Diabetes mellitus
Diabetes mellitus (IPA pronunciation: [ˌdaɪəˈbitəs]). is a metabolic disorder characterized by hyperglycemia (high blood sugar) and other signs, as distinct from a single disease or condition. The World Health Organization recognizes three main forms of diabetes: type 1, type 2, and gestational diabetes (occurring during pregnancy),[1] which have similar signs, symptoms, and consequences, but different causes and population distributions. Type 1 is usually due to autoimmune destruction of the pancreatic beta cells which produce insulin. Type 2 is characterized by tissue-wide insulin resistance and varies widely; it sometimes progresses to loss of beta cell function. Gestational diabetes is similar to type 2 diabetes, in that it involves insulin resistance; the hormones of pregnancy cause insulin resistance in those women genetically predisposed to developing this condition.
Types 1 and 2 are incurable chronic conditions, but have been treatable since insulin became medically available in 1921, and are nowadays usually managed with a combination of dietary treatment, tablets (in type 2) and, frequently, insulin supplementation. Gestational diabetes typically resolves with delivery.
Diabetes can cause many complications. Acute complications (hypoglycemia, ketoacidosis or nonketotic hyperosmolar coma) may occur if the disease is not adequately controlled. Serious long-term complications include cardiovascular disease (doubled risk), chronic renal failure (diabetic nephropathy is the main cause of dialysis in developed world adults), retinal damage (which can lead to blindness and is the most significant cause of adult blindness in the non-elderly in the developed world), nerve damage (of several kinds), and microvascular damage, which may cause erectile dysfunction (impotence) and poor healing. Poor healing of wounds, particularly of the feet, can lead to gangrene which can require amputation — the leading cause of non-traumatic amputation in adults in the developed world. Adequate treatment of diabetes, as well as increased emphasis on blood pressure control and lifestyle factors (such as smoking and keeping a healthy body weight), may improve the risk profile of most aforementioned complications.
Terminology
The term diabetes (Greek: διαβήτης) was coined by Aretaeus of Cappadocia. It is derived from the Greek word διαβαίνειν, diabaínein that literally means "passing through," or "siphon", a reference to one of diabetes' major symptoms—excessive urine production. In 1675 Thomas Willis added the word mellitus to the disease, a word from Latin meaning "honey", a reference to the sweet taste of the urine. This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, and Indians. In 1776 Matthew Dobson confirmed that the sweet taste was because of an excess of a kind of sugar in the urine and blood of people with diabetes.[2]
The ancient Indians tested for diabetes by observing whether ants were attracted to a person's urine, and called the ailment "sweet urine disease" (Madhumeha). The Korean, Chinese, and Japanese words for diabetes are based on the same ideographs (糖尿病) and also mean "sweet urine disease".
Diabetes, without qualification, usually refers to diabetes mellitus, but there are several rarer conditions also named diabetes. The most common of these is diabetes insipidus (insipidus meaning "without taste" in Latin) in which the urine is not sweet; it can be caused by either kidney (nephrogenic DI) or pituitary gland (central DI) damage.
The term "type 1 diabetes" has universally replaced several former terms, including childhood-onset diabetes, juvenile diabetes, and insulin-dependent diabetes. "Type 2 diabetes" has also replaced several older terms, including adult-onset diabetes, obesity-related diabetes, and non-insulin-dependent diabetes. Beyond these numbers, there is no agreed standard. Various sources have defined "type 3 diabetes" as, among others:
• Gestational diabetes[3]
• Insulin-resistant type 1 diabetes (or "double diabetes")
• Type 2 diabetes which has progressed to require injected insulin.
