How Diabetes Works

Since diabetes is a disease that affects your body's ability to use glucose, let's start by looking at what glucose is and how your body controls it. Glucose is a simple sugar that provides energy to all of the cells in your body. The cells take in glucose from the blood and break it down for energy (some cells, like brain cells and red blood cells, rely solely on glucose for fuel). The glucose in the blood comes from the food that you eat.

When you eat food, glucose gets absorbed from your intestines and distributed by the bloodstream to all of the cells in your body. Your body tries to keep a constant supply of glucose for your cells by maintaining a constant glucose concentration in your blood -- otherwise, your cells would have more than enough glucose right after a meal and starve in between meals and overnight. So, when you have an oversupply of glucose, your body stores the excess in the liver and muscles by making glycogen, long chains of glucose. When glucose is in short supply, your body mobilizes glucose from stored glycogen and/or stimulates you to eat food. The key is to maintain a constant blood-glucose level.

To maintain a constant blood-glucose level, your body relies on two hormones produced in the pancreas that have opposite actions: insulin and glucagon.

Insulin is made and secreted by the beta cells of the pancreatic islets, small islands of endocrine cells in the pancreas. Insulin is a protein hormone that contains 51 amino acids. Insulin is required by almost all of the body's cells, but its major targets are liver cells, fat cells and muscle cells. For these cells, insulin does the following:

As such, insulin stores nutrients right after a meal by reducing the concentrations of glucose, fatty acids and amino acids in the bloodstream.

See the next page to learn about glucagon.

So, what happens when you do not eat? In times of fasting, your pancreas releases glucagon so that your body can produce glucose. Glucagon is another protein hormone that is made and secreted by the alpha cells of the pancreatic islets. Glucagon acts on the same cells as insulin, but has the opposite effects:

In contrast to insulin, glucagon mobilizes glucose from stores inside your body and increases the concentrations of glucose in the bloodstream -- otherwise, your blood glucose would fall to dangerously low levels.

So how does your body know when to secrete glucagon or insulin? Normally, the levels of insulin and glucagon are counter-balanced in the bloodstream. For example, just after you eat a meal, your body is ready to receive the glucose, fatty acids and amino acids absorbed from the food. The presence of these substances in the intestine stimulates the pancreatic beta cells to release insulin into the blood and inhibit the pancreatic alpha cells from secreting glucagon. The levels of insulin in the blood begin to rise and act on cells (particularly liver, fat and muscle) to absorb the incoming molecules of glucose, fatty acids and amino acids. This action of insulin prevents the blood-glucose concentration (as well as the concentrations of fatty acids and amino acids) from substantially increasing in the bloodstream. In this way, your body maintains a steady blood-glucose concentration in particular.

In contrast, when you are between meals or sleeping, your body is essentially starving. Your cells need supplies of glucose from the blood in order to keep going. During these times, slight drops in blood-sugar levels stimulate glucagon secretion from the pancreatic alpha cells and inhibit insulin secretion from the beta cells. Blood-glucagon levels rise. Glucagon acts on liver, muscle and kidney tissue to mobilize glucose from glycogen or to make glucose that gets released into the blood. This action prevents the blood-glucose concentration from falling drastically.

As you can see, the interplay between insulin and glucagon secretions throughout the day help to keep your blood-glucose concentration constant, staying at about 90 mg per 100 ml of blood (5 millimolar).

Now that you know how your body handles glucose with insulin and glucagon, you are ready to understand diabetes. Diabetes is classified into three types: Type 1, Type 2 and gestational diabetes.

Type 1 (also called juvenile diabetes or insulin-dependent diabetes) is caused by a lack of insulin. This type is found in five percent to 10 percent of diabetics and usually occurs in children or adolescents. Type 1 diabetics have an abnormal glucose-tolerance test and little or no insulin in their blood. In Type 1 diabetics, the beta cells of the pancreatic islets are destroyed, possibly by the person's own immune system, genetic or environmental factors.

Type 2 (also called adult-onset diabetes or non-insulin-dependent diabetes) occurs when the body does not respond or can't use its own insulin (insulin resistance). Type 2 occurs in 90 percent to 95 percent of diabetics and usually occurs in adults over the age of 40, most often between the ages of 50 and 60. Type 2 diabetics have an abnormal glucose-tolerance test and higher than normal levels of insulin in their blood. In Type 2 diabetics, the insulin resistance is linked to obesity, but we do not know exactly how this occurs. Some studies suggest that the number of insulin receptors on liver, fat and muscle cells is reduced, while others suggest that the intracellular pathways activated by insulin in these cells are altered.

