Diabetes

Jai Ganesh · 2023-04-23 00:44:57

Diabetes

Gist

Diabetes mellitus (DM) is a disease of inadequate control of blood levels of glucose. It has many subclassifications, including type 1, type 2, maturity-onset diabetes of the young (MODY), gestational diabetes, neonatal diabetes, and steroid-induced diabetes.

Summary

Diabetes mellitus is a disorder of carbohydrate metabolism characterized by impaired ability of the body to produce or respond to insulin and thereby maintain proper levels of sugar (glucose) in the blood.

Diabetes is a major cause of morbidity and mortality, though these outcomes are not due to the immediate effects of the disorder. They are instead related to the diseases that develop as a result of chronic diabetes mellitus. These include diseases of large blood vessels (macrovascular disease, including coronary heart disease and peripheral arterial disease) and small blood vessels (microvascular disease, including retinal and renal vascular disease), as well as diseases of the nerves.

Causes and types

Insulin is a hormone secreted by beta cells, which are located within clusters of cells in the pancreas called the islets of Langerhans. Insulin’s role in the body is to trigger cells to take up glucose so that the cells can use this energy-yielding sugar. Patients with diabetes may have dysfunctional beta cells, resulting in decreased insulin secretion, or their muscle and adipose cells may be resistant to the effects of insulin, resulting in a decreased ability of these cells to take up and metabolize glucose. In both cases, the levels of glucose in the blood increase, causing hyperglycemia (high blood sugar). As glucose accumulates in the blood, excess levels of this sugar are excreted in the urine. Because of greater amounts of glucose in the urine, more water is excreted with it, causing an increase in urinary volume and frequency of urination as well as thirst. (The name diabetes mellitus refers to these symptoms: diabetes, from the Greek diabainein, meaning “to pass through,” describes the copious urination, and mellitus, from the Latin meaning “sweetened with honey,” refers to sugar in the urine.) Other symptoms of diabetes include itching, hunger, weight loss, and weakness.

There are two major forms of the disease. Type 1 diabetes, formerly referred to as insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes, usually arises in childhood. Type 2 diabetes, formerly called non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes, usually occurs after age 40 and becomes more common with increasing age.

Type 1 diabetes mellitus

Type 1 diabetes accounts for about 5 to 10 percent of cases of diabetes. Most cases of type 1 diabetes develop in children or adolescents, but about 20 percent of new patients are adults. The frequency of type 1 diabetes varies widely in different countries, from less than 1 case per 100,000 people per year in China and parts of South America to more than 20 cases per 100,000 people per year in places such as Canada, Finland, Norway, Sweden, and the United Kingdom. Most patients present with symptoms of hyperglycemia, but some patients present with diabetic ketoacidosis, a clear indication that insulin secretion has significantly deteriorated.

Type 1 diabetes is usually caused by autoimmune destruction of the islets of Langerhans of the pancreas. Patients with type 1 diabetes have serum antibodies to several components of the islets of Langerhans, including antibodies to insulin itself. The antibodies are often present for several years before the onset of diabetes, and their presence may be associated with a decrease in insulin secretion. Some patients with type 1 diabetes have genetic variations associated with the human leukocyte antigen (HLA) complex, which is involved in presenting antigens to immune cells and initiating the production of antibodies that attack the body’s own cells (autoantibodies). However, the actual destruction of the islets of Langerhans is thought to be caused by immune cells sensitized in some way to components of islet tissue rather than to the production of autoantibodies. In general, 2 to 5 percent of children whose mother or father has type 1 diabetes will also develop type 1 diabetes.

Type 2 diabetes mellitus

Type 2 diabetes is far more common than type 1 diabetes, accounting for about 90 percent of all cases. The frequency of type 2 diabetes varies greatly within and between countries and is increasing throughout the world. Most patients with type 2 diabetes are adults, often older adults, but it can also occur in children and adolescents. There is a stronger genetic component to type 2 diabetes than to type 1 diabetes. For example, identical twins are much more likely to both develop type 2 diabetes than to both develop type 1 diabetes, and 7 to 14 percent of people whose mother or father has type 2 diabetes will also develop type 2 diabetes; this estimate increases to 45 percent if both parents are affected. In addition, it is estimated that about half of the adult Pima Indian population in Arizona has type 2 diabetes, whereas in the entire United States it is estimated that about 10 percent of the population has type 2 diabetes.

