|
|
Diabetes mellitus is a medical disorder characterized by varying or persistent hyperglycemia (elevated blood sugar levels), especially after eating. All types of diabetes mellitus share similar symptoms and complications at advanced stages. Hyperglycemia itself can lead to dehydration and ketoacidosis. Longer-term complications include cardiovascular disease (doubled risk), chronic renal failure (it is the main cause for dialysis), retinal damage with eventual blindness, nerve damage and eventual gangrene with risk of amputation of toes, feet, and even legs.
The most important forms of diabetes are due to decreased production of insulin (diabetes mellitus type 1, the first recognized form), or decreased sensitivity of body tissues to insulin (diabetes mellitus type 2, the more common form). The former requires insulin injections, while the latter is generally managed with oral medication and only requires insulin if the tablets are ineffective.
Patient understanding and participation is vital as blood glucose levels change continuously, while successfully keeping blood sugar within normal limits has been compellingly shown to reduce or prevent development of some of the complications of diabetes. Other risk factors that can require addressing to reduce complications are: cessation of smoking, optimizing cholesterol levels, maintaining a stable body weight, controlling high blood pressure and having regular exercise.
Statistics
In 2004, according to the World Health Organization, more than 150 million people worldwide suffer from diabetes. Its incidence is increasing rapidly, and it is estimated that by the year 2025 this number will double. Diabetes mellitus occurs throughout the world, but is more common (especially type 2) in the more developed countries. The greatest increase in prevalence rate is, however, expected to occur in Asia and Africa, where most of the diabetic patients will be seen by 2025. The increase in incidence of diabetes in the developing countries follows the trend of urbanisation and life style changes.
Diabetes is in the top 10, and perhaps the top 5, of the most significant diseases in the developed world, and is gaining in significance (see big killers).
For at least 20 years, diabetes rates in North America have been increasing substantially. In 2002 there were about 18.2 million diabetics in the United States alone. The Centers for Disease Control has termed the change an epidemic. The National Diabetes Information Clearinghouse estimates that diabetes costs $132 billion in the United States alone every year.
Causes and types
The role of insulin
Mechanism of insulin release in normal pancreatic beta cells (ie, glucose dependence). Insulin production doesn't depend on blood glucose levels; insulin is stored pending releaseSince insulin is the principal hormone that regulates uptake of glucose into cells (primarily muscle and fat cells) from the blood, deficiency of insulin or its action plays a central role in all forms of diabetes.
Most of the carbohydrates in food are rapidly digested to glucose, the principal sugar in blood. Insulin is produced by beta cells in the pancreas in response to rising levels of glucose in the blood, as occurs after a meal. Insulin makes it possible for most body tissues to remove 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 unit) to glycogen for storage in liver and muscle cells. Lowered insulin levels result in the reverse conversion of glycogen to glucose when glucose levels fall -- though only in the liver not muscle tissue. Higher insulin level increase many anabolic ("building up") processes such as cell growth, cellular 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.
If the amount of insulin produced is insufficient, if cells respond poorly to the effects of insulin (insulin insensitivity or resistance), or if the insulin itself is defective, glucose is not handled properly by body cells (about 2/3 require it) nor stored appropriately in the liver and muscles. The net effect is persistent high levels of blood glucose, poor protein synthesis, and other metabolic derangements.
Type 1 diabetes mellitus
Type 1 diabetes is most commonly diagnosed in children and adolescents, but can occur in adults as well. It is an autoimmune disorder, in which the body's own immune system attacks the beta cells in the Islets of Langerhans of the pancreas, destroying them or damaging them sufficiently to reduce insulin production. The autoimmune attack may be triggered by reaction to an infection, for example by one of the viruses of the Coxsackie virus family. A subtype of type 1 (identifiable by the presence of antibodies against beta cells) develops slowly and so is often confused with Type 2. In addition, a small proportion of type 1 cases has the hereditary condition maturity onset diabetes of the young (MODY).
Some poisons (e.g. certain rat poisons) work by selectively destroying certain types of cells, including pancreatic beta cells, thus producing "artificial" type 1 diabetes. Other pancreatic problems including trauma, pancreatitis or tumors (either malignant or benign) can also lead to loss of insulin production.
Currently, type 1 is treated with insulin injections, lifestyle adjustments, and careful monitoring of blood glucose levels using blood test kits. The treatment must be continued indefinitely. Experimental replacement of beta cells (by transplant) is being investigated in several research programs and may become clinically available in the future.
About 5-10% of all North American cases of diabetes are Type 1 diabetics. The fraction of type 1 diabetics in other parts of the world differs; this is likely due to both differences in the rate of type 1 and differences in the rate of other types, most prominently type 2. Most of this difference is not currently understood.
Formerly, type 1 diabetes was called "childhood" or "juvenile" diabetes or "insulin dependent" diabetes. Each term is a misnomer, especially since the obesity epidemic in recent years has led to increased incidence of type 2 diabetes in children and adolescents in the USA, and insulin is used in some type 2 cases.
