Diabetes: When Blood Glucose Control Fails
In my last article, we saw that the body uses glucose for its energy needs and after a meal, stores it within the liver and other organs in the form of glycogen and fat. Since the brain cannot store glucose, it is totally dependent on the liver's ability to release this stored energy several hours after a meal.
Real numbers have real consequences and if the blood glucose drops below 50 units, symptoms of brain malfunction, like weakness, dizziness, and problems with concentration occur. If it drops below 40 units, then problems with speaking and increased confusion and drowsiness occur. If it goes below 30 units, seizures and coma result. And when the blood glucose drops under 20 units, brain death is certain. Being able to control the blood glucose is critical for human survival and it doesn't just happen because we eat and drink sugary things. It requires the body to know when to store glucose and when to release it so the brain is always receiving what it needs.
The body uses what biochemist Michael Behe would call an irreducibly complex system, involving beta and alpha cells in the pancreas that controls its blood glucose. After a meal, the beta cells, using glucosensors, react to a rise in blood glucose above 70 units by releasing insulin. Insulin travels in the blood and attaches to specific receptors on target cells, particularly in the liver, telling them to take in glucose and store it as glycogen and fat. In contrast, several hours after a meal, the alpha cells, also using glucosensors, react to a drop in blood glucose below 70 units by releasing glucagon, which travels in the blood and attaches to specific receptors on target cells, mainly in the liver, telling them to release the glucose from glycogen and other energy storage molecules into the blood. It is important to note that due to their breakdown by enzymes, the metabolic effect of a given amount of insulin or glucagon only lasts a few minutes allowing for moment-to-moment blood glucose control within the body, along with the ratio of insulin and glucagon.
However, since the blood glucose must stay above a certain level for proper brain function, it is clear that just being irreducibly complex is not enough for a system to survive. It also has to have natural survival capacity.It must inherently know what the blood glucose level should be and give the conscious mind fair warning to do something if it begins to fall, like eating something. Having a low blood glucose level (hypoglycemia) can take place due to liver failure and rare tumors called insulinomas that send out too much insulin. However, the commonest cause for life-threatening hypoglycemia is when diabetics, who are prone to having too high of a blood glucose, accidentally take too much medication.
The serious consequences of a blood glucose level that is too low make sense, because the body needs glucose for energy. But why should too high of a blood glucose level be a problem? The laws of nature, those mysterious powers that evolutionary biologists claim to be responsible for our own existence, are responsible for the terrible consequences of high blood glucose. Why?
In the early winter of 1922 the parents of Leonard Thompson, a 14 year-old boy suffering from the incurable sugar disease, brought him to the University of Toronto, hoping he could receive an experimental treatment. For the several months prior, the previously healthy teenager had been urinating very frequently, was always thirsty, had lost a lot of weight, and was very weak. The doctors had said that he had diabetes mellitus, a condition that derives its name from the frequent passing of large amounts of sweet smelling urine due to high blood levels of glucose. Dr. Frederick Banting and his assistant, Charles Best, had isolated the pancreatic hormone they had initially named isletin (later changed to insulin) and had used it to successfully treat dogs with the same condition. Banting and Best knew that it was a deficiency of insulin that caused this disorder in glucose metabolism. Leonard Thompson was the first human to receive insulin and the resulting dramatic improvement in his condition gave hope to following generations of diabetics.
Diabetes mellitus is a chronic disorder where glucose metabolism is inhibited by inadequate insulin activity. Medical science has classified diabetics as being of one of two types.
Type I diabetics tend to be diagnosed earlier in life due to frequent urination, weakness, and weight loss because they have a deficient production of insulin and therefore very low amounts of insulin in the blood. Their blood glucose levels are usually extremely high, usually between 500 to 1,000 units at the time of diagnosis. Because they have very low levels of insulin, they must be started on injections of insulin right away.
