Dr. S.M.Sadikot.
Hon. Endocrinologist,
Jaslok Hospital and Research Centre,
Mumbai 400026

In today's world, the big "buzz" word is that you must take charge of your own diabetes and that doctors should only be there to guide and advise.

Which is all very fine, but how is one expected to take charge of one's diabetes, unless one understands the basics of diabetes! Unless you understand the problem, you can rarely control it, leave alone take charge of it.

Many of you may have seen the famous film, "Patton" in which there is scene where General Patton defeats Rommel in tank warfare in the Arabian deserts. When Patton has won over Rommel, long considered the ultimate master of desert warfare, so much so that he was nicknamed the "desert rat", Patton waves a book on tank warfare on the desert written by Rommel and shouts, "I mastered your own book, you…!" Patton had defeated Rommel by having knowledge about desert tank warfare by learning from the master, and using this knowledge he was able to defeat Germans.

If you are to take charge of your diabetes, you also will similarly have to understand the problem before you will be able to take charge of it.

To put it very simply, diabetes mellitus is a chronic and currently incurable condition in which too much glucose (sugar) is present in the blood.

When you eat food, the carbohydrates in the food, and remember most of the diet is full of carbohydrates (starch, in popular parlance), gets broken down in the intestines into simple sugars such as glucose which are then absorbed into the bloodstream and get distributed all over the body for it to be used. When you have something with simple sugars, the glucose gets absorbed that much faster!

But we do not eat continuosly. So our body has a mechanism which closely regulates the level of glucose in the bloodstream so that the cells of the body can get their required supply at all times. Unless this is done, your cells would have too much 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. Think of this as some sort of a "depot" where you store excess materials for later use. So how does the body fine tune this mechanism by which a normal amount of glucose is available for use by the body at all times?

To maintain a constant blood-glucose level, your body relies on two hormones produced in the pancreas that have opposite actions: insulin and glucagon. Although things are not that simple and many other mechanisms do come into play, it will suffice for our purposes to understand the basic role played by these two hormones.

The pancreas is composed of two main parts, the exocrine part and the endocrine pancreas. The exocrine part secretes substances into the intestinal tract which help in digestion of the eaten food. These include lipase, which helps to digest fat, and amylase that helps to digest starchy foods. It also releases 'bicarbonate of soda' to neutralise any stomach acid that may otherwise damage the lining of the gut. The exocrine pancreas is directly connected to the intestinal tract through the pancreatic duct as seen below.

But we are basically concerned in diabetes with the endocrine pancreas which is the source of insulin, glucagon and other hormones, secreted directly into the bloodstream.

The pancreas is full of tiny cluster of cells called the Islets of Langerhans, which surround the cells of the "exocrine" pancreas.

The islet of Langerhans contains many types of cells

The pancreas has many islets that contain insulin-producing beta cells and glucagon-producing alpha cells.

In response to this rise the hormone insulin is released into the bloodstream to signal the body tissues to metabolize or burn the glucose for fuel, causing blood glucose levels to return to normal.

Glucose the body doesn't use right away goes to the liver, muscle or fat for storage. Under normal circumstances the hormone insulin, which is made by the pancreas, carefully regulates how much glucose is in the blood. Insulin stimulates cells to absorb enough glucose from the blood for the energy, or fuel, that they need. Insulin also stimulates the liver to absorb and store any glucose that's left over. After a meal the amount of glucose in the blood rises, and this triggers the release of insulin.

When blood glucose levels fall, during exercise for example, insulin levels fall too. A second hormone manufactured by the pancreas is called glucagon. It stimulates the liver to release glucose when it's needed, and this raises the level of glucose in the blood.

• Stimulates liver and muscle cells to store glucose in glycogen
• Stimulates fat cells to form fats from fatty acids and glycerol
• Stimulates liver and muscle cells to make proteins from amino acids
• Inhibits the liver and kidney cells from making glucose from intermediate compounds of metabolic pathways (gluconeogenesis) As such, insulin stores nutrients right after a meal by reducing the concentrations of glucose, fatty acids and amino acids in the bloodstream.

