Diabetes is a chronic disease in which the body’s ability to regulate blood sugar levels is impaired and is mainly classified into type 1 and type 2 diabetes. The onset of these diseases is largely influenced by lifestyle habits as well as genetic factors. In recent years, advances in genetic testing technology have made it possible to grasp an individual’s risk of diabetes in advance and take preventive measures.
More than 100 types of genetic polymorphisms related to diabetes have been reported, and genetic factors are believed to have a large influence especially in type 2 diabetes ( reference study ).
2. Major genes involved in type 2 diabetes
(1) TCF7L2 gene
The TCF7L2 (Transcription Factor 7-Like 2) gene is involved in regulating insulin secretion and blood glucose levels and is considered to be one of the most important genes that increases the risk of developing diabetes.
If you have a risk allele (e.g., the T allele of rs7903146)
Decreased insulin secretion
Increased blood sugar levels
Diabetes risk increases 1.4 to 1.8 times
Research has confirmed that mutations in the TCF7L2 gene have a significant impact on the development of type 2 diabetes in Western, Asian, and African populations ( reference study ).
(2) KCNJ11 gene
KCNJ11 (a potassium channel gene) plays a role in regulating insulin secretion in pancreatic β cells.
If you have a risk allele (e.g., E23K polymorphism of rs5219)
Insulin secretion is likely to decrease
Risk of developing diabetes increases by approximately 1.2 to 1.5 times
It has been reported that mutations in this gene specifically cause a decrease in insulin secretion function and are sensitive to the effects of diet and exercise ( reference study ).
(3) FTO gene
FTO (adipose-related gene) indirectly increases diabetes risk by affecting appetite regulation and fat metabolism.
If you have a risk allele (e.g., the A allele of rs9939609)
Increased BMI
Increased insulin resistance
Diabetes risk increases 1.2 to 1.6 times
People with this genetic mutation are particularly susceptible to the effects of high-fat, high-calorie diets, so dietary management is important ( reference study ).
3. Diabetes prevention using genetic testing
(1) Optimizing your diet
Because genes affect our ability to metabolize carbohydrates and lipids, it is important to adopt an appropriate nutritional strategy.
People with TCF7L2 genetic risk → Mainly focus their diet on low GI foods
Choose brown rice and whole grain products instead of white rice and bread
Control your sugar intake
People with FTO genetic risk → Reduce fat intake and control appetite
Exercise is very effective in preventing and improving diabetes, but the type of exercise that is best for you varies depending on your genes.
People with KCNJ11 genetic risk → Aerobic exercise that increases insulin sensitivity
Walk or jog for at least 150 minutes per week
People with a genetic risk of FTO should incorporate strength training.
Increasing muscle mass improves basal metabolism and prevents fat accumulation
(3) Reviewing lifestyle habits
Improving stress management and sleep habits based on the results of genetic testing can also be effective in preventing diabetes.
Get 7-8 hours of sleep, as lack of sleep worsens insulin resistance.
Implement stress management (mindfulness, yoga, etc.) to prevent excess cortisol production
4. Limitations of genetic testing and precautions for its use
Genetic testing is a powerful tool for assessing diabetes risk, but it is not 100% reliable.
(1) Interaction with environmental factors
Genes only indicate “risk,” and lifestyle habits have a major impact. For example, even if you have genes that are associated with a low risk of diabetes, your risk of developing the disease will increase if you continue to live an unhealthy lifestyle ( reference study ).
(2) Consideration of ethnic differences
The effects of diabetes-related genes may vary by ethnicity. For example, genes that show a strong association in Westerners may have a different effect in Asians. Therefore, it is important to take into account the latest research data when interpreting the results of genetic tests.
(3) How to use genetic testing
Knowing your diabetes risk is merely one part of preventative measures, so there is no need to worry excessively. Rather, it is important to have a positive perspective, knowing that your risk can be reduced by adopting appropriate diet, exercise, and lifestyle habits.
5. The relationship between genes and insulin sensitivity
Individual differences in insulin sensitivity, which is a measure of how well cells respond to insulin and process blood sugar, are also important in understanding diabetes risk. Genetic factors affect this sensitivity and thus the risk of developing diabetes.
(1) IRS1 gene and insulin signaling
The IRS1 (insulin receptor substrate 1) gene is involved in insulin signaling and promotes blood glucose uptake.
If you have a risk allele (e.g., the T allele of rs2943641)
Decreased insulin sensitivity
Increased risk of elevated blood sugar levels
Risk of developing diabetes increases by approximately 1.2 times
People with this genetic mutation are advised to be particularly careful about their carbohydrate intake and to adopt eating habits that prevent blood sugar levels from rising after meals ( reference study ).