• Latent autoimmune diabetes of adults (or LADA or "type 1.5" diabetes)
History
Although diabetes has been recognized since antiquity, and treatments of various efficacy have been known in various regions since the Middle Ages, and in legend for much longer, pathogenesis of diabetes has only been understood experimentally since about 1900.[4] The discovery of a role for the pancreas in diabetes is generally ascribed to Joseph von Mering and Oskar Minkowski, who in 1889 found that dogs whose pancreas was removed developed all the signs and symptoms of diabetes and died shortly afterwards.[5] In 1910, Sir Edward Albert Sharpey-Schafer suggested that people with diabetes were deficient in a single chemical that was normally produced by the pancreas—he proposed calling this substance insulin, from the Latin insula, meaning island, in reference to the insulin-producing islets of Langerhans in the pancreas.[4]
The endocrine role of the pancreas in metabolism, and indeed the existence of insulin, was not further clarified until 1921, when Sir Frederick Grant Banting and Charles Herbert Best repeated the work of Von Mering and Minkowski, and went further to demonstrate they could reverse induced diabetes in dogs by giving them an extract from the pancreatic islets of Langerhans of healthy dogs.[6] Banting, Best, and colleagues (especially the chemist Collip) went on to purify the hormone insulin from bovine pancreases at the University of Toronto. This led to the availability of an effective treatment—insulin injections—and the first patient was treated in 1922. For this, Banting and laboratory director MacLeod received the Nobel Prize in Physiology or Medicine in 1923; both shared their Prize money with others in the team who were not recognized, in particular Best and Collip. Banting and Best made the patent available without charge and did not attempt to control commercial production. Insulin production and therapy rapidly spread around the world, largely as a result of this decision.
The distinction between what is now known as type 1 diabetes and type 2 diabetes was first clearly made by Sir Harold Percival (Harry) Himsworth, and published in January 1936.[7]
Despite the availability of treatment, diabetes has remained a major cause of death. For instance, statistics reveal that the cause-specific mortality rate during 1927 amounted to about 47.7 per 100,000 population in Malta.[8]
Other landmark discoveries include:[4]
• identification of the first of the sulfonylureas in 1942
• the determination of the amino acid order of insulin (by Sir Frederick Sanger, for which he received a Nobel Prize)
• the radioimmunoassay for insulin, as discovered by Rosalyn Yalow and Solomon Berson (gaining Yalow the 1977 Nobel Prize in Physiology or Medicine)[9]
• the three-dimensional structure of insulin
• Dr Gerald Reaven's identification of the constellation of symptoms now called metabolic syndrome in 1988
• Demonstration that intensive glycemic control in type 1 diabetes reduces chronic side effects more as glucose levels approach 'normal' in a large longitudinal study,[10] and also in type 2 diabetics in other large studies
• identification of the first thiazolidinedione as an effective insulin sensitizer during the 1990s
Causes and types
Glucose metabolism
Mechanism of insulin release in normal pancreatic beta cells. Insulin production is more or less constant within the beta cells, irrespective of blood glucose levels. It is stored within vacuoles pending release, via exocytosis, which is triggered by increased blood glucose levels.
Because insulin is the principal hormone that regulates uptake of glucose into most cells from the blood (primarily muscle and fat cells, but not central nervous system cells), deficiency of insulin or the insensitivity of its receptors plays a central role in all forms of diabetes mellitus.
Much of the carbohydrate in food is converted within a few hours to the monosaccharide glucose, the principal carbohydrate found in blood. Some carbohydrates are not converted. Notable examples include fruit sugar (fructose) that is usable as cellular fuel, but it is not converted to glucose and does not participate in the insulin / glucose metabolic regulatory mechanism; additionally, the carbohydrate cellulose (though it is actually many glucose molecules in long chains) is not converted to glucose, as humans and many animals have no digestive pathway capable of handling cellulose. Insulin is released into the blood by beta cells (β-cells) in the pancreas in response to rising levels of blood glucose (e.g., after a meal). Insulin enables most body cells (about 2/3 is the usual estimate, including muscle cells and adipose tissue) to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage. Insulin is also the principal control signal for conversion of glucose (the basic sugar used for fuel) to glycogen for internal storage in liver and muscle cells. Reduced glucose levels result both in the reduced release of insulin from the beta cells and in the reverse conversion of glycogen to glucose when glucose levels fall, although only glucose thus recovered by the liver re-enters the bloodstream as muscle cells lack the necessary export mechanism.
Higher insulin levels increase many anabolic ("building up") processes such as cell growth and duplication, protein synthesis, and fat storage. Insulin is the principal signal in converting many of the bidirectional processes of metabolism from a catabolic to an anabolic direction, and vice versa. In particular, it is the trigger for entering or leaving ketosis (ie, the fat burning metabolic phase).
