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Diabetes mellitus is a name for any condition that is characterized by chronic hyperglycemia and disturbances of carbohydrate, protein and fat metabolism. There are several types of the disease of variable aetiology. In recent decades, understanding of underlying causes and pathological mechanisms leading to diabetes mellitus has progressed considerably. It has become possible to distinguish clearly among the different forms of the disease, sometimes tracing the cause to a single defective gene.
As of 2002, about 17 million United States nationals suffer from diabetes. For at least 20 years, diabetes rates in North America have been increasing substantially. The Centers for Disease Control has termed the changes an epidemic. This is a medically and economically important disease, easily in the top 10 and perhaps in the top 5 in the developed world, and is becoming rapidly more so (see big killers).
Long-term diabetes mellitus can have detrimental effects on numerous organs of the body. Prolonged high blood glucose levels can produce the chronic complications of diabetes mellitus. They include:
Generally, diabetes cannot now be cured (except experimentally in Type 1 diabetics) but it often can be treated effectively and there is emerging solid evidence that diabetes mellitus Type 2 can be evaded in people with impaired glucose tolerance6.
Traditionally (after the first use of insulin in 1922), the goal of treatment was prevention of either hyperglycemic or hypoglycemic coma and diabetic ketoacidosis. Lack of sufficiently frequent and sufficiently inexpensive blood glucose monitoring precluded much more specific intervention until about 20 years ago. Chronic side effects were not even recognized as preventable until the last few decades. Until the early 1920s, they couldn't be observed at all much less treated, because patients didn't survive long enough suffer from them.
Several large studies since 1980 have made it clear that the effort needed to keep blood glucose levels as close to normal (fasting levels below 126 mg/dl) is well worth while and that it is actuall possible in the real world of diabetic patients. The risk of complications is quite clearly inversely proportional to how well controlled blood glucose levels are kept. Several studies have recently shown that the beneficial effect of close control is a long term one as well. More recent studies of Type 2 diabetes also stress the need for stringent blood pressure control for them. Much of the vascular damage that is associated with diabetes mellitus seems to be due, in large part, to prolonged uncontrolled high blood pressure, which is common in diabetics.
The clinical aim today is to avoid or minimize chronic diabetic complications, as well as to avoid acute problems due to too high or too low blood glucose. For Type 1 diabetics, the chief tool is external insulin (of one, or more, types), heretofore always injected, but perhaps shortly to be available in other forms of application. For Type 2 diabetics, treatment usually begins with diet, exercise, and weight reduction, in any possible combination depending on the patient. Many Type 2 patients will require some form of oral hypoglycemic agents (ie, pills) in addition, but a substantial fraction eventually require insulin as well since there is a considerable number of patients who eventually fail to respond to the currently available oral hypoglycemic agents, or to diet/exercise/weight loss. In almost all cases, regular patient self-monitoring of blood glucose levels is extremely desirable.
The management of diabetes is almost always a major ongoing presence in patients' lives and activities. It need not be more than annoying for most; however, patient education is required for diabetes is both chronic and acute. Many treatments for it are potentially damaging if not deadly when misused. As well, there are (and appear to have long been) a great many 'alternative' treatments for diabetes, and many of these are dangerous, in themselves and/or by supplanting other treatments, and sometimes deadly.
"Diabetes" is a Greek word meaning "a passer through; a siphon". "Mellitus" comes from the Greek word "sweet". Apparently, the Greeks named it thus because the excessive amounts of urine that a diabetic (when in a hyperglycemic state) would excrete attracted flies and bees because of the glucose content. The ancient Chinese would test for diabetes by observing whether ants were attracted to a person's urine.
Passing abnormal amounts of urine can be a symptom of several diseases (most commonly of the kidneys), and the word diabetes is applied to many of them. The most common are diabetes insipidus and diabetes mellitus.
