blood sugar control
nutrition
TCF7L2

The Link Between Diabetes and High-Carb Foods (TCF7L2)

Written by Aleksa Ristic, MS (Pharmacy) on February 28th, 2020
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The TCF7L2 gene has the strongest known association with diabetes. Variants in this gene may determine how well you respond to high-carb foods — read on to get gene-based diet tips for improved blood sugar control.

TCF7L2 and Glucose Metabolism

The TCF7L2 (transcription factor 7 like 2) gene, previously known as TCF4, codes for a vital transcription factor. It controls the expression of other genes in digestive organs such as the gut and pancreas, with a particular role in glucose metabolism and insulin secretion [R, R].

This gene has the strongest association with type 2 diabetes observed so far. Specific variants in this gene, such as rs7903146, correlate with increased diabetes rates among all major populations [R, R, R].

As you are about to learn in this post, the impact of this gene on diabetes can be reduced—or worsened—by the type of food we eat.

How Does TCF7L2 Affect Blood Sugar?

From what we currently know, TCF7L2 variants can impair insulin secretion but not insulin sensitivity. This gene controls the activity of GLP-1, an intestinal peptide that stimulates insulin secretion in response to food [R, R, R].

During and after each meal, the body signals an enhanced secretion of insulin to balance blood sugar levels. GLP-1 is one of the crucial mediators of this response, known as incretins [R].

TCF7L2 variants—such as the “T” allele at rs7903146—likely prevent GLP-1 from stimulating the pancreas, raising insulin levels, and reducing blood sugar after meals [R, R].

Foods high in sugar and quickly digestible carbs have a high glycemic index (GI) and glycemic load (GL). They drastically increase blood glucose and insulin demand, thus magnifying the impact of TCF7L2 [R].

Image result for glycemic index

Source: https://www.glycemicindex.com

Specific TCF7L2 variants hinder GLP-stimulated insulin secretion in response to food. This effect comes to light after meals high in sugar and quickly digestible carbs.

Evolutive Perspective

The diabetes-associated “T” allele at rs7903146 is ancestral, while the other (C) evolved more recently. As we were transitioning from hunter-gatherers to agriculture-based societies, TCF7L2 adapted to carbohydrate-rich diets [R].

People with the variant allele metabolized high-starch foods such as grains more efficiently, which brought them an evolutionary advantage. The ancestral “T” allele is now much less common as it doesn’t “handle” modern diets well.

Dietary Factors That Impact the TCF7L2-Diabetes Link

In two studies of 4,000 participants, tailored nutritional and lifestyle interventions were able to lower or even remove the negative impact of TCF7L2 variants (rs12255372 and rs7903146) on diabetes risk. Patients were educated and motivated to reduce weight, exercise more, and improve their diets [R, R].

Dietary advice was general: it included a reduction in calories and saturated fat while increasing the consumption of vegetables and other fiber-rich foods. Given the study designs, it’s hard to estimate the impact of specific dietary changes on TCF7L2-associated diabetes risk.

Glycemic Index and Glycemic Load

A clinical trial of over 3,000 women took this further and examined the effect of food glycemic index (GI) and glycemic load (GL) on TCF7L2 variants:

Women with the “TT” genotype at rs12255372 who consumed foods with the highest GI and GL had 2.7 higher diabetes rates, compared with the “GG” carriers. On the other hand, those with the lowest GI and GL had only 1.66 and 1.82 higher incidence, respectively [R].

The authors concluded that carbohydrate quality and quantity might modify the association between TCF7L2 variants and diabetes in women. The same likely goes for men, but studies are yet to confirm that [R].

People with the “T” alleles at rs12255372 and rs7903146 have increased diabetes rates. The consumption of foods with high GI and GL may worsen the effects of TCF7L2 variations.

Whole Grains and Dietary Fiber

Increased consumption of whole grains and dietary fiber generally reduces the risk of diabetes, but the same may not hold for people with TCF7L2 risk alleles [R, R].

Namely, in a study of over 3,000 people, the intake of whole grains was inversely associated with diabetes rates only among the “CC” carriers at rs7903146. The authors concluded that “the “T” allele negated the protective effect of whole-grain intake” [R].

A large Sweedish study followed 24,800 participants for 12 years and examined the impact of dietary fiber intake on the TCF7L2-diabetes link.

People with the “T” allele at rs7903146 who ate less fiber had 24% higher diabetes rates, compared with the “CC” genotype. High fiber intake more than doubled their diabetes rates (from 24 to 56%) while having a protective effect among the “CC” carriers [R].

