In this essay, the author will explore diabetes, from the pathophysiology to management and treatment as well as the role of glucose in homeostasis. Diabetes as a general topic will be considered, aiming to cover all of the main aspects including risk factors, long-term and acute treatment, potential acute problems, and how diabetes occurs at a cellular level. Diabetes can be defined as a chronic disease, metabolic in nature presenting with raised blood glucose levels due to the body's inability to move glucose from extracellular to intracellular fluid (WHO).
To understand glucose homeostasis, it is important to understand homeostasis as a concept. Homeostasis is a self-managed process whereby an organism maintains stability, adjusting as required to surrounding conditions in order to survive and thrive. When successful homeostasis enables life, if unsuccessful the resulting outcome is detrimental to cells and may result in the death of the organism (Palaparthi). More specifically, glucose homeostasis is of vital importance to health as glucose is not synthesized by brain tissue and because glucose is our primary source of energy meaning without adequate blood glucose levels, survival is not possible (Hruby). Normal glucose levels (euglycemia) are maintained primarily by insulin and glucagon, these are naturally occurring hormones that are secreted by the pancreas (Dersarkissian). Insulin is made by the islets of Langerhans located in the pancreas, specifically released by beta cells in simple terms insulin is a key that unlocks cells so glucose can enter. Diabetes can be treated in multiple ways but where an insulin deficiency or absence occurs, supplementary insulin may be prescribed to allow cells to function (Petersen and Shulman). Also produced within the islets of Langerhans but by alpha cells, glucagon is responsible for converting both stored glycogen (glycogenesis) and amino acids (glucogenesis) into glucose. By converting these other products, the amount of glucose used by the liver is greatly reduced meaning a higher blood sugar level is possible (Jiang and Zhang). Once in the cells glucose is converted in a process called glycolysis, this is a process where glucose is hydrogenized and forms adenosine triphosphate (ATP) which is used by cells as energy. The catabolism of glucose into ATP and other small molecules as bi-products is one part of the process of cellular respiration whereby the product created is combined with oxygen to release energy in the cells, creating water and carbon dioxide as waste products (Brenner). It is an autonomic process whereby the above hormones work in conjunction with amylin and incretin, the balance is usually very consistent in healthy people, leading to diabetes where a glucose imbalance occurs.
There are two main types of diabetes mellitus, these can be categorized as either type 1 where the body is unable to produce insulin, and type 2 where the body is unable to produce enough insulin or the insulin produced is unable to be used by the body (Kharroubi). Gestational diabetes and steroid-induced diabetes are also relatively common conditions which will be discussed below. Other rarer forms of diabetes include type 3C and latent autoimmune diabetes, though of different origins share similar pathophysiology, symptoms, and treatment, the author will focus on the more common types (Papatheodorou et al.). In general terms, the pathophysiology of diabetes relates to the body's ability to allow glucose into cells, as this task is completed by insulin, levels of insulin and the body's propensity to use it are the main factor in this process (Kharroubi).
Type one diabetes is an autoimmune disease whereby very little or no insulin at all is produced by the islets of Langerhans inside the pancreas. The cause of type one is unknown though believed to be a combination of environmental and genetic elements; family predisposition is the main known risk factor (Katsarou et al.). Autoimmune destruction of the beta cells which produce insulin within the pancreas is the underlying process, this tends to have an early onset and the majority of cases are diagnosed by the age of 14. When testing for diabetes, type one can be distinguished by the existence of autoantibodies, in their absence the diagnosis would likely be type two diabetes. Prior to treatment people with type one diabetes will experience high blood sugar levels and often the following symptoms; increased thirst, frequent urination, increased hunger, weight loss, and tiredness. Following the onset of the condition, symptoms tend to arise within a short space of time, and those affected often fall acutely unwell prior to diagnosis. Once diagnosed, insulin is required as a treatment pathway due to the body's inability to produce any or enough to maintain glucose homeostasis and there for survival (Eisenbarth).
Type two diabetes is the most common form of diabetes, accounting for approximately 90% of cases diagnosed worldwide (WHO). Symptoms of diabetes are generally caused by chronic high blood sugar readings and so are broadly similar to type one diabetes symptoms, however, the onset time is much slower, and acute illness caused solely by type two diabetes is much less likely. Previously known as adult-onset diabetes (or in Norfolk 'sugar-diabetes'), it is characterized by high blood sugar levels, low insulin levels relative to need, and insulin resistance (DeFronzo et al.). Largely preventable by maintaining a healthy weight and balanced diet, type two diabetes is caused largely by obesity though some people are more genetically pre-disposed than others. Having a much later average onset age, type two diabetes is more common in the elderly population because over time the body develops increased insulin resistance and decreased pancreatic function leading to decreased insulin production. Once diagnosed, the first line of treatment is an altered lifestyle, including increased physical activity and a healthier, more balanced diet. Where lifestyle changes do not have the desired effect, medications such as Metformin are commonly used which improve the way the body handles insulin (van den Arend et al.), the author will discuss the treatment of diabetes further below.
