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Diabetes mellitus is the 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 which have variable aetiology (ie, causes). 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, and to adjust treatment more carefully than ever before.

Overview

In 2004, according to the World Health Organization, more than 150 million people worldwide suffer from some form of diabetes. In addition, it is estimated that, by the year 2025, this number will double. Unlike many other diseases, such as malaria, diabetes mellitus occurs everywhere, but it is more common (especially Type 2) in the economically developed world such as the United States and Western Europe. As of 2002, there are about 18.2 million diabetics in the United States. For at least 20 years, diabetes rates (and. of course, the number of diabetics) in North America have been increasing substantially. The Centers for Disease Control has termed the change an epidemic. This is a medically and economically important disease everywhere it occurs; the National Diabetes Information Clearinghouse estimates that in the United States diabetes accounts for $132 billion in expense each year. Diabetes is easily in the top 10, and perhaps in the top 5, most devastating diseases 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:

endothelial damage - manifesting as microvascular or macrovascular damage (ie, blood vessel damage);
proliferative retinopathy which can lead to blindness;
peripheral neuropathy which can lead to foot ulcers leading to necrosis and infection (including gangrene), eventually requiring amputation;
nephropathy which can cause chronic renal failure requiring dialysis or transplantation.
As well, ischemic heart disease and stroke are other possible complications -- probably stemming from blood vessel damage, as is
high blood pressure -- which is more common in diabetics.

Diabetes mellitus is the most common cause of adult renal failure (ie, kidney failure) worldwide. It is the most common, non-accidental, cause of amputation (usually toes and feet) in the US. It is also the most common cause of blindness among non-elderly adults in the US. It is similarly dangerous elsewhere.

Diabetes cannot now be cured (except experimentally in Type 1 diabetics) but it can almost always be treated effectively, and there is emerging solid evidence that diabetes mellitus Type 2 can be evaded in those with impaired glucose tolerance; that is, in those with 'beginning' Type 2.

Traditionally (after the first use of insulin in 1922), the goal of diabetes treatment was prevention of either hyperglycemic or hypoglycemic coma, and of diabetic ketoacidosis. Lack of sufficiently frequent and sufficiently inexpensive blood glucose monitoring precluded a much more nuanced intervention until the late 1970s when portable meters became available. The chronic complications of diabetes were not even known to be actually preventable until the last few decades. Until the 1920s, they couldn't even be observed -- much less treated -- because patients didn't survive long enough to suffer from them.

Several large, long duration, studies since 1980 have made it absolutely clear that the effort needed to keep blood glucose levels as close to normal (ie, fasting levels below 126 mg/dl and above 60 or 70 depending on the individual patient) is well worth while, and that it is actually possible to achieve such results 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; in short, "the more normal, the fewer and less severe are complications". Several studies have recently shown that the beneficial effect of close control is also a long term one. More recent studies in Type 2 diabetes also have shown the benefits of intensive blood pressure and cholesterol control. Much of the vascular damage associated with diabetes mellitus seems to be due, in large part, to prolonged uncontrolled high blood pressure which is common in diabetics -- probably due to insulin resistance or renal failure / damage or both.

Today's goal for diabetics is to avoid or minimize chronic diabetic complications, as well as to avoid acute problems due to too high or too low blood glucose (ie, coma at either end). For Type 1 diabetics, this means injecting insulin; for Type 2 diabetics, this means diet, exercise, and weight loss, in any achievable combination depending on the patient, followed by medication (usually oral, but possibly insulin as well).

Diabetes management is almost always a major ongoing presence in patients' lives and activities. It need not be more than 'merely' annoying for most. However, patient participation is so important to diabetes management that patient education is essentially required for diabetics as many treatments are potentially damaging (if not deadly) when administered improperly. Moreover, and also importantly, there are (and have long been) a large number of "alternative" treatments for diabetes; some are merely ineffectually expensive, but some are dangerous and occasionally deadly in themselves and/or by supplanting more conventional and effective, if not curative, treatments.

