DIABETES MELLITUS AND ITS MANAGEMENT

DIABETES MELLITUS AND ITS MANAGEMENT

C. Salmana BasheerHH, Anoop Philip

National College of Pharmacy, Manassery, Calicut

Cite this: C. Salmana Basheer, Anoop Philip, "DIABETES MELLITUS AND ITS MANAGEMENT", B. Pharm Projects and Review Articles, Vol. 1, pp. 1343-1381, 2006. (http://farmacists.blogspot.in/)

What is Diabetes?

    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 (and in this article will be referred to as "diabetes"), was first identified as a disease associated with "sweet urine," and excessive muscle loss in the ancient world. 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, the absence or insufficient production of insulin causes hyperglycemia. Diabetes is a chronic medical condition, meaning although it can be controlled, it lasts a lifetime¹.

What is the impact of diabetes?

    Over time, diabetes can lead to blindness, kidney failure, and nerve damage. Diabetes is also an important factor in accelerating the hardening and narrowing of the arteries (atherosclerosis), leading to strokes, coronary heart disease, and other blood vessel diseases. Diabetes 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 staggering¹.

    Diabetes is the third leading cause of death in the United States after heart disease and cancer.

 

What causes diabetes?

    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 properly and efficiently leads to hyperglycemia and diabetes. 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 affecting the insulin producing beta cells in the pancreas, is the main disorder in type 1 diabetes. In type 2 diabetes, there also is a steady decline of beta cells that adds to the process of elevated blood sugars. For more, please read the Insulin Resistance article².

    Glucose is a simple sugar found in food. Glucose is an essential nutrient that provides energy for the proper functioning of the body cells. Carbohydrates are broken down in the small intestine and the glucose in digested food is then absorbed by the intestinal cells into the bloodstream, and is carried by the bloodstream to all the cells in the body where it is utilized. However, glucose cannot enter the cells alone and needs insulin to aid in its transport into the cells. Without insulin, the cells become starved of glucose energy despite the presence of abundant glucose in the bloodstream. In certain types of diabetes, 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 more insulin into the bloodstream to help glucose enter the cells and lower blood glucose levels after a meal. When the blood glucose levels are lowered, the insulin release from the pancreas is turned down. It is important to note that even in the fasting state there is a low steady release of insulin than fluctuates a bit and helps to maintain a steady blood sugar level during fasting. In normal individuals, such a regulatory system helps to keep blood glucose levels in a tightly controlled range. As outlined above, in patients with diabetes, the insulin is either absent, relatively insufficient for the body's needs, or not used properly by the body. All of these factors cause elevated levels of blood glucose (hyperglycemia).

What are the different types of diabetes?

    There are two major types of diabetes, called type 1 and type 2. Type 1 diabetes was also called insulin dependent diabetes mellitus (IDDM), or juvenile onset diabetes mellitus. In type 1 diabetes, the pancreas undergoes an autoimmune attack by the body itself, and is rendered incapable of making insulin. Abnormal antibodies have been found in the majority of 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 survival⁴.

    In autoimmune diseases, such as type 1 diabetes, the immune system mistakenly manufactures antibodies and inflammatory cells 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 in the majority of patients, 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 of the population for type 1 diabetes, 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. Of all the patients with diabetes, only approximately 10% of the patients have type 1 diabetes and the remaining 90% have type 2 diabetes³.

    Type 2 diabetes 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 for their body's needs, particularly in the face of insulin resistance as discussed above. 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). Thus, larger quantities of insulin are produced as an attempt to get these cells to recognize that insulin is, in fact, present. In addition to the problems with an increase in insulin resistance, the release of insulin by the pancreas may also be defective and suboptimal. In fact, there is a known steady decline in beta cell production of insulin in type 2 diabetes that contributes to worsening glucose control. (This is a major factor for many patients with type 2 diabetes who ultimately require insulin therapy.) Finally, the liver in these patients continues to produce glucose through a process called gluconeogenesis despite elevated glucose levels. This control of gluconeogenesis becomes compromised.

    While it is said that type 2 diabetes 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. In fact, for the first time in the history of humans, type 2 diabetes is now more common than type 1 diabetes in childhood. 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 weight⁵.

    Regarding age, data shows that for each decade after 40 years of age regardless of weight there is an increase in incidence of diabetes. 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 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 later in life, especially in those who require insulin during pregnancy and those who are overweight after their delivery. 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 refers to elevated blood sugar levels from another medical condition. Secondary diabetes 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 and also with medications used in the treatment of HIV infection (AIDS)⁷.