Many patients with type 2 diabetes are asymptomatic, and they are often diagnosed with type 2 diabetes when routine measurements reveal high blood glucose concentrations. In some patients the presence of one or more symptoms associated with the long-term complications of diabetes leads to a diagnosis of type 2 diabetes. Other patients present with symptoms of hyperglycemia that have been present for months or with the sudden onset of symptoms of very severe hyperglycemia and vascular collapse.

Type 2 diabetes is strongly associated with obesity and is a result of insulin resistance and insulin deficiency. Insulin resistance is a very common characteristic of type 2 diabetes in patients who are obese, and thus patients often have serum insulin concentrations that are higher than normal. However, some obese persons are unable to produce sufficient amounts of insulin, and thus the compensatory increase in response to increased blood glucose concentrations is inadequate, resulting in hyperglycemia. If blood glucose concentration is increased to a similar level in a healthy person and in an obese person, the healthy person will secrete more insulin than the obese person.

People with type 2 diabetes can control blood glucose levels through diet and exercise and, if necessary, by taking insulin injections or oral medications. Despite their former classifications as juvenile or adult, either type of diabetes can occur at any age.

Gestational diabetes

Diabetes mellitus also may develop as a secondary condition linked to another disease, such as pancreatic disease; a genetic syndrome, such as myotonic dystrophy; or drugs, such as glucocorticoids. Gestational diabetes is a temporary condition associated with pregnancy. In this situation, blood glucose levels increase during pregnancy but usually return to normal after delivery. However, gestational diabetes is recognized as a risk for type 2 diabetes later in life. Gestational diabetes is diagnosed when blood glucose concentrations measure between 92 and 125 mg per 100 ml (5.1 and 6.9 millimoles [mmol] per litre) after fasting or when blood glucose concentrations equal or exceed 180 mg per 100 ml (10 mmol per litre) one hour after ingesting a glucose-rich solution.

Acute clinical manifestation

Hyperglycemia itself can cause symptoms but usually only when blood glucose concentrations are approximately 180 mg per 100 ml (10 mmol per litre) or higher. When blood glucose concentrations increase, more glucose is filtered by the glomeruli of the kidneys than can be reabsorbed by the kidney tubules, resulting in glucose excretion in the urine. High glucose concentrations in the urine create an osmotic effect that reduces the reabsorption of water by the kidneys, causing polyuria (excretion of large volumes of urine). The loss of water from the circulation stimulates thirst. Therefore, patients with moderate or severe hyperglycemia typically have polyuria and polydipsia (excessive thirst). The loss of glucose in the urine results in weakness, fatigue, weight loss, and increased appetite (polyphagia). Patients with hyperglycemia are prone to infections, particularly vaginal and urinary tract infections, and an infection may be the presenting manifestation of diabetes.

There are two acute life-threatening complications of diabetes: hyperglycemia and acidosis (increased acidity of the blood), either of which may be the presenting manifestation of diabetes. In patients with type 1 diabetes, insulin deficiency, if not recognized and treated properly, leads to severe hyperglycemia and to a marked increase in lipolysis (the breakdown of lipids), with a greatly increased rate of release of fatty acids from adipose tissue. In the liver, much of the excess fatty acid is converted to the keto acids beta-hydroxybutyric acid and acetoacetic acid. The increased release of fatty acids and keto acids from adipose, liver, and muscle tissues raises the acid content of the blood, thereby lowering the pH of the blood. The combination of hyperglycemia and acidosis is called diabetic ketoacidosis and leads to hyperventilation and to impaired central nervous system function, culminating in coma and death. Patients with diabetic ketoacidosis must be treated immediately with insulin and intravenous fluids.

In patients with type 2 diabetes, high blood glucose concentrations can lead to very severe and prolonged hyperglycemia and to marked polyuria, with the loss of a large volume of fluid and a very high serum osmolality. These factors place patients with type 2 diabetes at a high risk of developing central nervous system dysfunction and vascular collapse (hyperglycemia coma). Ketoacidosis is usually not a problem in patients with type 2 diabetes because they secrete enough insulin to restrain lipolysis. Patients with hyperglycemic coma should be treated aggressively with intravenous fluids and insulin.

Details

Diabetes, also known as diabetes mellitus, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body not responding properly to the insulin produced. Diabetes, if left untreated, leads to many health complications. Untreated or poorly treated diabetes accounts for approximately 1.5 million deaths per year.

