Diabetes and Personalized Medicine

Diabetes is sweeping the nation and the world. There are so many opinions on prevention and treatment due to the escalation in the prevalence of diabetes. However, one of the greatest concerns among researchers and especially people who control health insurance is the tendency that diabetic patients have toward other diseases and longer hospital stays. The risk of accruing additional diseases including heart disease and high blood pressure, in accordance with diabetes mellitus is significantly increased.  This increased risk has launched an initiative for preventative medicine. However, many diseases are more genetically linked than people presume. This genetic correlation between diabetes and other diseases may be coincidental, like many other correlational studies, but the question arises as to whether or not the correlation is actually causational. If the disease is causational the push for preventative medicine has merit. However, the preventability of the disease depends on individuals’ willingness to take the steps necessary as well as the genetic link of his/her diabetic diagnosis.

Type I diabetes is the genetic link in which beta cells of the pancreas do not produce adequate, if any, insulin in order to signal to the brain that there is enough sugar in the blood and gluconeogenesis does not need to occur. This genetic predisposition to type I diabetes could be considered autoimmune, and therein lies the gateway for the correlation between type I diabetes and other autoimmune diseases namely; vitiligo, thyroid disorders, celiac disease and Addison’s disease. Each of these disorders aforementioned causes a shift in the way sugar is metabolized, which causes other metabolic and hormonal imbalances.  We will use the example of vitiligo in order to more closely look at this correlation between diabetes and other autoimmune disorders. Vitiligo is a disorder characterized by white patches in the skin and is caused by the destruction of melanocytes in the Stratum Basale layer of the epidermis. Less than 2% of the human population is diagnosed with vitiligo, however of those with vitiligo a large portion of them also struggle with Type 1 diabetes. A study done by Mark Burge and J. David Carey revealed that with the subcutaneous injection of insulin, loss of skin pigmentation in close proximity to the site of injection frequently occurs (2003). This idea poses a question as to whether or not vitiligo is triggered by type I diabetes or if the treatment of type I diabetes simply causes signs and symptoms of the disorder, rather than the disorder itself. In understanding this we could explain the correlation of vitiligo or other autoimmune diseases altering hormones and type I diabetes.

This idea that vitiligo may or may not be genetically linked to type I diabetes led to looking at other diseases, which are also thought to be genetic in nature. Thyroid disorders consist of hyperthyroidism or hypothyroidism, which affects 15-20% of children with Type 1 diabetes.  Hyperthyroidism causes extreme weight loss, whereas hypothyroidism is consistent with unexplained weight gain, and a goiter may also be present in patients with hypothyroidism. Without iodine, which must be ingested through food or supplements, the body cannot activate the thyroid cells in order to activate the proper function of metabolism. Thus, stimulation of the release of the Thyroid Stimulating Hormone (TSH) from the hypothalamus receives a positive feedback signal and causes an overproduction of thyroid cells forming a goiter in the thyroid gland. Celiac disease is the inability to digest the protein known as gluten, which is found in wheat and is commonly used in bread and other products. Celiac disease causes pain and often extreme weight fluctuations. Addison’s disease is characterized by an adrenal insufficiency, often blood pressure does not rise as it should and people become tired, weak and fatigued.  These autoimmune diseases and disorders cause a shift in the homeostatic balance of a person. This same thing occurs in people with diabetes, hormone levels are altered causing the body to react in a way that puts a person’s life at risk. When looking at the genetic link of each of these diseases, there is always a hormonal imbalance associated with the disease. Does the body simply work as a tipping scale? In each case, one disease causes a hormonal imbalance, which then leads to the decline in other hormone levels resulting in the manifestation of these other diseases such as Addison’s disease or Celiac disease. If the previous statement is true, then we would likely see an escalation in other hormonal disorders as well. The complexity of each of these varies between individuals. It is difficult to isolate a cause or a treatment as each case seems to presents itself differently.