If the amount of insulin available is insufficient, if cells respond poorly to the effects of insulin (insulin insensitivity or resistance), or if the insulin itself is defective, glucose will not be handled properly by body cells (about ⅔ require it) or stored appropriately in the liver and muscles. The net effect is persistent high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as acidosis.
Type 1 diabetes mellitus
Main article: Diabetes mellitus type 1
Type 1 diabetes mellitus—formerly known as insulin-dependent diabetes (IDDM), childhood diabetes or also known as juvenile diabetes, is characterized by loss of the insulin-producing beta cells of the islets of Langerhans of the pancreas leading to a deficiency of insulin. It should be noted that there is no known preventative measure that can be taken against type 1 diabetes. Most people affected by type 1 diabetes are otherwise healthy and of a healthy weight when onset occurs. Diet and exercise cannot reverse or prevent type 1 diabetes. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. This type comprises up to 10% of total cases in North America and Europe, though this varies by geographical location. This type of diabetes can affect children or adults but was traditionally termed "juvenile diabetes" because it represents a majority of cases of diabetes affecting children.
The most common cause of beta cell loss leading to type 1 diabetes is autoimmune destruction, accompanied by antibodies directed against insulin and islet cell proteins. The principal treatment of type 1 diabetes, even from the earliest stages, is replacement of insulin. Without insulin, ketosis and diabetic ketoacidosis can develop and coma or death will result.
Currently, type 1 diabetes can be treated only with insulin, with careful monitoring of blood glucose levels using blood testing monitors. Emphasis is also placed on lifestyle adjustments (diet and exercise). Apart from the common subcutaneous injections, it is also possible to deliver insulin by a pump, which allows continuous infusion of insulin 24 hours a day at preset levels and the ability to program doses (a bolus) of insulin as needed at meal times. It is also possible to deliver insulin with an inhaled powder.
Type 1 treatment must be continued indefinitely. Treatment does not impair normal activities, if sufficient awareness, appropriate care, and discipline in testing and medication is taken. The average glucose level for the type 1 patient should be as close to normal (80–120 mg/dl, 4–6 mmol/l) as possible. Some physicians suggest up to 140–150 mg/dl (7-7.5 mmol/l) for those having trouble with lower values, such as frequent hypoglycemic events. Values above 200 mg/dl (10 mmol/l) are often accompanied by discomfort and frequent urination leading to dehydration. Values above 300 mg/dl (15 mmol/l) usually require immediate treatment and may lead to ketoacidosis. Low levels of blood glucose, called hypoglycemia, may lead to seizures or episodes of unconsciousness.
Type 2 diabetes mellitus
Main article: Diabetes mellitus type 2
Type 2 diabetes mellitus—previously known as adult-onset diabetes, maturity-onset diabetes, or non-insulin-dependent diabetes mellitus (NIDDM)—is due to a combination of defective insulin secretion and insulin resistance or reduced insulin sensitivity (defective responsiveness of tissues to insulin), which almost certainly involves the insulin receptor in cell membranes. In the early stage the predominant abnormality is reduced insulin sensitivity, characterized by elevated levels of insulin in the blood. At this stage hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose production by the liver, but as the disease progresses the impairment of insulin secretion worsens, and therapeutic replacement of insulin often becomes necessary. There are numerous theories as to the exact cause and mechanism for this resistance, but central obesity (fat concentrated around the waist in relation to abdominal organs, and not subcutaneous fat, it seems) is known to predispose individuals for insulin resistance, possibly due to its secretion of adipokines (a group of hormones) that impair glucose tolerance. Abdominal fat is especially active hormonally. Obesity is found in approximately 55% of patients diagnosed with type 2 diabetes.[11] Other factors include aging (about 20% of elderly patients are diabetic in North America) and family history (Type 2 is much more common in those with close relatives who have had it), although in the last decade it has increasingly begun to affect children and adolescents, likely in connection with the greatly increased childhood obesity seen in recent decades in some places.
Type 2 diabetes may go unnoticed for years in a patient before diagnosis, as visible symptoms are typically mild or non-existent, without ketoacidotic episodes, and can be sporadic as well. However, severe long-term complications can result from unnoticed type 2 diabetes, including renal failure, vascular disease (including coronary artery disease), vision damage, etc.
