What comes to mind as far as the risk of type 2 diabetes? Usually first up is the mental picture of someone eating donuts and slurping down soft drinks.  While diet definitely contributes to diabetes risk, not everyone who eats donuts and slurps soft drinks will get diabetes. Alternatively, not everyone with type 2 diabetes got it through poor dietary choices.

Obviously, the must be more to diabetes than just poor dietary choices. (Don’t get me wrong – you should still make good dietary choices…)

Genetics plays a role in diabetes, as anyone who has several diabetics in their family well knows.  This is a big, broad topic, though, since there isn’t just one gene that causes diabetes or even one way that people can have problems with regulating their blood sugar.

So what can looking at your genetic data tell you about either your risk for getting diabetes or why you have diabetes?  Quite a bit, actually.  Having a targeted, personalized approach to either how to try to reverse type 2 diabetes (for those who have it) or to prevent it (for those with a genetic predisposition) is an invaluable tool to have.

If you know where your genetic weakness lies, you can target that pathway and not waste time on diabetes prevention methods that probably wouldn’t benefit you.


Let’s start with a gene that has nothing to do with what you eat, but rather the diabetic risk is due to when you eat.

The MTNR1B gene codes for the melatonin receptor.  A genetic variant in MTNR1B (rs10830963 – G allele) has been tied to an increased risk of diabetes, but subsequent studies show that the increased risk is mainly for those who eat later at night – when melatonin levels are higher.[ref] [ref][ref][ref][ref][ref]

Melatonin is a signaling molecule that rises in the evening  (called dim light melatonin onset) and peaks in the night. Insulin sensitivity is lowest at night, and the melatonin receptors in the pancreatic islets modulate insulin secretion from the beta-cells.[ref]

Check your 23andMe data for rs10830963 (v4, v5):

  • GG: upregulation of MT2 receptors, increased fasting glucose levels, increased risk of type 2 diabetes
  • CG: upregulation of MT2 receptors, increased fasting glucose levels, slightly increased risk of type 2 diabetes
  • CC: normal

Lifehacks:
Eat dinner earlier: A recent randomized, cross-over clinical trial looked at the difference in glucose control from eating dinner early (4 or more hours before bedtime) or eating a late dinner (1 hour before bedtime). The study found that everyone had a better blood glucose response (less of a spike) when eating dinner earlier. The data showed that glucose peaked about 60 minutes after eating, with an average difference of about 20mg/dl decrease in peak glucose levels for eating earlier. But when they broke out the data by rs10830963 genotype, it was clear that those with a G allele had a much greater response to eating dinner early (~30 mg/dl decrease in glucose peak).  The study participants with the CC genotype actually had very little difference in peak glucose response from early dinner vs late dinner. [ref]

Don’t eat breakfast too early:  Another study found that carriers of the G allele had a longer duration of melatonin production — lasting further into the morning hours (41 minutes). It is possible that getting up early and eating breakfast immediately may not be ideal for this genetic variant. [ref]

Time restricted eating:  If you are eating dinner early and then waiting a little bit in the morning for breakfast, you may want to read about all the health benefits of time restricted eating, since that is essentially what you will be doing.  There is a great new book out on the topic called The Circadian Code.


The TCF7L2 (transcription factor 7-like 2) gene activates many genes involved in type 2 diabetes including glucagon-like peptide 1 GLP1. Genetic variants are associated with a decreased or impaired beta-cell function.[ref][ref]

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

  • TT: increased risk of diabetes, decreased beta-cell function[ref][ref]
  • CT: increased risk of diabetes
  • CC: normal

Check your 23andMe results for rs12255372 (v4, v5)

  • TT: increased risk of diabetes[ref][ref]
  • GT: increased risk of diabetes
  • GG: normal

Lifehacks:
Glycemic Index Matters:  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 that is written in stone for everyone.

Dietary fiber: One study found that higher dietary fiber intake reduced the risk of diabetes for those carrying the risk alleles. [ref]  Caveat: I don’t think it is clear if the benefit comes from adding fiber vs. swapping out the refined carbs for unrefined carbs. So just adding a fiber supplement may not do anything for you here.

Medication choices: One study found that people carrying a TCF7L2 variant did not respond as well to the class of diabetes medications known as sulfonylureas. This may be something to discuss with your doctor if you are on a diabetes medication that isn’t working well for you.  The study did note that metformin response was not impacted by TCF7L2 variants.[ref]


The SLC30A8 gene codes for the zinc transporter ZnT-8. This zinc transporter is found in pancreatic beta-cells and transports the zinc from the cytoplasm into insulin secretory vesicles where it stabilizes it and prevents degradation. [ref]

Check your 23andMe results for rs13266634 (v4,v5)

  • CC: (most common variant in most populations) increased  risk of type 2 diabetes [ref]
  • CT: somewhat increased risk of type-2 diabetes
  • TT: normal risk of type 2 diabetes

Lifehacks:
Vitamin A: A large study looked at the interaction between nutrient markers in diabetics and healthy controls. The strongest correlation that they found was that higher levels of trans-β-carotene and cis-β-carotene were protective against diabetes (about half the risk!) only for those with the rs13266634 CC or CT genotype.  There was no correlation for those with the TT genotype.  The study wasn’t able to determine if the correlation was due specifically to vitamin A or β-carotene — or if the correlation was due to eating a healthy diet with a high intake of fruits and vegetables.[ref]  My guess… the best bet here is to increase vegetable and fruit intake. β-carotene is found in orange vegetables and fruits, so carrots, pumpkin, and sweet potatoes are good sources. Spinach and collard greens are also good sources. Not everyone is good at converting β-carotene to vitamin A (check your conversion genes), so also including sources of true vitamin A may be important as well.[ref]