Etymology

"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 diabetics produce (when blood glucose is too high) attracted flies and bees because of the glucose content. The ancient Chinese tested for diabetes by observing whether ants were attracted to a person's urine.

It is probably important to note that passing abnormal amounts of urine is a symptom shared by several diseases (most commonly of the kidneys), and the word single word diabetes is applied to many of them. The most common of them are diabetes insipidus and the subject of this article, diabetes mellitus.

Causes, and types, of diabetes mellitus

The role of insulin

Insulin is a chemical (a hormone) normally produced within the body which 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 body cells), and electrolyte (ie, small ion) balance (by controlling potassium uptake in cells). All are vital for life and if deranged too much are fatal. Insulin is the central hormone which controls metabolism. It is produced in the endocrine part of the pancreas, which consists of multiple very small clumps of specialised cells scattered throughout that organ (ie, the 'Islets of Langerhans'). Hyperglycemia (ie, too high a blood glucose level) results if the amount of insulin produced 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:

Not enough insulin is produced by the pancreas Islet cells (in Type 1, and in some Type 2)
Body cells have become resistant to insulin action (in Type 2 and even in some Type 1)

Type 1

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 hormone-producing beta cells (actually the glutamate decarboxylase enzyme) of the Islets of Langerhans in the pancreas, preventing them from producing enough (or any) insulin. The autoimmune attack is typically triggered by an infection, often by one of the Coxsackie virus family (group B). The Coxsackie viruses force production of a protein (called P2-C), which is so similar in structure to glutamate decarboxylase that it leads the immune system to attack it as well (ie, molecular mimicry).

Some poisons (eg, one type of rat poison) work by selectively destroying the beta cells, thus producing 'artificial' Type 1 diabetes. Pancreatic trauma or tumor can also do so.

Currently, Type 1 is essentially always treated with insulin injections, ideally using intensive insulinotherapy on a sliding dose scale. Insulin type, and doses must be fitted to the individual patient's responses, and adjusted thereafter as required.

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" (IDDM) diabetes. All are misnomers, most especially since the obesity epidemic of recent years has lead to increased incidence of Type 2 diabetes in children and adolescents. The preferred term for many years is Type 1.

Type 1 diabetes sometimes occurs together with other autoimmune disorders of endocrine organs. This is called autoimmune polyendocrine syndrome; diabetes is asssociated with both major types of APS (15-20% have type 1 diabetes mellitus). Other diseases that commonly occur in this syndrome are Addison's disease and hypothyroidism.

Type 2

Type 2 diabetes is characterized by resistant to insulin in those body cells requiring insulin to permit uptake of glucose from the blood; about 2/3 of body cells do. It is typically a much more complex problem than Type 1. The four main characteristics of this disease ("the disharmonious quartet") are: (1) decreased insulin secretion, (2) increased lipolysis, (3) increased hepatic glucose production (gluconeogenesis), and (4) decreased muscular glucose uptake. All contribute to the development of hyperglycemia (ie, high 'blood sugar'), which far too often goes unnoticed for years and may produce complications (see below) before it is diagnosed; the complications are often the signs by which it is finally found. Type 2 diabetes often develops later in life, and is often accompanied by central obesity, hypertension (ie, high blood pressure), and combined dyslipidemia (ie, improper blood fat levels) (together these are termed Metabolic Syndrome X. However, it is currently believed that obesity is the most significant risk factor as several signals (ie, new hormones) produced in fat tissue have quite recently been discovered to affect metabolism. A person's chances of developing Type 2 diabetes increases by 4 percent for every pound of excess weight.

Type 2 diabetes was formerly called any of 'adult-onset' diabetes, 'obesity related'-diabetes, 'insulin resistant'-diabetes, or 'non-insulin dependent' (NIDDM) diabetes. All are misnomers and the preferred term for many years has been Type 2 diabetes.