Insulin is a hormone that enables blood glucose molecules to enter about 2/3 of the cells of the body (primarily muscle and fat cells). It also controls many other body mechanisms, from fat processing (in liver and fat cells), protein synthesis (by controlling amino acid uptake in cells), and electrolyte balance (by controlling potassium uptake in cells). It is the central hormone involved in controlling metabolism. It is produced in the endocrine part of the pancreas, which consists of very small clumps of specialised cells scattered throughout that organ (the 'Islets of Langerhans'). Hyperglycemia (too high blood glucose levels) results if the amount of insulin is not sufficient to cause the cells to take up the glucose from the blood, or if those cells which require insulin to absorb glucose no longer respond adequately to it. Hyperglycemia has two major causes, which may occur together:
Both Type 1 and Type 2 diabetes have genetic linkages. Type 1 diabetes may be triggered by infection, stress, or environmental factors (eg, substances of one kind or another). There is clearly a genetic element in the susceptibility of individuals to some of these triggers; it has been traced to particular HLA genotypes. Even with the susceptibility, Type 1 does not apparently occur without an environmental trigger. There is an even stronger genetic link in 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. 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.
In Type 2 diabetes there is almost always a slow onset (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 concomitant increased fluid intake). There may also be weight loss despite normal or increased eating, increased appetite, and unreduceable fatigue. These may also be symptoms of Type 2, though usually not until a later, more 'severe' stage.
Thirst develops because of osmotic effects—sufficient excess glucose (above the 'renal threshold') from the blood is eventually excreted by the kidneys but this causes fluid loss, which must be replaced.
Acute danger signs for diabetics include the smell of acetone on the patient's breath (a sign of ketoacidosis), Kussmaul breathing (rapid, deep breathing), and any altered state of consciousness or arousal (hostility and mania are both possible, as is confusion). The worst form of altered consciousness is the so-called "diabetic coma". Early symptoms of impending diabetic coma are polyuria, nausea, vomiting and abdominal pain, with lethargy and somnolence a later development, progressing to unconsciousness and coma if untreated.
Diabetic ketoacidosis (DKA) is an acute complication of diabetes, particularly in Type 1 diabetics, and is an serious medical emergency. DKA is an extremely dangerous and often fatal condition. It arises from incomplete fat breakdown. Production of fatty acids from stored lipids is entirely normal during metabolic ketosis, and is begun when insulin levels are low. It is therefore indirectly controlled by the blood glucose level (in non-diabetics) and so ultimately, though still more indirectly, controlled by carbohydrates in the diet. When glucose is persistently low or absent (and so when fat is being taken from body stores and converted to fatty acids for energy use, ie ketosis), glucose is produced from some amino acids after protein degradation. During glucose production from protein, fat metabolism (ie, ketosis) becomes abnormal because of competitive interference between the two processes. Under those conditions, the liver converts the metabolic chemical acetyl-CoA (an intermediate in ketosis) to ketone bodies without completing fat processing; these are together quite acidic, and if present in too high quantities cannot be removed from the blood fast enough to prevent acidosis. DKA is more common in Type 1 diabetics, probably because they do not secrete significant amounts of their own insulin. It is less common in Type 2 diabetics, even in those who require insulin due to partial or complete failure of their beta cells. Type 2 diabetics have their own similar, and equally dangerous, problem called hyperosmotic diabetic coma.
The brain (and a few other tissues, including parts of the kidneys) uses glucose from the blood regardless of diabetic status (ie, insulin insufficiency or cellular resistance) as nerve cells do not require insulin to absorb glucose; but neither it nor most of the rest of the body is able to survive acidosis if it is 'too severe' or continues 'too long'. The ketone bodies are acetone, acetoacetate and beta-hydroxybutyrate. Oddly, only two are, chemically, ketones; the name survives from a time when the biochemistry was poorly understood.
DKA is usually accompanied by hyperglycemia which also causes osmotic diuresis, leading to excessive losses of water, sodium and potassium. These electrolyte imbalances are also dangerous and can cause problems up to and including death.
A patient with DKA is always acidotic, almost always dehydrated, and nearly always hyperglycaemic. All are very dangerous conditions and together are no less so. The patient urgently requires IV fluids and, almost always, insulin -- typically intravenously. A bicarbonate infusion may be necessary if the pH of the blood is suffieintly low. DKA is an urgent medical emergency and requires immediate skilled treatment, supplies, and facilities; it cannot be adequately handled at home on a 'first aid' basis.
Hyperosmotic diabetic coma has some similar symptoms, but a different cause. In anyone with very high blood glucose levels (usually considered to be above 300 mg/dl) water will be osmotically driven out of cells into the blood. The kidneys will be dumping glucose, and the water necessary to carry it, from the blood. The osmotic effect of the high glucose levels combined with the (excessive) loss of water will eventually result in raised serum osmolality. Electrolyte imbalances often also occur. The combination of changes, if prolonged, will result in symptoms similar to ketoacidosis, including loss of consciousness. As with DKA, urgent medical treatment is necessary.
