Normal Physiology
The pancreas has two main functions: to secrete enzymes into the digestive tract and to secrete hormones from the alpha and beta cells located on the islets of Langerhans to regulate blood glucose levels. Normally, when food is eaten, glucose floods the body. The beta cells secrete insulin to lower blood glucose levels by signaling different cells in the body to use glucose for energy and to store the remaining glucose in the liver. The alpha cells then secrete glucagon, which signals the liver to release stored glucose. This prevents blood sugar levels from getting too low. Glucagon accomplishes this by stimulating glycogenolysis and gluconeogenesis. Together, the alpha and beta cells regulate blood glucose levels after each meal (khanacademymedicine, 2015). Lastly, while an individual is in the process of eating, the gut releases incretin, which signals the pancreas to secrete insulin to metabolize the glucose that will soon be present in the circulatory system (McCance & Huether, 2014).
Pathophysiology
In an individual who has type 2 diabetes mellitus (T2DM), a dysfunction exists with cells that are normally sensitive to insulin. The main cells that become insulin resistant/insensitive are the liver, skeletal muscles, and adipose tissue. Although many risk factors exist that contribute to the development of T2DM, only those who are genetically predisposed to a beta cell dysfunction will actually go on to develop this chronic disease. There are many mechanisms that contribute to insulin resistance. These include an abnormality with the insulin molecule, high amounts of insulin antagonists, down-regulation of the insulin receptor, decreased or abnormal activation of post-receptor kinases, and alterations in glucose transporter proteins (McCance & Huether, 2014).
Furthermore, obesity is present in 60-80% of those who have this disease process and can lead to insulin resistance in different ways. The first way is through alterations in the production of adipokines, hormones produced in adipose tissue, which leads to leptin resistance and a decreased level of adiponectins. Normally, leptin contributes to feeling sated and adiponectins regulate glucose levels. Secondly, obese individuals have elevated levels of serum free fatty acids and intracellular lipid deposits such as cholesterol and triglycerides. This can be detrimental because it leads to an interference of intracellular insulin signaling, decreased tissue responses to insulin, alterations in insulin, incretin, and glucagon secretion, and promotes inflammation. Another possible mechanism is the release of inflammatory cytokines from intra-abdominal adipocytes and activated macrophages in other tissues. These cytokines induce insulin resistance and the genesis of fatty liver, atherosclerosis, and dyslipidemia. Obesity can also reduce insulin-stimulated mitochondrial activity. This can result in the triggering of insulin resistance, especially in skeletal muscles and hepatocytes. Lastly, obesity is associated with hyperinsulinemia (a condition where excess insulin is circulating in the blood in relation to the amount of glucose) and decreased insulin receptor density. As a result of hyperinsulinemia, symptoms of T2DM can take a while to manifest (McCance & Huether, 2014).
Eventually, beta-cell dysfunction occurs as a result of a decrease in beta-cell mass. Beta cells are very sensitive to high levels of glucose and free fatty acids, two consequences of obesity, and undergo apoptotic cell death. However, although beta cells are under attack, alpha cells still continue to release glucagon which results in hyperglycemia often seen in type 2 diabetics. Moreover, amylin, another beta-cell hormone, is also decreased in type 2 diabetics. Normally, amylin increases satiety and decreases the release of glucagon from alpha cells. Lastly, hyperinsulinemia and hyperleptinemia, excess leptin in the circulatory system, lead to decreased levels of ghrelin in T2DM. Ghrelin is a peptide produced in the stomach and pancreatic islets. Decreased levels are associated with alterations in insulin secretion, insulin resistance, and obesity (McCance & Huether, 2014).
Clinical Manifestations
Generally, symptoms can be vague and unalarming, therefore many people go years without diagnosis and treatment. Classic symptoms of T2DM include polyuria, polydipsia, and polyphagia (Berkowitz, 2007). However, fatigue, pruritus, recurrent infections, visual changes, or symptoms of neuropathy (paresthesia or weakness) may be experienced. Uncontrolled T2DM and chronic hyperglycemia can greatly increase the risk of secondary diseases and therefore symptoms of Coronary Artery Disease, Peripheral Artery Disease, and Cardiovascular Disease can be present (McCance & Huether, 2014)
In the history of present illness, Ms. Yazzie stated that she has been feeling “fatigued and weak at times, as well as having symptoms of sinusitis and two back-to-back yeast infections. She recently bought a water bottle because she noticed she was thirsty ‘all the time.’” The reason why Ms. Yazzie has been feeling fatigued and weak is because her skeletal muscle cells and her adipose cells are not effectively utilizing glucose for energy. The receptors on these cells have become unresponsive to insulin, which inhibits glucose from entering into these cells. Additionally, the sinusitis and yeast infections are a result of an increase in the inflammatory response due to elevated levels of inflammatory cytokines in the body. Lastly, the reason why Ms. Yazzie suffers from polydipsia (increased thirst) is due to polyuria (increased urination). When there is an increased amount of glucose in the circulatory system, as is the case with diabetics, the kidney will excrete glucose, resulting in the passive movement of fluids out of the body.