Gene Mutations, Obesity, and Type 2 Diabetes Mellitus
As the study of pharmacogenomics and the importance of personalizing medication to optimize health outcomes for patients continues to grow, the knowledge to understand and target gene mutations through drug-gene targeted therapies will be the medicine of the future.
While gene mutations may consist of altered DNA or RNA sequences which are permanently altered, their differences in size and sequence affected can cause differing degrees of severity within an individual. Carrying particular gene mutations; however, may increase the risk or predispose an individual to a certain genetic or health condition.
It is found that over 70 million adults are obese within the United States — that is nearly 40% of the United States population of adults. As obesity rates continue to rise, the main factors contributing may consist of unhealthy eating habits and a sedentary lifestyle that involves little to no exercising — yet additional factors such as gene mutation may be overlooked. To date, nine genes have been associated with monogenic obesity: Lep (ob), LepR (db), POMC, MC4R, AgRP, PC-1, Fat, Tub, and TrkB. While there are additional psychological factors, cultural factors, hormones, metabolites, gut peptides, and neural afferents that regulate appetite by increasing or decreasing satiety, the body type that has the lower potential to develop obesity related complications would be pear shape compared to that of the apple body shape.
Those that have an apple body shape have more weight above the waist and are at greater risk for comorbid conditions such as Type 2 Diabetes Mellitus, Cardiovascular disease, Liver disease, and Cancer, compared to those who have more weight below the waist in the hips and buttocks with a pear body shape.
When obesity occurs, the level of energy expenditure is lower than that of the excessive nutrient intake, therefore weight begins to increase. Obese individuals are at a higher risk to develop Type 2 Diabetes as adipose cells store excess subcutaneous adipose tissue (SAT) that lies directly beneath the skin and visceral adipose tissue (VAT) which surrounds internal organs (excluding the heart).
Similarly to obesity, Type 2 Diabetes has a range of factors that can cause the condition to manifest. Obesity, body mass index (BMI), family history, high blood pressure, high cholesterol and triglyceride levels, and a history of gestational diabetes are accurate predictors that come to mind. There are also genes associated with Type 2 Diabetes which may include: ABCC8, CAPN10, GCGR, GLUT2, and TCF7L2. While having one of these gene mutations does not necessarily mean that an individual will develop Diabetes, having multiple gene mutations surely does increase the risk of developing the condition.
Overall, genetic testing may be conducted to confirm whether or not someone has these particular genes of interest and additional steps can be taken to reduce one’s risk of developing Type 2 Diabetes. Weight loss and increased physical activity under an exercise program, creating a healthy meal plan, and additional lifestyle changes can be conducted for a better outlook. It is important for doctors, pharmacists, and other healthcare providers alike to encourage healthy eating habits and promote exercise for patients that are interested in losing weight and/or have Type 2 Diabetes. Lastly, as gene mutations continue to be discovered and links are made to the effects they exert within the body, personalized treatments through drug-gene targeted medication may become the way of the future to help prevent or treat conditions that may have detrimental implications on society.
References
Adult Obesity Facts. Centers for Disease Control and Prevention. https://www.cdc.gov/obesity/data/adult.html. Published February 27, 2020. Accessed June 3, 2020.
Genetics of Type 2 Diabetes: Environmental Factors, Prevention, More. Healthline. https://www.healthline.com/health/type-2-diabetes/genetics. Published December 3, 2018. Accessed June 3, 2020.
What Your Body Shape Reveals About Your Health — Penn Medicine. — Penn Medicine. https://www.pennmedicine.org/updates/blogs/health-and-wellness/2019/september/body-shape. Accessed June 3, 2020.