Gestational diabetes is the development of high blood sugar levels during pregnancy in a female who has not previously suffered from the condition. Though generally, few symptoms are present in gestational diabetes, there are increased risks of developing complications in pregnancy such as pre-eclampsia, mental health issues, and an increased rate of cesarean in those suffering from the condition (Plows et al.). The common related issues for babies once born are hypoglycemia, being overweight, liver problems leading to jaundice, and also an increased risk of having a stillbirth if poorly controlled. The cause of gestational diabetes can be either increased insulin resistance or decreased insulin production, similar to type two diabetes, being overweight is a significant risk factor for developing the condition as are previous episodes of the condition, polycystic ovaries, and a family history of type two diabetes. As with type two diabetes, prevention of the condition involved maintaining a healthy weight, good levels of physical activity, and a balanced diet. Though 90% of cases fully resolve once the baby is born, there is an increased risk of developing type two diabetes as a result of gestational diabetes (McIntyre et al.). The treatment for gestational diabetes is identical to that of type two diabetes though due to its quicker onset of symptoms, it is less uncommon for those suffering from the condition to require insulin injections as a treatment pathway (van den Arend et al.).
Steroid-induced diabetes is a condition whereby long-term use of corticosteroids as a treatment for a separate condition results in chronically high blood sugar levels. The mechanism by which steroids increase blood sugar levels varies but includes the following; increased glucose production in the liver, reduced glucose absorption by the muscle and fat cells, and reduced sensitivity to insulin (Hwang and Weiss). Whatever the mechanism, high blood sugars result and can be mild to severe in nature depending on the body's sensitivity to the steroids as well as the dosage and which steroids are being used. Similar to gestational diabetes, steroid-induced diabetes will often resolve once steroid therapy is ceased however there is a much greater risk associated with developing type two diabetes as a result of the condition. Though obesity, high blood pressure, and other risk factors do increase the risk of developing steroid-induced diabetes, the prevalence of the condition in those who are not overweight is much higher than both type two diabetes and gestational diabetes as a percentage. For those who already have a diagnosis of diabetes and commence steroid therapy, control may become an issue and steroid-induced hyperglycemia is often the result (Baldwin and Apel).
Poorly controlled diabetes can affect the body in many ways, in particular the cardiovascular system, the respiratory system, the gastrointestinal system, the neurological system, and the endocrine system. The cardiovascular system is affected by high cholesterol (commonly associated with diabetes) as well as vessel damage, leaving them less elastic causing hypertension. Damage to cardiac nerve cells can cause arrhythmia along with other complications such as congestive cardiac failure and generally poor circulation (Schmidt). The respiratory system is also affected by chronic hyperglycemia, increasing the risk of chronic respiratory illnesses such as asthma and COPD by as much as 60% according to Morse, 2018. Hardening of respiratory structures and loss of elasticity result in reduced respiratory function and therefore increased risk of disease. The gastrointestinal system is adversely affected because nerves that force food through the digestive tract become paralyzed due to chronic high blood sugars, making it a much longer process for food to digest and for gastric emptying (Kim). When blood glucose levels remain high for long periods of time, all nerves in the body have the potential to become affected. Because of this the neurological system is at high risk and can result in diabetic neuropathy, as a result of neuropathy poorly controlled diabetics may require limb of digit amputations or simply suffer reduced sensation (Callaghan et al.). Being the most common endocrine disorder, diabetes is bound to have adverse effects on other aspects of the system and their hormones; the thyroid, adrenal, and gonadal functions are all documented to be adversely affected by diabetes, even with well-controlled blood glucose levels (Steger and Rabe).
Though diabetes of all forms can affect people from any race or ethnic background, the rate of diabetes continues to be higher in certain ethnic minorities (Rebolledo and Arellano). Not only are ethnic minorities more likely to suffer from diabetes, but also less likely to be well managed after diagnosis leading to increased microvascular complications and therefore increased lower limb amputations (Spanakis and Golden). Some of the disparity in rates of diabetes is genetics however there are also cultural differences that affect both rates and management of the condition. From religion to socio-economic status there are many cultural differences affecting diabetes, it is important as healthcare professionals that differences are both acknowledged and overcome to effectively manage diabetes (Caballero).
The author will now discuss how diabetes is treated, including both long-term management and managing diabetic emergencies. As previously mentioned, in type one diabetes supplemental insulin is required due to the inability to produce any or enough insulin for glucose homeostasis. Insulin comes in numerous forms, some quick acting and some slow-release (appendix 2). A combination of these forms is often required for adequate blood sugar management and is prescribed on an individual basis, often involving carb counting and other factors to manage a person's requirements (Haller et al.). As medicine moves forwards, there are automated devices such as an insulin pumps that will accurately dose a person based on their needs according to input data (Lenhard and Reeves). In the event a patient with type one diabetes develops insulin resistance they may also require medication such as metformin which increases the ability of the body to use the supplemental insulin (Beysel et al.). In type two diabetes where lifestyle changes are not adequate, metformin is the most commonly used medication to help reduce blood sugar levels by increasing the amount of insulin the body can utilize (van den Arend et al.). In conjunction with metformin, gliclazide may be used; this is a medication that aids the production of insulin where a person is not making adequate volumes (Khunti et al.). Where this combination is inadequate and blood sugar level remains high, supplemental insulin is required, often in conjunction with these in order to maintain glucose homeostasis and control diabetes. The treatment for both gestational diabetes and steroid diabetes are identical to type two diabetes but depending on the severity of the condition and onset duration may require insulin at an earlier stage (Khursheed et al.).
