Diabetes Mellitus Medical Revision Author: Ruchi Mathur, MD
Medical Editor: William C. Shiel, Jr., MD, FACP, FACR
What is diabetes mellitus?
Diabetes mellitus is a group of metabolic diseases characterized by high blood sugar ( glucose ) levels, which result from defects in insulin secretion, or action, or both. Diabetes mellitus, commonly referred to as diabetes, means "sweet urine." Elevated levels of blood glucose (hyperglycemia) lead to spillage of glucose into the urine, hence the term sweet urine. Normally, blood glucose levels are tightly controlled by insulin, a hormone produced by the pancreas . Insulin lowers the blood glucose level. When the blood glucose elevates (for example, after eating food), insulin is released from the pancreas to normalize the glucose level. In patients with diabetes mellitus, the absence or insufficient production of insulin causes hyperglycemia. Diabetes mellitus is a chronic medical condition, meaning it can last a lifetime.
What is the impact of diabetes?
Over time, diabetes mellitus can lead to blindness, kidney failure , and nerve damage. Diabetes mellitus is also an important factor in accelerating the hardening and narrowing of the arteries ( atherosclerosis ), leading to strokes, coronary heart diseases, and other blood vessel diseases. Diabetes mellitus affects 15 million people (about 8% of the population) in the United States. In addition, an estimated 12 million people in the United States have diabetes and don't even know it. From an economic perspective, the total annual economic cost of diabetes in 1997 was estimated to be 98 billion dollars in the United States. The per capita cost resulting from diabetes in 1997 amounted to $10,071, while to health care costs for people without diabetes incurred a per capita cost of $2,699. During this same year, 13.9 million days of hospital stay were attributed to diabetes, while 30.3 million physician office visits were diabetes related. Remember, these numbers reflect only the population in the United States. Globally, the statistics are staggering.
Diabetes is the third leading cause of death in the United States after heart disease and cancer .
What causes diabetes mellitus?
Insufficient production of insulin (either absolutely or relative to the body's needs), production of defective insulin (which is uncommon), or the inability of cells to use insulin leads to hyperglycemia and diabetes mellitus. This latter condition affects mostly the cells of muscle and fat tissues, and results in a condition known as "insulin resistance." This is the primary problem in type 2 diabetes. The absolute lack of insulin, usually secondary to a destructive process in the pancreas, is the particular disorder in type 1 diabetes.
Glucose is a simple sugar found in food. Glucose is an essential nutrient that provides energy for the proper functioning of the body cells. After meals, food is digested in the stomach and the intestines. The glucose in digested food is absorbed by the intestinal cells into the bloodstream, and is carried by blood to all the cells in the body. However, glucose cannot enter the cells alone and needs insulin to aid in its transport into the cells. Without insulin, cells become starved of glucose energy despite the presence of abundant glucose in the blood. In certain types of diabetes mellitus, the cells' inability to utilize glucose gives rise to the ironic situation of "starvation in the midst of plenty". The abundant, unutilized glucose is wastefully excreted in the urine.
Insulin is a hormone that is produced by specialized cells (beta cells) of the pancreas. (The pancreas is a deep-seated organ in the abdomen located behind the stomach.) In addition to helping glucose enter the cells, insulin is also important in tightly regulating the level of glucose in the blood. After a meal, the blood glucose level rises. In response to the increased glucose level, the pancreas normally releases insulin into the bloodstream to help glucose enter the cells and lower blood glucose levels. When the blood glucose levels are lowered, the insulin release from the pancreas is turned off. In normal individuals, such a regulatory system helps to keep blood glucose levels in a tightly controlled range. In patients with diabetes mellitus, the insulin is either missing (as in type 1 diabetes mellitus), or insulin is relatively insufficient for the body's needs (as in type 2 diabetes mellitus). Both cause elevated levels of blood glucose (hyperglycemia).
What are the different types of diabetes mellitus?
There are two major types of diabetes mellitus, called type 1 and type 2. Type 1 diabetes mellitus was also called insulin dependent diabetes mellitus (IDDM), or juvenile onset diabetes mellitus. In type 1 diabetes mellitus, the pancreas undergoes an autoimmune attack by the body itself, and is rendered incapable of making insulin. Abnormal antibodies have been found in patients with type 1 diabetes. Antibodies are proteins in the blood that are part of the body's immune system . The patient with type 1 diabetes must rely on insulin medication for survival.
In autoimmune diseases, such as type 1 diabetes, the immune system mistakenly manufactures antibodies that are directed against and cause damage to patients' own body tissues. It is believed that the tendency to develop these abnormal antibodies in type 1 diabetes is, in part, genetically inherited, though the details are not fully understood. (Exposure to certain viral infections ( mumps and Coxsackie viruses) or other environmental toxins may serve to trigger abnormal antibody responses that cause damage to the pancreas cells where insulin is made. These antibodies can be measured, and may help determine which individuals are at risk for developing type 1 diabetes. At present, the American Diabetes Association does not recommend general screening, though screening of high risk individuals, such as those with a first degree relative (sibling or parent) with type 1 diabetes should be encouraged. Type 1 diabetes tends to occur in young, lean individuals, usually before 30 years of age, however, older patients do present with this form of diabetes on occasion. This subgroup is referred to as latent autoimmune diabetes in adults (LADA). LADA is a slow, progressive form of type 1 diabetes. Only approximately 10% of the patients with diabetes mellitus have type 1 diabetes and the remaining 90% have type 2 diabetes mellitus.
