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Diabetes Mellitus

Dalya Tobea

King University

Diabetes Mellitus

Diabetes mellitus is a condition in which the body has too much glucose in the bloodstream. There are three major types of diabetes mellitus: type 1 diabetes mellitus, type 2 diabetes mellitus, and gestational diabetes. Type 1, formally known as juvenile diabetes or insulin-dependent diabetes, is a chronic autoimmune disease that is caused by the destruction of the beta cells in the pancreatic islets. The purpose of the beta cells is to store and release insulin when the blood glucose becomes too high (McCance & Huether, 2014). Destruction of the beta cells will leave the body with no insulin to decrease blood glucose levels. This population of individuals will need to be given insulin to survive as their bodies are no longer able to produce insulin. In type 2 diabetes, these individuals make insulin but the body becomes resistance to insulin therefore requiring supplements. The diagnosis of diabetes mellitus is based on glycosylated hemoglobin (HbA1c) level that is greater than 6.5%, fasting blood sugar level that is greater than 126 mg/dl, patients with signs of hyperglycemia with a random glucose check that is greater than 200 mg/dl, or blood sugar greater than 200 during an oral glucose tolerance test. The criteria for increased risk for developing diabetes are fasting blood sugar 100 to 125 mg/dl, 2-hour plasma glucose in the range of 75 to 199 mg/dl during an oral glucose tolerance test or HbA1C that is 5.7% to 6.4% (Uphold & Graham, 2013). Type 1 diabetes mellitus is an autoimmune disease that is associated by absolute insulin deficiency.

Risk Factors

Risk factors for type 1 diabetes mellitus include family history, genetics, age, geography, and exposure to viruses. Family history of diabetes mellitus is a major risk factor to develop diabetes. The recurrence risk of an offspring having diabetes from a parent is elevated compared to the normal population. The risk is greater when the farther passes the disease (Knip et al., 2005). The literature supports that humans are at higher chance of developing diabetes if either parents were diagnosed with the disease. This is caused by the gene polymorphisms in the major histocompatibility complex. The major histocompatibility complex consists of alpha and beta chains that bond to form a bind in which the antigens involved in the pathogenesis of diabetes mellitus are compelled (Massimo, 2014). This causes the release of T cells which will lead to the destruction of beta cells through the release of toxins and interleukins.

Environment factors are another major risk factor for diabetes mellitus. The concordance rate in identical twins with type 1 diabetes is 50%. However, the concordance rate in fraternal twins is 5 to 10% (McCance & Huether, 2014). This indicates that genetics are not fully responsible for causing this disease or the accordance rates in the identical twins would be 100%. Environmental factors, such as virus exposure, increases the risk of diabetes by creating an autoimmune response that results in self-destruction in the beta cells. The enteroviruses, such as coxsackieviruses B, damages the beta cells and stimulates the cytotoxic T cell. The cytotoxic T cells will attack the beta cells through release of toxins that causes the islet cells to apoptosis. Family predisposition and environmental factors are associated aspects that leads to the diagnosis of diabetes mellitus (Massimo, 2014). Literature supports both influences to contribute to type 1 diabetes. An individual can be genetically predisposed to acquiring diabetes and an environmental triggered the cause the autoimmune process.

Role of genetics and epigenetics

The exact cause of diabetes is unknown, however, it is believed to be caused by genetics and environmental factors. Recent developments have classified diabetes mellitus to be a heterogeneous group. In diabetics, the beta cells of the pancreas are destroyed by the T-cell infiltration. The T-cell infiltrations are caused by the autoantigens that form on the beta cells and circulate in the bloodstream (Knip et al., 2005). The antigen-processing cells consume the autoantigen which activates the helper T cells. The activated helper T cell release interleukins, causing production of T cytotoxic lymphocytes leading to attack the beta cells. Autoantibodies, which are caused by the activation of the B lymphocytes, are formed against the beta cells causing an inflammatory response which leads to apoptosis (McCance & Huether, 2014). As a result of the T-cell infiltration and release of autoantibodies, the beta cells are destroyed thereby rendering insulin production in the body.

Pathophysiology

There are two categories of diabetes mellitus that have been identified: autoimmune and nonimmune. In autoimmune-mediated diabetes, it is believed that environmental factors and genetic susceptibility trigger cell-mediated constructions of the beta cells in the pancreas (McCance & Huether, 2014). Nonimmune is less common and typically occurs secondary to other diseases, such as pancreatitis or cancers. Nonimmune is found commonly in Asian or African Americans (McCance & Huether, 2014).

