A Clinical Perspective on Diabetes Mellitus and Ketone Bodies

Diabetes Mellitus and Ketone Bodies

More than one person, found unconscious on the streets of some metropolis, has been carted to jail only to die of complications arising from uncontrolled diabetes mellitus. Others are fortunate enough to arrive in hospital emergency rooms. A quick test for diabetes mellitus-induced coma is the odor of acetone on the breath of the afflicted person. Acetone is one of several metabolites produced by diabetics that are known collectively as ketone bodies.

The term “diabetes” was used by the ancient Greeks to designate diseases in which excess urine is produced. Two thousand years later, in the eighteenth century, the urine of certain individuals was found to contain sugar, and the name “diabetes mellitus” (L.: mellitus, sweetened with honey) was given to this disease. People suffering from diabetes mellitus waste away as they excrete large amounts of sugar-containing urine.

The cause of insulin-dependent-diabetes mellitus is an inadequate production of insulin by the body. Insulin is secreted in response to high blood glucose levels. It binds to the membrane receptor protein on its target cells. Binding increases the rate of transport of glucose across the membrane and stimulates glycogen synthesis, lipid biosynthesis, and protein synthesis. As a result, the blood glucose level is reduced. Clearly, the inability to produce sufficient insulin seriously impairs the body’s ability to regulate metabolism.

Individuals suffering from diabetes mellitus do not produce enough insulin to properly regulate blood glucose levels. This generally results from the destruction of the β cells of the islets of Langerhans. One theory to explain the mysterious disappearance of these cells is that a virus infection stimulates the immune system to produce antibodies that cause the destruction of the β cells.

In the absence of insulin the uptake of glucose into the tissues is not stimulated, and a great deal of glucose is eliminated in the urine. Without insulin, then, adipose cells are unable to take up the glucose required to synthesize triglycerides. As a result, the rate of fat hydrolysis is much greater than the rate of fat resynthesis, and large quantities of free fatty acids are liberated into the bloodstream. Because glucose is not being efficiently taken into cells, carbohydrate metabolism slows, and there is an increase in the rate of lipid catabolism. In the liver this lipid catabolism results in the production of ketone bodies: acetone, acetoacetate, and β-hydroxybutyrate.

A similar situation can develop from improper eating, fasting, or dieting-any situation in which the body is not provided with sufficient energy in the form of carbohydrates. These ketone bodies cannot all be oxidized by the citric acid cycle, which is limited by the supply of oxaloacetate. The acetone concentration in blood rises to levels so high that acetone can be detected in the breath of untreated diabetics. The elevated concentration of ketones in the blood can overwhelm the buffering capacity of the blood, resulting in ketoacidosis. Ketones, too, will be excreted through the kidney. In fact, the presence of excess ketones in the urine can raise the osmotic concentration of the urine so that it behaves as an “osmotic diuretic,”
causing the excretion of enormous amounts of water. As a result, the patient may become severely dehydrated. In extreme cases the combination of dehydration and ketoacidosis may lead to coma and death.

It has been observed that diabetics also have a higher than normal level of glucagon in the blood. As we have seen, glucagon stimulates lipid catabolism and ketogenesis. It may be that the symptoms described above may result from both the deficiency of insulin and the elevated glucagon levels. The absence of insulin may cause the elevated blood glucose and fatty acid levels, while the glucagon, by stimulating ketogenesis, may be responsible for the ketoacidosis and dehydration.

There is no cure for diabetes. However, when the problem is the result of the inability to produce active insulin, blood glucose levels can be controlled moderately well by the injection of either animal insulin or human insulin produced from the cloned insulin gene. Unfortunately, one or even a few injections of insulin each day cannot mimic the precise control of blood glucose accomplished by the pancreas.

As a result, diabetics suffer progressive tissue degeneration that leads to early death. One primary cause of this degeneration is atherosclerosis, the deposition of plaque on the walls of blood vessels. This causes a high frequency of strokes, heart attack, and gangrene of the feet and lower extremities, often necessitating amputation. Kidney failure causes the death of about 20% of diabetics under 40 years of age, and diabetic retinopathy (various kinds of damage to the retina of the eye) ranks fourth among the leading causes of blindness in the United States. Nerves are also damaged, resulting in neuropathies that can cause pain or numbness, particularly of the feet.

There is no doubt that insulin injections prolong the life of diabetics, but only the presence of a fully functioning pancreas can allow a diabetic to live a life free of the complications noted here. At present, pancreas transplants do not have a good track record. Only about 50% of the transplants are functioning after one year. It is hoped that improved transplantation techniques will be developed so that diabetics can live a normal life span, free of debilitating disease.


This information is provided by © Copyright 2017 Genesis Health Inc. All rights reserved. This is not intended to replace the medical advice of your doctor or nutritionist. Please consult your nutritionist for advice about a specific medical condition.

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