Type 2 Diabetes & the TCF7L2 Gene

A significant association between Type 2 diabetes risk and the TCF7L2 gene has been demonstrated in many studies.

Every individual has 2 copies (or alleles) of a gene inherited from each parent.  Genes are made up of DNA and often encode for a protein.  Polymorphisms (variants) are slightly different versions of each gene. 

The TCF7L2 gene encodes for a protein called transcription factor 7 like 2.  TCF7L2 is a master metabolic regulator involved in glucose and fat metabolism. 

Individuals with variants (polymorphisms) of this gene are at increased risk of type 2 diabetes and gestational diabetes. 

TCF7L2 polymorphisms have been associated with low incretin hormones and impaired insulin secretion.

Incretins are GI hormones that assist in the regulation of insulin secretion and satiety.  They are released in response to eating and include GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide).  Increasing incretin sensitivity may decrease the risk of Type 2 diabetes. 

TCF7L2 regulates the sensitivity of pancreatic beta cells to incretins.  

Newer diabetic and anti-obesity medications are founded on this principle.  Semaglutide and liraglutide are GLP-1 receptor agonists, while tirzepatide activates both the GLP-1 and GIP receptors.

Additionally, fat cell (adipocyte) size is regulated by TCF7L2.

TCF7L2 also plays a role in prostate, colon, and breast cancer.  The risk of these cancers is correlated with blood glucose level/control.

Individuals with a TCF7L2 polymorphism fair better with a Mediterranean dietary pattern, which is high in monounsaturated fatty acids (olive oil, avocado) and polyunsaturated fatty acids (fish), whole grains, fruits, diversified prebiotic foods, and non-starchy vegetables. 

These individuals should also avoid starchy foods, saturated fats, simple sugars, and refined grains. 

The Mediterranean diet has shown beneficial metabolic effects in individuals with TCF7L2 polymorphisms. 

Homozygous individuals (2 copies of the risk allele) have higher fasting glucose, total cholesterol, LDL, triglycerides, and stroke risk than heterozygous (one copy) and wild type (no risk allele).  When adherence to a Mediterranean diet is high, however, these differences are not seen.  Thus, the Mediterranean diet modulates the unfavorable genetic predisposition offsetting its risk. 

Protein and dietary fiber slow gastric emptying and stimulate incretins, thus increasing satiety and insulin secretion.

Turmeric increases the secretion of GLP-1, while cinnamon has been shown to lower blood glucose levels and increase satiety. 

A diet high in polyphenol-rich foods, spices high in phytochemicals, fish, and fiber-rich foods results in a significant increase in incretin levels and perceived satiety. 

Cordyceps mushroom extract has also demonstrated preservation of pancreatic beta cell function. 

Mild caloric restriction and fasting have also demonstrated improvement in fasting blood glucose levels as well as pancreatic cell reprogramming with the restoration of insulin secretion.

Exercise improves beta cell insulin sensitivity, upregulates the expression of GLUT4, the receptor involved in controlling glucose uptake into fat and muscle cells, and increases glucose transport into cells via GLUT4.

A short walk right after a meal helps blunt the immediate glucose spike which occurs after eating, helping to control blood sugar levels.

Stress management and mindfulness-based stress reduction have also been shown to improve glycemic control.

Poor sleep is associated with higher fasting blood glucose levels. Sleep apnea is also a significant risk factor for type 2 diabetes.

In addition to sleep quality, the quantity of sleep is also important. Four- six hours of sleep significantly reduces insulin sensitivity and impairs beta-cell function (compared to 8 hours of sleep).

Moreover, cortisol levels are also impacted if sleep loss occurs in the early morning hours (waking up at 3 am and not falling back to sleep).

Vitamin D, magnesium deficiency, and elevated body iron stores are associated with an increased risk of Type 2 diabetes.

Other nutritional supplements that may help with glycemic control include chromium, zinc, allicin (active compound from garlic), guar gum fiber, omega-3 fatty acids, vitamin C, alpha lipoic acid, and berberine.  Consult with your healthcare provider before beginning any supplementation to ensure it is right for you.

While our genetic makeup may put us at risk of certain diseases and health concerns, it is not our destiny.  Epigenetics is how our environment interacts with our genes to turn them on or off.  This includes MANY aspects of our lives including stress, food, sleep, emotions, adverse childhood events, in utero exposure, physical activity, age, and time in nature. 

Consult with a trained healthcare provider to correctly interpret nutrigenetics results and minimize your health risks through lifestyle and dietary changes.