Type 2 diabetes can be caused by (or at least is associated with) a number of diseases (e.g. hemochromatosis and polycystic ovary syndrome) and is caused by certain types of medications (e.g. as a side effect of 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 reasons (probably lifestyle differences, and most probably obesity distribution). There is also a very strong inheritable genetic connection in Type 2 diabetes. For example, in late 2000, researchers found that a variant of the gene Caplain-10, is associated with the development of Type 2 diabetes. Relatives, especially close ones, with Type 2 are a considerable risk factor.

Type 2 is initially treated by weight loss, which can restore insulin sensitivity even when the weight lost is modest (10-15 lbs (5 kg)), and changes in diet. Often, the next step, if necessary, is treatment with oral antidiabetic drugs (eg, sulphonylureas, metformin, or thiazolidinediones). When a combination of the above has failed, insulin therapy may be necessary.

Type 3

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

Type 4 or Gestational diabetes mellitus appears in about 2-5% of all pregnancies. It is temporary and fully treatable, but if untreated often causes 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 (ie, have genetic links). Type 1 diabetes appears to be triggered by infection, stress, or environmental factors (eg, exposure to one another substance). But there is clearly a genetic element in the susceptibility of individuals to some of these triggers; it has been traced to particular HLA genotypes (ie, genetic 'self' identifiers used by the immune system). But, even in those who have inherited the susceptibility, Type 1 seems to require an environmental trigger.

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, and so inheriting a tendency toward a portly shape 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.

Signs and symptoms of diabetese mellitus (clinical presentation)

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 consequent 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 they are usually not until a later, more 'severe' stage in the progression of Type 2.

Thirst develops because of osmotic effects—sufficiently high glucose (ie, above the 'renal threshold') in the blood is excreted by the kidneys but this requires water to carry it and so causes increased fluid loss, which must be replaced. The lost blood volume will be replaced from water held inside body cells, which will cause dehydration without additional fluid intake. Hence the thirst.

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 worst form of altered consciousness is the so-called "diabetic coma" which includes unconsciousness. Early symptoms of impending diabetic coma include polyuria, nausea, vomiting and abdominal pain, with lethargy and somnolence (ie, unusual sleepiness) a later development, progressing to unconsciousness (ie, coma) and death if continued and untreated.

Diabetic ketoacidosis and coma

See also the more detailed articles diabetic ketoacidosis and diabetic coma

Diabetic ketoacidosis (DKA) is an acute, dangerous complication in diabetes and is always a medical emergency. If left without prompt proper treatment, patients with diabetic ketoacidosis have substantial chance of death.

DKA arises from incomplete fat breakdown. Production of fatty acids from stored lipid (eg, fat in fat tissue) is entirely normal (and is called metabolic ketosis). It is is begun when insulin levels are low. It is therefore indirectly controlled by the blood glucose level (in non-diabetics) and so is ultimately, though still more indirectly, controlled by carbohydrates in the diet. When blood glucose is low (especially persistently), and thus when fat is being taken from body stores and converted to fatty acids for energy use (ie, during ketosis), glucose is produced from a few of the amino acids in protein. This requires net protein degradation to make them available, which is itself not usually beneficial. During glucose production from amino acids (ie, from disassembled 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 (a normal 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 much rarer in Type 2 diabetics.

The brain (and a few other tissues, including parts of the kidneys) uses glucose from the blood regardless of anything else (eg, diabetic status as in loo little insulin or cellular resistance to it) as nerve cells do not require insulin to absorb glucose. But neither the brain 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 involved was poorly understood.

DKA is usually accompanied by hyperglycemia which also causes osmotic diuresis (ie, increased urine output), leading to excessive losses of water and blood electrolytes (eg, sodium and potassium ions). Dehydration, and these electrolyte imbalances are themselves dangerous, and can also cause problems up to and including death.

A patient with DKA is always acidotic, almost always dehydrated, usually has electrolyte problems, and is nearly always hyperglycaemic. All are very dangerous conditions and together are no less so. The patient urgently requires IV fluids, electorlytes, and, almost always, insulin -- typically intravenously. A bicarbonate infusion may be necessary if the pH of the blood is sufficiently low. DKA is a frank medical emergency. It requires immediate skilled treatment, supplies, and facilities, and cannot be adequately handled at home on a 'first aid' basis.