There is no widely-accepted cure for most cases of diabetes. The most common treatment for type 1 diabetes is insulin replacement therapy (insulin injections). Anti-diabetic medications such as metformin and semaglutide, as well as lifestyle modifications, can be used to prevent or respond to type 2 diabetes. Gestational diabetes normally resolves shortly after delivery.

As of 2019, an estimated 463 million people had diabetes worldwide accounting for 8.8% of the adult population. Type 2 diabetes makes up about 90% of all diabetes cases. The prevalence of the disease continues to increase, most dramatically in low- and middle-income nations. Rates are similar in women and men, with diabetes being the 7th-leading cause of death globally. The global expenditure on diabetes-related healthcare is an estimated USD760 billion a year.

Signs and symptoms

The classic symptoms of untreated diabetes are unintended weight loss, polyuria (increased urination), polydipsia (increased thirst), and polyphagia (increased hunger). Symptoms may develop rapidly (weeks or months) in type 1 diabetes, while they usually develop much more slowly and may be subtle or absent in type 2 diabetes.

Several other signs and symptoms can mark the onset of diabetes although they are not specific to the disease. In addition to the known symptoms listed above, they include blurred vision, headache, fatigue, slow healing of cuts, and itchy skin. Prolonged high blood glucose can cause glucose absorption in the lens of the eye, which leads to changes in its shape, resulting in vision changes. Long-term vision loss can also be caused by diabetic retinopathy. A number of skin rashes that can occur in diabetes are collectively known as diabetic dermadromes.

Diabetic emergencies

People with diabetes (usually but not exclusively in type 1 diabetes) may also experience diabetic ketoacidosis (DKA), a metabolic disturbance characterized by nausea, vomiting and abdominal pain, the smell of acetone on the breath, deep breathing known as Kussmaul breathing, and in severe cases a decreased level of consciousness. DKA requires emergency treatment in hospital. A rarer but more dangerous condition is hyperosmolar hyperglycemic state (HHS), which is more common in type 2 diabetes and is mainly the result of dehydration caused by high blood sugars.

Treatment-related low blood sugar (hypoglycemia) is common in people with type 1 and also type 2 diabetes depending on the medication being used. Most cases are mild and are not considered medical emergencies. Effects can range from feelings of unease, sweating, trembling, and increased appetite in mild cases to more serious effects such as confusion, changes in behavior such as aggressiveness, seizures, unconsciousness, and rarely permanent brain damage or death in severe cases. Rapid breathing, sweating, and cold, pale skin are characteristic of low blood sugar but not definitive. Mild to moderate cases are self-treated by eating or drinking something high in rapidly absorbed carbohydrates. Severe cases can lead to unconsciousness and must be treated with intravenous glucose or injections with glucagon.

Complications

All forms of diabetes increase the risk of long-term complications. These typically develop after many years (10–20) but may be the first symptom in those who have otherwise not received a diagnosis before that time.

The major long-term complications relate to damage to blood vessels. Diabetes doubles the risk of cardiovascular disease and about 75% of deaths in people with diabetes are due to coronary artery disease. Other macrovascular diseases include stroke, and peripheral artery disease. These complications are also a strong risk factor for severe COVID-19 illness.

The primary complications of diabetes due to damage in small blood vessels include damage to the eyes, kidneys, and nerves. Damage to the eyes, known as diabetic retinopathy, is caused by damage to the blood vessels in the retina of the eye, and can result in gradual vision loss and eventual blindness. Diabetes also increases the risk of having glaucoma, cataracts, and other eye problems. It is recommended that people with diabetes visit an optometrist or ophthalmologist once a year. Damage to the kidneys, known as diabetic nephropathy, can lead to tissue scarring, urine protein loss, and eventually chronic kidney disease, sometimes requiring dialysis or kidney transplantation. Damage to the nerves of the body, known as diabetic neuropathy, is the most common complication of diabetes. The symptoms can include numbness, tingling, sudomotor dysfunction, pain, and altered pain sensation, which can lead to damage to the skin. Diabetes-related foot problems (such as diabetic foot ulcers) may occur, and can be difficult to treat, occasionally requiring amputation. Additionally, proximal diabetic neuropathy causes painful muscle atrophy and weakness.

There is a link between cognitive deficit and diabetes. Compared to those without diabetes, those with the disease have a 1.2 to 1.5-fold greater rate of decline in cognitive function. Having diabetes, especially when on insulin, increases the risk of falls in older people.