Gestational diabetes can occur in some pregnant women and is similar to Type 2 diabetes. Gestational diabetics have an abnormal glucose-tolerance test and slightly higher levels of insulin. During pregnancy, several hormones partially block the actions of insulin, thereby making the woman less sensitive to her own insulin. She develops a diabetes that can be managed by special diets and/or supplemental injections of insulin. It usually goes away after the baby is delivered.

Regardless of the type of diabetes, diabetics exhibit several (but not necessarily all) of the following symptoms:

These symptoms can be understood when we see how insulin deficiency or insulin resistance affects the body's physiology.

Now that you know the symptoms of diabetes -- high blood glucose, excessive hunger and thirst, frequent urination -- let's look at what happens to your body during diabetes. For the purposes of this discussion, let's suppose that you have undiagnosed, and therefore unmanaged, diabetes.

Now, let's see how the lack of insulin or insulin-resistance affects your body to produce the clinical symptoms and signs of diabetes:

Your lack of insulin or insulin resistance directly causes high blood-glucose levels during fasting and after a meal (reduced glucose tolerance).

High blood glucose causes glucose to appear in your urine.

High blood glucose causes you to urinate frequently.

The high blood glucose and increased urine flow make you constantly thirsty.

You are constantly hungry. It's not clear exactly what stimulates your brain's hunger centers, possibly the lack of insulin or high glucagon levels.

You feel tired because your cells cannot absorb glucose, leaving them with nothing to burn for energy.

Your poor blood circulation causes numbness in your hands and feet, changes in vision, slow-healing wounds and frequent infections. High blood glucose or lack of insulin may also depress the immune system. Ultimately, these can lead to gangrene in the limbs and blindness.

Fortunately, these consequences can be managed by correcting your high blood glucose through diet, exercise and medications, as we'll discuss next.

As of now, there is no cure for diabetes; however, the disease can be treated and managed successfully. The key to treating diabetes is to closely monitor and manage your blood-glucose levels through exercise, diet and medications. The exact treatment regime depends on the type of diabetes.

If you have Type 1 diabetes, you lack insulin and must administer it several times each day. Insulin injections are usually timed around meals to cope with the glucose load from digestion. You must monitor your blood-glucose levels several times a day and adjust the amounts of insulin that you inject accordingly. This keeps your blood-glucose concentration from fluctuating wildly.

There are some implantable insulin infusion pumps that allow you to press a button and infuse insulin. If you inject too much insulin, you can drive your blood-glucose level well below normal (hypoglycemia). This can cause you to feel light-headed and shaky because your brain cells are not receiving enough glucose (mild episodes can be relieved by eating a candy bar or drinking juice). If your blood glucose goes really low, you can lapse into a coma (insulin shock), which can be life-threatening. In addition to insulin injections, you have to watch your diet to keep track of the carbohydrate and fat contents, and you must exercise frequently. This treatment continues for the rest of your life.

If you have Type 2 diabetes, you can usually manage it by reducing your body weight through dieting and exercise. You may have to monitor your blood glucose either daily or just when you visit your doctor. Depending on the severity of your diabetes, you may have to take medication to aid in controlling your blood glucose. Most of the medicines for Type 2 diabetes are oral medications, and their actions fall into the following categories:

Like a Type 1 diabetic, a Type 2 diabetic is on this treatment for the rest of his or her life.

There are a number of alternative treatments for diabetes. These alternative treatments are not widely accepted, mainly due to lack of scientific research on their effectiveness or lack of scientific consensus. Such treatments include:

As with any medical treatment, you should discuss treatment options with your physician. For more information on alternative treatments, see the NIDDK bulletin Alternative Therapies for Diabetes.

One of the most promising developments for future, perhaps permanent, treatments for Type 1 diabetes is pancreatic islet transplantation. In this technique, islets are removed from the pancreas of a deceased donor and injected through a thin tube (catheter) into the liver of a diabetic patient. After some time, the islet cells attach to new blood vessels and begin releasing insulin. Although early studies have shown some success, rejection of the donor's tissue is a major problem. Research continues in this field because of its great potential to treat diabetes.

To learn more about diabetes and related topics, check out the links on the next page.