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Type 1 Diabetes(T1D) is a insulin-dependent diabetes caused by autoimmune reactions in which T cells cause damages to pancreatic Î² cells. T1D is characterized by a significant deficiency of Î² cells followed by a shortage of insulin. Multiple genetic and environmental factors are related to the initiation of T1D. CD4+ and CD8+ T cell and cytokine play an important role in the development of T1D. The introduce of recombinant insulin provided a efficient treatment of T1D. However, there is no cure for this disease.
Diabetes, or Diabetes mellitus, is a disease caused by defects of insulin production or function. Diabetes has a typical symptom of diabetes is high blood glucose levels and further causes metabolic disorders and other complications. Nowadays, diabetes has become one of the severest chromic diseased and one of the biggest health issues in the world, only ranked after cancer and cardiocascular disease(Matthews et al., 2008).
There are three main clinical types of diabetes: type 1 diabetes(T1D), type 2 diabetes(T2D) and gestational diabetes(GD). Type 1 diabetes (also called juvenile diabetes or insulin-dependent diabetes) is an autoimmune disease caused by the impairment of pancreatic Î² cells function. In T1D, the Î² cells are unable to produce insulin properly, thus result in the deficiency of insulin and the increase of glucose levels in blood. This type is usually diagnosed in children, teenagers and young adults. About 7%-10% of diabetes patients have type 1 diabetes. Type 2 diabetes is the most common form of diabetes. It can be diagnosed at any age, but most patients of T2D are elderly people. In T2D, liver cells cannot take in or use insulins and therefore the glucose is accumulated in blood. Gestational diabetes is diagnosed in pregnant women and is usually happen at late stage of pregnancy. T2D is also the most commonly seen diabetes. About 90% of the population with diabetes has T2D. The cause of GD is still not very clear. It is believed to be related to the hormones of pregnancy.
In this essay, stress will be put in type 1 diabetes and the symptoms, pathogens, diagnosis and treatments of type 1 diabetes will be presented and discussed.
2 Signs and Symptoms
2.1 Clinical Fetures
Clinical features of type 1 diabetes include the following symptoms:
Unexplained weight loss
Delayed wound healing
The causes mainly lay in the in the difficulties for cells to turn glucose into energy and the inhibitor of fat cells to store fats.
3.1 Genetics Factors
The type 1 diabetes-associated genes are mainly located in HLA loci, which contribute approximately half of the risk of development of T1D. Examples are DQ2 and DQ8 molecules encoded by HLA class II genes. With a specific set of peptides, they significantly contribute to T1D susceptibility.
Non-HLA genes related to T1D includes CTLA4 (located on 2q33) and PTPN22. CTLA4 gene encodes Cytotoxic T-lymphocyte antigen 4 (CTLA-4) protein. Mutations in CTLA4 can increase immune activities through regulate the behavior of T cells and are related to several immune disease including T1D(Vaidya and Pearce, 2004). PTPN22 expresses lymphoid tyrosine phosphatase protein(LYP) in lymphocytes. LYP-Trp620, a gain-of-function veriant of LYP, efficiently inhibit the activation of T cells in autoimmune reactions. (Vang et al., 2005).
3.2 Environment Factors
It is general believed that type 1 diabetes has a gene and environment associated mechanism. Genetic factors combined with environmental stimulant largely increase the risk of T1D.
3.2.2 milk proteins
3.3 Autoimmune Regulation
In 1974, Bottazzo first discovered that there was antibody of pancreatic Î² -cell antigen. Nowadays T1D has been recognized as an autoimmune disease characterized by pancreatic Î² cells deficiencies involved with High-avidity autoreactive T cells. The role of autoimmune regulation in the development of T1D will be discussed in the next chapter.
4 Cellular and Molecular Mechanism
Type 1 diabetes is a autoimmune disease induced by T cell. In cellular level, T1D is characterized by large scale of deficiencies in pancreas Î² cells followed by significantly decrease of insulin levels. Studies have indicated that CD4+ and CD8+ T cells and cytokines is playing a pivot role in the pathogenesis of T1D.