Insulin and glucagon have opposite effects on liver and other tissues for controlling blood-glucose levels So, what happens when you do not eat? In times of fasting, or when there has been a long time after a meal and the blood levels of glucose drop significantly, 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.

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.

Thus, one can say that insulin is the key that opens the door to let glucose into the cells.

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, it is this "Balance" between insulin and glucagon secretions throughout the day and night which helps to keep your blood-glucose concentration within normal bounds.

In diabetes, this balance gets tilted and this leads to a rise in the blood glucose levels to what we call "diabetic" values. This arises because the body cannot use the glucose properly, either because of a lack of the hormone insulin or because the insulin available does not work effectively. Not only is excess sugar found in the blood but it may appear in the urine too.

In people with diabetes, the pancreas either produces little or no insulin, or the cells do not respond appropriately to the insulin that is produced. Glucose builds up in the blood, overflows into the urine, and passes out of the body. Thus, the body loses its main source of fuel even though the blood contains large amounts of glucose. Diabetes mellitus is a disease in which the cells are starving in a sea of glucose.

As you are aware, there are two main types of diabetes:

• Type 1 diabetes
• Type 2 diabetes

In Type 1, the body is unable to produce any insulin. Type 1 diabetes is an autoimmune disease. An autoimmune disease results when the body's system for fighting infection (the immune system) turns against a part of the body. In diabetes, the immune system attacks the insulin-producing beta cells in the pancreas and destroys them. The pancreas then produces little or no insulin.

At present, scientists do not know exactly what causes the body's immune system to attack the beta cells, but they believe that autoimmune, genetic, and environmental factors, possibly viruses, are involved. In a Type 1 diabetic, the beta cells produce little or no human insulin. When this happens the blood sugar level begins to rise to a dangerous level.

Type 1 diabetes develops most often in children and young adults, but the disorder can appear at any age. Symptoms of type 1 diabetes usually develop over a short period, although beta cell destruction can begin years earlier.

Symptoms include increased thirst and urination, constant hunger, weight loss, blurred vision, and extreme fatigue. If not diagnosed and treated with insulin, a person can lapse into a life-threatening diabetic coma, also known as diabetic ketoacidosis.

In Type 2 diabetes, not enough insulin is produced or the insulin that is made does not work properly.

The most common form of diabetes is type 2 diabetes. Type 2 diabetes is often part of a metabolic syndrome that includes obesity, elevated blood pressure, and high levels of blood lipids.

When type 2 diabetes is diagnosed, the pancreas is usually producing enough insulin, but, for unknown reasons, the body cannot use the insulin effectively, a condition called insulin resistance. After several years, insulin production decreases. The result is the same as for type 1 diabetes--glucose builds up in the blood and the body cannot make efficient use of its main source of fuel.

Type 2 diabetes can be strongly triggered by a person's lifestyle, weight, exercise level on a strong genetic background

How are the "Classical" signs and symptoms of diabetes caused? This excess of blood glucose is the direct cause of the classic diabetes symptoms.

The high blood glucose in diabetes produces glucose in the urine and frequent urination through effects on the kidneys.

Now, let's see how the lack of insulin as seen in Type 1 diabetes and the insulin resistance of type 2 DM affect your body to produce the typical signs and symptoms associated with diabetes.

The lack of insulin or insulin resistance directly causes high blood glucose levels both after a meal and also during times of "fasting". Right after a meal, there is no insulin to act as the key to allow the glucose to enter the cells, as we have seen above and this leads to raised blood glucose values.