(2) PPARG gene and the function of adipocytes
The PPARG (peroxisome proliferator-activated receptor gamma) gene is an important gene that regulates adipocyte differentiation and insulin sensitivity.
If you have a risk allele (e.g., Pro12Ala mutation in rs1801282)
Increased insulin resistance
Blood sugar regulation is likely to worsen
Increased risk of obesity
Certain PPARG mutations are sensitive to diet, and it is believed that avoiding a high-fat diet can reduce the risk of diabetes ( reference study ).
6. Relationship between diabetes risk and intestinal bacteria
In recent years, the relationship between intestinal bacteria and diabetes risk has been attracting attention. The intestinal flora is also influenced by genetic factors, and the balance of certain bacteria may affect blood sugar control.
(1) TLR4 gene and intestinal inflammation
The TLR4 (Toll-like receptor 4) gene regulates immune responses in the intestine and is involved in inflammation and insulin resistance.
If you have a risk allele (e.g., the A allele of rs4986790)
Promotes inflammation in the intestines
Increased insulin resistance and increased risk of diabetes
Reduction of certain intestinal bacteria (Bacteroides)
People with this genetic mutation may be able to improve their intestinal environment and reduce their risk of diabetes by actively consuming fermented foods and prebiotics ( reference study ).
(2) FUT2 gene and gut bacterial diversity
The FUT2 (fucosyltransferase 2) gene influences the composition of gut bacteria and has been linked to diabetes risk.
If you have a risk allele (e.g., the G allele of rs601338)
The diversity of intestinal bacteria is likely to decrease
Elevated inflammatory markers
Increased insulin resistance
It is important for people with this genotype to be conscious of eating a diet rich in dietary fiber and maintain the diversity of intestinal bacteria ( reference study ).
7. Diabetes and personalized drug therapy based on genes
It is known that the effectiveness of drugs used to treat diabetes also varies depending on genes. By utilizing genetic testing, it is possible to select the most appropriate drug and reduce the risk of side effects.
(1) KCNJ11 gene and sulfonylurea drugs (SU drugs)
Mutations in the KCNJ11 gene affect the effectiveness of sulfonylureas (SUs).
If you have a risk allele (e.g., the E23K mutation in rs5219)
The effectiveness of sulfonylurea drugs is likely to decrease
Increased risk of hypoglycemia
Other treatments (such as metformin) may be recommended for patients with this genotype ( reference study ).
(2) SLC22A1 gene and metformin
Metformin is the first-choice drug for treating diabetes, but its effectiveness varies depending on mutations in the SLC22A1 gene.
If you have a risk allele (e.g., the T allele of rs628031)
Metformin absorption is reduced, making it less effective
Higher doses are needed in more cases
Appropriate dose adjustments and combination use with other drugs are recommended for patients with this genotype ( reference study ).
8. Interaction between genes and lifestyle-related diseases
Diabetes is closely related to other lifestyle-related diseases (hypertension, dyslipidemia, cardiovascular disease). Depending on your genes, the risk of these diseases may increase at the same time.
(1) APOE gene and lipid metabolism
The APOE (apolipoprotein E) gene is involved in cholesterol metabolism and influences both diabetes and cardiovascular disease.
If you have a risk allele (e.g., APOE4 allele)
Increased LDL cholesterol (bad cholesterol)
Increased insulin resistance and increased risk of diabetes
For people with this genotype, lipid management is important, and dietary therapies such as the Mediterranean diet are considered effective ( reference study ).
9. Nutritional strategies to reduce diabetes risk
It is known that the risk of diabetes varies depending on genes, but it is possible to reduce the risk by making adjustments to your diet. It is important to utilize genetic testing and implement nutritional strategies that are tailored to each individual’s constitution.
(1) Relationship between carbohydrate types and genes
People with genetic mutations that put them at risk of diabetes need to be particularly careful about the type of carbohydrates they consume and how they consume them.
People with TCF7L2 genetic risk → Mainly focus their diet on low GI foods
Choose brown rice and whole wheat bread instead of white rice and white bread
Use alternative sweeteners such as stevia and erythritol instead of sugar
Eat fiber before meals to prevent a sudden rise in blood sugar levels
People with SLC30A8 genetic risk : Moderately limit carbohydrate intake
Limit carbohydrate intake to 45-50% of total energy intake
Limit your daily carbohydrate intake to around 100-150g
A balanced diet with protein and healthy fats
(2) Relationship between lipids and diabetes risk
Lipids are not just a source of energy; they also affect insulin sensitivity and inflammatory responses.