Autoimmune is a disease in which the body’s immune system recognizes healthy normal cells to be foreign and attacks the cells. The helper and cytotoxic T cells attack and destroy beta cells. B lymphocytes produce antigens against the beta cells, which the cytotoxic T cells recognizes the autoantigens on the beta cells leading to destruction (Hassan, Silem, Ellethy, & Salama, 2012). This results in the activation of the innate immune response resulting release of cytokines and activation of the complement cascade to identify the activated cells.

Diabetes affects the breakdown of fats, amino acids, and glucose. A person that has uncontrolled glucose levels will have high glucose levels in the blood. This results in glucose being excreted by the glomeruli of the kidneys as it exceeds the amount that can be reabsorbed by the renal tubules which contributes to diabetic nephropathy (McCance & Huether, 2014). Large amounts of water follow the glucose that is excreted by the kidneys which results in osmotic diuresis. High glucose levels attracts water as it pulls water out of the cells resulting in intracellular dehydration (McCance & Huether, 2014). The body will turn to protein and fat breakdown to use for energy, known as gluconeogenesis, if there is no insulin to utilize to have the glucose to go into the cells. The metabolism of fatty acids yields ketones. Large amounts of ketones will drop the pH causing metabolic acidosis. This is referred as Diabetic Ketones Acidosis (DKA) which a life threatening complication of diabetes mellitus.

Elevated blood glucose acts as sharp crystals damaging macrovascular and microvascular blood vessels in the body. Elevated blood glucose levels cause damages to the fine delicate nerve fibers resulting in numbness or tingling. This is known as diabetic neuropathy. Elevated blood glucose disturbs the nerves capabilities to transmit signals and deteriorates the walls of the blood capillaries that supplies the nerve with oxygen and nutrients (Mayo Clinic, 2015). Diabetic retinopathy is damages to the tiny capillaries in the retina caused by high blood glucose levels. It can cause the capillaries in the retina to leak fluids or hemorrhage (Mayo Clinic, 2015). Individuals with diabetes have an increased risk for peripheral, coronary artery, and cerebrovascular disease. Diabetes causes abnormalities in the vascular smooth muscle and platelet functions. High glucose levels stimulate increase production of prothrombotic factors which can cause cerebrovascular accidents and atherosclerosis. High glucose levels changes platelet function by impairing calcium homeostasis resulting in platelet conformation and release of mediators (Creagor & Luscher, 2003). The high blood sugar levels in the bloodstream causes release of fatty acids with the by-product of ketones to be used to energy. Ketones stimulate the release oxidative stress which causes damage to the endothelial vascular system and causes narrowing of the vessels resulting in poor circulation which leads to diabetic ulcers to lower extremities (Creagor & Luscher, 2003).

The clinical manifestations of diabetes mellitus are high glucose levels checks, fatigue, weight loss, polydipsia, polyuria, and polyphagia. The disease commonly develops before the age of 30 (Mayo Clinic, 2015). These individuals are usually not overweight and their bodies produces little or no insulin therefore making prone to ketoacidosis. Diabetes mellitus occurs gradually with the destruction of the beta cells instead of abruptly (McCance & Huether, 2014). The onset of clinical manifestations appears abrupt, however, the beta cells are slowly destructed therefore creating a long period of latency before symptoms present. The peak onset for diabetes mellitus is 11-13 years of age, rarely occurring under the age of 1 or over the age of 30 (Mayo Clinic, 2015).

Complications

A serious complication of diabetes mellitus is ketoacidosis (DKA). DKA develops in type 1 diabetes where there is no insulin production as the blood sugars dramatically increased to the high 600-800mg/dl. This complication commonly occurs when a person has an infection with decreased appetite or nausea/vomiting and decrease or ceased their insulin injections. The human body’s response to insulin deficiency is increasing the amount of catecholamines, cortisol, and glucagon (McCance & Huether, 2014). These hormones result in increase glucose production; the glucose will continue to raise as there is no insulin to bring the glucose into the cell to use for energy. Gluconeogenesis occurs with the release of fatty acids to utilize for energy, which results in ketones as a by-product. Ketones are strong acids and with increased concentration, a person will develop metabolic acidosis. Ketones are used by the body to regenerate bicarbonate. Bicarbonate is an alkalotic that the kidney uses as a buffer to maintain the body’s pH (McCance & Huether, 2014). The kidneys are not able to buffer the bicarbonate when the ketones are elevated; however, the kidney will increase filtering the ketones out of the body. These people exhibit Kussmal respirations which is breathing very fast too blow off carbon dioxide to increase the pH to normal levels. The treatment for DKA is fluid and insulin administration. These people are severely dehydrated as osmotic diuresis occurs when the kidneys excrete glucose and water follows (Gosmanov, Gosmanova & Dillard-Cannon, 2014). Electrolytes such as sodium and phosphorus become deficit and potassium is increased as a result of the osmotic diuresis. Education is important to inform patients to continue to administer insulin with infections.