Type 2 diabetes mellitus was also referred to as non-insulin dependent diabetes mellitus (NIDDM), or adult onset diabetes mellitus (AODM). In type 2 diabetes, patients can still produce insulin, but do so relatively inadequately. In many cases this actually means the pancreas produces larger than normal quantities of insulin. A major feature of type 2 diabetes is a lack of sensitivity to insulin by the cells of the body (particularly fat and muscle cells) these larger quantities of insulin are produced as an attempt to get these cells to recognize that insulin is present. In addition to the problems with an increase in insulin resistance , the release of insulin by the pancreas may also be defective, and occur late in response to increased glucose levels. Finally, the liver in these patients continues to produce glucose despite elevated glucose levels.
While it is said that type 2 diabetes mellitus occurs mostly in individuals over 30 years old and the incidence increases with age, we are seeing an alarming number patients with type 2 diabetes who are barely in their teen years. Most of these cases are a direct result of poor eating habits, higher body weight, and lack of exercise. While there is a strong genetic component to developing this form of diabetes, there are other risk factors - the most significant of which is obesity . There is a direct relationship between the degree of obesity and the risk of developing type 2 diabetes, and this holds true in children as well as adults. It is estimated that the chance to develop diabetes doubles for every 20% increase over desirable body weight and for each decade after 40 years of age regardless of weight. The prevalence of diabetes in persons 65 to 74 years of age is nearly 20%. Type 2 diabetes is more common in certain ethnic groups. Compared with a 6% prevalence in Caucasians, the prevalence in African Americans and Asian Americans is estimated to be 10%, in Hispanics 15%, and in certain Native American tribes 20% to 50%. Finally, diabetes occurs much more frequently in women with a prior history of diabetes that develops during pregnancy ( gestational diabetes - see below). Type 2 diabetes is often associated with a strong familial, probably genetic predisposition. This is less common in the autoimmune form of type 1 diabetes.
Diabetes mellitus can occur temporarily during pregnancy. Significant hormonal changes during pregnancy can lead to blood sugar elevation in genetically predisposed individuals. Blood sugar elevation during pregnancy is called gestational diabetes. Gestational diabetes usually resolves once the baby is born. However, 25-50% of women with gestational diabetes will eventually develop diabetes mellitus later in life, especially in those who require insulin during pregnancy and those who are overweight. Patients with gestational diabetes are usually asked to undergo an oral glucose tolerance test about 6 weeks after giving birth to determine if their diabetes has persisted beyond the pregnancy.
"Secondary" diabetes mellitus refers to elevated blood sugar levels from another medical condition. Secondary diabetes mellitus also develops when the pancreatic tissue responsible for the production of insulin is absent because it is destroyed by disease, such as chronic pancreatitis (inflammation of the pancreas by toxins like excessive alcohol), trauma, or surgical removal of the pancreas. Diabetes can also result from other hormonal disturbances, such as excessive growth hormone production ( acromegaly ) and Cushing's syndrome . In acromegaly, a pituitary gland tumor at the base of the brain causes excessive production of growth hormone, leading to hyperglycemia. In Cushing's syndrome, the adrenal glands produce an excess of cortisol , which promotes blood sugar elevation. In addition, certain medications may worsen diabetes control, or "unmask" latent diabetes. This is seen most commonly when steroid medications (such as prednisone ) are taken.
What are the symptoms of diabetes mellitus?
The early symptoms of untreated diabetes mellitus are related to elevated blood sugar levels, and loss of glucose in the urine. High amounts of glucose in the urine can cause increased urine output and lead to dehydration . Dehydration causes increased thirst and water consumption. The inability to utilize glucose energy eventually leads to weight loss despite an increase in appetite. Some untreated diabetes patients also complain of fatigue , nausea , and vomiting. Patients with diabetes are prone to developing infections of the bladder, skin, and vaginal areas. Fluctuations in blood glucose levels can lead to blurred vision. Extremely elevated glucose levels can lead to lethargy and coma ( diabetic coma ).
How is diabetes mellitus diagnosed?
The fasting blood glucose (sugar) test is the preferred way to diagnose diabetes. It is easy to perform and convenient. After the person has fasted overnight (at least 8 hours), a single sample of blood is drawn and sent to the laboratory for analysis.
Normal fasting plasma glucose levels are less than 110 milligrams per deciliter (mg/dl). Fasting plasma glucose levels of more than 126 mg/dl on two or more tests on different days indicate diabetes. If the overnight fasting blood glucose is greater than 126 mg/dl on two different tests on different days, the diagnosis of diabetes mellitus is made. A random blood glucose test can also be used to diagnose diabetes. Random blood samples (if taken shortly after eating or drinking) may be used to test for diabetes when symptoms are present. A blood glucose level of 200 mg/dl or higher indicates diabetes, but it must be reconfirmed on another day with a fasting plasma glucose or an oral glucose tolerance test.
When fasting a blood glucose stays above 110 mg/dl, but in the range of 110-126mg/dl, this is known as impaired fasting glucose (IFG). While patients with IFG do not have the diagnosis of diabetes, this condition carries with it its own risks and concerns, and is addressed elsewhere.
What is the oral glucose tolerance test?
Though not routinely used anymore, the oral glucose tolerance test (OGTT) is the gold standard for making the diagnosis of type 2 diabetes. It is still commonly used for diagnosing gestational diabetes. With an oral glucose tolerance test, the person fasts overnight (at least 8 but not more than 16 hours). Then first, the fasting plasma glucose is tested. After this test, the person receives 75 grams of glucose (100 grams for pregnant women). There are several methods employed by obstetricians to do this test, but the one described here is standard. Usually, the glucose is in a sweet-tasting liquid that the person drinks. Blood samples are taken up to four times to measure the blood glucose.
For the test to give reliable results, the person must be in good health (not have any other illnesses, not even a cold). Also, the person should be normally active (not lying down, for example, as an inpatient in a hospital) and should not be taking medicines that could affect the blood glucose. For 3 days before the test, the person should have eaten a diet high in carbohydrates (150- 200 grams per day). The morning of the test, the person should not smoke or drink coffee.