People with FTO genetic risk : Reduce intake of saturated fatty acids
Use olive oil or avocado oil instead of butter or lard
Choose lean cuts of meat (chicken breast, red meat)
Eat fish (salmon, mackerel) rich in omega-3 fatty acids (EPA and DHA)
People with APOA5 genetic risk → completely avoid trans fats
Limit your intake of processed foods and margarine
Avoid fast food and fried foods
(3) Dietary fiber and improving intestinal environment
It is known that improving the intestinal environment contributes to reducing the risk of diabetes.
People with TLR4 genetic risk: Actively take in prebiotics
Eat fermented foods (yogurt, natto, kimchi) every day
Increase soluble fiber (oatmeal, avocado)
People with FUT2 gene risk → Increase gut bacterial diversity
Balanced intake of fermented foods and dietary fiber
Use supplements to regulate your intestinal flora
10. Diabetes risk and genetic fitness for exercise
Exercise is a powerful tool for reducing diabetes risk, but the type of exercise that is best for you depends on your genes.
(1) Suitability for endurance exercise
Endurance exercise can improve blood sugar control and increase insulin sensitivity.
People with PPARGC1A genetic risk → Endurance training is effective
Aerobic exercise (jogging, cycling) for 30-60 minutes, 3-5 times a week
Incorporate high-intensity interval training (HIIT) into your routine once or twice a week
People with ACE gene risk:moderate intensity exercise is appropriate
Prioritize exercises that are easy to continue, such as walking and yoga.
Avoid overtraining and adjust your training to avoid fatigue.
(2) Strength training and genes
Increasing muscle mass contributes to improved glucose metabolism.
People with ACTN3 gene risk:Strengthen muscle training
Strength training 2-3 times a week (squats, deadlifts)
Combine resistance and aerobic exercise
People with NRF2 genetic risk:Training with recovery in mind
Stretching and massage after exercise
Lifestyle changes to improve sleep quality
11. Genetics and risk of diabetic complications
People with a genetic risk of diabetes should also be aware of their risk of developing complications.
(1) Diabetic nephropathy and genes
As diabetes progresses, kidney function declines and the risk of developing diabetic nephropathy increases.
People with EPO genetic risk → Regular checkups of kidney function are required
Limit salt intake and thoroughly manage blood pressure
Regularly check creatinine levels and urine protein
People with SLC22A12 genetic risk → Managing uric acid levels is important
Limit foods high in purines (liver, fish eggs)
Stay hydrated and maintain kidney function
(2) Diabetic neuropathy and genes
As diabetes progresses, peripheral neuropathy can develop.
People with NGF gene risk → Maintains nervous system health
Actively take in B vitamins (B6, B12)
Maintaining proper blood sugar control to minimize nerve damage
People with SOD2 gene risk → Antioxidant measures are necessary
Eat foods rich in vitamins C and E
Avoid excessive stress and lack of sleep
12. Genetic influences on diabetes risk and stress management
Stress is one of the factors that increase blood sugar levels and worsen insulin resistance. In particular, the secretion of the stress hormone cortisol varies from person to person due to genetic factors, and it is known to affect the risk of diabetes.
(1) NR3C1 gene and cortisol sensitivity
The NR3C1 (glucocorticoid receptor) gene regulates the action of cortisol (the stress hormone) and determines the body’s response to stress.
If you have a risk allele (e.g., the G allele of rs6198)
Decreased cortisol sensitivity and stress tolerance
Chronic stress increases the risk of high blood sugar levels
Diabetes risk increased 1.3 to 1.5 times
It is important for people with this genetic mutation to incorporate stress management techniques such as yoga, meditation, and deep breathing into their daily lives ( reference study ).
(2) COMT gene and stress resistance
The COMT (catechol-O-methyltransferase) gene is involved in the metabolism of dopamine and norepinephrine, which are secreted during stress.
If you have a risk allele (e.g., Val158Met mutation in rs4680)
Stress hormones are broken down slowly, making them vulnerable to pressure
Long-term stress linked to increased diabetes risk
Blood sugar levels fluctuate more dramatically
People with this gene mutation may be able to reduce stress and improve their blood sugar control by engaging in moderate exercise and relaxation habits ( reference study ).
13. Genetic factors in sleep and diabetes risk
It is known that lack of sleep or poor-quality sleep worsens insulin resistance and increases the risk of developing diabetes. Genes involved in sleep affect individual sleep patterns and are also associated with diabetes risk.
(1) CLOCK gene and circadian clock
The CLOCK (circadian rhythm control gene) gene regulates the body’s internal clock and affects sleep quality and blood sugar control.