4.1 T cells and the deficiencies of Î²cells
T cells play an important role in the pathogenesis of type 1 diabetes. Figure 1 demostrate the signaling pathway of autoimmune reactions in which CD4+ and CD8+ T cells caused damage to Î² cells. High-avidity autoreactive CD4+ and CD8+ T cells that flee away from thymus travel to and stay around lymphoid organs. When environmental factors (viruses, proteins, chemicals, etc.) reach the pancreas, they stimulate the Î² cells to release autoantigens. The autoantigens are processed by antigen-presenting cells(APC) and then carried to pancreatic lymph nodes(PLNs). APC also act as the prime activator of the HA autoreactive T cells. The CD4+ and CD8+ T cells proliferate and differentiate into cytotoxic T cells(CTLs). The CTLs travel through blood vascular to pancreatic islet. When the CTLs reach autoantigens in Î² cells, they secrete cytokines that cause impairment and apoptosis of Î² cells. The mechanism of which T cells function on Î² cells is still unclear. There is a hypothesis that CLTs recognize autoantigen on Î² cells. However, when and how insulin will act as an autoantigen remain unknown.
4.2 Cytokine and deficiencies of pancreas islet Î² cells
More and more researches have indicated that apoptosis is the major type of Î² cells dificiencies. The cell death of Î² cells provided autoantigens in the autoimmune reactions.Â
Studies have shown that Î² cells will conduct cytoclasis under the environment of Â oxygen radical and NO. Under the environment ofÂ proinflammtory cytokinesÂ andÂ low concentration of glucose, on the other hand, Î² cells will conduct apoptosis(Pozniakovsky and Knorre, 2005). Cytokine released by CTLs induce the apoptosis of Î² cells and thus caused T1D.
5 Diagnostic methods
To diagnose type 1 diabetes, the glucose levels in blood must be tested. There are several methods in testing blood glucose concentration: fasting blood glucose (FBG) test, random blood glucose test and oral glucose tolerance test (OGTT)
Fasting Blood Glucose (FBG) Test Just as the name implies, testee has to conduct at least eight hours fasting (without any drink or food, except water) before his or her blood sample is obtained. Fasting blood glucose test is the most commonly used diagnostic methods in T1D. However, it can not be used in emergency cases.
Random Blood Glucose Random blood glucose test is more applicable than FBG test in medical emergencies. The blood glucose level is tested without fasting before testing. In this case, typical T1D patients have a glucose level higher than 200mg/dl.
Oral Glucose Tolerance Test (OGTT)
6.1 Insulin Injection
While type 1 diabetes remains incurable these days, insulin rejection has provided a efficient treatment to control the glucose level of T1D patients. Insulin is the only drug that enables the cells to take in glucose from blood and thus reduce the accumulation of glucose in blood. As the enzymes in digestive system of human body will digest insulin and inhibit its activities like other proteins, insulin is usually taken in by under skin injection and insulin pump infusion.
There are different choices of insulin due to the needs of patient in different cases. Usually a combination of several types of insulin is applied in clinical treatment. Standard plan includes ... The types and doses of insulin injected will be adjusted according to the glucose levelsÂ throughout the treatment process.
6.2 Diet Plan and Carb Counting
In patients with type 1 diabetes, the blood glucose levels increases significantly accompanying any food taken in. As a result, diet plan is an important method to keep the blood glucose levels within the target range. Diet plan usually includes breakfast, lunch and dinner. Appropriate snacks are allowed. Not only nutrition but also the patient's acitivity levels and daily routines must be taken into account in the plan. Carb counting in every meal is necessary with any food the patient takes in. Counting the carbs allowing the patient to get a understanding of how much sugar has been take in ang ajust the amount of insulin injected.
6.3 Regularly Exercise
Type 1 Diabetes(T1D) is a insulin-dependent diabetes caused by autoimmune reactions in which T cells cause damages to pancreatic Î² cells. Although the signaling pathways of T1D is characterized by a significant deficiency of Î² cells followed by a shortage of insulin. Multiple genetic and environmental factors are related to the initiation of T1D. CD4+ and CD8+ T cell and cytokine play an important role in the development of T1D. Insulin injection combined with appropriate diet and exercise plan provides a efficient way to control blood glucose level in T1D.
MATTHEWS, D., MESTON, N. & DYSON, P. 2008. Diabetes : The Facts. Oxford: OUP Oxford.
POZNIAKOVSKY, A. I. & KNORRE, D. A. 2005. Role of mitochondria in the pheromone- and amiodarone-induced programmed death of yeast. The Journal of Cell Biology, 168, 13.
VAIDYA, B. & PEARCE, S. 2004. The emerging role of the CTLA-4 gene in autoimmune endocrinopathies. European Journal of Endocrinology, 150, 619-626.
VANG, T., CONGIA, M., MACIS, M. D., MUSUMECI, L., ORRU, V., ZAVATTARI, P., NIKA, K., TAUTZ, L., TASKEN, K., CUCCA, F., MUSTELIN, T. & BOTTINI, N. 2005. Autoimmune-associated lymphoid tyrosine phosphatase is a gain-of-function variant. Nat Genet, 37, 1317-1319.