The classic oral glucose tolerance test measures blood glucose levels 5 times over a period of 3 hours. Some physicians simply get a baseline blood sample followed by a sample 2 hours after drinking the glucose solution. In a person without diabetes, the glucose levels rise and then fall quickly. In someone with diabetes, glucose levels rise higher than normal and fail to come back down as fast.
People with glucose levels between normal and diabetic have impaired glucose tolerance (IGT). People with IGT do not have diabetes. Each year, 1-5% of people whose test results show IGT actually develop diabetes. Weight loss and exercise may help people with IGT return their glucose levels to normal. In addition, some physicians advocate the use of medications, such as metformin (Glucophage), to help prevent/delay the onset of overt diabetes. Recent studies have shown that IGT itself may be a risk factor for the development of heart disease, and whether IGT turns out to be an entity that deserves treatment itself is something that physicians are currently debating.
What may the results of the oral glucose tolerance test indicate?
Glucose tolerance tests may lead to one of the following diagnoses: - Normal response: A person is said to have a normal response when the 2-hour glucose level is less than 140 mg/dl, and all values between 0 and 2 hours are less than 200 mg/dl.
- Impaired glucose tolerance : A person is said to have IGT when the fasting plasma glucose is less than 126 mg/dl and the 2-hour glucose level is between 140 and 199 mg/dl.
- Diabetes: A person has diabetes when two diagnostic tests done on different days show that the blood glucose level is high.
- Gestational diabetes: A woman has gestational diabetes when she has any two of the following: a 100g OGTT, a fasting plasma glucose of more than 95 mg/dl, a 1-hour glucose level of more than 180 mg/dl, a 2-hour glucose level of more than 155 mg/dl, or a 3-hour glucose level of more than 140 mg/dl.
Why is blood sugar checked at home?
Home blood sugar (glucose) testing is an important part of controlling blood sugar. One important goal of diabetes treatment is to keep the blood glucose levels near the normal range of 70 to 120 mg/dl before meals and under 140 mg/dl at 2 hours after eating. Blood glucose levels are usually tested before and after meals, and at bedtime. The blood sugar level is typically determined by pricking a fingertip with a lancing device and applying the blood to a glucose meter, which reads the value. There are many meters on the market, for example- Accu-Check Advantage, One Touch Ultra, Sure Step and Freestyle. Each meter has it's own advantages and disadvantages (some use less blood, some have a larger digital readout, some take a shorter time to give you results, etc). The test results are then used to help patients make adjustments in medications, diets, and physical activities.
Since blood glucose levels can fluctuate widely, even frequent home glucose testing may not accurately reflect the degree of success in controlling blood sugar. The hemoglobin A1C test is a valuable measure of the overall effectiveness of blood glucose control over a period of time.
What is a hemoglobin A1c (A1c)?
To explain what an A1c is, think in simple terms. Sugar sticks, and when it's around for a long time, it's harder to get it off. In the body, sugar sticks too, particularly to proteins. The red blood cells that circulate in the body live for about 3 months before they die off. When sugar sticks to these cells, it gives us an idea of how much sugar is around for the preceding 3 months. In most labs, the normal range is 4-5.9 %. In poorly controlled diabetes, its 8.0% or above, and in well controlled patients it's less than 7.0%. The benefits of measuring A1c is that is gives a more reasonable view of what's happening over the course of time (3 months), and the value does not bounce as much as finger stick blood sugar measurements.
There is a correlation between A1c levels and average blood sugar levels as follows:
While there are no guidelines to use A1c as a screening tool, it gives a physician a good idea that someone is diabetic if the value is elevated. Right now, it is used as a standard tool to determine blood sugar control in patients known to have diabetes.
| A1c(%) | Mean blood sugar (mg/dl) | | 6 | 135 | | 7 | 170 | | 8 | 205 | | 9 | 240 | | 10 | 275 | | 11 | 310 | | 12 | 345 |
The American Diabetes Association currently recommends an A1c goal of less than 7.0%.
Of interest, studies have shown that there is a 10% decrease in relative risk for every 1 % eduction in A1c. So, if a patients starts off with an A1c of 10.7 and drops to 8.2, though there are not yet at goal, they have managed to decrease their risk of microvascular complications by about 20%. The closer to normal the A1c, the lower the absolute risk for microvascular complications.
What are the acute complications of diabetes mellitus?
1. Severely elevated blood sugar levels due to an actual lack of insulin or a relative deficiency of insulin.
2. Abnormally low blood sugar levels due to too much insulin or other glucose-lowering medications.
Insulin is vital to patients with type 1 diabetes. Without insulin, patients with type 1 diabetes can develop severely elevated blood sugar levels. This leads to increased urine glucose, which in turn leads to excessive loss of fluid and electrolytes in the urine. Lack of insulin also causes the breakdown of fat cells, with the release of ketones into the blood. Ketones turn the blood acidic, a condition called diabetic ketoacidosis . Symptoms of diabetic ketoacidosis include nausea, vomiting, and abdominal pain . Without prompt medical treatment, patients with diabetic ketoacidosis can rapidly go into shock, coma, and even death. Diabetic ketoacidosis can be caused by infections, stress , or trauma. Urgent treatment of diabetic ketoacidosis involves the intravenous administration of fluid, electrolytes, and insulin, usually in a hospital intensive care unit. Antibiotics are given for infections. With treatment, abnormal blood sugar levels, acidosis , and dehydration can be reversed rapidly, and patients can recover remarkably well.