Type 2 diabetes is usually first treated by attempts to change physical activity (generally an increase is desired), the diet (generally to decrease carbohydrate intake), and weight loss. These can restore insulin sensitivity, even when the weight loss is modest, for example, around 5 kg (10 to 15 lb), most especially when it is in abdominal fat deposits. Some Type 2 diabetics can achieve satisfactory glucose control, sometimes for years, as a result. However, the underlying tendency to insulin resistance is not lost, and so attention to diet, exercise, and weight loss must continue. The usual next step, if necessary, is treatment with oral antidiabetic drugs. As insulin production is initially unimpaired in Type 2s, oral medication (often used in various combinations) can still be used to improve insulin production (e.g., sulfonylureas), to regulate inappropriate release of glucose by the liver (and attenuate insulin resistance to some extent (e.g., metformin), and to substantially attenuate insulin resistance (e.g., thiazolidinediones). When these fail (cessation of beta cell insulin secretion is not uncommon amongst Type 2s), insulin therapy will be necessary to maintain normal or near normal glucose levels. A disciplined regimen of blood glucose checks is recommended in most cases, most particularly and necessarily when taking medications.
Gestational diabetes
Main article: Gestational diabetes
Gestational diabetes also involves a combination of inadequate insulin secretion and responsiveness, resembling type 2 diabetes in several respects. It develops during pregnancy and may improve or disappear after delivery. Even though it may be transient, gestational diabetes may damage the health of the fetus or mother, and about 20%–50% of women with gestational diabetes develop type 2 diabetes later in life.
Gestational diabetes mellitus (GDM) occurs in about 2%–5% of all pregnancies. It is temporary and fully treatable but, if untreated, may cause problems with the pregnancy, including macrosomia (high birth weight), fetal malformation and congenital heart disease. It requires careful medical supervision during the pregnancy.
Fetal/neonatal risks associated with GDM include congenital anomalies such as cardiac, central nervous system, and skeletal muscle malformations. Increased fetal insulin may inhibit fetal surfactant production and cause respiratory distress syndrome. Hyperbilirubinemia may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental profusion due to vascular impairment. Induction may be indicated with decreased placental function. Cesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia.
Diabetes mellitus (IPA pronunciation: [ˌdaɪəˈbitəs]). is a metabolic disorder characterized by hyperglycemia (high blood sugar) and other signs, as distinct from a single disease or condition. The World Health Organization recognizes three main forms of diabetes: type 1, type 2, and gestational diabetes (occurring during pregnancy),[1] which have similar signs, symptoms, and consequences, but different causes and population distributions. Type 1 is usually due to autoimmune destruction of the pancreatic beta cells which produce insulin. Type 2 is characterized by tissue-wide insulin resistance and varies widely; it sometimes progresses to loss of beta cell function. Gestational diabetes is similar to type 2 diabetes, in that it involves insulin resistance; the hormones of pregnancy cause insulin resistance in those women genetically predisposed to developing this condition.
Types 1 and 2 are incurable chronic conditions, but have been treatable since insulin became medically available in 1921, and are nowadays usually managed with a combination of dietary treatment, tablets (in type 2) and, frequently, insulin supplementation. Gestational diabetes typically resolves with delivery.
Diabetes can cause many complications. Acute complications (hypoglycemia, ketoacidosis or nonketotic hyperosmolar coma) may occur if the disease is not adequately controlled. Serious long-term complications include cardiovascular disease (doubled risk), chronic renal failure (diabetic nephropathy is the main cause of dialysis in developed world adults), retinal damage (which can lead to blindness and is the most significant cause of adult blindness in the non-elderly in the developed world), nerve damage (of several kinds), and microvascular damage, which may cause erectile dysfunction (impotence) and poor healing. Poor healing of wounds, particularly of the feet, can lead to gangrene which can require amputation — the leading cause of non-traumatic amputation in adults in the developed world. Adequate treatment of diabetes, as well as increased emphasis on blood pressure control and lifestyle factors (such as smoking and keeping a healthy body weight), may improve the risk profile of most aforementioned complications.
