Type II Diabetes – Genetic Connections

According to the American Diabetes Association, 9.3% of the US population has diabetes (2012 numbers). Diabetes was the 7th leading cause of death in the US in 2010.

The genes involved in increasing risk for type-2 diabetes indicate some of the variations in causes: insulin release, metabolic syndrome, response to sugar, and zinc deficiency. If you are genetically susceptible to diabetes, knowing your risk may help you modify your diet appropriately.


Genes involved in type-2 diabetes:

Log in to see your data below Not a member? Join now.

SLC30A8 gene:

A zinc transporter gene, SLC30A8, has been associated with type 2 diabetes in many different studies.  Insulin contains a high amount of zinc, and zinc is also involved in other functions in the pancreas. Zinc seems to play an important role in insulin production and secretion.

Higher plasma concentrations of zinc are associated with a lower risk of diabetes – especially for those without the SLC30A8 polymorphism.[ref] There are several studies on the influence of zinc supplementation with regards to diabetes and the SLC30A8 polymorphism.[ref][ref][ref] The SLC30A8 polymorphism is associated with reduced insulin secretion but not with insulin resistance.[ref]

There are quite a few new research studies on this gene. One study from 2014 states that (emphasis added): “As expected, a strong interaction was observed for the SLC30A8 rs13266634 variant and plasma zinc concentrations in relation to T2D and IGR&T2D. The inverse association between increasing plasma zinc concentrations and T2D could significantly attenuate in the C/T and C/C genotype groups compared within the T/T genotype group. We also observed that the association between the C/C genotype and T2D was mitigated by increasing plasma zinc concentrations.”[ref]

Check your genetic data for rs13266634 (23andMe v4, v5)

  • T/T: typical risk
  • C/T: somewhat higher than normal risk for type 2 diabetes
  • C/C: 1.5 – 3x higher risk of type 2 diabetes[ref]

Members: Your genotype for rs13266634 is .

How much zinc should you take a day?

The U.S. recommended daily allowance for zinc is 11 mg/day for men and 8 mg/day for women. Zinc supplementation can interact with other minerals. The University of Oregon has a good resource for more information on types of zinc and interactions: Linus Pauling Institute Zinc.

Related article: Zinc genes: The healing power of zinc

HHEX gene:

HHEX (homeobox) is another gene with polymorphisms associated with a higher risk of developing type 2 diabetes. The HHEX protein interacts with signaling molecules and plays a role in embryonic development of the liver, thyroid, and pancreas.  A European study in 2007 found that rs7923837 was associated with impaired glucose-stimulated insulin response.[ref][ref]

Check your genetic data for rs7923837 (23andMe v4,v5)

  • G/G: 3.2x risk for type 2 diabetes
  • A/G: 1.9x risk for type 2 diabetes
  • A/A:  typical risk

Members: Your genotype for rs7923837 is .

Check your genetic data for rs1111875 (23andMe v4,v5)

  • C/C: increased risk for type 2 diabetes (OR = 1.36)[ref]
  • C/T: increased risk for type 2 diabetes (OR =1.16)
  • T/T: typical risk

Members: Your genotype for rs1111875 is .

How can I lower my glycemic index?

Vegetables and whole foods generally require the release of less insulin after eating them (compared with processed foods). The key for carriers of the HHEX variants may be to figure out which foods spike glucose levels (via frequent testing or a continuous blood glucose monitor) and avoid those foods.

TCF7L2 gene:

A strong genetic risk factor for type 2 diabetes is a polymorphism in the TCF7L2 gene. The TCF7L2 gene helps control blood sugar levels. It plays a role in adipogenesis (formation of fat cells), and it has associations with glucose intolerance and impaired insulin secretion.[ref]

Check your genetic data for rs7903146 (23andMe v4,v5)

  • T/T: 2x increased risk of type 2 diabetes[ref]
  • C/T: 1.4x increased risk of type 2 diabetes
  • C/C: typical risk

Members: Your genotype for rs7903146 is .

Does glycemic index matter?

A study found that those with the TCF7L2 variant had a much higher risk of diabetes (over twice the risk) if they had a diet with a high glycemic index. Here is a chart of the glycemic load of common foods: Glycemic Index Chart.  Keep in mind that everyone is individual when it comes to how their body reacts to foods, so use the glycemic index charts and cookbooks as more of a starting point rather than something written in stone for everyone.

KCNJ11 gene:

One more gene associated with type-2 diabetes is the KCNJ11 gene. The KCNJ11 gene codes a protein involved in insulin release. Sugar (glucose) activates this protein which releases insulin from the pancreas. The T allele gives a decreased insulin response to glucose. It is also associated with plasma leptin levels.[ref][ref]

Check your genetic data for rs5219 (23andMe v4,v5)

  • T/T: 2.5x increased risk of type 2 diabetes
  • C/T: 1.3x increased risk of type 2 diabetes
  • C/C: typical risk

Members: Your genotype for rs5219 is .

Should I cut out carbs?

Reducing sugar and refined carbs should help people with the KCNJ11 gene variants. Everyone’s insulin response to food is somewhat unique, so a continuous glucose monitor or frequently checking your blood glucose level after eating different foods can give you a better idea of which foods to avoid.

Related article: Carbohydrate metabolism: Your genes play a role in insulin and blood glucose levels

 


Interested and want more to read?


Related Articles and Genes:

Metformin: Longevity research and genetics
A decades-old diabetes drug now holds promise for increasing healthspan. Research shows that metformin may reduce the risk of some of the diseases of aging, thus increasing the number of years someone is healthy.