If you have a risk allele (e.g., the C allele of rs1801260)
Sleep quality is likely to decline
They tend to be nocturnal and have irregular mealtimes.
Increased fluctuations in blood sugar levels and increased risk of diabetes
People with this genetic mutation may be able to reduce their risk of diabetes by avoiding blue light before bed and getting into the habit of going to bed and waking up at the same time every day ( reference study ).
(2) PER2 gene and sleep rhythm
The PER2 (Period Circadian Regulator 2) gene maintains the rhythm of the body’s internal clock and controls sleep patterns.
If you have a risk allele (e.g., the A allele of rs2304672)
Sleep time tends to be shorter
Difficulty adapting to shift work or staying up late
Decreased insulin sensitivity and increased risk of diabetes
It is important for people with this genotype to ensure they get 7 to 8 hours of sleep and maintain a regular daily rhythm ( reference study ).
14. Genetic Influences on Diabetes and the Immune System
The function of the immune system influences the risk of developing diabetes. In particular, type 1 diabetes is an autoimmune disease in which mutations in immune-related genes play an important role.
(1) HLA genes and type 1 diabetes
HLA (human leukocyte antigen) genes regulate the function of the immune system and are involved in the development of type 1 diabetes.
If you have a risk allele (e.g., HLA-DR3/DR4)
prone to excessive autoimmune response
Pancreatic islet cells (cells that secrete insulin) are easily attacked, increasing the risk of developing diabetes
People with this genotype are advised to maintain a balanced immune system by actively consuming foods that prevent infection and have anti-inflammatory properties (omega-3 fatty acids, vitamin D) ( reference study ).
(2) IL6 gene and chronic inflammation
The IL6 (interleukin 6) gene regulates inflammatory responses and is involved in the development of diabetes.
If you have a risk allele (e.g., the C allele of rs1800795)
Increased levels of inflammation
Increased insulin resistance and increased risk of type 2 diabetes
People with this genotype may be able to reduce their risk of diabetes by actively consuming anti-inflammatory foods (turmeric, green tea, and dark chocolate) ( reference study ).
15. Genes and the possibility of early detection of diabetes
Genetic testing is a powerful tool for advance warning of diabetes risk, but it is not diagnostic in its own right.
Genetic testing is only one part of risk assessment, and regular health checkups are necessary.
If there is a family history, blood glucose testing (HbA1c, fasting blood glucose) is recommended in addition to genetic testing.
Combined with lifestyle changes, the chances of preventing the onset of the disease are increased.
16. Potential for personalized medicine to reduce diabetes risk
In recent years, personalized medicine (precision medicine) has been attracting attention, and diabetes risk management using genetic testing is progressing.
(1) Genetic-based prevention programs
By utilizing the results of genetic testing, we can implement personalized prevention programs such as the following:
People with high-risk genes : Strict blood sugar control and lifestyle changes
A meal plan centered around the intake of low GI foods
Participate in aerobic exercise at least five times a week
Regular blood sugar testing and follow-up with your doctor
Those at medium risk : Maintain a balanced lifestyle
Adjust the balance of carbohydrate and fat intake
Moderate exercise 3 to 4 times a week (muscle training + walking)
Improve stress management and sleep quality
Low-risk people → General health care
Maintain a healthy diet and exercise regularly
Don’t neglect regular blood sugar checks
(2) Preventive medicine using genetic data and AI
Advances in AI technology are helping to analyze large amounts of genetic data and conduct precise evaluations of each individual’s risk of diabetes. The benefits of preventive medicine using AI are as follows:
Improve accuracy of diabetes risk prediction → Risk assessment combining genetic and lifestyle data
Recommendation of optimal treatment → Selection of drug therapy based on individual genetic characteristics
Promoting behavioral change → Lifestyle monitoring using smartphone apps
If this technology develops further, it is expected to become a new method for preventing the onset of diabetes.
Summary
The risk of developing diabetes is determined by the interaction of genetic and environmental factors. In particular, genes such as TCF7L2, KCNJ11, FTO, and PPARG are known to be involved in insulin secretion and sensitivity, fat metabolism, and appetite regulation, and increase the risk. However, by utilizing genetic testing, it is possible to practice diet, exercise, and lifestyle habits that are appropriate for each individual’s constitution and reduce the risk.
In addition, stress management and improved sleep habits are also important factors in preventing diabetes, and NR3C1, COMT, and CLOCK genes are involved. In the future, it is expected that more precise diabetes risk assessment and prevention strategies will be realized with the advancement of personalized medicine using AI. Understanding genetic information and taking appropriate measures will make it possible to prevent the onset of diabetes.
