blood sugar control
nutrition
PPM1K

The Role Of Amino Acids In Diet, Obesity, & Diabetes (PPM1K)

Written by Mathew Eng, PharmD on February 28th, 2020
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BCAAs, a type of amino acid commonly found in the food we eat, is metabolized with help from the PPM1K gene. However, certain variants in this gene may impair this process, potentially leading to greater risk of type 2 diabetes, higher insulin resistance, and poor response to specific diets.

The PPM1K Gene

The PPM1K gene helps create a protein named mitochondrial protein phosphatase 1K [R].

This protein plays an important role in the metabolism of certain amino acids called branched chain amino acids (BCAAs), such as leucine [R].

There’s some evidence that certain genetic variants of PPM1K may impair the body’s ability to metabolize BCAAs, ultimately leading to an increase in BCAA levels [R].

This may be an issue as several studies have linked high BCAA levels to metabolic problems, such as insulin resistance, obesity, and type 2 diabetes [R, R, R].

Research also suggests that certain variants of PPM1K may affect how the body responds to certain diets [R, R].

PPM1K, Diet, & Blood Glucose

How Does PPM1K Affect Diet And Blood Glucose?

Studies show that certain genetic variants of PPM1K may have negative effects on the body.

More specifically, research suggests that the ‘C’ allele in rs1440581 may be associated with risk of type 2 diabetes and poor response to certain diets [R, R, R].

According to researchers, this occurs because the ‘C’ allele may impair the body’s ability to metabolize BCAAs, leading to a higher than normal level of BCAAs [R].

High levels of BCAAs in the blood have been strongly linked to insulin resistance and type 2 diabetes in a number of studies [R, R, R].

However, it’s not entirely clear why high BCAA levels have this effect. 

Some researchers suggest that BCAAs may activate the mTOR signaling pathway, which can induce insulin resistance [R].

Research On PPM1K

The POUNDS LOST Trial

Short for “Preventing Overweight Using Novel Dietary Strategies”, the POUNDS LOST trial is a study that followed 734 overweight or obese adults for a 2-year period [R].

During this time, subjects were randomly assigned to 1 of 4 calorie-restricted diets that were either high-fat or low-fat and either high-protein or average-protein [R].

At the end of the trial, researchers found some interesting results.

Subjects who were on the high-fat diet and carried the ‘C’ allele in rs1440581 had less weight loss and smaller improvements to insulin resistance compared to the ‘T’ allele [R].

Participants in the study were predominantly white, but there were also black, Hispanic, and Asian groups included [R].

According to the POUNDS LOST trial, people with the ‘T’ allele in rs1440581 may benefit more from a calorie-restricted high-fat diet in terms of weight loss and insulin sensitivity compared to those without this allele.

The NUGENOB Trial

The NUGENOB trial, which stands for “Nutrient Gene Interactions in Human Obesity”, studied 757 obese adults who were put on a calorie-restricted diet for 10 weeks [R].

Participants were randomly assigned to 2 different controlled diets, a low-fat diet and a high-fat diet [R].

Similar to the POUNDS LOST trial, researchers found that those carrying the ‘C’ allele experienced smaller improvements to weight and insulin resistance while on a calorie-restricted high-fat diet [R].

On the other hand, the ‘C’ allele was associated with better weight loss and insulin resistance improvements for those on the low-fat diet compared to the ‘T’ allele [R].

Subjects in this study were all from European countries, including the United Kingdom, Netherlands, France, Spain, Czech Republic, Sweden, and Denmark [R].

The NUGENOB trial suggests that people carrying the ‘T’ allele in rs1440581 may benefit more from calorie-restricted high-fat diets. On the other hand, those with the ‘C’ allele may benefit more from calorie-restricted low-fat diets in terms of weight loss and improvements to insulin resistance.

Other Studies

One study followed over 6,000 Chinese non-diabetic patients for a 5-year period [R].

For those carrying the ‘C’ allele in rs1440581, an increase in BMI resulted in greater increases in insulin levels and insulin resistance compared to those with the ‘T’ allele [R].

The researchers also found that each ‘C’ allele in rs1440581 is associated with a 20% higher risk of type 2 diabetes [R].

A study of Chinese patients found that the ‘C’ allele in rs1440581 is associated with higher insulin levels, insulin resistance, and risk of type 2 diabetes.

Your PPM1K Results for Diet

You can see your genotype for PPM1K 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

variant genotype frequency risk allele
rs1440581

 

Primary SNP: 

PPM1K rs1440581

  • ‘T’ = Associated with better improvements to weight and insulin sensitivity when consuming a calorie-restricted high-fat diet
  • ‘C’ = Associated with better improvements to weight and insulin sensitivity when consuming a calorie-restricted low-fat diet
  • The ‘C’ allele is also associated with a higher risk of type 2 diabetes in Chinese populations
  • About 19% of all people worldwide have the ‘TT’ genotype
  • About 33% of all people worldwide have the ‘CC’ genotype

 

Recommendations

Lifestyle

Get Enough Sleep

While sleeping, the body goes through important metabolic changes. Not getting enough sleep can disrupt this process, potentially leading to an imbalance of blood glucose and insulin [R, R].

Many 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].

Some research suggests 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 each night [R].

Exercise Regularly

Research consistently shows that exercise reduces blood glucose levels, improves insulin sensitivity, and lowers the risk of type 2 diabetes [R, R].

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

According to some studies, a combination of aerobic exercise and resistance training (weightlifting) may produce greater benefits than either type of exercise alone [R, R].

Physical activity is also, of course, one of the best ways to lose weight and improve overall health [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].

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].

Research suggests that stress management techniques, such as mindfulness-based stress reduction, may help 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 help prevent the disease [R, R].

Even for those that do have diabetes, quitting smoking can make it easier to manage your blood glucose levels [R, R].

Diet

As mentioned earlier, your specific genotype of PPM1K can affect how the body responds to certain diets.

The NUGENOB and POUNDS LOST trials found the following results in regards to PPM1K rs1440581 [R, R]:

  • Those carrying the ‘C’ allele may benefit more from a calorie-restricted low-fat diet
  • Those carrying the ‘T’ allele may benefit more from a calorie-restricted high-fat diet

What exactly was the benefit? 

These studies suggest that when an allele is matched with a beneficial diet type (such as a calorie-restricted high-fat diet for those with the ‘C’ allele), the individual may experience more weight loss and better improvements to insulin resistance [R, 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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