In patients with type 2 diabetes mellitus, stress, infection, and medications (such as corticosteroids) can also lead to severely elevated blood sugar levels. Accompanied by dehydration, severe blood sugar elevation in patients with type 2 diabetes mellitus can lead to an increase in blood osmolality ( hyperosmolar state). This condition can lead to coma (hyperosmolar coma). A hyperosmolar coma usually occurs in elderly patients with type 2 diabetes mellitus. Like diabetic ketoacidosis, a hyperosmolar coma is a medical emergency. Immediate treatment with intravenous fluid and insulin is important in reversing the hyperosmolar state. Unlike patients with type 1 diabetes mellitus, patients with type 2 diabetes mellitus do not generally develop ketoacidosis.
Hypoglycemia means abnormally low blood sugar (glucose). In patients with diabetes, the most common cause of low blood sugar is excessive use of insulin or other glucose-lowering medications, to lower the blood sugar level in diabetic patients. When low blood sugar levels occur because of too much insulin, it is called an insulin reaction. Sometimes, low blood sugar can be the result of an insufficient caloric intake or sudden excessive physical exertion. Blood glucose is essential for the proper functioning of nerve cells in the brain. Therefore, low blood sugar can lead to nervous system symptoms such as dizziness, confusion, weakness, and tremors. Untreated, severely low blood sugar levels can lead to coma, seizures, and, in the worse case scenario, irreversible brain death. The treatment of low blood sugar consists of administering glucose drinks, such as orange juice, soft drinks (not sugar-free), or glucose tablets. If the individual becomes unconscious , glucagon can be given by intramuscular injection. Glucagon causes the release of glucose from the liver, and should be part of the emergency kit of a diabetic, especially if the patient uses insulin. Families and friends of those with diabetes need to be taught how to administer glucagon, since obviously the patients will not be able to do it themselves in an emergency situation.
What are the chronic complications of diabetes mellitus?
These complications are related to blood vessel diseases and are generally classified into small vessel disease, such as those involving the eyes, kidneys and nerves (microvascular disease) and large vessel disease involving the heart and blood vessels (macrovascular disease). Diabetes accelerates hardening of the arteries (atherosclerosis) of the larger blood vessels, leading to coronary heart disease (angina or heart attack), strokes, and pain in the lower extremities because of lack of blood supply ( claudication ). For more information, please read the following articles: Stroke , Angina and Heart Attack.
The major eye complication of diabetes is called diabetic retinopathy. Diabetic retinopathy occurs in patients who have had diabetes for at least 5 years. Diseased small blood vessels in the back of the eye cause the leakage of protein and blood in the retina . Disease in these blood vessels also causes the formation of small aneurysms (microaneurysms), and new but brittle blood vessels (neovascularization). Spontaneous bleeding from the new and brittle blood vessels can lead to retinal scarring and retinal detachment , thus impairing vision. To treat diabetic retinopathy a laser is used to destroy and prevent the recurrence of the development of these small aneurysms and brittle blood vessels. Approximately 50% of patients with diabetes will develop some degree of diabetic retinopathy after 10 years of diabetes, and 80% of diabetics have retinopathy after 15 years of the disease. Poor control of blood sugar and blood pressure further aggravates eye disease in diabetes. Cataracts and glaucoma are also more common among diabetics. It is also important to note that since the lens of the eye lets water through, if blood sugar concentrations vary a lot, the lens of the eye will shrink and swell with fluid accordingly. As a result, blurry vision is very common in poorly controlled diabetes. Patients are usually discouraged from getting a new eyeglass prescription until their blood sugar is controlled. This allows for a more accurate assessment of what kind of glasses prescription is required.
Kidney damage from diabetes is called diabetic nephropathy. The onset of kidney disease and its progression is extremely variable. Initially, diseased small blood vessels in the kidneys cause the leakage of protein in the urine. Later on, the kidneys lose their ability to cleanse and filter blood. The accumulation of toxic waste products in the blood leads to the need for dialysis . Dialysis involves using a machine that serves the function of the kidney by filtering and cleaning the blood. In patients who do not want to undergo chronic dialysis, kidney transplantation can be considered. For more about dialysis, please see the Kidney Dialysis article. The progression of nephropathy in patients can be significantly slowed by controlling high blood pressure , and by aggressively treating high blood sugar levels. Angiotensin converting enzyme inhibitors ( ACE inhibitors ) or angiotensin receptor blockers (ARBs) used in treating high blood pressure may also benefit kidney disease in diabetic patients.
Nerve damage in diabetes is called diabetic neuropathy and is also caused by disease of small blood vessels. In essence, the blood flow to the nerves is limited, leaving the nerves without blood flow, and they get damaged or die as a result (a term known as ischemia ). Symptoms of diabetic nerve damage include numbness, burning, and aching of the feet and lower extremities. When the nerve disease causes a complete loss of sensation in the feet, patients may not be aware of injuries to the feet, and fail to properly protect them. Shoes or other protection should be worn as much as possible. Seemingly minor skin injuries should be attended to promptly to avoid serious infections. Because of poor blood circulation, diabetic foot injuries may not heal. Sometimes, minor foot injuries can lead to serious infection, ulcers, and even gangrene , necessitating surgical amputation of toes, feet, and other infected parts. Diabetic nerve damage can affect the nerves that are important for penile erection, causing erectile dysfunction (ED). ED can also be caused by poor blood flow to the penis from diabetic blood vessel disease. Diabetic neuropathy can also affect nerves to the stomach and intestines, causing nausea, weight loss, diarrhea , and other symptoms of gastroparesis (delayed emptying of food contents from the stomach into the intestines, due to ineffective contraction of the stomach muscles).