The brain requires many things to function correctly, but two things are critically important at all times: oxygen and fuel. The fuel is ordinarily glucose, but can be ketone bodies under stavation conditions. Breathing (lungs) and blood circulation (heart and blood vessels) supply the oxygen, without which brain cells very quickly (minutes) die. Blood circulation also supplies fuel, without which brain cells starve (they maintain very little internal fuel stores -- ie glucose in normal conditions) and brain function is immediately (also minutes) impaired. consciousness is altered, physiological functions are impaired, and ultimately the patient with hypoglycemia (too little blood glucose) will die if untreated.
Patients with hyperglycemia (too much blood glucose) also will eventually (months, up to a few years) die without treatment for the same basic reason: cell starvation as glucose (fuel) cannot get into about 2/3 of the cells. Protein will be used for glucose production (catabolism) regardless of the damage caused, and despite the fact that there is abundant blood glucose. Muscle cells are prominently affected and the result is 'muscle wasting'.
The treatment in one case (hypoglycemia) is to raise blood glucose levels, and in the other (hyperglycemia) to adjust blood chemistry values back to something more nearly normal, including lowering glucose levels. In hypoglycemia, if patient is conscious, feeding with some simple carbohydrate (eg, orange juice or skim milk (ordinary milk has too much fat which delays sugar absorption)) may be sufficient to normalize blood glucose. Recovery is usually rapid. Unconscious patients cannot swallow and may choke; medical intervention will usually be needed in such cases. In severe hyperglycemia, medical treatment is generally required because of its complex, interconnected, and quite dangerous biochemical disturbances.
Diabetes is currently a life-long disease—with several serious acute or chronic complications possible. It requires complex therapy, education and life-style modifications to minimize bad outcomes. At this writing, there is no cure for either Type 1 or 2 diabetes and treatment is necessarily a longterm continuous effort. The goals of diagbetes management are several: not only near-normal glycemic control (and so avoidance of both acute and chronic hyperglycemia), but also prevention of hypoglycemia episodes, thus reducing the risk of long-term complications and preserving quality of life for patients.
Several major studies (involving very large numbers of patients) have shown, clearly and convincingly and beyond reasonable doubt, that keeping blood glucose levels as close as possible to 'normal', nondiabetic, values really does prevent, retard, and delay chronic diabetic complications: diabetic retinopathy, nephropathy, microangiopathic and macroangiopathic damage as well as neuropathy1,2. Close glucose control should be undertaken with care, as keeping blood glucose levels 'normally' low in diabetics leaves less room for medication / diet / exercise error and so increases the possibility of a (possibly dangerous) hypoglycemic episode.
There are several different ways of delivering drugs for treating Type 2 diabetes: insulin injections, insulin pumps, pills, and implants. Common drugs in pill form (for Type 2 ONLY at this writing) include the biguanides (eg, metformin), and the sulfonylureas (e.g, Orinase, Diabinase, and Tolinase among many others).
Hypoglycemia means an excessively low blood glucose level. It arises in diabetics who have too much insulin (from injections or from insulin release stimulating drugs -- usually pills) for the amount of food they eat and exercise they get. On days when, for whatever reason, less food is taken, less insulin will be required; the previously satisfactory amount may now be too much and cause a hypoglycemic reaction. When more exercise is gotten, less insulin will be required, and vice versa; exercise increase glucose uptake by body cells nominally under insulin control for glucose uptake. Since there are many different insulin preparations, since foods vary in their effect on blood glucose levels (even if they have exactly the same calories), and since the 'glucose absorption' effect of exercise varies depending on many factors (including patient variations), getting the right amount and timing of diabetic medication (most particularly insulin) is not trivial. For most diabetics, it takes time and effort to 'get the hang of it'. Adjusting insulin and other diabetic drugs is hardly impossible for the average patient, but it is not simple, nor trivially safe either. The consequences of making an error include death, and so great caution, and expert advice (especially at the beginning), are both mandatory. Especially for newly diagnosed diabetics, medication changes should be done only in consultation with a physician.