Terminology
The term diabetes (Greek: διαβήτης) was coined by Aretaeus of Cappadocia. It is derived from the Greek word διαβαίνειν, diabaínein that literally means "passing through," or "siphon", a reference to one of diabetes' major symptoms—excessive urine production. In 1675 Thomas Willis added the word mellitus to the disease, a word from Latin meaning "honey", a reference to the sweet taste of the urine. This sweet taste had been noticed in urine by the ancient Greeks, Chinese, Egyptians, and Indians. In 1776 Matthew Dobson confirmed that the sweet taste was because of an excess of a kind of sugar in the urine and blood of people with diabetes.[2]
The ancient Indians tested for diabetes by observing whether ants were attracted to a person's urine, and called the ailment "sweet urine disease" (Madhumeha). The Korean, Chinese, and Japanese words for diabetes are based on the same ideographs (糖尿病) and also mean "sweet urine disease".
Diabetes, without qualification, usually refers to diabetes mellitus, but there are several rarer conditions also named diabetes. The most common of these is diabetes insipidus (insipidus meaning "without taste" in Latin) in which the urine is not sweet; it can be caused by either kidney (nephrogenic DI) or pituitary gland (central DI) damage.
The term "type 1 diabetes" has universally replaced several former terms, including childhood-onset diabetes, juvenile diabetes, and insulin-dependent diabetes. "Type 2 diabetes" has also replaced several older terms, including adult-onset diabetes, obesity-related diabetes, and non-insulin-dependent diabetes. Beyond these numbers, there is no agreed standard. Various sources have defined "type 3 diabetes" as, among others:
• Gestational diabetes[3]
• Insulin-resistant type 1 diabetes (or "double diabetes")
• Type 2 diabetes which has progressed to require injected insulin.
• Latent autoimmune diabetes of adults (or LADA or "type 1.5" diabetes)
History
Although diabetes has been recognized since antiquity, and treatments of various efficacy have been known in various regions since the Middle Ages, and in legend for much longer, pathogenesis of diabetes has only been understood experimentally since about 1900.[4] The discovery of a role for the pancreas in diabetes is generally ascribed to Joseph von Mering and Oskar Minkowski, who in 1889 found that dogs whose pancreas was removed developed all the signs and symptoms of diabetes and died shortly afterwards.[5] In 1910, Sir Edward Albert Sharpey-Schafer suggested that people with diabetes were deficient in a single chemical that was normally produced by the pancreas—he proposed calling this substance insulin, from the Latin insula, meaning island, in reference to the insulin-producing islets of Langerhans in the pancreas.[4]
The endocrine role of the pancreas in metabolism, and indeed the existence of insulin, was not further clarified until 1921, when Sir Frederick Grant Banting and Charles Herbert Best repeated the work of Von Mering and Minkowski, and went further to demonstrate they could reverse induced diabetes in dogs by giving them an extract from the pancreatic islets of Langerhans of healthy dogs.[6] Banting, Best, and colleagues (especially the chemist Collip) went on to purify the hormone insulin from bovine pancreases at the University of Toronto. This led to the availability of an effective treatment—insulin injections—and the first patient was treated in 1922. For this, Banting and laboratory director MacLeod received the Nobel Prize in Physiology or Medicine in 1923; both shared their Prize money with others in the team who were not recognized, in particular Best and Collip. Banting and Best made the patent available without charge and did not attempt to control commercial production. Insulin production and therapy rapidly spread around the world, largely as a result of this decision.
The distinction between what is now known as type 1 diabetes and type 2 diabetes was first clearly made by Sir Harold Percival (Harry) Himsworth, and published in January 1936.[7]
Despite the availability of treatment, diabetes has remained a major cause of death. For instance, statistics reveal that the cause-specific mortality rate during 1927 amounted to about 47.7 per 100,000 population in Malta.[8]
Other landmark discoveries include:[4]
• identification of the first of the sulfonylureas in 1942
• the determination of the amino acid order of insulin (by Sir Frederick Sanger, for which he received a Nobel Prize)
• the radioimmunoassay for insulin, as discovered by Rosalyn Yalow and Solomon Berson (gaining Yalow the 1977 Nobel Prize in Physiology or Medicine)[9]
• the three-dimensional structure of insulin
• Dr Gerald Reaven's identification of the constellation of symptoms now called metabolic syndrome in 1988
• Demonstration that intensive glycemic control in type 1 diabetes reduces chronic side effects more as glucose levels approach 'normal' in a large longitudinal study,[10] and also in type 2 diabetics in other large studies
• identification of the first thiazolidinedione as an effective insulin sensitizer during the 1990s
Causes and types
Glucose metabolism
Mechanism of insulin release in normal pancreatic beta cells. Insulin production is more or less constant within the beta cells, irrespective of blood glucose levels. It is stored within vacuoles pending release, via exocytosis, which is triggered by increased blood glucose levels.
