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 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.  Globally, the statistics are staggering.

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, 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. 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? <.....more>