Symptoms and Prognosis of Diabetes

Molecular/Cellular Basis of Diabetes

Diabetes is a type of lifestyle disorder that is long-lasting and comes by when the body fails to produce enough insulin or does not use it in an effective manner. From the onset, it would be prudent to note that there are various types of diabetes i.e. diabetes type 1, diabetes type 2, gestational, and type 3 diabetes. To a large extent, Type 1 and 2 happen to be the most common types of diabetes. Diabetic patients may present with various symptoms – which may differ from person to person. The said symptoms should be managed properly so as to avoid poor clinical outcomes, some of which may be severe and long-term. Therefore, risks of diabetes as well as its symptoms should be minimized or brought down by embracing a healthy lifestyle as well as seeking and adhering to the relevant interventions when diagnosed with the same. To be able to manage diabetes effectively, it is important to understand what causes diabetes. Diabetes results when insulin is deleted after ? cells are destroyed. At present, Metformin happens to be one of the most effective medications used in the treatment of diabetes owing to its safety profile. Various research pieces have been drafted in an attempt to explain or clarify the molecular mechanism of action for metformin. Indeed, various studies including recent studies indicate that metformin suppresses the production of hepatic gluconeogenesis by activating adenosine 5?-monophosphate (AMP)-activated protein kinase (AMPK). This essay will explain the history, symptoms, and prognosis of diabetes focusing on diabetes type 1 and type 2. The molecular/cellular basis will also be explained as well as the mechanism of action for the relevant diabetes medications.

History

Diabetes, which is also referred to as diabetes mellitus, is a disease that is characterized by having excess sugar in urine. The said disease holds its antiquity from the ancient Egyptians. Essentially, the ancient Egyptian physicians were the first individuals to describe clinical features that were similar to diabetes around 1500 B. C. (Ahmed, 2019). Aretateus the Cappadocian fist coined the word diabetes between 980-1037 A. D. Physicians in India used to refer diabetes as honey urine and would test it by determining whether it attracted ants. In 1776, the presence of sugar in blood and urine was confirmed by Gibson.

Symptoms

The symptoms of diabetes are different depending on the elevation of blood sugar in the body. Individuals with type 3 diabetes may not show any symptoms. However, individuals with type 1 and 2 have symptoms that are more severe (Mayo Clinic, 2020). However, individuals with type 2 diabetes may be asymptomatic and their symptoms develop slowly compared to type 1 diabetes whose symptoms develop rather fast (Kharroubi and Darwish, 2015). Individuals who are diabetic may present with symptoms which are inclusive of, but they are not limited to; frequent infections, slow healing sores, blurred vision, irritability, fatigue, ketones in urine, unexplained weight loss, extreme hunger, frequent urination, and increased thirst. The said symptoms vary with differences in age group. For instance, in adolescents and children, ketoasidosis presents as the first symptom of diabetes (Kahanovits et al, 2017). According to the authors, fatigue, weight loss, increased thirst, frequent urination, and increased appetite are caused by fluid losses, concomitant calories, and elevated glucose levels in urine owing to faulty transport of glucose in the body.

Diabetes Prognosis

Diabetes prognosis also depends on the type of diabetes. According to Goyal and Jialal (2021), diabetes type 2 increases the risk of cardiovascular disease. The said risk can be ameliorated by smoking cessation, regular exercise, statin use, and treating blood pressure. On the other hand, Elsamahy et al (2017) indicate that diabetes type 1 tends to have poor clinical outcomes in children and the female gender in terms of glycemic index and insulin requirements. It is also important to note that if diabetes is poorly managed, it may lead to coma, unconsciousness, mental confusion, cerebral edema, and even death. Apart from the said outcomes, diabetic symptoms that are not managed properly may lead to other long-term conditions. For instance, untreated diabetes may lead to damage of blood vessels which may in turn be associated with peripheral vascular disease, stroke, and heart disease (Kahanovits et al, 2017). Small blood vessels may also be destroyed leading to blindness as a consequence of retinopathy.

