL2 are tied to type-2 diabetes, obesity, higher BMI,  and larger waist circumference. The SNPs listed below have been found to up-regulate TCF7L2 in pancreatic beta cells.[ref]  The up-regulation is thought to impair insulin secretion from the beta cells rather than causing insulin resistance. [ref] [ref]

Why is this important? If you have one of the TCF7L2 variants that increase your risk of diabetes, there are lifestyle and diet choices that have been shown in studies to negate that increased risk.

Genetic Variants in TCF7L2:

Check your 23andMe results for rs7903146 (v4, v5):

  • CC: normal
  • CT: increased risk for type-2 diabetes, higher glucose levels,
  • TT: strong tie to increased risk for type-2 diabetes [ref][ref][ref] [ref] and higher glucose levels [ref]

Studies on this variant have found:

  • A higher intake of omega-6 polyunsaturated fats caused T allele carriers to have higher fasting glucose and a higher risk of metabolic syndrome. [ref]
  • T allele carriers are at an increased risk of gestational diabetes.[ref]
  • Several studies have shown that people with the T allele have higher fasting or night time glucose levels. [ref][ref]
  • A Mediterranean diet normalized the blood glucose level for those with the risk genotype. [ref]
  • A study of Indian diabetics found that 70% of patients with the GT or TT genotype who took a sulfonylurea (diabetes medication type) failed to achieve the therapeutic target (compared to 19% with the GG genotype). [ref]

Check your 23andMe results for rs12255372 (v4, V5):

  • GG: normal
  • CT: increased risk for type-2 diabetes
  • TT: increased risk for type-2 diabetes[ref]

Studies on this variant have concluded: 

  • While net carbohydrate intake made no difference, high glycemic index or glycemic load caused an increased risk for TT individuals in regards to metabolic syndrome[ref]
  • A low-fat diet was found to work better to decrease BMI and fat mass for those with the TT genotype [ref]
  • Those on a low-fat diet lost more weight with the TT genotype. [ref]
  • Hispanics with the minor allele have a lower avg BMI, thus showing that the effects could be population specific since most of the larger studies were predominantly Caucasian European populations. [ref]
  • A study found that people eating a low amount of fat along with the T allele had the highest HDL cholesterol levels, while those eating higher fat diet had lower HDL levels. [ref]

Check your 23andMe results for rs4506565 (v4, v5):

  • AA: normal
  • AT: increased risk of type 2 diabetes
  • TT: increased risk of type 2 diabetes[ref] [ref][ref]


Cut out fried food: Quite a few studies (above) looked at the amount and type of fat and the effect on the risk of type 2 diabetes. Overall, decreasing fat, specifically omega-6 polyunsaturated fats such as sunflower, safflower, corn, cottonseed, sesame, soybean and peanut oils, seems to reduce the risk of diabetes for those with the risky genotypes.

Check your glucose: The above variants can lead to higher fasting blood glucose levels.  Blood glucose meters aren’t expensive and are widely available. Watch your glucose levels and look into a lower glycemic index diet. Everyone has individual differences in how their blood glucose levels change in response to foods, so regular testing can help you know if you are on the right track.

Blame your mom: Inheriting the TCF7L2 variants from your mother instead of your father may increase your risk of diabetes.  [ref]

More to read:

Color TV has made us fat: melatonin, genetics, and light at night

Diet – Gene Interaction in Type 2 Diabetes Risk




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