blood sugar control
nutrition
GIPR

How An Insulin Gene Influences Diet and Blood Sugar (GIPR)

Written by Mathew Eng, PharmD on February 29th, 2020
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The body naturally secretes insulin in response to rising glucose levels, such as after eating a meal. The GIPR gene plays a key role in this insulin secretion process. However, certain variants in this gene can interfere with insulin function, potentially resulting in metabolic problems.

The GIPR Gene

The GIPR gene is responsible for encoding a protein with the same name, GIPR (which is short for gastric inhibitory polypeptide receptor) [R].

The GIPR gene and the protein it helps create play an important role in insulin production in the body [R].

Research has found that certain variants in the GIPR gene can alter the body’s ability to secrete insulin. As a result, these variants may be associated with insulin resistance, diabetes, obesity [R, R, R].

How GIPR Works

The GIPR protein is created from the GIPR gene.

The ‘R’ in GIPR stands for receptor, as it acts as a receptor for the GIP protein [R].

The GIP protein belongs to a class of hormones called incretins, which are responsible for regulating blood sugar (glucose) levels [R].

When glucose levels become high, such as after a meal, GIP is secreted from special intestinal cells called K cells [R].

This newly secreted GIP binds to GIPR located on the pancreas, which causes insulin secretion [R].

Insulin allows the body to use or store glucose, which helps lower blood glucose levels [R].

GIPR and Blood Sugar

How Do GIPR Variants Affect Metabolic Health?

Research suggests that certain variants in the GIPR gene may influence aspects of metabolic health, such as insulin resistance, type 2 diabetes, and body fat [R, R].

This is because the primary function of GIPR (along with GIP) is to stimulate the production of insulin in response to a rise in blood sugar (glucose) levels, such as after a meal [R].

Certain GIPR variants can impair this function, leading to reduced secretion of insulin [R].

This reduced ability to produce insulin can hinder the body’s ability to process glucose, which can lead to elevated blood glucose levels. This may lead to metabolic disorders, such as diabetes and obesity [R, R].

Who Is Affected?

There are several specific variants in GIPR that are associated with metabolic disorders. 

In the following sections, we’ll go over each of these variants and highlight which groups of people may be affected.

The rs10423928 Variant

One of the more well-researched SNPs in the GIPR gene is rs10423928.

There are two possible alleles in rs10423928: the more common ‘T’ allele and the less common ‘A’ allele.

Carrying the ‘T’ allele usually results in normal gene function, while the ‘A’ allele is associated with decreased insulin secretion [R].

According to a meta-analysis of 16 studies including over 57,000 patients of European descent, the ‘A’ allele is moderately associated with an increased risk of type 2 diabetes [R].

Similar results were found in a study of over 6,800 individuals from Shanghai, China. The ‘A’ allele was linked to type 2 diabetes susceptibility in this Chinese population [R].

Another study looked at over 5,000 pregnant women from Northern India. Researchers found that the ‘A’ allele was linked to worse insulin resistance and a trend towards gestational diabetes (a type of diabetes that can occur during pregnancy) [R].

The ‘A’ allele is associated with insulin resistance and type 2 diabetes in European and Chinese groups. It has also been linked to gestational diabetes in Indian women.

The rs2302382 Variant

The two alleles in rs2302382 are the more common ‘C’ allele and the rare ‘A’ allele.

There is evidence that the ‘A’ allele in rs2302382 is linked to metabolic disorder, likely due to impaired insulin secretion [R, R].

For example, a study of 300 Egyptian patients suggests that the ‘A’ allele is associated with type 2 diabetes [R].

A study of over 700 German families found that the ‘A’ allele is significantly more common in obese adults and children [R].

However, there is conflicting evidence. Based on a population study of over 4,300 German individuals, the ‘A’ allele was actually linked to lower BMI [R].

In rs2302382, the ‘A’ allele is associated with type 2 diabetes in Egyptian individuals. The ‘A’ allele may also be linked to obesity in German populations, although there is conflicting evidence.

The rs11671664 Variant

The two possible alleles in rs11671664 are the common ‘G’ allele and the much more uncommon ‘A’ allele.

In this case, the more common ‘G’ allele appears to be associated with higher BMI, according to a study of close to 28,000 individuals of East Asian descent [R].

It’s not entirely clear how the ‘G’ allele in this SNP affects the function of the GIPR gene.

The ‘G’ allele in rs11671664 may be associated with higher BMI in East Asians.

Your GIPR Results for Blood Sugar

You can see your genotypes for GIPR in the table below. However, keep in mind that these associations are based on studies from certain ethnic populations — so you should interpret your results with caution if you are not descended from one of these specific groups!

