Diabetes Mellitus

| What is diabetes mellitus? | What is the impact of diabetes? | What causes diabetes mellitus? | What are the different types of diabetes mellitus? | What are the symptoms of diabetes mellitus? | How is diabetes mellitus diagnosed? | What is the oral glucose tolerance test? | What may the results of the oral glucose tolerance test indicate? | Why is blood sugar checked at home? | What is a hemoglobin A1c (A1c)? | What are the acute complications of diabetes mellitus? | What are the chronic complications of diabetes mellitus? | What can be done to slow diabetes complications? | How is diabetes treated? | Medications for type 2 diabetes mellitus? | Medications that increase the insulin output by the pancreas - sulfonylureas and meglitinides | Medications that decrease the amount of glucose produced by the liver | Medications that increase the sensitivity of cells to insulin | Medications that decrease the absorption of carbohydrates from the intestine | Treatment of diabetes with insulin | Different methods of delivering insulin | The future of pancreas transplantation | Diabetes Mellitus At A Glance | Diabetes Associated Bladder Dysfunction in Older Adult |

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.  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.

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. 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 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 diabetes 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.  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 <.....more>