Hyperosmotic diabetic coma

Hyperosmotic diabetic coma is another acute problem associated with imporper (or no) management of diabetes mellitus. It has some symptoms in common with DKA, but a different cause, and requires different treatment. 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 also be "dumping" glucose into the urine, and the water necessary will come from the blood, and will have to be replaced. In the absence of sufficient fluid intake, that water will come from inside body cells. The osmotic effect of the high glucose levels combined with the (excessive) loss of water will eventually result in too high blood 'thickness' (ie, raised serum osmolality). Electrolyte imbalances are also common. This combination of changes, especially if prolonged, will result in symptoms similar to ketoacidosis, including loss of consciousness (ie, coma). As with DKA, urgent medical treatment is necessary. This is the diabetic coma to which Type 2 diabetics are prone; it is less common in Type 1 diabetics.

Hypoglycemia

Low 'blood sugar' levels (ie, hypoglycemia) in diabetics is almost always a complication of poor management (too much exercise, not enough food, or poor timing of either), or inappropriate treatment (primarily, too high insulin and sulphonylureas). If blood glucose is low enough ('how low' varies with patient and with circumstance) the patient is often agitated (sometimes irrational), sweaty, and has many (or even all) symptoms of sympathetic activation of the autonomic nervous system (or, in ordinary terms, how one feels during dread and immobilized panic). Consciousness can be altered, or even lost, in extreme cases, leading to coma and/or seizures. Death and brain damage are possible as well. A diabetic, particularly an experienced one, can often recognise the symptoms early on (though some have lost or become physically unaware, of the warning signs) and all should always carry something with easily available sugar to eat or drink. If noticed early enough, all symptoms will be reduced quite rapidly. Or injection of glucagon (only once until a couple of hours after a meal) can be used to force the liver to put its internal stores of glucose into the blood. Otherwise, oral or intravenous dextrose (ie, glucose) administration will can be used. Longstanding hypoglycemia may require hospital admission to allow supervised recovery.

Diabetes treatment

The need for treatment

Diabetes is a chronic disease (the most common such disease) and, as there is no cure, it can only be managed. Often, but not always, this is by life-long treatment with medication. Moreover, it can lead to several serious acute or chronic complications that can result in kidney failure (requiring dialysis or transplant), blindness, or amputation if not managed adequately and systematically.

Diabetes mellitus requires complex therapy, education, and (generally) life-style modifications to minimize bad longterm outcomes. The goals of diabetes management and therapy are several: not only near-normal glycemic control (and so avoidance of both acute and chronic hyperglycemia or hypoglycemia), but also reduction in the risk of long-term complications, thus preserving quality of life.

Several major studies (involving very large numbers of patients followed for extended periods) have shown, clearly and convincingly and beyond every reasonable doubt, that keeping blood glucose levels as close as possible to 'normal', nondiabetic, values really does prevent, reduce, or delay, chronic diabetic complications:

diabetic retinopathy (ie, eye damage including blindness)
nephropathy (ie, kidney damage including kidney failure)
microangiopathic and macroangiopathic damage (atherosclerosis) (ie, blood vessel damage leading to increased risk of heart attack or stroke, and impaired healing leading to prolonged infection, including gangrene, leading to surgery or amputation)
as well as neuropathy (ie, nerve damage both sensory and autonomic).

An effort to achieve 'close' glucose control should be undertaken with care, as keeping blood glucose levels close to 'normal' leaves less room for medication / diet / exercise error and so increases the risk of a (possibly dangerous) hypoglycemic episode (see above). However, close control is not only possible, but should in nearly all cases be attempted.

Treatment modalities

Treatment therapy for diabetes mellitus depends on the Type:

Type 1 is generally treated with insulin (via needle or jet injection) as a first-line therapy, sometimes proceeding to an insulin pump. There is no oral treatment for Type 1 diabetes as of 2004. Islet transplants are still experimental as common practice.
Type 2 can often be managed with: a diet and medication, and these should usually be tried as a first resort. Common antidiabetic drugs include the biguanides (primarily metformin), the sulfonylureas (e.g., Orinase®, Diabinase®, and Tolinase® among a great many others) and the newer thiazolidinediones (eg, rosiglitazone and pioglitazone). Some Type 2 diabetics require insulin therapy when combinations of diet, exercise, weight control, and of antidiabetic drugs have failed to bring glucose levels under control (or have intolerable side effects).