Because insulin is the principal hormone that regulates uptake of glucose into most cells from the blood (primarily muscle and fat cells, but not central nervous system cells), deficiency of insulin or the insensitivity of its receptors plays a central role in all forms of diabetes mellitus.
Much of the carbohydrate in food is converted within a few hours to the monosaccharide glucose, the principal carbohydrate found in blood. Some carbohydrates are not converted. Notable examples include fruit sugar (fructose) that is usable as cellular fuel, but it is not converted to glucose and does not participate in the insulin / glucose metabolic regulatory mechanism; additionally, the carbohydrate cellulose (though it is actually many glucose molecules in long chains) is not converted to glucose, as humans and many animals have no digestive pathway capable of handling cellulose. Insulin is released into the blood by beta cells (β-cells) in the pancreas in response to rising levels of blood glucose (e.g., after a meal). Insulin enables most body cells (about 2/3 is the usual estimate, including muscle cells and adipose tissue) to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage. Insulin is also the principal control signal for conversion of glucose (the basic sugar used for fuel) to glycogen for internal storage in liver and muscle cells. Reduced glucose levels result both in the reduced release of insulin from the beta cells and in the reverse conversion of glycogen to glucose when glucose levels fall, although only glucose thus recovered by the liver re-enters the bloodstream as muscle cells lack the necessary export mechanism.
Higher insulin levels increase many anabolic ("building up") processes such as cell growth and duplication, protein synthesis, and fat storage. Insulin is the principal signal in converting many of the bidirectional processes of metabolism from a catabolic to an anabolic direction, and vice versa. In particular, it is the trigger for entering or leaving ketosis (ie, the fat burning metabolic phase).
If the amount of insulin available is insufficient, if cells respond poorly to the effects of insulin (insulin insensitivity or resistance), or if the insulin itself is defective, glucose will not be handled properly by body cells (about ⅔ require it) or stored appropriately in the liver and muscles. The net effect is persistent high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as acidosis.
Type 1 diabetes mellitus
Main article: Diabetes mellitus type 1
Type 1 diabetes mellitus—formerly known as insulin-dependent diabetes (IDDM), childhood diabetes or also known as juvenile diabetes, is characterized by loss of the insulin-producing beta cells of the islets of Langerhans of the pancreas leading to a deficiency of insulin. It should be noted that there is no known preventative measure that can be taken against type 1 diabetes. Most people affected by type 1 diabetes are otherwise healthy and of a healthy weight when onset occurs. Diet and exercise cannot reverse or prevent type 1 diabetes. Sensitivity and responsiveness to insulin are usually normal, especially in the early stages. This type comprises up to 10% of total cases in North America and Europe, though this varies by geographical location. This type of diabetes can affect children or adults but was traditionally termed "juvenile diabetes" because it represents a majority of cases of diabetes affecting children.
The most common cause of beta cell loss leading to type 1 diabetes is autoimmune destruction, accompanied by antibodies directed against insulin and islet cell proteins. The principal treatment of type 1 diabetes, even from the earliest stages, is replacement of insulin. Without insulin, ketosis and diabetic ketoacidosis can develop and coma or death will result.
Currently, type 1 diabetes can be treated only with insulin, with careful monitoring of blood glucose levels using blood testing monitors. Emphasis is also placed on lifestyle adjustments (diet and exercise). Apart from the common subcutaneous injections, it is also possible to deliver insulin by a pump, which allows continuous infusion of insulin 24 hours a day at preset levels and the ability to program doses (a bolus) of insulin as needed at meal times. It is also possible to deliver insulin with an inhaled powder.
Type 1 treatment must be continued indefinitely. Treatment does not impair normal activities, if sufficient awareness, appropriate care, and discipline in testing and medication is taken. The average glucose level for the type 1 patient should be as close to normal (80–120 mg/dl, 4–6 mmol/l) as possible. Some physicians suggest up to 140–150 mg/dl (7-7.5 mmol/l) for those having trouble with lower values, such as frequent hypoglycemic events. Values above 200 mg/dl (10 mmol/l) are often accompanied by discomfort and frequent urination leading to dehydration. Values above 300 mg/dl (15 mmol/l) usually require immediate treatment and may lead to ketoacidosis. Low levels of blood glucose, called hypoglycemia, may lead to seizures or episodes of unconsciousness.