SNP Table

 

Primary SNPs: 

GIPR rs10423928

  • ‘T’ = Normal metabolic function
  • ‘A’ = Associated with insulin resistance, type 2 diabetes, and gestational diabetes
  • These associations have only been found in European, Chinese, and Indian populations
  • Only about 3% of all people worldwide have the ‘AA’ genotype (highest risk)

GIPR rs2302382

  • ‘C’ = Normal metabolic function
  • ‘A’ = Associated with insulin resistance, type 2 diabetes, and obesity
  • These associations have only been found in Egyptian and German populations
  • Only about 4% of all people worldwide have the ‘AA’ genotype (highest risk)

GIPR rs11671664

  • ‘A’ = Not associated with metabolic disorder
  • ‘G’ = Associated with higher BMI
  • This association has only been found in East Asian populations
  • About 73% of all people worldwide have the ‘GG’ genotype (highest risk)

 

Recommendations

Lifestyle

Get Enough Sleep

The body goes through important metabolic changes during sleep. A lack of sleep can disrupt this process, leading to an imbalance of blood glucose, insulin, and other hormones [R, R].

A number of studies show that short sleep duration and poor sleep quality are strongly linked to insulin resistance, type 2 diabetes, and obesity [R, R, R, R].

Studies show that even sleep durations of 4 to 5 hours are linked to insulin resistance [R, R].

How much sleep should you get? The ideal sleep duration varies for each person, but most experts recommend that adults get about 7 to 9 hours of sleep [R].

Exercise Regularly

Regular physical activity is one of the best ways to improve metabolic health.

Research consistently shows that exercise helps reduce blood glucose levels and improve insulin sensitivity. Physical activity can also significantly lower the risk of type 2 diabetes [R, R].

Many studies suggest that exercise produces a dose effect, meaning that longer or more intense exercise sessions can have greater benefits to insulin sensitivity [R, R].

There’s also evidence that a combination of aerobic exercise and resistance training (weightlifting) may produce greater benefits than either type of exercise alone [R, R].

Reduce Stress

Psychological stress can cause several biological changes in the body, including an increase in inflammatory compounds and cortisol (the stress hormone) [R].

Research also suggests that stress can have negative effects on metabolic health [R].

A number of studies show that mental stress is associated with insulin resistance and is a risk factor for type 2 diabetes [R].

Cortisol itself is also linked to higher blood glucose, insulin resistance, and waist circumference [R].

Stress management techniques, such as mindfulness-based stress reduction, have been shown to improve glucose control in patients with type 2 diabetes [R, R].

Quit Smoking

Cigarette smoking increases blood glucose, insulin resistance, and the risk of type 2 diabetes [R, R].

According to some estimates, smokers are 30-40% more likely to develop type 2 diabetes compared to non-smokers [R].

Smoking also increases the risk of diabetes-related complications such as diabetic nephropathy (kidney damage caused by diabetes) [R].

For those without diabetes, quitting smoking can immediately help prevent the disease. Even for those that do have diabetes, quitting smoking can make it easier to manage your blood glucose levels [R, R].

Diet

It’s no surprise that diet has a direct impact on glucose levels and overall metabolic health.

Generally speaking, those concerned about their blood glucose and insulin levels should avoid foods high in sugar or carbohydrates [R].

Some foods to avoid include [R]:

  • Sugary sweets, including candy, ice cream, and other desserts
  • Sugary drinks, such as soda and fruit juices
  • Starchy vegetables, such as potatoes
  • Refined grains, including white bread, rice, and pasta

Healthy food choices to improve metabolic health include [R]:

  • Vegetables, especially leafy greens such as spinach and kale
  • Fish and other seafood
  • Healthy cooking oils, such as olive oil
  • Foods high in fiber

The GIPR Gene and Diet

Interestingly enough, there is evidence that the GIPR gene may affect how the body responds to dietary intake.

A population study of almost 25,000 people from Sweden found that people who carry the ‘AA’ genotype in rs10423928 had a reduced risk of type 2 diabetes when eating a high-fat, low-carbohydrate diet [R].

On the other hand, those with the ‘TT’ allele benefited more from eating a high-carbohydrate, low-fat diet [R].

Author photo
Mathew Eng
PharmD

Mathew received his PharmD from the University of Hawaii and an undergraduate degree in Biology from the University of Washington.

Mathew is a licensed pharmacist with clinical experience in oncology, infectious disease, and diabetes management. He has a passion for personalized patient care and believes that education is essential to living a healthy life. His goal is to motivate individuals to find ways to manage their chronic conditions.

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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