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. The previously satisfactory dosing may now be too much and cause a hypoglycemic reaction if not intelligently adjusted. As well, more exercise decreases insulin requirements, and vice versa: exercise increases glucose uptake by body cells whose glucose uptake is controlled by insulin.

Since there are many different insulins (ie, different 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 individual patient variations), getting the right amount and timing of diabetic medication (especially 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 certainly an attainable goal for the average patient, but it is not simple, nor trivially safe to do so. The consequences of making an error include death, and so great caution, and expert advice (especially when beginning drug therapy), are both mandatory. Especially for newly diagnosed diabetics, medication changes should be done only in consultation with a physician.

Illness, surgery, and stress generally 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 and that particular patient.

Associated risks

Too high blood glucose levels, that is diabetes mellitus, should cause a physician to search for other risks leading to cardiovascular disease (ie, heart attack and stroke), mainly hypertension (ie, high blood pressure) and hypercholesterolemia (ie, high blood cholesterol and other blood lipid problems). Diabetics have had substantially increased rates of cardivascular disease, and controlling other known risk factors is well advised.

In addition, a large in the medical journal Lancet seems to show that diabetics benefit substantially from treatment with one of the statin drugs (that in this study was simvastatin, 40 mg or equivalent), irrespective of their cholesterol levels. The treatment seems to reduce (by 24-27%) the rate of myocardial infarction (ie, heart attack), death from heart attack, and stroke, as well as the need for peripheral arterial revascularization procedures (eg, bypass, stent, etc). The reason is now thought to be an anti-inflammatory reaction, and not just the modification of cholesterol levels. In short, the effect seems clear, but the mechanism remains obscure.

Monitoring of blood glucose levels

a typical portable blood glucose meter

Sensible management of diabetes depends almost entirely on blood glucose testing. This is because mild to moderate hyperglycemia (ie, high blood glucose levels) causes no obvious symptoms in most patients. Other reasons include the fact that, while food takes several hours to be digested and absorbed, insulin administration can have glucose lowering effects for as little as 2 hours or 24 hours or more (depending on the nature of the insulin preparation used and individual patient reaction). And, the onset time and duration of the effects of oral hypoglycemic agents (nearly always pills) vary from type to type and from patient to patient.

Since blood glucose levels normally change regularly and rapidly (within minutes), portable meters are effectively the only reasonable way to monitor them. 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 a diabetic patient is obliged to make in actual life.

Urine glucose testing is only slightly more useful, no matter where or how often done, except perhaps for detecting ketones in the early stages of diabetic ketoacidosis. Urine glucose readings include all glucose levels since the last urination, not only what they are at the time of the test. Even in an emergency, this is not likely to be of much help beyond perhaps confirming a suspicion that someone is likley diabetic, and every diabetic should, against accident, wear a necklace or wrist band announcing the fact for emergency attendants.

There are multiple suppliers, most with several models of blood glucose meters (all of which must be individually approved by the FDA in the US). Differences among the models include size of the blood droplet required, where it can be taken (from a finger, or a forearm, or ...), 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 techniques), and compatibility with computer programs for keeping records of readings and other information. Cost also varies, though not for inherent technical reasons; these are all devices of quite similar complexity and inherent cost.

a blood test strip

The cost per test strip varies quite substantially, though again not for any inherent reason -- cost differences of more than 3x are found in the US as this is written. Thus, strips for one meter model may be as little as 1/3 the cost for strips for another. Cumulative strip costs, over even short periods, completely swamp all other meter cost issues. Strip cost should be a major (and probably the most important by far) contributor to the choice of meter. How often to test, and what to do with/about the results should be closely coordinated with medication schedules (especially for insulin), with food, with exercise, and with other blood glucose influences (eg, illness or surgery). At least when beginning to test, medical supervision is a very sensible, and in many cases necessary.