Type 2 diabetes mellitus
Type 2 diabetes is characterized by "insulin resistance" as body cells do not respond appropriately when insulin is present. This is a more complex problem than type 1, but is sometimes easier to treat, since insulin is still produced, especially in the initial years. Type 2 may go unnoticed for years in a patient before diagnosis, since the symptoms are typically milder (no ketoacidosis) and can be sporadic. However, severe complications can result from unnoticed type 2 diabetes, including renal failure, and coronary artery disease.
Type 2 diabetes was formerly known by a variety of partially misleading names, including "adult-onset diabetes", "obesity-related diabetes", "insulin-resistant diabetes", or "non-insulin-dependent diabetes" (NIDDM). It may be caused by a number of diseases, such as hemochromatosis and polycystic ovary syndrome, and can also be caused by certain types of medications (e.g. long-term steroid use). About 90-95% of all North American cases of diabetes are type 2, and about 20% of the population over the age of 65 is a type 2 diabetic. The fraction of type 2 diabetics in other parts of the world varies substantially, almost certainly for environmental and lifestyle reasons. There is also a strong inheritable genetic connection in type 2 diabetes: having relatives (especially first degree) with type 2 is a considerable risk factor for developing type 2 diabetes. The majority of patients with type 2 diabetes mellitus are obese - chronic obesity leads to increased insulin resistance that can develop into diabetes, most likely because adipose tissue is a (recently identified) source of chemical signals (hormones and cytokines).
Type 2 is initially treated by changes in diet and through weight loss. This can restore insulin sensitivity, even when the weight lost is modest e.g. around 5 kg (10 to 15 lb). The next step, if necessary, is treatment with oral antidiabetic drugs: the sulphonylureas, metformin, or (if these are insufficient) thiazolidinediones. When these have failed, insulin therapy may be necessary to maintain normal glucose levels.
Type 3 diabetes mellitus
All other specific forms of diabetes, accounting for up to 5% of all diagnosed cases of diabetes, are termed Type 3:
Type 3A: genetic defect in beta cells.
Type 3B: genetically related insulin resistance.
Type 3C: diseases of the pancreas.
Type 3D: caused by hormonal defects.
Type 3E: caused by chemicals or drugs.
Type 4 diabetes mellitus
Type 4 or gestational diabetes mellitus appears in about 2-5% of all pregnancies. It is temporary and fully treatable, but if untreated it may cause problems with the pregnancy. It requires careful medical supervision during the pregnancy. In addition, about 20-50% of these women go on to develop type 2 diabetes.
Genetics
Both type 1 and type 2 diabetes are at least partly inherited. Type 1 diabetes appears to be triggered by infection, stress, or environmental factors (e.g. exposure to a causative agent). There is a genetic element in the susceptibility of individuals to some of these triggers which has been traced to particular HLA genotypes (i.e. genetic "self" identifiers used by the immune system). However, even in those who have inherited the susceptibility, type 1 diabetes mellitus seems to require an environmental trigger. A small proportion of type 1 diabetics carry a mutation that causes maturity onset diabetes of the young (MODY).
There is an even stronger inheritance pattern for Type 2 diabetes; those with type 2 ancestors or relatives have very much higher chances of developing Type 2. It is also often connected to obesity, which is found in approximately 85% of (North American) patients diagnosed with that form of the disease, so inheriting a tendency toward obesity seems also to contribute. Age is also thought to be a contributing factor, as most type 2 patients in the past were older. The exact reasons for these connections are unknown.
Diagnosis
Signs and symptoms
Type 2 diabetes almost always has a slow onset (often years), but in type 1, particularly in children, onset may be quite fast (weeks or months). Early symptoms of type 1 diabetes are often polyuria (frequent urination) and polydipsia (increased thirst, and consequent increased fluid intake). There may also be weight loss (despite normal or increased eating), increased appetite, and irreduceable fatigue. These symptoms may also manifest in Type 2 diabetes in patients who present with frank poorly controlled diabetes.
Thirst develops because of osmotic effects — sufficiently high glucose (above the 'renal threshold') in the blood is excreted by the kidneys but this requires water to carry it and causes increased fluid loss, which must be replaced. The lost blood volume will be replaced from water held inside body cells, causing dehydration.
Another common presenting symptom is altered vision. Prolonged high blood glucose causes changes in the shape of the lens in the eye, leading to blurred vision and, perhaps, a visit to an optometrist. All unexplained quick changes in eyesight should force a fasting blood glucose test. These are now quick (less than 5 minutes total), inexpensive (materials less than US$1), and can be safely performed by almost anyone with trivial training.