According to the authors, the “T” allele may prevent dietary fiber from increasing GLP-1 and stimulating insulin secretion.

Increased intake of whole grains and dietary fiber reduces the risk of diabetes in general, but it may have the opposite effect among the “T” allele carriers at rs7903146.

Your TCF7L2 Results for Response to High-Carb Foods

SNP Table

variant genotype frequency risk allele
rs7903146
rs12255372

 

SNP Summary and Table

Primary SNP:

TCF7L2 rs7903146

  • ‘C’ = no association with diabetes; good response to whole grains and fiber
  • ‘T’ = associated with diabetes; poor response to whole grains and fiber

Other Important SNP:

TCF7L2 rs12255372

  • ‘G’ = no association with diabetes; typical response to moderate- and high-GI foods
  • ‘T’ = associated with diabetes; poor response to moderate- and high-GI foods

Population Frequency

These two variants are almost always inherited together, which means they act as a single genetic factor.

About 40% of European descendants carry one copy of the problematic “T” allele while 10-12% carry both copies. In East-Asian populations, this allele is much less common (2-4%).

 

Recommendations

Diet

In general, diets rich in low-GI foods may protect against type 2 diabetes and improve insulin secretion. They may be particularly beneficial for people with TCF7L2 risk variants such as rs7903146-T [R, R].

More precisely, suitable food items for the “T” allele carriers include [R]:

  • Fish and seafood
  • Eggs
  • Meat and organs
  • Olives and olive oil
  • Non-starchy vegetables
  • Nuts and seeds
  • Fruits (in moderation)
  • Grass-fed dairy (in moderation, if tolerant)

On the other hand, people with the “C” allele may want to cut back on animal products and increase the intake of whole grains, legumes, fruits, and vegetables. 

Everyone looking to improve blood sugar control, especially those with TCF7L2 risk variants, should avoid or minimize the intake of [R, R]:

  • Sweets
  • Juices and sodas with added sugar
  • White rice
  • Instant breakfast cereals
  • White flour bread and pastry
  • White four and instant pasta

GLP-1 Stimulants

Olive oil, nuts, avocados, and eggs are particularly beneficial as they stimulate GLP-1 secretion and may thus lower the impact of TCF7L2 [R].

Folks praise cinnamon and bitter melon as age-old remedies that may reduce blood sugar, and preliminary clinical research has confirmed their effectiveness. What’s more, they partly work by boosting GLP-1 [R, R, R, R].

People with TCF7L2 risk variants should increase the intake of low-GI foods and cut back on refined carbs and starches. Olive oil, nuts, avocados, eggs, and cinnamon may help by boosting GLP-1.

Lifestyle

Specific lifestyle adjustments may work in synergy with diet to beat the negative effect of TCF7L2. In the studies described above, weight reduction and moderate physical activity likely contributed to positive results [R, R].

The American Diabetes Association recommends the combination of moderate aerobic and resistance training, at least 150 min/week. Also, it’s crucial to avoid a sedentary lifestyle and interrupt longer periods of sitting every 30 min [R].

Supplements

Keep in mind that the FDA hasn’t approved the below supplements for the prevention or treatment of diabetes. Consult with your doctor before supplementing.

The following supplements may lessen the effect of TCF7L2 variations by boosting GLP-1:

They have shown beneficial effects on blood sugar control in clinical trials. Still, the research behind them is limited and warrants further investigation [R, R, R, R, R].

Author photo
Aleksa Ristic
MS (Pharmacy)

Aleksa received his MS in Pharmacy from the University of Belgrade, his master thesis focusing on protein sources in plant-based diets.  

Aleksa is passionate about herbal pharmacy, nutrition, and functional medicine. He found a way to merge his two biggest passions—writing and health—and use them for noble purposes. His mission is to bridge the gap between science and everyday life, helping readers improve their health and feel better.

Disclaimer

The information on this website has not been evaluated by the Food & Drug Administration or any other official medical body. This information is presented for educational purposes only, and may not be used to diagnose or treat any illness or disease.

Also keep in mind that the “Risk Score” presented in this post is based only on a select number of SNPs, and therefore only represents a small portion of your total risk as an individual. Furthermore, these analyses are based primarily on associational studies, which do not necessarily imply causation. Finally, many other (non-genetic) factors can also play a significant role in the development of a disease or health condition — therefore, carrying any of the risk-associated genotypes discussed in this post does not necessarily mean you are at increased risk of developing a major health condition.

Always consult your doctor before acting on any information or recommendations discussed in this post — especially if you are pregnant, nursing, taking medication, or have been officially diagnosed with a medical condition.

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