Type 2 diabetes mellitus
Main article: Diabetes mellitus type 2
Type 2 diabetes mellitus—previously known as adult-onset diabetes, maturity-onset diabetes, or non-insulin-dependent diabetes mellitus (NIDDM)—is due to a combination of defective insulin secretion and insulin resistance or reduced insulin sensitivity (defective responsiveness of tissues to insulin), which almost certainly involves the insulin receptor in cell membranes. In the early stage the predominant abnormality is reduced insulin sensitivity, characterized by elevated levels of insulin in the blood. At this stage hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose production by the liver, but as the disease progresses the impairment of insulin secretion worsens, and therapeutic replacement of insulin often becomes necessary. There are numerous theories as to the exact cause and mechanism for this resistance, but central obesity (fat concentrated around the waist in relation to abdominal organs, and not subcutaneous fat, it seems) is known to predispose individuals for insulin resistance, possibly due to its secretion of adipokines (a group of hormones) that impair glucose tolerance. Abdominal fat is especially active hormonally. Obesity is found in approximately 55% of patients diagnosed with type 2 diabetes.[11] Other factors include aging (about 20% of elderly patients are diabetic in North America) and family history (Type 2 is much more common in those with close relatives who have had it), although in the last decade it has increasingly begun to affect children and adolescents, likely in connection with the greatly increased childhood obesity seen in recent decades in some places.
Type 2 diabetes may go unnoticed for years in a patient before diagnosis, as visible symptoms are typically mild or non-existent, without ketoacidotic episodes, and can be sporadic as well. However, severe long-term complications can result from unnoticed type 2 diabetes, including renal failure, vascular disease (including coronary artery disease), vision damage, etc.
Type 2 diabetes is usually first treated by attempts to change physical activity (generally an increase is desired), the diet (generally to decrease carbohydrate intake), and weight loss. These can restore insulin sensitivity, even when the weight loss is modest, for example, around 5 kg (10 to 15 lb), most especially when it is in abdominal fat deposits. Some Type 2 diabetics can achieve satisfactory glucose control, sometimes for years, as a result. However, the underlying tendency to insulin resistance is not lost, and so attention to diet, exercise, and weight loss must continue. The usual next step, if necessary, is treatment with oral antidiabetic drugs. As insulin production is initially unimpaired in Type 2s, oral medication (often used in various combinations) can still be used to improve insulin production (e.g., sulfonylureas), to regulate inappropriate release of glucose by the liver (and attenuate insulin resistance to some extent (e.g., metformin), and to substantially attenuate insulin resistance (e.g., thiazolidinediones). When these fail (cessation of beta cell insulin secretion is not uncommon amongst Type 2s), insulin therapy will be necessary to maintain normal or near normal glucose levels. A disciplined regimen of blood glucose checks is recommended in most cases, most particularly and necessarily when taking medications.
Gestational diabetes
Main article: Gestational diabetes
Gestational diabetes also involves a combination of inadequate insulin secretion and responsiveness, resembling type 2 diabetes in several respects. It develops during pregnancy and may improve or disappear after delivery. Even though it may be transient, gestational diabetes may damage the health of the fetus or mother, and about 20%–50% of women with gestational diabetes develop type 2 diabetes later in life.
Gestational diabetes mellitus (GDM) occurs in about 2%–5% of all pregnancies. It is temporary and fully treatable but, if untreated, may cause problems with the pregnancy, including macrosomia (high birth weight), fetal malformation and congenital heart disease. It requires careful medical supervision during the pregnancy.
Fetal/neonatal risks associated with GDM include congenital anomalies such as cardiac, central nervous system, and skeletal muscle malformations. Increased fetal insulin may inhibit fetal surfactant production and cause respiratory distress syndrome. Hyperbilirubinemia may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental profusion due to vascular impairment. Induction may be indicated with decreased placental function. Cesarean section may be performed if there is marked fetal distress or an increased risk of injury associated with macrosomia, such as shoulder dystocia.