Diabetes Metillus, diabetes for short is an incurable lifelong disease, categorized into two types: 1. Type 1 Diabetes (T1D) and 2. Type 2 Diabetes (T2D). Type 1 Diabetes is classified as an autoimmune disease, where one individual’s immune system mistakenly destroys insulin-producing pancreatic beta cells, resulting in little to no production of insulin, a hormone used to regulate blood sugar levels to provide energy for the body (MayoClinic 2017). Type 2 Diabetes is classified as a developmental disease, where one individual’s body gains resistant to insulin and as it worsens their pancreas eventually stops producing enough insulin, known as insulin deficiency. Type 2 Diabetes are influenced by genetics and environmental factors, such as imbalance nutrition, excessively overweight (obesity), inactivity and many more. Diabetes are known to affect all ages of people, with Type 1 Diabetes known to be juvenile diabetes, typically diagnosed in children or young adult, however, can also be diagnosed in adults, while Type 2 Diabetes is most commonly found in adults (WebMD 2015).
Clinical features and descriptions similarly related to diabetes had existed in ancient Egyptian, Indian and Chinese medical literature, but due to the limited knowledge no one was able to identify the disease (Karamanou et al. 2016). In the 2nd century AD diabetes was first discovered by Aretaeus of Cappadocia, an ancient Greek physician who had detailed knowledge about the disease based off of his own observations. He also gave diabetes its name derived from a Greek root with the meaning of siphon, to pass through referring to diabetes’ symptoms of intense thirst and frequent urination, the excessive production of fluids (Hormones 2012). The second word of the disease Metillus, derived from a Latin root was defined as “sweet urine” was later added by Thomas Willis in 1675, a Britain and English physician when he rediscovered the sweetness in patients’ urine after the first discovery of it from ancient Indians. However, it wasn’t until 1776 when Matthew Dobson, another English physician proved that the reason for the sweetness in urine was due to the presence of excessive sugar in patients’ urine. In 1857, Claude Bernard, a French physiologist discovered the liver’s glycogenic action and also realized that excessive glucose was the main cause of diabetes. Oskar Minkowski and Joseph von Mering also discovered the role of the pancreas in diabetes through their famous experiment of removing a dog’s pancreas (Khartoum 2002). In 1927, based off of Minkowski and Mering’s discovery, Fredrick Banting and Charles Best continued further research on the pancreas through isolation of the pancreatic cells and administration of type 1 diabetes patients. This lead to the discovery of insulin and the invention of the first diabetes treatment (Karamanou et al. 2016).
The first treatment for diabetes helped saved millions of lives (Karamanou et al. 2016). However as of today, only a treatment exists.
I will never forget the day, the day my grandma lost her battle to diabetes and its’ gifts of other health diseases. My grandma was diagnosed with diabetes at the age of 45 before I was even born and started her insulin treatment the day of diagnosis. After being born and as I grew older, I was always wondering what the daily injections were that she poked her stomach for, but also what was the point of pushing blood out after pricking her own finger with a needle. Like similar to these questions
Section 2: Cellular Etiology
Type 1 Diabetes is a T-cell mediated autoimmune disease, that leads to the destruction of insulin producing β-cells of islets of Langerhans in the pancreas. According to Dr. Kelly, insulitis, the infiltration of pancreatic cells by lymphocytes, similarly characterizes the early stages of diabetes pathogenesis. Although insulitis could be a normal inflammatory response to general tissue damage or viral infections, Dr. Kelly believed that lymphocytic infiltrate directly contributed to the destruction of β-cells. In order to support this thought, Dr. Kelly conducted an experiment where autoreactive T-cells specific for β-cells containing insulin, glutamic acid decarboxylase (GAD) and protein tyrosine phosphate (IA-2) were isolated from the peripheral blood in individuals newly diagnosed with Type 1 Diabetes. Some of those individuals in the study showed the capability of destroying β-cells, but also animal studies have showed the significance of T-cells in diabetes pathogenesis because a non-obese diabetic (NOD) mouse developed insulin deficiency resulting in diabetes and had seemed to share many similar immunological and pathological features with Type 1 Diabetes. The development of Type 1 Diabetes in this mouse showed T-cell dependency and needed both CD4 and CD8 positive T-cells. Not only that, but this study also showed that autoreactive T-cells isolated from NOD mice can actually transfer the diabetes to non-diabetics and that it catalyzes the early onset of diabetes in NOD neonates (Kelly 2003).
Type 1 Diabetes is also found to be reflected by the presence autoantibodies that are specific for β-cell proteins such as insulin, GAD and IA-2. Although there is no clear distinction of whether or not these proteins participate directly in β-cell destruction or is a response to the diabetes pathogenesis, it is still a good distinctive reference marker to help identify the disease. Besides looking at the physiological cause of type 1 diabetes, genetic factors also play a huge role in type 1 diabetes. The first susceptible diabetics gene identified was the human leukocyte antigen (HLA) gene, located on chromosome 6p21. HLA gene showed linkage to Type 1 Diabetes in various data sets over 20 loci and all the studies showed linkage to the HLA gene region (designated IDDMI) while several of other genomic screenings showed a role for the insulin gene region (IDDM2). Although many other IDDM regions were discovered, genomic screenings confirm that the HLA gene region (IDDM1 locus) was the major genetic determinant, accounting for about 42% of inheritance in Type 1 Diabetes. Therefore, digging deeper into the HLA region, designated IDDM1, the class I genes encode for peptide chains that bind with β2 microglobulin to form the class I molecules. These molecules are then expressed on the surface of all nucleated cells to restrict the cytotoxic T-cell activities. However, the gene encoding for this molecules that surfaced are susceptible to many T-cell mediated autoimmune disease with one of them being Type 1 Diabetes. Also, recent genetic mapping studies suggested that HLA class II genes, DRB1 and DQB1 were the major determinants of IDDM1 allowing for the susceptibility to type 1 diabetes by activating the autoreactive T-cells responsible for β-cell destructions. (Kelly 2003). These genetic factors are the building blocks towards the cause of immune cells self-attacking pancreatic insulin producing β-cells and is the very underlying main reason why Type 1 Diabetes occurs.
Due to the genetic factors involved in Type 1 Diabetes, the susceptibility is due to the HLA genes, DRB1 and DQB1 since these are the instructions to signal for the activation of autoreactive T-cells. Once autoreactive T-cells are activated, the T-cells follow the instructions given by the IDDM1 determinants and breaks through the nucleated cells in the pancreatic islets to destroy the β-cells. In these β-cells insulin is produced. Insulin is a hormone, chemical messenger responsible for the regulation of blood glucose levels to achieve homeostasis. Insulin usually has two modes of activity on an individual, one is excitatory while the other is inhibitory. An excitatory response stimulates glucose uptake into the blood and lipid synthesis, while an inhibitory response does the opposite, inhibits the breakdown of lipids and protein along with inhibiting processes such as gluconeogenesis and ketogenesis.