 

What are diabetes symptoms?

    The early symptoms of untreated diabetes 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 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 100 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 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 plasma⁶ glucose or an oral glucose tolerance test.

    When fasting a blood glucose stays above 100mg/dl, but in the range of 100-126mg/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.

The oral glucose tolerance test

    Though not routinely used anymore, the oral glucose tolerance test (OGTT) is a 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 at specific intervals 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 impaired glucose tolerance do not have diabetes, but are at high risk for progressing to diabetes. Each year, 1-5% of people whose test results show impaired glucose tolerance actually eventually develop diabetes. Weight loss and exercise may help people with impaired glucose tolerance 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 impaired glucose tolerance itself may be a risk factor for the development of heart disease. In the medical community, most physicians are now understanding that impaired glucose tolerance is nor simply a precursor of diabetes, but likely its own clinical disease entity that requires treatment and monitoring.

Evaluating the results of the oral glucose tolerance test

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 impaired glucose tolerance 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 its 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 activities⁸.

There are some interesting developments in home blood glucose monitoring. One of them is the Guardian system. This system involves an implantable cannula place just under the skin in the abdomen. This cannula allows for frequent sampling of blood glucose levels, similar to the currently available continuous glucose monitoring system (CGMS). However, with continuous glucose monitoring system, real time information and feedback is not available, and patients need to bring the device back to the physician's office to have the device downloaded and retrospectively reviewed. This new system will allow for access to the blood glucose values immediately via a visual readout, and this will allow the patient to respond as needed at that specific time. Ultimately, this system will be infrared linked to an insulin pump and will be able to pass on the glucose information to the pump. The pump will then be able to use a mathematical calculation to determine if insulin is needed, and if so, how much. This option will be presented to the patient to help him/her make a management decision. This kind of system takes us one step closer to closing the loop and to the development of an artifical pancreas that senses insulin requirements based on glucose levels and the body's needs and releases insulin accordingly-the ultimate goal.

    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 time¹⁰.

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 follows⁹.

    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%. Other Groups such as the American Association of Clinical Endocrinologists feel that an A1c of < 6.5% should be the goal.

    Of interest, studies have shown that there is about a 10% decrease in relative risk for microvascular disease for every 1 % reduction in A1c. So, if a patient 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. Data also suggests that the risk of macrovascular disease decreases by about 24% for every 1% reduction in A1c values.

    It should be mentioned here that there are a number of conditions in which an A1c value may not be accurate. For example, with significant anemia, the red blood cell count is low, and thus the A1c is falsely low as is similarly in cases of sickle cell disease and other hemoglobinopathies. For more, please read the Hemoglobin A1c article.

What are the acute complications of diabetes?

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.
3. Insulin is vital to patients with type 1 diabetes - they cannot live with out a source of exogenous insulin. Without insulin, patients with type 1 diabetes 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 inability to store fat and protein along with breakdown of existing fat and protein stores. This dysregulation, results in the process of ketosis and the release of ketones into the blood. Ketones turn the blood acidic, a condition called diabetic ketoacidosis (DKA). 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.
4. Diabetic ketoacidosis can be caused by infections, stress, or trauma all which may increase insulin requirements. In addition, missing doses of insulin is also an obvious risk factor for developing diabetic ketoacidosis. Urgent treatment of diabetic ketoacidosis involves the intravenous administration of fluid, electrolytes, and insulin, usually in a hospital intensive care unit. Dehydration can be very severe, and it is not unusual to need to replace 6-7 liters of fluid when a person presents in diabetic ketoacidosis. Antibiotics are given for infections. With treatment, abnormal blood sugar levels, ketone production, acidosis, and dehydration can be reversed rapidly, and patients can recover remarkably well.
5. In patients with type 2 diabetes, 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 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. 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, patients with type 2 diabetes do not generally develop ketoacidosis solely on the basis of their diabetes.

    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 in the presence of a delayed or absent meal. 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 exertion¹¹.

    Blood glucose is essential for the proper functioning of brain cells. Therefore, low blood sugar can lead to nervous system symptoms such as dizziness, confusion, weakness, and tremors. The actual level of blood sugar at which these symptoms occur varies with each person, but usually it occurs when blood sugars are less than 65 mg/dl. Untreated, severely low blood sugar levels can lead to coma, seizures, and, in the worse case scenario, irreversible brain death. At this point, the brain is suffering from a lack of sugar, and this usually occurs somewhere around levels of 40 mg/dl.