A useful laboratory measure of long term diabetic glucose control is the 'glycated haemoglobin' level (aka, "HbA1c"). Non-diabetics typically have an HbA1c reading of less than 7%. This is a sensible target for most (but not all) diabetics; since diabetic situations differ, determining an HbA1c target should be determined in cooperation with a physician. HbA1c readings are an indication of the average of glucose levels in the recent past (ie, about 3 months in most people as the lifetime of a red blood cell is typically 120 days). What HbA1c level indicates inadequate blood glucose control will vary with each patient. There is now a commercial test kit (in the US, anyway) for taking samples for HbA1c measurement at home. In addition there is another test which indicates average blood glucose levels over the past month or so; it is called the fructosamine test and measures the level of another protein affected by glucose. A portable meter is available (in the US) for this test.

Progress of Diabetes Mellitus (likely prognosis)

Short term (acute) problems

Since insulin became available in 1922, short term benefits of its sensible use have been, on the whole, excellent. At the very least, diabetics didn't die more or less promptly after diagnosis 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 insulins 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. TThat they are not always treated properly, results in part because many don't pay sufficient attention to their diabetes even after diagnosis, nor behave sensibly, and in part because some care givers have not taken into account the past few years developments regarding best treatments for diabetics.

Long term (chronic) problems

The long-term consequences of diabetes mellitus are another story altogether. 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, not one of them beneficial.

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). Blindness and kidney failure can result. Diabetes is the leading cause of both in North American adults. 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 (ie, nerve damage) as well. Peripheral sensory neuropathy affects sensation, first, and primarily, in the feet and lower legs, and eventually even fingers and hands. Feeling decreases, and with it protective reactions to damage, eg from thumb tacks, blisters, ill fitting shoes, .... Combined with vascular damage slowing healing, the effect is to greatly increase the risk of severe trauma damage (eg, can't feel the pebble or pin or developing blister), and the risk of serious infection (eg, infection not noticed (from no or reduced pain) and no measures taken until 'too late'). Diabetes is the leading cause of non-traumatic amputation in North American adults. Autonomic neuropathy can cause problems with balance, with intestinal functions (ie, digestion), with balance and coordination, with sexual responses and other reflexes, and indeed, with 'automatic' compensating adjustments of many kinds.

It is welcome news then, that several quality studies have demonstrated that, for both Types of diabetes mellitus, the rate and severity of all of these long term complications is substantially reduced, or eliminated, by keeping blood glucose levels at or near 'normal'. Blood glucose testing, and close glucose control, are important if only because it helps with this.

Public health, policy and health economics

The Declaration of St Vincent was the result of international efforts to improve the care accorded to diabetics. Doing so is important if only economically. 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, all extremely expensive evetns.

Work in the Puget Sound area of North America (by the health 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 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.

History

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 Joseph Von Mering and Oskar Minkowski, two European researchers who, in 1889, found that when they completely removed the pancreas of dogs, the dogs developed all the signs and symptoms of diabetes and died shortly afterward. In 1910, Sir Edward Albert Sharpey-Schafer 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 of 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, et al, received the Nobel Prize in Medicine in 1923. The two researchers did not patent their discovery and the therapy rapidly spread around the world.

References

"Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus." N Engl J Med 329:977-986, 1993 (abstract)
"World Health Organisation, Department of Noncommunicable Disease Surveillance. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications." Geneva: WHO; 1999. Available in PDF
"UK Prospective Diabetes Study Group: Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)." Lancet 352:837-853, 1998
"Conditions in Occupational Therapy: effect on occupational performance." ed. Ruth A. Hansen and Ben Atchison (Baltimore: Lippincott Williams & Williams, 2000), 298-309. ISBN 0-683-30417-8
"Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial." Lancet 2003 Jun 14;361(9374):2005-2016
"Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M : Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance." N Engl J Med 2001 May 3;344(18):1343-50

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Endocrinology