Illness, surgery, and stress also affect glucose levels (eg, several of the stress hormones force increases in glucose levels), so all diabetics should be aware that their insulin and other drug routines may have to change if any of these occur. Previously prepared "sick day rules" may be a reasonable approach, but must actually be suitable to the diabetic situation during illness, stress, etc. for that particular patient.
Sensible treatment of diabetes depends almost entirely on blood glucose testing, since grossly observable signs and symptoms almost never appear immediately, and urine tests only summarize high blood glucose levels since the last urination. The food you ate hours ago is still being digested and absorbed, the insulin you injected can have glucose lowering effects for as long as 24+ hours or can be over as quickly as 2 hours(depending on the nature of the insulin preparation used), and the timing of diabetic pill effects also varies from pill type to pill type and from patient to patient. And, since blood glucose levels change regularly and rapidly (hours or less), portable meters are effectvely the only reasonable choice. Testing only during visits to a clinic, at a doctor's office, or in hospital is entirely inadequate as a basis for almost every decision about food, exercise, drug dosage and timing that a diabetic patient is obliged to make.
Regular urine glucose testing is only slightly more useful, except perhaps in an emergency. It reflects all glucose levels since the last urination, not only what they are now.
There are multiple suppliers of blood glucose meters (all of which must be approved by the FDA in the US). Differences among them include size of the blood droplet required, whether the blood sample may be applied to a test strip before or after it is inserted in the meter, length of delay until results are available, size and packaging of the disposable test strips, the underlying detection technique (optical reflectance or electrochemical are the usual), and compatibility with computer programs for keeping records of readings and other information. Cost also varies, but not generally for inherent technical reasons; these are all quite similar machines.
The cost per test strip varies quite substantially -- cumulative strip costs over even short periods completely swamp all other meter cost factors. Strip cost should be a major (probably the major) contributor to the decision of which meter to use. How often to test, and what to do with/about the results should be closely coordinated with medication schedules (especially for insulin), food, and exercise. At least when beginning to test, medical supervision is a very good idea.
A useful laboratory test of long term diabetic glucose control is to measure the patient's blood level of glycosylated haemoglobin (ie, "HbA1c"). Non-diabetics have an HbA1c level of less than 7%. This is a good target for most (but not all) diabetics; since diabetic situations differ, determining an HbA1c target should be determined in cooperation with a physician. Higher HbA1c levels indicate higher glucose levels in the recent past (up to 3 months in most people); generally the higher, the poorer. But an HbA1c reading is not at all useful for checking the need for medication, food, or exercise just now, which is when you must make the decision(s). There is now a commercial test kit (available at least in the US) for doing this at home.
Results from an important study in the journal Lancet5 suggest that diabetics should be treated with a statin drug irrespective of their cholesterol levels. The treatment seems to reduce, by 24-27%, the rate of myocardial infarction (ie, haeart attack), coronary death, and stroke, as well as the need for peripheral arterial revascularization procedures. At this writing, the reason is thought to be an anti-inflammatory reaction effect. Other factors may possibly be operating independent of the hypolipemic effect. The effect seems clear, but the cause remains obscure.
Distinct forms of microangiopathy include damage to the retina of the eye (diabetic retinopathy) and damage to the kidneys (nephropathy). The damage in both cases seems to be primarily due to high glucose levels, probably via assorted reactions between glucose and various proteins which thereupon change their behaviour and so the behaviour of the tissue in which the protein is found (eg, small blood vessel walls). Keeping glucose levels at or near 'normal' reduces the risk of any of these complications of diabetes mellitus without any question.
There are distinct forms of neuropathy as well. Peripheral sensory neuropathy
affects feeling at first, and primarily, in the feet and lower legs, and eventually fingers and hands. Sensation decreases and with it protective reaction to damaging incidents, eg thumb tacks, blisters, ill fitting shoes, .... Combined with vascular damage leading to slower healing, the effect is to greatly increase the risk of trauma (eg, can't feel the pebble or pin or developing blister) and the risk of spread of serious infection (eg, infection not noticed and no measures taken until 'too late'). Autonomic neuropathy can cause problems with balance, with intestinal operations (ie, digestion), with balance and coordination, with sexual responses and other reflexes, and indeed, with 'automatic' compensating adjustments of many kinds.