Hypertension Risk Factor: CYP11B2 Variant
Hypertension risk can be modifiable in terms of diet and exercise; however, genetics can play a part in risk. Learn more about how the CYP11B2 variant can increase the risk of hypertension.

Diabetes: Genetic Risk Report
We often talk about diabetes as though it is one disease, but diabetes can have several different causes or pathways impacting glucose regulation. Tailoring your diabetes prevention (or reversal) efforts to fit your genetic susceptibility may be more effective.

Blood glucose levels: how your genes impact blood sugar regulation
Genetics plays a big role in your blood glucose regulation. Some people may be able to get by eating some junk food and not exercising as much. Still, for others, our genetic susceptibility combines with poor choices to cause elevated blood glucose levels.

References:

Cai, Yu, et al. “Meta-Analysis of the Effect of HHEX Gene Polymorphism on the Risk of Type 2 Diabetes.” Mutagenesis, vol. 26, no. 2, Mar. 2011, pp. 309–14. Silverchair, https://doi.org/10.1093/mutage/geq095.
—. “Meta-Analysis of the Effect of HHEX Gene Polymorphism on the Risk of Type 2 Diabetes.” Mutagenesis, vol. 26, no. 2, Mar. 2011, pp. 309–14. Silverchair, https://doi.org/10.1093/mutage/geq095.
“Glycemic Index Chart: GI Ratings for Hundreds of Foods.” University Health News, 22 June 2020, https://universityhealthnews.com/daily/nutrition/glycemic-index-chart/.
Hernandez-Escalante, Victor M., et al. “Replication of Obesity and Diabetes-Related SNP Associations in Individuals from Yucatán, México.” Frontiers in Genetics, vol. 5, Nov. 2014, p. 380. PubMed Central, https://doi.org/10.3389/fgene.2014.00380.
Lyssenko, Valeriya, et al. “Mechanisms by Which Common Variants in the TCF7L2 Gene Increase Risk of Type 2 Diabetes.” Journal of Clinical Investigation, vol. 117, no. 8, Aug. 2007, pp. 2155–63. PubMed Central, https://doi.org/10.1172/JCI30706.
Maruthur, Nisa M., et al. “Effect of Zinc Supplementation on Insulin Secretion: Interaction between Zinc and SLC30A8 Genotype in Old Order Amish.” Diabetologia, vol. 58, no. 2, Feb. 2015, pp. 295–303. PubMed, https://doi.org/10.1007/s00125-014-3419-1.
Nielsen, Eva-Maria D., et al. “The E23K Variant of Kir6.2 Associates with Impaired Post-OGTT Serum Insulin Response and Increased Risk of Type 2 Diabetes.” Diabetes, vol. 52, no. 2, Feb. 2003, pp. 573–77. PubMed, https://doi.org/10.2337/diabetes.52.2.573.
Rs13266634 – SNPedia. https://snpedia.com/index.php/Rs13266634. Accessed 21 Oct. 2021.
Rutter, Guy A. “Think Zinc: New Roles for Zinc in the Control of Insulin Secretion.” Islets, vol. 2, no. 1, Feb. 2010, pp. 49–50. PubMed, https://doi.org/10.4161/isl.2.1.10259.
Shan, Zhilei, et al. “Interactions between Zinc Transporter-8 Gene (SLC30A8) and Plasma Zinc Concentrations for Impaired Glucose Regulation and Type 2 Diabetes.” Diabetes, vol. 63, no. 5, May 2014, pp. 1796–803. PubMed, https://doi.org/10.2337/db13-0606.
—. “Interactions Between Zinc Transporter-8 Gene (SLC30A8) and Plasma Zinc Concentrations for Impaired Glucose Regulation and Type 2 Diabetes.” Diabetes, vol. 63, no. 5, May 2014, pp. 1796–803. diabetes.diabetesjournals.org, https://doi.org/10.2337/db13-0606.
Staiger, Harald, Alena Stančáková, et al. “A Candidate Type 2 Diabetes Polymorphism Near the HHEX Locus Affects Acute Glucose-Stimulated Insulin Release in European Populations : Results from the EUGENE2 Study.” Diabetes, vol. 57, no. 2, Feb. 2008, pp. 514–17. diabetes.diabetesjournals.org, https://doi.org/10.2337/db07-1254.
Staiger, Harald, Fausto Machicao, et al. “Polymorphisms within Novel Risk Loci for Type 2 Diabetes Determine Beta-Cell Function.” PloS One, vol. 2, no. 9, Sept. 2007, p. e832. PubMed, https://doi.org/10.1371/journal.pone.0000832.
Type 2 Diabetes Mellitus and TCF7L2: Practice Essentials, Clinical Implications. Feb. 2021. eMedicine, https://emedicine.medscape.com/article/1788533-overview.
Weedon, Michael N., et al. “Combining Information from Common Type 2 Diabetes Risk Polymorphisms Improves Disease Prediction.” PLOS Medicine, vol. 3, no. 10, Oct. 2006, p. e374. PLoS Journals, https://doi.org/10.1371/journal.pmed.0030374.
Zhuang, Langen, et al. “The E23K and A190A Variations of the KCNJ11 Gene Are Associated with Early-Onset Type 2 Diabetes and Blood Pressure in the Chinese Population.” Molecular and Cellular Biochemistry, vol. 404, no. 1–2, June 2015, pp. 133–41. PubMed, https://doi.org/10.1007/s11010-015-2373-7.
“Zinc.” Linus Pauling Institute, 23 Apr. 2014, https://lpi.oregonstate.edu/mic/minerals/zinc.