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

When it comes to advice about the best diet, the things that everyone seems to accept as gospel don’t always hold true when researchers actually look into them.  Take the glycemic index for example: Around since the 1980’s, accepted dogma holds that white bread will very quickly raise everyone’s blood glucose levels with a GI score of 73, while a banana gives a slower increase in glucose with a GI score of 48.

Turns out that when scientist decided to look at a large group of individuals’ glycemic responses to foods, people’s responses vary a lot from what the glycemic index shows.

CarbsThere have been a couple of good studies over the last couple of years that have shown the huge variation in blood glucose levels in response to carbohydrates. For example, some people may have blood sugar spikes from eating a banana, while others may have their blood sugar drop from eating bread.  The individual variation found in the studies is striking.

The study in the journal Cell in 2015 summarized the findings on the individual postprandial glycemic responses (PPGR): “we demonstrate on 800 individuals that the PPGR of different people to the same food can greatly vary. The most compelling evidence for this observation is the controlled setting of standardized meals, provided to all participants in replicates. This high interpersonal variability suggests that at least with regard to PPGRs, approaches that grade dietary ingredients as universally “good” or “bad” based on their average PPGR in the population may have limited utility for an individual.”

A recent Science Daily article (Is white bread or brown bread ‘healthier’? It depends on the person) sums up another study on the glycemic response of 20 individuals to white bread and to brown bread.  Turns out that for about half the people in the study white bread caused less of a blood glucose spike, while for the other half, brown bread is better.

One reason for the individual variation is differences in the gut microbes of each individual.  The types of microbes in your gut depend on a lot of factors including early childhood experiences, types of food that you currently eat, antibiotic exposure, and also your genes. genetic variations in how people react to carbohydrates in the diet.  (If you are interested in getting your microbiome tests, you can use my referrer link for a 15% discount on uBiome tests.)

Genetic variations also play a role in how people react to carbohydrates in the diet.  (It seems that everything comes down to the microbiome and your genes!)

Why is this important?  Diet advice is everywhere — from the doctor on TV to your own doctor telling you to drop a few pounds.  But generic recommendations may do nothing for you, and, if your goal is to prevent type 2 diabetes, the recommendations may actually work against you.  Why not look into what actually works for your body…  Below are a few genes that affect insulin or glucose levels based on carbohydrate consumption.

Genetic Variants Affected by Diet

UCP3 gene:
Variants in UCP3 (uncoupling protein 3) have been linked in many studies to obesity and insulin resistance.  One study found that people with one variant had a better response (lower glucose levels, more weight loss) on a diet higher in protein and lower in carbs.  Those without the variant lost a little weight on the diet, but it had no impact on their blood glucose levels.

Check your 23andMe results for rs1800849:

  • AA: less weight loss, no decrease in glucose or insulin levels on high protein/low carb diet [study]
  • AG: less weight loss, no decrease in glucose or insulin levels on high protein/low carb diet
  • GG: lower glucose levels, better weight loss on high protein/low carb diet

Another study on the same variant looked a the response to a reduced calorie, but higher in monounsaturated fat, diet.  Both those with the GG genotype and those with an A allele lost weight, but the GG genotype lost quite a bit more weight (over 10lbs more on average).  Additionally, those with the GG genotype had improved cholesterol levels and other cardiovascular parameters.

IRS1 Gene:
The insulin receptor substrate 1 (IRS1) plays a role in insulin signaling.  Variants of the gene have been tied to the risk of type 2 diabetes.

A large study of over 25,000 people without diabetes looked at the role of an IRS1 variant in conjunction with diet.  The results found that for women with the T allele who ate fewer carbs had a lower risk of diabetes; while for men, it was a low-fat diet that, along with the T allele, that resulted in a lower risk of diabetes.

Check your 23andMe results for rs2943641:

  • TT: women had lower T2D risk with low-carb, men had lower T2D risk with lower fat diet
  • CT: women had lower T2D risk with low-carb, men had lower T2D risk with lower fat diet
  • CC: no differences due to diet

BDNF gene:
The brain-derived neurotrophic factor (BDNF) is essential for neuron development and repair. A Jan 2017 study of 8,840 Korean adults looked at the interaction between diet and a BDNF variant in regards to the risk of type 2 diabetes.  The study found that a high carb/low protein diet that did not have excess calories was protective against T2D for those with the rs6265 Met variant.  Excess calories in the diet negated the protective effect of the variant.  The study concluded: “BDNF Val/Met and Met/Met variants (rs6265) decreases the risk for glucose intolerance and type 2 diabetes. BDNF variants interacted with nutrient intake, especially energy and protein intake: Middle-aged individuals with BDNF Val/Val are prone to developing type 2 diabetes even with low energy and protein intake.”

Check your 23andMe results for rs6265:

  • TT: (Met/Met) low-protein, high-carb (but not excessive calories) protective against T2D [study]
  • CT: (Val/Met) low-protein, high-carb (but not excessive calories) protective against T2D
  • CC: (Val/Val) no dietary protection against T2D


FTO gene:

The FTO gene has been linked in a lot of studies to obesity and weight gain.  A 2009 trial that investigated the outcome of a lower carb/higher fat vs higher carb/lower fat diet found that a variant of the gene was linked to a greater decrease in HOMA-IR (measure of insulin resistance) when on a lower fat/higher carb diet.

Check your 23andMe results for rs9939609:

  • TT: greater decrease in HOMA-IR on a lower fat/higher carb diet [study]
  • AA: generally associated with higher BMI

CLOCK gene:
Variations in circadian rhythms have been shown to play a role in obesity and insulin levels.  Studies have shown that the CLOCK gene variants are involved.

Switching gears from looking at carbohydrates, a 2013 study looked at two different diets – low-fat diet vs. Mediterranean (high in monounsaturated fat) diet- and the effect of a CLOCK gene variant on the outcome of each diet.

Check your 23andMe results for rs1801260:

  • AA: lower insulin levels, lower insulin resistance on a low-fat vs Mediterranean diet [study] (this is the most common variant)
  • AG: no differences in response to the two diet types
  • GG: no differences in response to the two diet types

Final thoughts:
Individual response to a diet is not nearly as simple and easy as most diet gurus make it out to be in their numerous books and websites selling supplements.  If you are struggling with keeping your blood glucose levels in a good range, it may be that you need to throw out the diet books and experiment with what actually works for your body. The studies that I’ve listed above may give you a genetic scaffold on which to start.

I would love to see more trials that look at the way people respond to different types of diets.  Unfortunately, there isn’t a lot of money in it, so those studies may never get funded.

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