Several studies have demonstrated that, for both types of diabetes mellitus, the rate and severity of these long term complication is substantially reduced, or eliminated, by keeping blood glucose levels at or near 'normal'. Blood glucose testing is important if only because it helps with this.
The Declaration of St Vincent was the result of international efforts to
improve the care accorded to diabetics. Diabetes is enormously expensive for healthcare systems and governments. In North America, it is the largest single non-traumatic cause in adults of amputation, blindness, and dialysis (from diabetic nephropathy, ie, kidney failure).
Work in the Puget Sound area of North America (by the heath organization Group Health) shows that, over its large and varied patient population, specially retaining medical information on diabetic patients, keeping it up to date, and basing their continuing care on that data reduced total healthcare costs for those patients by US$1000 per year per patient for the rest of his life. Recognition of this reality drove the Hawkes Bay initiative which established such a system, and resulted in various activities throughout the world including the Black Sea Telediab project which produced elements of a distributed diabetic record and management system as an open source computer program.
Until 1922, when insulin was first discovered and made clinically available, a clinical diagnosis of diabetes was an invariable death sentence, more or less promptly. Non-progressing Type 2 diabetics almost certainly often went undiagnosed then — many still do.
The discovery of the role of the pancreas in diabetes is generally credited to Von Mering and Minkowski, two European researchers who, in 1889, found that when they completely removed the pancreas of test dogs, the dogs developed all the signs and symptoms of diabetes and died shortly afterward. In 1910, Sharpey-Shafer in Edinburgh suggested that diabetics were deficient in a single chemical that was normally produced by the pancreas — he proposed calling this substance insulin.
The endocrine role of the pancreas in metabolism, and indeed the existence of insulin, was not fully clarified until 1921, when Frederick Grant Banting and Charles Herbert Best repeated the work of Von Mering and Minkowski but went a step further and managed to show that they could reverse the induced diabetes in dogs by giving them an extract from the pancreatic islets of Langerhans from healthy dogs. They went on to isolate the hormone insulin from bovine pancreases at the University of Toronto in Canada.
This led to the availability of an effective treatment - insulin injections - and the first clinical patient was treated in 1922. For this, Banting received the Nobel Prize in Medicine in 1923. The two researchers did not patent their discovery and the therapy rapidly spread around the world.
Further reading on history of insulin
Overview
Diabetes mellitus is the most common cause of adult renal failure worldwide. It is the most common non-accidental cause of amputation in the US. It is the most common cause of blindness among non-elderly adults in the US.Etymology
Causes and types
There are several types of diabetes mellitus:
The older names, juvenile or insulin-dependent (IDDM) for Type 1, and adult-onset, or non-insulin dependent (NIDDM), or obesity-related, for Type 2 diabetes, have long been discouraged as they are misleading. Type 2 diabetes sometimes requires treatment with insulin, and is increasingly diagnosed among juveniles. Many Type 2 diabetics have reduced or absent insulin production even though they are not likely to have classic Type 1 diabetes caused by an autoimmune reaction. Presentation (signs and symptoms)
Diabetic ketoacidosis
Diabetic coma
Diabetes Treatment
Monitoring of blood glucose levels
Prognosis
short term -- acute -- problems
Since insulin became available, short term benefits of its sensible use have been, on the whole, excellent. At the very least, they didn't inevitably die in the short term as they had inevitably done previously. Impurities in insulin preparations have been decreasing steadily since 1922, and allergic reactions have decreased with them. Insulin has never been purer, by and large, than it is now. Insulin use has not become trivial and side effect reactions to commercial insulin products have not disappeared, but the situation is better now than it has ever been. The acute problems of diabetes mellitus, such as DKA, are _fully_ treatable today. They are not always treated properly, in part because many people don't pay sufficient attention to their diabetes, or beahve sensibly, and in part because some care givers have not taken into account the discoveries of the past few years about best treatments for diabetics. long term -- chronic -- problems
The long-term consequences of diabetes mellitus are another story. Long term complications of diabetes mellitus include damage to small blood vessels (microangiopathy), larger blood vessels (macroangiopathy), kidneys nephropathy, and to the peripheral and autonomic nervous systems (diabetic neuropathy). Each of these causes its own symptoms, most of them unfortunate.Public Health, Policy and Health Economics
History
References
See also