Autoimmune diseases, which affect a person’s hormone levels that often reveal themselves in conjunction with type I diabetes, are not the only diseases and disorders linked to diabetes. People’s genetic make-up is so diverse, and yet transcription and translation occur with such precision that a person becomes a person with all of the normal functions one would expect. However, sometimes there is a mistake and evolution does not always win in the lives of some individuals. One case is a variant of the PTPN22 gene, which is linked to not only type I diabetes, but rheumatoid arthritis and systemic lupus erythematosus as well (Siminovitch 2004). These diseases are caused by an abnormality in the protein-tyrosine phosphatase family. This disruption in the molecular adapter protein CBL causes T-cell receptor signaling pathways to become unregulated. This disrupts the ubiquitination pathway, which is involved in protein modification (Type I diabetes 2016). Due to this malfunctioning pathway cascade there are many issues that arise. This explains the wide array of diseases that come from the single genetic mutation of the PTPN22 gene. In the case of having this particular genetic link to type I diabetes we are able to see the complexity of the system this one gene controls. However, this is not the only gene that can be linked to type I diabetes, or other diseases such as rheumatoid arthritis and systemic lupus erythematosus, as aforementioned. Genes such as HLA-DQA1, HLA-DQB1 and HLA-DRB1 all encode for the Human Leukocyte Antigen or MHC complex, which allows for proper attachment of the T-cells in all animal cells. Each gene that interferes with proper function of the MHC/HLA complexes will result in serious repercussions for the health of the individual with the abnormality or genetic mutation (European Bioinformatics, 2016). Since T-cells are involved in the immune system of animals. This lack of antibody production by the immune system due to the insufficient MHC/HLA complexes may be the source of many diseases in individuals with type I diabetes. Given these variations on type I diabetes, is there a better way to treat those with type I diabetes than has already been presented to the medical world?

While there is a strong connection between an individual’s genetic makeup and their chance of getting diabetes, many believe that the main cause of the disease is diet and exercise, which is the deciding factor in our gut microbiota. Humans are born with a ‘sterile’ gut that has been unaffected by outside sources. However, each time we ingest something, it changes the flora of our system, which in turn adds to the metabolic processes of the body. This leads to billions of microbial bacteria, both good and bad, to thrive within our small and large intestines. Every person has a slightly different flora of microbiota in their intestinal tract; however there are more similarities with those who eat and participate in similar things, such as family members or others with whom a person lives. There are different types of bacteria that help to metabolize foods within the intestines. This allows a human or other organism to digest different things, such as a cow’s ability to digest grass. A cow wouldn’t normally be able to digest grass, however the bacteria in his/her gut allows for the breakdown and extraction of nutrients. This is similar in humans in that there are bacteria that help to metabolize and extract nutrients from various foods. In addition, the food we ingest helps to control the types of foods we crave and thus the fat, sugar or other nutrient content of a food (Burcelin 2011). With this in mind we know that diabetic patients are often overweight and this leads to lipedema and other issues involving fatty tissues, which led to the onset of a person’s diabetes. If the use of gut flora transplants could help to reduce the risk of pre-diabetic patients we could reduce the epidemic of diabetes that seems to be sweeping the world, especially in the United States.

Many different views on the subject of diabetes and the treatment and prevention have been considered. Among the diseases aforementioned including autoimmune diseases affecting hormone balance, as well as an improperly functioning genes which causes a disturbance in the normal cascade, and the microbiota of the human body, found there does not seem to be one absolute way to prevent or treat diabetes. Every person reacts differently and with the many different types of diabetes, which are culminated in type I and type II diabetes, but vary with every person. Each type of diabetes can be treated differently forcing medicine to move in the direction of personalized medicine rather than treating every patient the same way. It is necessary that medicine evolves in such a way that statistics, while relevant, are not the only thing that physicians rely upon. As science changes and discoveries are made about the diversity of people’s reactions there is a need to personalize medicine. Not everyone will assimilate to a certain treatment in the same way and medicine has to adjust for the good of human kind.

References

Burcelin, R., Serino, M., Chabo, C., Blasco-Baque, V., & Amar, J. (2011). Gut microbiota and diabetes: From pathogenesis to therapeutic perspective. Acta Diabetol Acta Diabetologica, 48(4), 257-273. doi:10.1007/s00592-011-0333-6

Burge, M. R., & Carey, J. D. (2003). Vitiligo Associated With Subcutaneous Insulin Lispro Infusion in Type 1 Diabetes. Diabetes Care, 27(1), 275-276. doi:10.2337/diacare.27.1.275

European Bioinformatics InstituteProtein Information ResourceSIB Swiss Institute of Bioinformatics. (2016). E3 ubiquitin-protein ligase CBL. Retrieved September 1, 2016, from http://www.uniprot.org/uniprot/P22681

Siminovitch, K. A. (2004). PTPN22 and autoimmune disease. Nature Genetics Nat Genet, 36(12), 1248-1249. doi:10.1038/ng1204-1248  

Type 1 diabetes - Genetics Home Reference. (n.d.). Retrieved September 1, 2016, from https://ghr.nlm.nih.gov/condition/type-1-diabetes#genes