Treatments

Every person with type 1 diabetes mellitus will need insulin administration as their body is not able to produce insulin. Insulin is a hormone that is released by the beta cells in the Langerhans of the pancreas as a response to high blood glucose levels. It causes the cells to take up glucose to utilized for energy or convert it to glycogen for storage. Insulin can not be taken orally for it is digested in the stomach by the pancreatic enzymes rendering its effectiveness. Therefore, insulin must be injected to subcutaneous tissue.

Treatment regimens will be tailored towards maintaining HbA1C less than 7% without frequent episodes of hypoglycemia. Hypoglycemia occurs when blood glucose levels drop below 60 or 70 mg/dl. Feelings of shaky, lightheaded, or sweating are symptoms of hypoglycemia. The two types of insulin regimens are intensive insulin treatment and standard insulin treatment. Intensive insulin treatment is used to maintain a strict glucose level in the body by injecting insulin several times a day with frequent glucose checks (McCulloch, 2015). Strict blood glucose levels are enforced to prevent microvascular and macrovascular changes associated with diabetes mellitus. People have an option to utilized an insulin pump. The advantages with the pump include less insulin injections and less fluctuations of how much insulin is absorbed by the body compared to drawing and injecting insulin. The disadvantages with the insulin pump are greater cost than manually injecting insulin and feelings of embarrassment of people seeing the pump on the body (McCulloch, 2015). Individuals need to be able to recognized the signs and symptoms of hypoglycemia and hyperglycemia. Diabetics need to eat foods with low glycemic index. Glycemic index is a measure used to analyze carbohydrates and its impact on blood glucose levels. Low glycemic index foods do have large amount of fluctuations of glucose levels compared to the high glycemic index foods. Low glycemic foods include vegetables, nuts, and fruits. High glycemic index foods include dairies, potatoes, and bread. Exercise improves glycemic control; it is uncertain of the exact pathophysiology. Regular physically activity lowers the severity of the complications related to diabetes mellitus (Yardley et al, 2012).

Immunomodulation is an adjustment of the immune response to potentiate or suppress the immune system (McCance & Huether, 2014). Immunomodulation is a new approach that is currently being reviewed to prevent and treat diabetes mellitus. Vaccinations can be given to high risk patients for diabetes. Vaccines that have been tested are glutamic acid decarboxylase and insulin. A study conducted by Ludvigsson (2009) concluded that maintaining of the remaining insulin secretion in new onset of diabetes can occur with the glutamic acid decarboxylase vaccines and treatment with anti-CD3 monoclonal antibodies. Anti-CD3 monoclonal antibodies have been showed to blocked the destruction of beta cells for a short period of time. Anti-CD3 monoclonal antibodies acts to blocked the antigen presented on the beta cells to the cytotoxic T cells. According to Ludvigsson (2009) it is the most effective modulation at this time. Side effects are not specific including critically low platelet and white blood cell count, anemia, nausea, and vomiting. If immunomodulation therapy manipulates the body to preserve insulin, then the individual would not have all their beta cells destroyed. Stem cells are being reviewed to preserve beta cells by engraftment of beta cells that produce insulin (McCance & Huether, 2014).

Diabetes mellitus is a chronic autoimmune disease that occurs when an individual is genetically predisposed and an environmental trigger occurs. The beta cells are destroyed by the body’s inmate response resulting in no insulin production. These individuals need supplement of insulin to prevent the complications of diabetes. It is important to have glucose levels well-controlled and regulated fairly often to prevent the macrovascular and microvascular changes in the body. These individuals need to be thoroughly educated about the disease such as signs and symptoms of hyperglycemia or hypoglycemia and which treatments to follow with their symptoms. These individuals need to be assessed by a primary physician several times a year with education on meal planning, preparation of insulin, and self-monitoring of glucose levels.

References

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