First use of insulin to treat diabetes in a human patient.
Diabetes mellitus, commonly known as diabetes, is a group of metabolic disorders characterized by a high blood sugar level (hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased appetite. If left untreated, diabetes can cause many health complications. Acute complications can include diabetic ketoacidosis, hyperosmolar hyperglycemic state, or death. Serious long-term complications include cardiovascular disease, stroke, chronic kidney disease, foot ulcers, damage to the nerves, damage to the eyes and cognitive impairment.Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body not responding properly to the insulin produced. Insulin is a hormone which is responsible for helping glucose from food get into cells to be used for energy. There are three main types of diabetes mellitus:
Type 1 diabetes results from failure of the pancreas to produce enough insulin due to loss of beta cells. This form was previously referred to as "insulin-dependent diabetes mellitus" or "juvenile diabetes". The loss of beta cells is caused by an autoimmune response. The cause of this autoimmune response is unknown. Although Type 1 diabetes usually appears during childhood or adolescence, it can also develop in adults.
Type 2 diabetes begins with insulin resistance, a condition in which cells fail to respond to insulin properly. As the disease progresses, a lack of insulin may also develop. This form was previously referred to as "non insulin-dependent diabetes mellitus" or "adult-onset diabetes". Type 2 diabetes is more common in older adults, but a significant increase in the prevalence of obesity among children has led to more cases of type 2 diabetes in younger people. The most common cause is a combination of excessive body weight and insufficient exercise.
Gestational diabetes is the third main form, and occurs when pregnant women without a previous history of diabetes develop high blood sugar levels. In women with gestational diabetes, blood sugar usually returns to normal soon after delivery. However, women who had gestational diabetes during pregnancy have a higher risk of developing type 2 diabetes later in life.Type 1 diabetes must be managed with insulin injections. Prevention and treatment of type 2 diabetes involves maintaining a healthy diet, regular physical exercise, a normal body weight, and avoiding use of tobacco. Type 2 diabetes may be treated with oral antidiabetic medications, with or without insulin. Control of blood pressure and maintaining proper foot and eye care are important for people with the disease. Insulin and some oral medications can cause low blood sugar (hypoglycemia). Weight loss surgery in those with obesity is sometimes an effective measure in those with type 2 diabetes. Gestational diabetes usually resolves after the birth of the baby.As of 2019, an estimated 463 million people had diabetes worldwide (8.8% of the adult population), with type 2 diabetes making up about 90% of the cases. Rates are similar in women and men. Trends suggest that rates will continue to rise. Diabetes at least doubles a person's risk of early death. In 2019, diabetes resulted in approximately 4.2 million deaths. It is the 7th leading cause of death globally. The global economic cost of diabetes-related health expenditure in 2017 was estimated at US$727 billion. In the United States, diabetes cost nearly US$327 billion in 2017. Average medical expenditures among people with diabetes are about 2.3 times higher.
Insulin (, from Latin insula, 'island') is a peptide hormone produced by beta cells of the pancreatic islets; it is considered to be the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of glucose from the blood into liver, fat and skeletal muscle cells. In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both. Glucose production and secretion by the liver is strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism, especially of reserve body fat.
Beta cells are sensitive to blood sugar levels so that they secrete insulin into the blood in response to high level of glucose; and inhibit secretion of insulin when glucose levels are low. Insulin enhances glucose uptake and metabolism in the cells, thereby reducing blood sugar level. Their neighboring alpha cells, by taking their cues from the beta cells, secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high. Glucagon increases blood glucose level by stimulating glycogenolysis and gluconeogenesis in the liver. The secretion of insulin and glucagon into the blood in response to the blood glucose concentration is the primary mechanism of glucose homeostasis.Decreased or absent insulin activity results in diabetes mellitus, a condition of high blood sugar level (hyperglycaemia). There are two types of the disease. In diabetes mellitus type 1, the beta cells are destroyed by an autoimmune reaction so that insulin can no longer be synthesized or be secreted into the blood. In diabetes mellitus type 2, the destruction of beta cells is less pronounced than in type 1, and is not due to an autoimmune process. Instead, there is an accumulation of amyloid in the pancreatic islets, which likely disrupts their anatomy and physiology. The pathogenesis of type 2 diabetes is not well understood but reduced population of islet beta-cells, reduced secretory function of islet beta-cells that survive, and peripheral tissue insulin resistance are known to be involved. Type 2 diabetes is characterized by increased glucagon secretion which is unaffected by, and unresponsive to the concentration of blood glucose. But insulin is still secreted into the blood in response to the blood glucose. As a result, glucose accumulates in the blood.
The human insulin protein is composed of 51 amino acids, and has a molecular mass of 5808 Da. It is a heterodimer of an A-chain and a B-chain, which are linked together by disulfide bonds. Insulin's structure varies slightly between species of animals. Insulin from animal sources differs somewhat in effectiveness (in carbohydrate metabolism effects) from human insulin because of these variations. Porcine insulin is especially close to the human version, and was widely used to treat type 1 diabetics before human insulin could be produced in large quantities by recombinant DNA technologies.Insulin was the first peptide hormone discovered. Frederick Banting and Charles Herbert Best, working in the laboratory of J. J. R. Macleod at the University of Toronto, were the first to isolate insulin from dog pancreas in 1921. Frederick Sanger sequenced the amino acid structure in 1951, which made insulin the first protein to be fully sequenced. The crystal structure of insulin in the solid state was determined by Dorothy Hodgkin in 1969. Insulin is also the first protein to be chemically synthesised and produced by DNA recombinant technology. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.