Molecular/Cellular Basis of Diabetes

The molecular basis of diabetes is not known. However, various authors indicate that diabetes results from depletion of insulin owing to severe destruction of ? cells which are located in islets of lingerhands, which are domiciled in the pancrease (Kelly et al, 2003). In diabetes type 1, depletion of insulin leads to hyperglycaemia which is caused by autoimmunity in T cells owing to decreased cellular uptake of glucose and hepatic gluconeogenesis.(Dimeglio et al, 2018). In addition, depleted insulin in the body may lead to increase in fatty acid oxidation and breakdown (Kelly et al, 2003). In diabetes type 2, Tamarai et al (2019) found that depletion of insulin is caused by four cellular processes, i.e. autoimmunity and inflammation, oxidative stress, glucotoxicity, and lipotoxicity. Glucotoxicity changes the cellular components during insulin secretion. Lipotoxicity leads to increased fatty acids in the pancreas resulting in damage. The said processes impairs ? cells which then lead to overproduction of reactive oxygen system. This overproduction decreases insulin sensitivity and insulin secretion, decreases the calcium influx resulting in apoptosis, decreases the ATP-to-ADP ratio, and increases the protein kinase inhibitor (Tamarai et al, 2019). This is largely contributed by the fact that ? cells become susceptible to oxidative stress owing to the fact that the said cells do not have several antioxidants which are inclusive of, but they are not limited to; catalase, glutathione, and SOD.

Treatment

Diabetes can be treated using different methods - depending on the type of diabetes. However, lifestyle changes are associated with better outcomes in all types of diabetes. This is more so the case given that diabetes is a lifestyle disease. One of the lifestyle changes would include eating a healthy diet. While there is no specific or special diet for diabetes, Mayo Clinic (2020) recommends that patients with diabetes center their diet on whole grains, lean proteins, more fruits, and more vegetables. Diabetic patients are also encouraged to engage in regular physical activity which helps lower the level of blood sugar in the body. Other treatments for type 1 and 2 diabetes may be inclusive of, but they may not be limited to; pancreas transplant, bariatric surgery, and insulin therapy. Monitoring blood sugar levels is also a crucial diabetes management activity. Medications may also be used in the treatment of diabetes - some of which stimulate the pancreas to release of insulin while others suppress the production of glucose in the liver (Mayo Clinic, 2020). For instance, metformin medications are used in treating diabetes type 2. According to Li et al (2018), metformin is a synthetic derivative of guanidine. According to the authors, metformin is deemed as a rather effective medication for the treatment of diabetes compared to other drugs such as buformin and phenformin.

Molecular Mechanism of Action of Metformin medication

Li et al (2018) indicates that metformin lowers glucose levels by inhibiting hepatic gluconeogenesis. Even though the exact mechanism of action of metformin is not well understood, Li et al (2018) suggest various ongoing studies are being conducted to help understand the molecular mechanism of metformin. For instance, one of the study showed that metformin might activate adenosine 5?-monophosphate (AMP)-activated protein kinase (AMPK), which regulates multiple metabolic pathways. After it has been activated, AMPK could then inhibit the production of glucose in hepatocytes. In another study, it was observed that metformin may suppress hepatic gluconeogenesis whereby CREB binding protein (CBP) is phosphorylated through AMPK-PKC?/? at cerine 436. As a result, CBP-CRTC2 transcription complex is dissociated while gluconeogenic genes are down-regulated (Li et al, 2018). AMPK may also phosphoryrate both acetyl-coA carbohydrase 1 and 2 to prevent acetyl-CoA from being converted to malony-CoA. Therefore, it would be prudent to note that when metformin activates AMPK, it leads to a reduction in liver hepatosteatosis and lipogenesis which contributes to hyperglycemia and improved insulin resistance.