    The treatment of low blood sugar consists of administering a quickly absorbed glucose source. These include glucose containing drinks, such as orange juice, soft drinks (not sugar-free), or glucose tablets in doses of 15-20 grams at a time (i.e., half a glass of juice). Even cake frosting applied inside the cheeks can work in a pinch if patient cooperation is difficult. If the individual becomes unconscious, glucagon can be given by intramuscular injection. Glucagon causes the release of glucose from the liver (i.e., it promotes gluconeogenesis). Glucagon can be lifesaving and every patient with diabetes who has a history of hypoglycemia (particularly those on insulin) should have a glucagon kit. 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. Another lifesaving device that should be mentioned is very simple; a medic alert bracelet should be worn by all patients with diabetes.

.What are the chronic complications of diabetes?

    These diabetes 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.

Eye Complications

    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. For more, please read the Diabetic Eye Disease article.

    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

    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.

    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

    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 parts¹⁰.

    Diabetic nerve damage can affect the nerves that are important for penile erection, causing erectile dysfunction (ED, impotence). Erectile dysfunction 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 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.

    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 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, 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 is controlling elevated blood sugars (glucose) without causing abnormally low levels of blood sugar. Type 1 diabetes is treated with insulin, exercise, and a diabetic diet. Type 2 diabetes 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. 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. For more, please read the Weight Loss and Fitness articles.

Medications for type 2 diabetes

All the information listed below applies to patients who are not pregnant or breastfeeding. 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:

1. Increase the insulin output by the pancreas.
2. Decrease the amount of glucose released from the liver.
3. Increase the sensitivity (response) of cells to insulin.
4. Decrease the absorption of carbohydrates from the intestine.
5. Slow gastric emptying to delay the presentation of carbohydrates for absorption in the small intestine.

 

 

When selecting therapy for the treatment of type 2 diabetes, consideration should be given to:

1. The magnitude of change in blood sugar control that each medication will provide.
2. Other coexisting medical conditions (hypertension high cholesterol, etc.)
3. Adverse effects
4. Contraindications
5. Issues that may affect compliance (timing of medication, frequency of dosing)
6. Cost to patient and healthcare 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 risks⁶.

    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 agents⁸.

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. For more, please read the drug information pamphlet on repaglinide (Prandin).

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. For more, please read the drug information pamphlet on nateglinide (Starlix).

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 United States. 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 normally⁴.

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, and a suggestion that Actos may be superior in LDL reduction as a side benefit. 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 delayed³.

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. .

New medications that effect glycemic control

Symlin (pramlintide)

    Symlin is the first in a new class of injected antihyperglycemic medications for use in patients with type 2 or type 1 diabetes treated with insulin. Pramlintide, the active ingredient in Symlin, is a synthetic analog of human amylin, a naturally occurring neuroendocrine hormone synthesized from pancreatic beta cells that contributes to glucose control during the postprandial period. Amylin, similar to insulin, is absent or deficient in patients with diabetes. When used with insulin, this compound can help patients achieve improved glycemic control with additional benefits that cannot be realized with insulin alone.

    According to published data, Symlin reduces post meal blood sugar peaks, reduces glucose fluctuations throughout the day, enhances satiety (the sensation of fullness) leading to potential weight loss, and lowers mealtime insulin requirements. Studies have shown it improves A1C beyond the effect of insulin alone.

Symlin is taken just prior to meals, three times a day. It is given in injection form and is indicated for:

• Type 2 diabetes, as an adjunct treatment in patients who use mealtime insulin therapy and have failed to achieve desired glucose control despite optimal insulin therapy, with or without a concurrent sulfonylurea agent and/or metformin.
• Type 1 diabetes, as an adjunct treatment in patients who use mealtime insulin therapy and who have failed to achieve desired glucose control despite optimal insulin therapy.

    Symlin is considered a therapy option in patients with insulin-using type 2 or type 1 diabetes who are unable to achieve adequate glycemic control despite individualized insulin management. Insulin-using patients with type 2 diabetes may also be taking a concurrent sulfonylurea agent and/or metformin.

    The major side effect of Symlin is nausea, and this can be abated with a slow steady increase in dosing. The other major concern is the risk of hypoglycemia. To avoid this, the dose of mealtime insulin should be cut in half when starting Symlin. Of note is the degree of weight loss seen with Symlin therapy. Studies out to 6 months show weight loss of greater than 6 pounds more than placebo (inactive pills for comparison)¹.