Hypoglycaemia is a medical emergency in which a patient's blood sugar level drops too low resulting in drowsiness, sweating, slurred speech, confusion, a generally altered mental state, and eventually unconsciousness. The reason a person will have an altered mental state is the brain does not store any glucose which leaves brain cells unable to function as they should (Kaufmann et al.). Where a person remains conscious, the treatment for hypoglycemia is oral carbohydrates, usually with simple sugars such as glucose-gel or a sugary drink followed by complex carbohydrates such as bread to maintain sugar levels once raised. If a person is unable to maintain their airway or becomes unconscious the condition would need to be treated with glucagon which is a hormone that releases glycogen stores into the blood by converting them into glucose. Or Intravenous glucose administration is the gold standard for treating a hypo as stores are replenished and usually results in a maintained sugar level depending on the cause of the condition (Mukherjee et al.). Whenever treatment is given for a hypoglycaemic attack it is important to monitor all vitals as well as regular testing of blood sugar levels post-treatment to assess the efficacy of treatment and patient stability. Whenever a person is conscious and has capacity consent should be gained for any interventions, if a person lacks capacity at any point, treatment may be given in their best interest in order to preserve life (Steer) (Appendix 3).
Hyperglycaemia is not usually a condition that in itself requires immediate attention or presents with symptoms however prolonged hyperglycemia is the cause of potentially life-threatening conditions including diabetic ketoacidosis (DKA) and hyperglycaemic hyperosmolar non-ketonic coma (HONK). The reason hyperglycemia does not present with symptoms in the same way as hypoglycemia is that glucose remains accessible to brain cells, so although the blood-brain barrier may be affected in the long term, in the acute setting brain cells are able to function adequately (Koziel et al.). DKA is a condition where prolonged high blood sugar levels and a lack of insulin result in the build-up of ketones, causing the body's PH to reduce becoming acidotic. The condition usually occurs in type one diabetics though can occur in poorly manages type two diabetic patients where inadequate insulin is produced. Because of this the body breaks down fat at a very high rate and causes the individual to become acutely unwell. Symptoms of DKA include increased urination and thirst, nausea vomiting, confusion, lethargy, and abnormal (Kussmaul's) breathing. This deep, rapid breathing is the response of the respiratory system to decreased blood PH, rapid breathing is designed to blow off carbon dioxide and therefore cause respiratory alkalosis and balance body PH levels (Schumann and Faust). In the pre-hospital setting, treatment for DKA is fluid therapy which helps to dilute the blood and therefore reduce the rate at which fat is being burnt in the body. Once in the hospital, treatment includes further fluid therapy alongside a sliding scale of insulin in order to bring blood balance back to the correct PH and reinstate glucose homeostasis (Rohrlich et al.). HONK is a condition that primarily occurs in type two diabetic patients, again it is caused by hyperglycemia over a period of time and results in similar symptoms to DKA without the presence of ketones. The treatment for HONK is also similar to that of DKA and may include the administration of potassium to help cells function correctly (Schumann and Faust).
Blood glucose levels can be affected by multiple illnesses besides diabetes, some of these include infection, pancreatitis, pancreatic cancer, Cushing's syndrome, and certain medications. Infection can affect blood glucose levels because of the associated stress response from the body, releasing hormones such as adrenaline and cortisol. Working against the actions of insulin, these hormones also promote the production of glucose resulting in hyperglycemia, giving the body more energy to fight infection (Butler et al.). Pancreatitis can inhibit the ability to make either enough insulin or effective insulin resulting in hyperglycemia and in cases of chronic pancreatitis may lead to diabetes (Gillies et al.). Pancreatic cancer can have a similar effect on the body to pancreatitis, inhibiting pancreatic function and resulting in inadequate insulin levels. Pancreatic cancer however may also result in too much insulin in the presence of an insulinoma, where too much insulin is produced this will result in hypoglycaemia and if not surgically removed, is likely to cause acute illness secondary to the cancer itself (Okabayashi). In Cushing's syndrome, the chronically high levels of cortisol excreted result in increased glucogenesis and increased insulin resistance. Around 40-45% of people who suffer from Cushing's syndrome develop diabetes due to the chronic effect of hypercortisolism (Colao et al.). Multiple medications can cause both hyper and hypoglycemia through prolonged use, as previously mentioned corticosteroids are a common cause of hyperglycemia. Managing a patient's medications as well as drug interactions and risk factors such as obesity is both complex and important when managing chronic illness (Hamdy).
To conclude, diabetes is a complex condition that can negatively affect the whole body when not managed well. From genetic predisposition to cultural beliefs and lifestyle choices, there are many different aspects influencing diabetes and how it affects an individual. As a clinician it is important to take a patient-centered approach when helping with the management of the condition, understanding that all variables must be considered whilst being sensitive to a person's beliefs and needs.