The pain of diabetic nerve damage may respond to treatment with gabapentin (Neurontin), phenytoin (Dilantin), carbamazepine (Tegretol), desipramine (Norpraminine), amitriptyline (Elavil), or with topically-applied capsaicin (an extract of pepper). Neurontin, Dilantin and Tegretol are medications that are traditionally used in the treatment of seizure disorders. Elavil and Norpraminine are medications that are traditionally used for depression . The pain of diabetic nerve damage may also improve with better blood sugar control. New medications for nerve pain are being studied.
What can be done to slow diabetes complications?
Findings from the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS) have clearly shown that aggressive and intensive control of elevated levels of blood sugar in patients with type 1 and type 2 diabetes mellitus decreases the complications of nephropathy, neuropathy, retinopathy, and may reduce the occurrence and severity of large blood vessel diseases. Aggressive control with intensive therapy means achieving fasting glucose levels between 70-120 mg/dl; glucose levels of less than 180 mg/dl after meals; and a near normal hemoglobin A1C levels (see below). Studies in type 1 patients have shown that in intensively treated patients, diabetic eye disease decreased by 76%, kidney disease decreased by 54%, and nerve disease decreased by 60%. However, the price for aggressive blood sugar control is a 2 to 3 fold increase in the incidence of abnormally low blood sugar levels (caused by the diabetes medications). For this reason, tight control of diabetes to achieve glucose levels between 70-120 mg/dl is not recommended for children under 13 years of age, patients with severe recurrent hypoglycemia, patients unaware of their hypoglycemia, and patients with far advanced diabetes complications. To achieve optimal glucose control without an undue risk of abnormally lowering blood sugar levels, patients with type 1 diabetes mellitus must monitor their blood glucose at least 4 times a day and administer insulin at least 3 times per day. In patients with type 2 diabetes mellitus, aggressive blood sugar control has similar beneficial effects on the eyes, kidneys, nerves and blood vessels.
How is diabetes treated?
The major goal in treating diabetes mellitus is controlling elevated blood sugars (glucose) without causing abnormally low levels of blood sugar. Type 1 diabetes mellitus is treated with insulin, exercise, and a diabetic diet. Type 2 diabetes mellitus is first treated with weight reduction, a diabetic diet, and exercise. When these measures fail to control the elevated blood sugars, oral medications are used. If oral medications are still insufficient, insulin medications are considered.
Adherence to a diabetic diet is an important aspect of controlling elevated blood sugar in patients with diabetes mellitus. The American Diabetes Association (ADA) has provided guidelines for a diabetic diet. The ADA diet is a balanced, nutritious diet that is low in fat, cholesterol , and simple sugars. The total daily calories are evenly divided into three meals. In the past two years, the ADA has lifted the absolute ban on simple sugars. Small amounts of simple sugars are allowed when consumed with a complex meal.
Weight reduction and exercise are important treatments of diabetes. Weight reduction and exercise increase the body's sensitivity to insulin, thus helping to control blood sugar elevations.
Medications for type 2 diabetes mellitus
WARNING: All the information listed below applies to patients who are not pregnant or breast-feeding. At present the only recommended way of controlling diabetes in these situations is by diet, exercise and insulin therapy. You should refer to your doctor if you are on these medications and are considering becoming pregnant, or if you have become pregnant while taking these medications.
Based on what is known, medications for type 2 diabetes are designed to: - Increase the insulin output by the pancreas
- Decrease the amount of glucose released from the liver
- Increase the sensitivity (response) of cells to insulin
- Decrease the absorption of carbohydrates from the intestine
When selecting therapy for the treatment of type 2 diabetes, consideration should be given to: - The magnitude of change in blood sugar control that each medication will provide
- Other coexisting medical conditions (hypertension high cholesterol, etc.)
- Adverse effects
- Contraindications
- Issues that may affect compliance (timing of medication, frequency of dosing)
- Cost to patient and health system
It's important to remember that if a drug can provide more than one benefit (lower blood sugar and have a good effect on cholesterol, for example), it should be preferred. It's also important to bear in mind that the cost of drug therapy is relatively small compared to the cost of managing the long-term complications associated with poorly controlled diabetes.
Varying combinations of medications that perform the above functions are also used to correct abnormally elevated levels of blood glucose in diabetes. As the list of medications continues to expand, treatment options for type 2 diabetes can be better tailored to meet an individuals needs. Not every patient with type 2 diabetes will benefit from every drug, and not every drug is suitable for each patient. Patients with type 2 diabetes should work closely with their physicians to achieve an approach that provides the greatest benefits while minimizing risks.
Patients with diabetes should never forget the importance of diet and exercise. The control of diabetes starts with a healthy lifestyle regardless of what medications are being used.
Medications that increase the insulin output by the pancreas - sulfonylureas and meglitinides
Sulfonylureas
Historically, increasing the insulin output by the pancreas has been the major area targeted by medications used to treat type 2 diabetes. These medications belong to a class of drugs called sulfonylureas. Sulfonylureas primarily lower blood glucose levels by increasing the release of insulin from the pancreas. Older generations of these drugs include chlorpropamide and tolbutamide, while newer drugs include Glyburide (DiaBeta), glipizide (Glucotrol), and glimepiride (Amaryl). These drugs are effective in rapidly lowering blood sugars, but run the risk of causing hypoglycemia. In addition, they are sulfa compounds, and should be avoided in patients with sulfa allergies.
Meglitinides [repaglinide (Prandin) and nateglinide (Starlix)]
Recently, a new class of drugs that affect insulin release has been approved by the FDA for use in type 2 diabetes. This class is known as meglitinides and these drugs also work on the pancreas to promote insulin secretion. Unlike sulfonylureas that bind to receptors on the insulin producing cells, meglitinides work through a separate potassium based channel on the cell surface. Repaglinide (Prandin) and nateglinide (Starlix) are short acting agents that are taken 30 minutes before meals. Unlike the sulfonylureas, which last longer in the body, Prandin and Starlix are very short acting, with peak effects within one hour. For this reason, they are given up to 3 times a day just before meals. Since these drugs also increase circulating insulin levels, they may also cause hypoglycemia, but the literature suggests this is less frequent than the hypoglycemia seen with sulfonylurea agents.