 

Byetta (exenatide)

    Byetta (exenatide) is a new medication on the market that has it's origins in an interesting place--the Gila monster's saliva. Scientists studying this small lizard noted it could go a long time without eating. They found a substance in it's saliva that slowed stomach emptying, thus making the lizard feel fuller longer. This substance was similar in nature to a gut hormone found in humans known as GLP-1. Thus, the studies began. Ultimately, after modifying this hormone, exenatide (with the trade name Byetta) was developed. Byetta is the first in a new class of drugs for the treatment of type 2 diabetes called incretin mimetics. Byetta has been shown to have many of the same effects on sugar regulation as GLP-1, so it mimics the body's natural physiology for self-regulating blood sugar.

    Byetta is indicated as adjunctive therapy to improve glycemic control in patients with type 2 diabetes who are taking metformin, a sulfonylurea, or a combination of metformin and a sulfonylurea, but who have not achieved adequate sugar control. It enhances the way the insulin producing beta cells in the pancreas work. Insulin secretion increases only when blood sugars are high and decreases as blood sugars approach normal. In addition to enhancing the normal physiology of the beta cell, Byetta suppresses glucose release from the liver, slows stomach emptying and the absorption of nutrients including carbohydrate, and reduces the food intake.

    Just like Symlin, Byetta is given by an injection, but it is given twice a day (usually before breakfast and dinner meals). It comes in a disposable pen form, and is available in 2 doses. The goal is to start with the lower dose for a month or so then move up to the higher dose if needed and if tolerated. Similar to Symlin, the main side effect is nausea, most likely due to its effects on stomach emptying. This medication is temperature sensitive and most be stored at 36-46 degrees F. The risk of hypoglycemia is still a possibility with Byetta especially when used in combination with sulfonylureas. Your physician may choose to decrease the dose of some of your other medications when initially evaluating how you respond to Byetta.

Similar to Symlin, weight reduction is seen with Byetta in the majority of patients. This makes it particularly suitable for the typical patient with Type 2 diabetes who is also overweight.

Combination Medications

    Glyburide/metformin (Glucovance), rosiglitazone/metformin (Avandamet), and glipizide/metformin (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. Insulin is also important in type 2 diabetes when blood glucose levels cannot be controlled by diet, weight loss, exercise, and oral medications².

    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 ago 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. In many cases the entire pen is disposed of. These insulin delivery devices are discreet and less cumbersome than traditional methods⁵.

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. Some of the newer technology includes the Guardian system, described above in this article

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 (alv    t]yyyyeoli) 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. These trials are well into phase III, meaning that human subjects have already used inhaled insulin and the results are promising. Inhaled insulin will likely be on the market within the next 1-2 years.

 

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 bloodstream⁹.

 

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.

CONCLUSION

• Diabetes 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 include increased urine output, thirst and hunger as well as fatigue.
• Diabetes is diagnosed by blood sugar (glucose) testing.
• The major complications of diabetes 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 is treated with insulin, exercise, and a diabetic diet. Type 2 diabetes 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.

 

REFERENCE

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4. Braunstein S., White J. Trends in the management of type 2 diabetes An emerging role for insulin of managed care pharmacy 11(1), S2511, 2005.
5. Chand J.L., Abrahamson M.J., Pharmacological management of type 2 diabetes mellitus Rashnale for rational use of insulin, Mayo Clin. Proc, 78 459467, 2003.
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7. Herman W, Dirani R, Horblyuk R, O'Neill MC, et. al, The result study group, Reduction in use of healthcare services with combination sulfonylures and resiglitazone: Findings from the rosiglitazone early vs sulfonylurea titration (Result) study, Am J Manag Care 11(2005), 273278, 2005.
8. Mudaliar S, Henry R, New oral therapies for type 2 diabetes mellitus: The glitazones or inslulin sensitizers, Annu Rev Med. 52, 239257, 2001.
9. National diabetes fact sheet http://www.cdc.gov/diabetes/pubs/factsheet.htm, 2003.
10. O' Moore-Sullivan T, Prins J, Thiazolidinediones and type 2 diabetes: New drugs for an old disease, MJA 176 (15 April 2002), 381386, 2002.
11. Shaya F, Compliance with medicine, Ophalmol Clin. N. Am 18(2005); 611617, 2005.

Shaya F, Deshpande G, Looking at compliance at the physician level - creating a patient-centered focus for addressing adherence. CBIs 5tyh Annual forum on patient compliance, adherence and persistency - improved product utilization through patient centered initiatives April 1011, 2006.

Cite this: C. Salmana Basheer, Anoop Philip, "DIABETES MELLITUS AND ITS MANAGEMENT", B. Pharm Projects and Review Articles, Vol. 1, pp. 1343-1381, 2006. (http://farmacists.blogspot.in/)