1.0 Pathogenesis and Risk factors
Type 1 diabetes (T1DM) is a form of diabetes caused by destruction of pancreatic insulin producing cells; β-cells. This results in low or no insulin production resulting in increased blood as well as urine glucose levels. T1DM can be further subdivided into Type 1 A diabetes mellitus which is caused by autoimmune destruction of the β-cells and Type 1 B diabetes mellitus which arises from non-autoimmune destruction of the β-cells. The auto immune destruction of β-cells is carried out by auto reactive CD4+, CD8+ and macrophage upon infiltration of the islets. This process is known to occur in genetically susceptible individuals and it is thought to be triggered by one or several environmental factors. These can progress over a long period of time during which the individual is euglycenic and asymptomatic. The genetic marker for Type 1 A diabetes are present in such individuals from birth. In addition both immune and metabolic markers can be detected after the initiation of the auto immune process using sensitive test after enough B cells have been damaged. This test can be carried out along time prior to hyperglycemia manifestation.
Several risk factors are associated with T1DM and more research is being undertaken to determine more risk factors. Some of the documented risk factors include:
Genetics and Geographical position. Several genes have been associated with the onset T1DM e.g. IDDM (thus the disease is polygenic) so that an individual with these genes is at a higher risk of developing this condition. Therefore, genetic testing can be used to determine if an individual from a family with a known history of T1DM is at a higher risk of developing this condition. Geographical position is also known to be a risk factor of T1DM in the sense that the incidences of Type 1 diabetes Mellitus has been found to be higher in regions far away from the equator such as Venezuela. There are also other risk factors associated with T1DM which include viral infections such as Mumps virus, Epstein- Barr virus which are known to destroy the islets. Other viruses such as the Coxsackie virus are implicated in inducing the immune system to attack the infected cells together with the pancreatic β-cells. Chemical drugs such as N-3-pyridylmethyl-N'-p-nitrophenyl urea and drugs such as streptozotocin have also been associated with T1DM as a result of destruction of the pancreatic β- cells. It has also been shown that Vitamin D protects an individual from T1DM. However, low vitamin D levels can be a risk factor for T1DM. In addition, infants exposed to cows’ milk, which is a common source of vitamin D, are at a higher risk of developing T1DM. There are other dietary factors which are known to cause T1DM such as increased nitrates in drinking water, wheat products and cow milk proteins. The diet contribute to the development of T1DM by affecting the permeability of the gut, intestinal flora as well as the immune function in the intestines . Suffice to say that whatever the risk factor involved, the pathophysiology of T1DM always involves the destruction of pancreatic β-cells and more often than not it is through the process of autoimmunity.
2.0 Symptoms and Complications associated with T1DM
TD1M affects the biochemistry as well as the anatomy of several organs and organ systems resulting in a diverse array of signs and symptoms as enumerated below.
2.1Diabetes Ketoacidosis
This is a life threatening complication, induced by deficiency of insulin and is often the initial T1DM indication. The hypoinsulinemea associated with TD1M leads to the inability of the body cells to utilize glucose and consequently there is increased metabolism of fats to fuel the body which results in production of ketones. The increased levels of ketones in the circulatory systems lowers the blood pH resulting in the condition referred to as Ketoacidosis. The symptoms associated with these complications include vomiting, frequent urination, nausea, extreme thirst, fast heartbeat, abdominal pain, severe dehydration, weight loss, weakness, fruity breath, confusion and cold skin.
2.2 Cardiovascular disorders
T1DM is known to increase risk of cardiovascular disorder such as atherosclerosis, hypertension, coronary heart disease, stroke and heart attacks due to the consequent elevation of blood glucose, cholesterol and blood pressure all of which result in plaque build-up and other macrovascular damages. In T1DM, hypertension often results from diabetes related kidney damage. The high blood pressure is the main cause of stroke, heart failure and heart attack. In addition, T1DM is associated with impaired nerve function which causes heart abnormalities.
2.3 Microvascular complication
These are complications that result from damage to the small blood vessels and include nephropathy (damaged kidney nephrons), neuropathy (damaged nerves) and retinopathy (damaged retina). Since T1DM is associated with hypertension, the high blood pressure is known to cause glomeruli rapture. The damaged, glomeruli result in leaking of proteins into the urine. This condition can result in kidney failure over a long period of time. Nephropathy is also known to cause end-stage renal disease (ESRD). Symptoms of Nephropathy include swelling of ankles and feet, fatigue, pale skin colour and itching. Diabetes is known to cause nerve dysfunction. Peripheral neuropathy is known to affect nerves of the arms, hands, feet and toes causing loss of sensation. It also causes ulcers and in severe cases it can lead to amputation. The symptoms of Peripheral Neuropathy include; tingling, burning sensation, deep pain, loss of cold or warm sensation and numbness. On the other hand, autonomic Neuropathy affects nerves responsible for regulating boil, bladder, sex function, digestion and the heart. Their dysfunction can lead to digestive problems, erectile dysfunction, bladder infection, orthrostatic hypotension and rapid heart rate. T1DM results in the damage of the retina leading to blindness. In addition, Diabetes patients are at a higher risk of developing glaucoma and cataract. Retinopathy results from weakening of retina blood vessels and capillary obstruction by small blood clots.
Reference
John, E., & Guyton, A. H. (2006). Text book of Medical Physiology 11Ed. Philedephia: Saunders.
Kumar, V., Fausto, N., Abbas, A. K., Cotran, R. S., & Robbins, S. L. (2005). Robbins and Cotran Pathologic Basis of Disease (7th ed.). Philadelphia: Pa. Saunders..
Raina, E. C., & Kenealy, T. (2008). "Lifestyle interventions reduced the long-term risk of diabetes in adults with impaired glucose tolerance". Evid Based Med , 13(6):173.
World Health Organization. (2006). "Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycemia" . Retrieved 11 3, 2011, from www.who.int. : http://www.who.int/diabetes/publications/Definition%20and%20diagnosis%20of%20diabetes_new.pdf