Prandin
In a 3-month study, repaglinide (Prandin) dropped fasting blood glucose values by 61 mg/dL and post meal blood glucose values by 100 mg/dL. Because Prandin is short acting and given before meals, it is particularly beneficial in lowering blood glucose after meals and does not tend to lower fasting glucose levels to the same degree. Prandin has been used in combination with other medications, such as metformin (Glucophage), with impressive results. In 83 patients with type 2 diabetes, blood sugar control improved significantly with the addition of Prandin to Glucophage.
Prandin does interact with other medications. The doctor must be aware of all other medications the patient is taking before prescribing Prandin. The usual starting dose is 0.5mg before each meal, and can be increased to 4 mg. The maximum daily dose is 16 mg. Prandin is used with caution in people with kidney or liver abnormalities. Since Prandin increases insulin levels, it has the risk of causing abnormally low blood sugars. Blood sugars that remain severely low, can result in sweating, tremors, confusion, and may lead to coma and seizure. In addition, the use of Prandin has been associated with headaches, muscle and joint aches, along with sinus infections in some individuals. This drug should not be used in pregnancy or by nursing mothers. The dose may need to be adjusted in older people, since they may metabolize (eliminate) medications at a slower rate.
Starlix
Nateglinide (Starlix) has essentially the same profile of side effects and interactions as Prandin. The major benefit of Starlix is that the starting dose of 120mg does not need to be adjusted upward, but rather remains constant. These medications are also relatively safe to use in people with impaired kidney function.
Medications that decrease the amount of glucose produced by the liver
A class of drugs called biguanides has been used for many years in Europe and Canada. In 1994, the FDA approved the use of metformin (Glucophage) for the treatment of type 2 diabetes in the USA. Glucophage is unique in its ability to decrease glucose production from the liver. Briefly, because metformin does not increase insulin levels, when used alone, it does not usually cause hypoglycemia. In addition, metformin has an effect whereby it tends to suppress appetite, which may be beneficial in this population. Metformin may be used by itself or in conjunction with other oral agents, or insulin. It should not be used in patients with kidney impairment, and should be used with caution in those with liver impairment. The older parent compounds of metformin were associated with a serious condition called lactic acidosis with a dangerous acid build up in the blood resulting from accumulation of the drug and its breakdown products. While metformin is safer in this regard, it is recommended that the drug be discontinued for 24 hours before any dye-related procedure (such as IVP kidney study) or surgery is performed. The dyes may impair kidney function and cause a build up of the drug in the blood. Metformin can be restarted after these procedures once the patient has urinated normally.
Medications that increase the sensitivity of cells to insulin
At present in the United States, the class of drugs known as thiazolidinediones lowers blood glucose by improving target cell response to insulin (increasing the sensitivity of the cells to insulin). Troglitazone (Rezulin) was the first of this type of compound introduced in the United States. Because of severe toxic liver effects, troglitazone has been taken off the market. Sister compounds are now available with a better safety profile. These drugs include pioglitazone (Actos) and rosiglitazone (Avandia).
Pioglitazone (Actos) and rosiglitazone (Avandia) are new thiazolidinediones that have been approved for use in the United States. While they are sister compounds to Rezulin, extensive studies have failed to show any liver problems associated with these particular drugs. Patients should be aware, however, that these drugs are still relatively new, and its long-term safety profile is not yet known. Both Avandia and Actos act by increasing the sensitivity (responsiveness) of cells to insulin. It improves sensitivity to insulin in muscle and fat tissue. These drugs have been effective in lowering blood sugars in patients with type 2 diabetes, Actos and Avandia act within 1 hour of administration and are dosed daily. It is important to note that it takes up to 6 weeks to see a drop in blood glucose levels on these agents and up to 12 weeks to see a maximum benefit. Actos and Avandia have been approved as first line therapy in diabetes, and for use in combination. Both medications may be used in patients taking other oral agents as well as those using insulin
While reported liver problems on these agents are mild (and reversible with discontinuation of the drug) if present, most physicians choose to follow recommendations and do blood tests on patients to follow their liver test every 2 months or so during the first year of therapy. After that point, the frequency of monitoring may be decreased. If at any point the liver tests increase to 3 times the normal limit, the drug should be stopped. The most significant contraindications to these medications include any type of liver disease, and heart failure . These medications may cause a significant increase in fluid retention. While the reports are 3-8 pounds, clinical experience shows up to 12-15 pounds of weight gain can occur. Usually the majority of this is fluid, but an absolute body weight gain can also occur. This is likely dose dependent, and increases with higher dosages of medication, and occurs more pronounced in patients who are also on insulin therapy. In general, the resulting ankle swelling and puffiness can be controlled with the addition of a diuretic such as lasix, or by reducing the dose. On occasion, patients may be symptomatic enough to warrant the withdrawal of the medication.
As an aside, Actos and Avandia have an added benefit of changing cholesterol patterns in diabetes. HDL (or good cholesterol) increases on these medications, and triglycerides often decrease, while there is some controversy regarding what happens to bad cholesterol ( LDL ) levels. In this population that is already at an increased risk for heart disease, a benefit in cholesterol profile is a beneficial outcome. As more and more data becomes available there is mounting evidence that this class of drugs may provide direct benefits on the heart and large blood vessels, and may actually be valuable in preventing the progression of diabetes in high-risk individuals. As time goes on, I have no doubt that the uses for this class of medications will expand.