Type II diabetics usually have a silent disease for many years; often it isn't diagnosed until they have a routine blood test or they suffer a complication (like a heart attack, recurrent skin infections, or numbness of the feet). Their symptoms are caused by normal or increased amounts of insulin, to which tissues, like the liver and muscles, do not respond well enough (insulin resistance). When diagnosed, most Type II diabetics are overweight. Insulin resistance and their blood glucose can improve with dietary restriction and weight loss, in addition to oral medical therapy, often foregoing the need for insulin injections.
Leonard Thompson was a Type I diabetic and, without adequate insulin activity, his body had problems with uptake, usage, and storage of glucose in the tissues. In addition, having inadequate insulin activity released his alpha cells from insulin suppression, thereby increasing the relative effects of glucagon in his body. The effect of having more than normal glucagon activity compared to insulin activity meant that his body tended not to store glucose, synthesize protein or make fat. Instead, under the influence of glucagon, his body constantly thought it needed to make glucose from the breakdown of protein and fat, and to convert free fatty acids into ketones to help energize his brain. In other words, without enough insulin, the body has difficulty informing the tissues that they are in the fed state and should be storing glucose. Since glucagon dominates the metabolism, the tissues think that the body is always in starvation mode despite having a high blood level of glucose.
Without having enough insulin to promote the efficient uptake of glucose in the liver, muscles, and fat cells, the amount of glucose absorbed from the digestive system results in very high levels of blood glucose. This is where the laws of nature take hold. High blood glucose causes high glucose in the fluid filtered within the kidney tubules, overwhelming its ability to reabsorb it. This causes the body to lose glucose and calories. Additionally, the high glucose content of the filtered fluid in kidneys causes an osmotic diuresis. Because the total chemical content in the filtered fluid is so high, by the power of osmosis, the kidneys must give up too much water, losing the ability to maximally concentrate the urine, causing excessive water loss.
In addition, the high blood glucose level also makes water naturally move out of the cells through osmosis. The combination of too much water leaving the cells and the kidneys, and losing too much water, all due to osmosis, ultimately results in profound dehydration, often leading very low blood pressure. Finally, since the body thinks it is in starvation mode and doesn't have enough glucose, it starts forming alternative chemicals for energy use for the brain by producing more ketones, which are acids. The build-up of these ketones causes a rise in the H+ ion level resulting in acidosis, which is toxic to cells and ultimately leads to death.
It was this one-two punch of severe dehydration and acidosis that alterted Leonard Thompson's doctors to the fact that he didn't have long to live. Receiving the insulin injections from Banting and Best helped correct his body's ratio of insulin and glucagon and allowed him to live another thirteen years, dying of pneumonia at the age of 27. It is important to note, however, that although a person can live for only a few months without insulin, the absence of glucagon is incompatible with life.
The laws of nature determine what blood glucose level is necessary for the body to survive. Since the body, the brain in particular, requires a certain amount of energy to function properly, there must be sufficient glucose in the blood at all times. In addition, because of osmosis, if the blood glucose rises too high, this can lead to severe dehydration. Finally, because the lack of insulin makes the body produce other sources of energy that the brain can use (ketones) it causes the H+ ion level in the blood to increase to toxic levels which can cause death from diabetic ketoacidosis.
When it comes to controlling the blood glucose, these are the three ways the laws of nature affect human life. Without the irreducibly complex system that uses glucosensors on pancreatic cells that produce insulin and glucagon, human life would be impossible. Evolutionary biologists expect us to believe that all of this developed by chance and the laws of nature alone. But life is still more complicated. When the body breaks down glucose in the presence of oxygen, most of the energy is released as heat. This means that the higher the metabolic rate, such as with increased activity, the more heat the body generates.
However, since the enzymes in the cells only work properly within an optimal temperature range, this means that with changes in metabolic activity, the body must make sure it keeps its core temperature within certain limits. How does the body maintain control and does it make sense that it came about by chance and the laws of nature alone? That's what we'll begin to explore next time.