Especially dangerous symptoms in diabetics include the smell of acetone on the patient's breath (a sign of ketoacidosis), Kussmaul breathing (a rapid, deep breathing), and any altered state of consciousness or arousal (hostility and mania are both possible, as is confusion and lethargy). The most dangerous form of altered consciousness is the so-called "diabetic coma" which produces unconsciousness. Early symptoms of impending diabetic coma include polyuria, nausea, vomiting and abdominal pain, with lethargy and somnolence a later development, progressing to unconsciousness and death if untreated.
Hypoglycemia
Hypoglycemia in diabetic patients almost always arises as a result of poor management of the disease either from too much or poorly timed insulin or oral hypoglycemics or too much exercise, not enough food, or poor timing of either. If blood glucose levels are low enough, the patient may become agitated, sweaty, and have many symptoms of sympathetic activation of the autonomic nervous system - they may experience feelings similar to dread and immobilized panic. Consciousness can be altered, or even lost, in extreme cases, leading to coma and/or seizures or even death and brain damage. Experienced diabetics can often recognise the symptoms early on - all diabetics should always carry something sugary to eat or drink as these symptoms can be rapidly reduced if treated early enough. In the case of children, this can be a type of candy disliked by the patient, to prevent concerns about unnecessary use.
Other ways of treating hypoglycemia include an injection of glucagon which causes the liver to convert its internal stores of glycogen to be released as glucose into the blood. Oral or intravenous dextrose can also be given. In most cases, recovery is rapid and troublefree. Longstanding hypoglycemia may require hospital admission to allow supervised recovery and adjustment of diabetic medications.
Long-term complications
Among the major risks of the disorder are chronic problems affecting multiple organ systems which will eventually arise in patients with poor glycemic control. Many of these arise from damage to the blood vessels. These illnesses can be divided into those arising from large blood vessel diseases, macroangiopathy, and those arising from small blood vessel disease, microangiopathy. Interestingly, small vessel disease is minimized by tight blood glucose control, but large vessel disease is unaffected by tight blood glucose control.
Small vessel disease complications:
proliferative retinopathy which can lead to blindness;
peripheral neuropathy which, particularly when combined with damaged blood vessesls, can lead to foot ulcers, and possibly progressing to necrosis, infection and gangrene, sometimes requiring limb amputation, see below
nephropathy which can lead to renal failure
Large vessel disease complications:
ischemic heart disease caused by both large and small vessel disease
stroke
peripheral vascular disease which contributes to foot ulcers and the risk of amputation
Diabetes mellitus is the most common cause of adult kidney failure worldwide. It also the most common cause of amputation in the US, usually toes and feet, often as a result of gangrene, and almost always as a result of peripheral vascular disease. Retinal damage (from microangiopathy) makes it the most common cause of blindness among non-elderly adults in the US.
Treatment
Diabetes is a chronic disease with no cure (except experimentally in type 1 diabetics) as of 2004. There have also been proposed vaccines for Type I using Glutamic Acid Decarboxylase (GAD), but these are currently not being tested by the pharmaceutical companies that have sublicensed the patents to them. However, it can almost always be managed effectively. Management of this disease may include lifestyle modifications such as losing weight, diet and exercise to long-term use of oral hypoglycemics or insulin therapy. Nowadays, the goal for diabetics is to avoid or minimize chronic diabetic complications, as well as to avoid acute problems of hyperglycemia or hypoglycemia.
Adequate control of diabetes leads to a lower risk of the complications of uncontrolled diabetes which include kidney failure (requiring dialysis or transplant), blindness, heart disease and limb amputation.
There is emerging solid evidence that full-blown diabetes mellitus type 2 can be evaded in those with only mildly impaired glucose tolerance6.
Patients with type 1 diabetes mellitus require direct injection of insulin as their bodies cannot produce enough (or even any) insulin. As of 2004, there is no other clinically available form of insulin administration other than injection for patients with type 1: injection can be done by insulin pump, by jet injector, or any of several forms of hypodermic needle. There are several insulin application mechanisms under experimental development as of 2004.
For type 2 diabetics, diabetic management consists of a combination of diet, exercise, and weight loss, in any achievable combination depending on the patient. Patients who have poor diabetic control after lifestyle modifications are typically placed on oral hypoglycemics. Some Type 2 diabetics eventually fail to respond to these and must proceed to insulin therapy.
Patient education and compliance with treatment is very important in managing the disease. Improper use of medications and insulin can be very dangerous causing hypo- or hyper-glycemic episodes.
Insulin therapy requires close monitoring and a great deal of patient education, as improper administration is quite dangerous. For example, when food intake is reduced, less insulin is required. A previously satisfactory dosing may be too much if less food is consumed causing a hypoglycemic reaction if not intelligently adjusted. In addition, exercise decreases insulin requirements as exercise increases glucose uptake by body cells whose glucose uptake is controlled by insulin. And vice versa. In addition, there are available several types of insulin with varying times of onset and duration of action.
|
|
This article is licensed under the GNU Free Documentation License.
It uses material from the Wikipedia article "Diabetes"
|
|
|