Medications that decrease the absorption of carbohydrates from the intestine
Before being absorbed into the bloodstream, carbohydrates must be broken down into smaller sugar particles, such as glucose, by enzymes in the small intestine. One of the enzymes involved in breaking down carbohydrates is called alpha glucosidase. By inhibiting this enzyme, carbohydrates are not broken down as efficiently and glucose absorption is delayed.
Precose
The name of the alpha glucosidase inhibitor available in the United States is Precose. In clinical trials with over 700 patients, the use of acarbose (Precose) showed a reduction in hemoglobin A1c values (a well known measurement of 3 month average blood sugars) significantly greater than the placebo (no treatment). However, as a single agent, Precose is not as effective as the other medications listed. Since Precose works on the intestine, its effects are additive to diabetic medications that work at other sites, such as sulfonylureas. Clinical studies have shown statistically better blood glucose control in patients treated with Precose and a sulfonylurea versus the sulfonylurea alone. Precose is currently used alone or in combination with a sulfonylurea.
Precose is taken three times a day at the beginning of meals. The dosage varies from 25 mg to 100 mg with each meal. The maximum recommended dose is 100 mg three times a day. At doses greater than this, reversible liver abnormalities may be seen. Because of its mechanism of action, Precose has significant gastrointestinal side effects. Abdominal pain, diarrhea, and gas are common and are seen in up to 75% of patients taking Precose. For this reason, Precose is administered using a low initial dose that is increased over weeks depending on the patient's tolerance. Most of the gastrointestinal symptoms tend to subside over the course of a few weeks, although some patients report persistent problems.
Combination Medications:
Glucovance, Avandamet, and Metaglip are 3 relatively new combination pills that are on the market to treat diabetes. Glucovance combines glyburide with metformin in varying doses. Avandamet is a combination of varying doses of Avandia and metformin. And Metaglip is a combination pill containing glipizide and metformin in varying strengths. The benefit to these agents is fewer pills to take, hopefully leading to better compliance. While they work well, I personally like to give patients individual medications, until I know what doses are working, and then switch to a combination pill once the patient has been stable on the doses of individual medications for a period of time.
Treatment of diabetes with insulin
Insulin is the mainstay of treatment for patients with type 1 diabetes mellitus. Insulin is also important in type 2 diabetes when blood glucose levels cannot be controlled by diet, weight loss, exercise, and oral medications.
Ideally, insulin medication should be administered in a manner that mimics the natural pattern of insulin secretion by a healthy pancreas. The complex pattern of insulin secretion by the pancreas is difficult to duplicate. Still, adequate blood glucose control can be achieved with careful attention to diet, regular exercise, home blood glucose monitoring, and multiple insulin injections throughout the day. For more, please see the Diabetes and Home Care Monitoring article.
In the past, the insulin used was being derived from animal sources, particularly cows and pigs. Not only was there a problem with the supply of insulin meeting the demand, but beef and pork insulin also had specific problems. Originating from animals, these types of insulin caused immune reactions in people. Patients would become intolerant or resistant to animal insulin. With the acceleration of scientific research in the latter half of this century, beef and pork insulin were replaced by human insulin. In 1977, the gene for human insulin was cloned, and through modern technology, manufactured human insulin was made available. Human insulin is now widely used.
Insulin now comes in a variety of preparations that differ in time of onset and length of action. Because of these differences, combinations of insulin are often used to allow for a more tailored regimen of blood sugar control. The table below lists the most common types of insulin currently in use in the United States, and their specific properties. | Name of Insulin | Onset of Action | Peak Effect After Injection | | Humalog and Novolog//Very Short Acting | 5-15 minutes | 30-60 minutes | | Regular/Short Acting | 30 minutes | 2-5 hours | | NPH/Intermediate Acting | 1-2.5 hours | 8-14 hours | | Lente/Intermediate Acting | 1-2.5 hours | 8-12 hours | | Ultra Lente/Long Acting | 4-6 hours | 10-18 hours | | Lantus | 2-3 hours | Stable from 2-3 hours to @20 hours | | Combinations - 75/25, 70/30, 50/50 | 30 minutes | 7-12 hours |
For example, a patient may take an injection of Lente in the morning and evening to provide a baseline of insulin throughout a 24-hour period. In addition, the same patient may take an injection of Humalog just before meals to cover the increase in carbohydrate load after eating.
Different methods of delivering insulin
Not only is the variety of insulin preparations available growing, so are the methods for administering insulin.
Pre-filled insulin pens
In the past, insulin was available only in an injectable form. This involved carrying syringes (which a few decades age were made of glass and required sterilization), needles, vials of insulin, and alcohol swabs. Needless to say, patients often found it difficult to take multiple shots a day, and as a result, good blood sugar control was often compromised. Many pharmaceutical companies are now offering discreet and convenient methods of insulin delivery. Both Novo Nordisk and Lily have an insulin pen delivery system. This system is similar to an ink cartridge in a fountain pen. A small pen-sized device holds an insulin cartridge (usually containing 300 units). Cartridges are available in the most widely used insulin formulations, such as those listed in the table above. The amount of insulin to be injected is dialed in by turning the bottom of the pen until the required number of units is seen in the dose-viewing window. The tip of the pen consists of a needle that is replaced with each injection. A release mechanism allows the needle to penetrate just under the skin and deliver the required amount of insulin. The cartridges and needles are disposed of when finished and new ones are simply inserted. These insulin delivery devices are discreet and less cumbersome than traditional methods.