Causes

[Diabetes mellitus is classified into six categories: type 1 diabetes, type 2 diabetes, hybrid forms of diabetes, hyperglycemia first detected during pregnancy, "unclassified diabetes", and "other specific types". "Hybrid forms of diabetes" include slowly evolving, immune-mediated diabetes of adults and ketosis-prone type 2 diabetes. "Hyperglycemia first detected during pregnancy" includes gestational diabetes mellitus and diabetes mellitus in pregnancy (type 1 or type 2 diabetes first diagnosed during pregnancy). The "other specific types" are a collection of a few dozen individual causes. Diabetes is a more variable disease than once thought and people may have combinations of forms.

Type 1

Type 1 diabetes is characterized by loss of the insulin-producing beta cells of the pancreatic islets, leading to insulin deficiency. This type can be further classified as immune-mediated or idiopathic. The majority of type 1 diabetes is of an immune-mediated nature, in which a T cell-mediated autoimmune attack leads to the loss of beta cells and thus insulin. It causes approximately 10% of diabetes mellitus cases in North America and Europe. Most affected people are otherwise healthy and of a healthy weight when onset occurs. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. Although it has been called "juvenile diabetes" due to the frequent onset in children, the majority of individuals living with type 1 diabetes are now adults.

"Brittle" diabetes, also known as unstable diabetes or labile diabetes, is a term that was traditionally used to describe the dramatic and recurrent swings in glucose levels, often occurring for no apparent reason in insulin-dependent diabetes. This term, however, has no biologic basis and should not be used. Still, type 1 diabetes can be accompanied by irregular and unpredictable high blood sugar levels, and the potential for diabetic ketoacidosis or serious low blood sugar levels. Other complications include an impaired counterregulatory response to low blood sugar, infection, gastroparesis (which leads to erratic absorption of dietary carbohydrates), and endocrinopathies (e.g., Addison's disease). These phenomena are believed to occur no more frequently than in 1% to 2% of persons with type 1 diabetes.

Type 1 diabetes is partly inherited, with multiple genes, including certain HLA genotypes, known to influence the risk of diabetes. In genetically susceptible people, the onset of diabetes can be triggered by one or more environmental factors, such as a viral infection or diet. Several viruses have been implicated, but to date there is no stringent evidence to support this hypothesis in humans.

Type 1 diabetes can occur at any age, and a significant proportion is diagnosed during adulthood. Latent autoimmune diabetes of adults (LADA) is the diagnostic term applied when type 1 diabetes develops in adults; it has a slower onset than the same condition in children. Given this difference, some use the unofficial term "type 1.5 diabetes" for this condition. Adults with LADA are frequently initially misdiagnosed as having type 2 diabetes, based on age rather than a cause.

Type 2

Type 2 diabetes is characterized by insulin resistance, which may be combined with relatively reduced insulin secretion. The defective responsiveness of body tissues to insulin is believed to involve the insulin receptor. However, the specific defects are not known. Diabetes mellitus cases due to a known defect are classified separately. Type 2 diabetes is the most common type of diabetes mellitus accounting for 95% of diabetes. Many people with type 2 diabetes have evidence of prediabetes (impaired fasting glucose and/or impaired glucose tolerance) before meeting the criteria for type 2 diabetes. The progression of prediabetes to overt type 2 diabetes can be slowed or reversed by lifestyle changes or medications that improve insulin sensitivity or reduce the liver's glucose production.

Type 2 diabetes is primarily due to lifestyle factors and genetics. A number of lifestyle factors are known to be important to the development of type 2 diabetes, including obesity (defined by a body mass index of greater than 30), lack of physical activity, poor diet, stress, and urbanization. Excess body fat is associated with 30% of cases in people of Chinese and Japanese descent, 60–80% of cases in those of European and African descent, and 100% of Pima Indians and Pacific Islanders. Even those who are not obese may have a high waist–hip ratio.

Dietary factors such as sugar-sweetened drinks are associated with an increased risk. The type of fats in the diet is also important, with saturated fat and trans fats increasing the risk and polyunsaturated and monounsaturated fat decreasing the risk. Eating white rice excessively may increase the risk of diabetes, especially in Chinese and Japanese people. Lack of physical activity may increase the risk of diabetes in some people.

Adverse childhood experiences, including abuse, neglect, and household difficulties, increase the likelihood of type 2 diabetes later in life by 32%, with neglect having the strongest effect.

Antipsychotic medication side effects (specifically metabolic abnormalities, dyslipidemia and weight gain) and unhealthy lifestyles (including poor diet and decreased physical activity), are potential risk factors.

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Diabetes

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