Because your cells have no glucose coming into them from your blood, your body "thinks" that it is starving. Your pancreatic alpha cells secrete glucagon, and glucagon levels in your blood rise. Glucagon acts on your liver and muscles to breakdown stored glycogen and release glucose into the blood. Glucagon also act on your liver to produce and release glucose by gluconeogenesis. Both of these actions of glucagon further raise your blood-glucose levels.

High blood glucose causes glucose to appear in your urine. High blood-glucose levels increase the amount of glucose filtered by your kidneys. The amount of glucose filtered exceeds the amount that your kidneys can reabsorb. The increased urine flow causes you to urinate frequently.

Now, let's see how the lack of insulin as seen in Type 1 diabetes and the insulin resistance of type 2 DM affect your body to produce the typical signs and symptoms associated with diabetes. The lack of insulin or insulin resistance directly causes high blood glucose levels both after a meal and also during times of "fasting". Right after a meal, there is no insulin to act as the key to allow the glucose to enter the cells, as we have seen above and this leads to raised blood glucose values.

Because your cells have no glucose coming into them from your blood, your body "thinks" that it is starving. Your pancreatic alpha cells secrete glucagon, and glucagon levels in your blood rise. Glucagon acts on your liver and muscles to breakdown stored glycogen and release glucose into the blood. Glucagon also act on your liver to produce and release glucose by gluconeogenesis. Both of these actions of glucagon further raise your blood-glucose levels.

High blood glucose causes glucose to appear in your urine. High blood-glucose levels increase the amount of glucose filtered by your kidneys. The amount of glucose filtered exceeds the amount that your kidneys can reabsorb. The increased urine flow causes you to urinate frequently.

The excess glucose gets lost into the urine and can be detected by glucose test strips.

The high blood glucose and increased urine flow make you very thirsty. High blood-glucose levels increase the osmotic pressure of your blood and directly stimulate the thirst receptors in your brain. Your increased urine flow causes you to lose body sodium, which also stimulates your thirst receptors.

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

You lose weight despite the fact that you are eating more frequently. Since the cells are not receiving fuel, they trigger the hunger sensation. Because the cells are unable to use the glucose, they pull fuel from other sources-fat stores and muscle-and the diabetic person begins to lose weight. Of course, the weight loss is usually seen in people who have a very high blood glucose levels and/or very little insulin in their bodies.

You feel tired because your cells cannot absorb glucose, leaving them with nothing to burn for energy. The ketones in the blood and urine seen above are usually associated with Type 1 diabetes but can occur in people with Type 2 diabetes also.

Many of you with Type 2 diabetes show a very different clinical picture from that seen in the West and described in many text-books as "typical" of Type 2 diabetes. Unlike people with Type 2 diabetes in the West, the vast majority of whom are overweight, if not obese, many of you with Type 2 diabetes in India (and this is true of most developing or newly developed countries) have a normal weight and may even be underweight.

If you come into this category, your pancreas does secrete insulin (unlike Type 1 diabetes), but this is not adequate enough to meet the requirements, especially in view of the added burden of insulin resistance in the peripheral organs. Thus, although you do not go into ketosis if not injected with insulin, you may do so in times of stress when the demand for insulin increases and your pancreas is unable to increase the amount of insulin which it can secrete.

Such people are often said to have "insulin-requiring" Type 2 diabetes. They, rarely,will show good diabetes control in the absence of insulin injections in spite of some lowering of the raised blood glucose levels with the use of oral drugs whether they act on the pancreas to try and stimulate the pancreas into secreting more insulin or they act on the peripheral organs such as the liver and muscle to decrease the resistance to insulin action.

People with Type 2 diabetes often present with the long term complications of diabetes at the time of diagnosis in contrast to people with Type 1 diabetes who usually present with acute complications such as ketosis.

People with Type 2 diabetes who are diagnosed before they show the long term complications, and even those with Type 1 diabetes, who are not optimally controlled may later show some evidence of the long term complications of diabetes. Whilst diabetes can affect practically any organ, the most common are seen below

For a quick interactive look at the basics of diabetes, Click here