Insulin pump
The most recently available advance in insulin delivery is the insulin pump. In the United States, MiniMed, Deltec and Disetronic market the insulin pump. An insulin pump is composed of a pump reservoir similar to that of an insulin cartridge, a battery-operated pump, and a computer chip that allows the user to control the exact amount of insulin being delivered. Currently, pumps on the market are about the size of a beeper. The pump is attached to a thin plastic tube (an infusion set) that has a soft cannula (or needle) at the end through which insulin passes. This cannula is inserted under the skin, usually on the abdomen. The cannula is changed every 2 days. The tubing can be disconnected from the pump while showering or swimming. The pump is used for continuous insulin delivery, 24 hours a day. The amount of insulin is programmed and is administered at a constant rate (basal rate). Often, the amount of insulin needed over the course of 24 hours varies depending on factors like exercise, activity level, and sleep . The insulin pump allows for the user to program many different basal rates to allow for this variation in lifestyle. In addition, the user can program the pump to deliver a "bolus" during meals to cover the excess demands of carbohydrate ingestion. Over 50,000 people worldwide are using an insulin pump. This number is growing dramatically as these devices become smaller and more user-friendly. Insulin pumps allow for tight blood sugar control and lifestyle flexibility while minimizing the effects of low blood sugar (hypoglycemia). At present, the pump is the closest device on the market to an artificial pancreas . Naturally, the next step would be a pump that can also sense blood sugar levels and adjust the insulin delivery accordingly. Much effort is being concentrated on this area of research and possibly, even within the next year, a prototype device will be available for trial.
Inhalation
Another promising route of insulin administration is through inhalation. Inhaled insulin is currently being tested but has not been approved by the United States Food and Drug Administration (FDA). Many devices are available that allow for other medications to be used in this manner, the best example of which is asthma therapy. Insulin is not absorbed through the bronchial tubes (airways), and must reach the air sacks at the end of the bronchial tubes ( alveoli ) to be absorbed. Once at the alveoli, insulin can be absorbed and enter the bloodstream. Currently, powdered inhalers and nebulizers are being studied to determine which delivery system is the most reliable. The safety of inhaled insulin still needs to be established before a product for consumer use can be made available. Trials are currently underway to establish the safety of inhaled insulin.
Intranasal, Transdermal, PILL
Other routes for the delivery of insulin have also been tried. Intranasal insulin delivery was thought to be promising. However, this method was associated with poor absorption and nasal irritation. Transdermal insulin (skin patch delivery) has also yielded disappointing results to date. Insulin in pill form is also not yet effective since the digestive enzymes in the gut break it down.
The future of pancreas transplantation
Ultimately, the goal in the management of type 1 diabetes is to provide insulin therapy in a manner that mimics the natural pancreas. Perhaps the closest therapy available at this time is a transplant of the pancreas. Several approaches to pancreatic transplantation are currently being studied, including the whole pancreas and isolated islet cells (these groups of cells contain beta cells that are responsible for insulin production). Data available from 1995 indicates that almost 8,000 patients underwent pancreatic transplantation. Most patients undergo pancreatic transplantation at the time of kidney transplantation for diabetic kidney disease.
Transplantation is not without risk. Both the surgery itself and the immunosuppression that must occur afterward pose significant risks to the patient. For these reasons, the kidney and pancreas are usually transplanted at the same time. At present, there is disagreement about whole pancreas transplantation in patients not currently requiring kidney transplantation. The issue of whether the benefits outweigh the risks in these patients is under debate. There is also a chance that diabetes will occur in the transplanted pancreas. Selectively transplanting islet cells is an interesting alternative to whole pancreas transplantation. However, the concern over rejection remains. Attempts to disguise the islet cells in tissues that the body won't reject (for example, by surrounding the islet cells by the patient's own cells and then implanting them) are underway. In addition, researchers are exploring artificial barriers that can surround the islet cells, provide protection against rejection, and still allow insulin to enter the bloodstream.
A Final Word
The next few years promise to be an exciting time in diabetes care. Many agents for the treatment of type 2 diabetes are under development and the options for insulin therapy continue to grow and methods for insulin delivery continue to become more refined. While research continues to expand in these areas, one thing remains constant. Achieving the best blood sugar control possible remains the ultimate goal in both type 1 and type 2 diabetes. We now know, beyond a doubt, that good blood sugar control minimizes the long-term complications of diabetes, including blindness, nerve damage, and kidney damage. Finally, a healthy lifestyle can do nothing bad...it should remain the cornerstone of management for diabetes. - Diabetes mellitus is a chronic condition associated with abnormally high levels of sugar (glucose) in the blood.
- Insulin produced by the pancreas lowers blood glucose.
- Absence or insufficient production of insulin causes diabetes.
- The two types of diabetes are referred to as type 1 (insulin dependent) and type 2 (non-insulin dependent).
- Symptoms of diabetes mellitus include increased urine output, thirst and hunger as well as fatigue.
- Diabetes mellitus is diagnosed by blood sugar (glucose) testing.
- The major complications of diabetes mellitus are both acute and chronic. Acutely: dangerously elevated blood sugar, abnormally low blood sugar due to diabetes medications may occur. Chronically: disease of the blood vessels (both small and large) which can damage the eye, kidneys, nerves, and heart may occur
- Diabetes treatment depends on the type and severity of the diabetes. Type 1 diabetes mellitus is treated with insulin, exercise, and a diabetic diet. Type 2 diabetes mellitus is first treated with weight reduction, a diabetic diet, and exercise. When these measures fail to control the elevated blood sugars, oral medications are used. If oral medications are still insufficient, insulin medications are considered.
How to Order | Price
List | Refill Orders
Home |
About Us | Contact
Us | FAQ
Buy cheap canadian prescriptions from a Canadian Internet Pharmacy leader.
cheap online pharmacy canadian pharmacy prescription drugs online discount medicine pharmacies
online mail order prescription medication canadian online pharmacy search for online drugs
canada pharmacies discount canadian medication drugstore Plavix Fosamax Lipitor Celebrex
Actonel Flomax Glucophage Premarin Prevacid Evista .
|