Increase your zinc? Studies are a bit contradictory on whether increasing zinc reduces the risk for those with the risk alleles listed above.[ref]  One study showed that increasing zinc levels by 10 ug/dl decreased the odds of type-2 diabetes for everyone by a little bit, but those with the TT genotype had a greater decrease than those who carried the C allele (risk genotype). So how do you best increase your zinc levels? Food sources of zinc include oysters (really great source!), beef, crab, pork, beans (soaked first), and chicken.[ref] Zinc supplements can easily be purchased at health food stores or from online sources.  Note that higher doses of zinc can cause an upset stomach for some people. More information on zinc supplements.


IRS1 (insulin receptor substrate 1) variants have also been linked to an increased risk of type-2 diabetes.  The IRS1 gene codes for a key protein in the insulin-stimulated signal pathway. [ref] The genetic variants of this gene are associated with insulin resistance and hyperinsulinemia, rather than impaired beta-cell function. [ref]

Check your 23andMe results for rs2943641 (v4, v5)

  • CC: (most common genotype) increased risk for type 2 diabetes[ref]
  • CT: slightly increased risk for type 2 diabetes
  • TT: normal risk of type 2 diabetes

Note that for this gene, studies refer to the C allele as increasing the risk for type 2 diabetes.  Since it is the most prevalent allele, you could also look at it as the TT genotype being protective.

Lifehacks:
Get enough vitamin D:  Carriers of the TT allele had an even greater reduction in risk of diabetes with higher levels of vitamin D.[ref] Sunshine is your best bet for vitamin D. Get outside!  A lab test can tell you if you are low in vitamin D.  You can even get a home vitamin D test kit now in the US.  If you decide to supplement with vitamin D, be sure to choose one that includes a good type of oil (as opposed to a cheap vitamin D with soybean oil).  I personally like this one with coconut oil, K2 and vitamin D. (In general, it is good to combine vitamin K and D, but be aware of interactions if you are on a blood thinning medication.)

Weight loss diet: If you need to lose weight, one trial of different types of diets found that a low-fat diet (high in non-refined carbs with fiber) worked best for people with the IRS1 rs2943641 CC genotype, but not for the CT or TT genotypes.[ref]  Another (small) study found that a low-fat diet worked best for those with rs2943641 CT genotype.[ref]


Conclusion:

There are many different risk factors for type 2 diabetes.  Knowing which genetic variants you carry can help you target a plan for reversing type 2 diabetes.

The list above of genetic variants just covers the most common ones, but there are many other less common genetic mutations that can increase the risk for diabetes. So take this article as a starting point instead of being a complete blueprint for you.

One thing that is not included on any of the Lifehacks above is a ketogenic or very low carb diet.  I didn’t find any studies looking at a ketogenic diet in relation to the genetic variants for type 2 diabetes, but I wanted to include it here as an option because a lot of people are having success on it for weight loss and reversing diabetes.  A 2016 study comparing low calorie vs low-carb ketogenic diets found the ketogenic diet more effective for lowering HbA1c and fasting blood glucose levels (although both diets had positive effects!).[ref]  A ketogenic diet isn’t for everyone, but if you have diabetes or pre-diabetes, it is worth considering and talking with your doctor about.

 


4 Comments

Barbara · August 7, 2018 at 11:03 pm

Regarding the Ketogenic Diet. the Plant Based Nutrition folks (Dr Gregor and others)
had impressive research to indicate that the Insulin levels on a Keto diet are misleading
and not very healthy overall. Also, many people shouldn’t have a high saturated fat diet
due to their heart as well as those at risk for Alzheimers (the AOPE 4 gene). Paleo Diet
also has some of the same issues, but not as imbalanced. How many ancestors mostly
ate a lot of fats? Or meat, for that matter? Maybe the Eskimos and a few cultures.
Short term benefits with long term losses in health and the environment (meat).

Thanks for your good work.

Sarah Cummings · August 9, 2018 at 1:23 am

Most people think that diabetes can only get by eating too many sweets. This is a very informative post. Thank you for sharing Debbie! This really helps readers to understand the cause and prevention of diabetes.

Michael Robinson · August 11, 2018 at 7:45 am

Hello Debbie,

Just discovered your excellent work. Had a look at diabetes out of interest.

I think there must be something wrong when you say
“Check your 23andMe results for rs12255372 (v4, v5)

TT: increased risk of diabetes[ref][ref]
CT: increased risk of diabetes
CC: normal”
– gave me a bit of a fright as I’m GG!

Here’s a reference that perhaps sets the record straight:
https://www.ncbi.nlm.nih.gov/pubmed/17697858
It says:
Logistic regression analysis of the rs12255372(G/T) polymorphism showed that the odds ratio (adjusted for age, sex, and body mass index) was 1.56 (95% confidence interval [CI], 1.03-2.37; P = .034) for the TT genotype and 1.29 (95% CI, 1.06-1.58; P = .011) for the TG genotype when compared with the GG genotype

As I said, excellent work, will continue reading.

    Debbie Moon · August 11, 2018 at 11:05 am

    Thanks so much for catching that typo and for letting me know about it. And now you can probably guess that I’m TT on that genotype and thus didn’t catch it when I checked the page! A very good reminder to double check everything.
    Thanks again!
    Debbie

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