14.20: Diabetes Mellitus (DM)

Definition and Types

Diabetes mellitus (DM) is a group of diseases characterized by chronic hyperglycemia, poor glucose tolerance, and usually other abnormalities in metabolism. Diabetics have FPG values above 140 mg/dl (above 126 mg/dl according to the American Diabetes Association) and final OGTT values above 200 mg/dl . High glucose levels, which may exceed 800 mg/dl, persist because of inadequate insulin production or high insulin resistance. As a result, muscle, liver, and fat cells cannot lower blood glucose adequately and the effect of glucagon, which raises blood glucose, remains unchecked.

There are four types of DM. Individuals with type I, or insulin-dependent diabetes mellitus (IDDM) cannot survive less they receive insulin therapy. This type of DM is also frequently called juvenile-onset diabetes mellitus because most cases develop before age 20 and very few develop after age 30. A third name is ketosis-prone diabetes mellitus because these patients usually develop high blood levels of ketoacids. Many individuals who develop IDDM as children or young adults receive adequate treatment and survive long enough to enter the elderly population.

Victims of type II, or non-insulin-dependent diabetes mellitus (NIDDM) have low insulin levels or high insulin resistance but do not require insulin therapy to survive. However, insulin treatment may be of significant help in more severe cases. NIDDM is frequently called maturity-onset diabetes mellitus because most cases develop after age 40. It is also called non-ketosis-prone diabetes mellitus because few cases involve high ketoacid levels. NIDDM may advance to become IDDM.

Another type of DM is called secondary diabetes mellitus because it develops as a complication from another abnormality or disease, such as alcoholism, pancreatitis, excess growth hormone, or excess glucocorticoids. The fourth type is gestational diabetes, which occurs in some women during pregnancy because high sex hormone levels reduce the effectiveness of insulin. We will consider only IDDM and NIDDM in detail because no cases of gestational diabetes occur among older people and because most cases of secondary diabetes, though differing in cause, have the same effects as NIDDM.

Incidence

Diabetes mellitus ranks as the eighth leading chronic condition among both people over age 45 and those over age 65. Its incidence nearly doubles between ages 45 and 65. Because of its many complications, DM is among the most common factors causing older people to visit a physician, and it is the sixth or seventh leading cause of death among people over age 65.

NIDDM is the most common type of DM among the elderly. It is estimated that 10 percent of all people over age 56 have NIDDM. Furthermore, the incidence increases with age, and NIDDM is present in approximately 20 percent of those age 65 to 74 years and approximately 40 percent of those over age 85.

Causes

IDDM seems to be caused by autoimmune reactions against insulin-producing cells in the pancreas. Virtually no insulin can be produced because essentially all the insulin-producing cells are destroyed.

NIDDM has a strong tendency to run in families, certain ethnic groups, and blacks. Therefore, it seems to rely heavily on genetic predispositions that interact with other factors. One important factor is obesity; another is eating large quantities of carbohydrates. These factors are important because they are associated with high insulin resistance. The significance of high insulin resistance becomes evident when one realizes that though some people with NIDDM produce little insulin, many have normal or high insulin levels but high insulin resistance. Finally, contrary to previous beliefs, aging makes little or no contribution to the development of NIDDM.

Main Effects and Complications

The most important effect of diabetes mellitus is the maintenance of abnormally high blood glucose levels. The glucose causes several alterations, each of which contributes to one or more of the complications of DM. The development and consequences of most of the complications mentioned below are described in greater detail in Chaps. 3-10, 12, 13, and 15 on the body systems in which these complications appear. (Suggestion 309.01.06)

For some photos of the effects and complications from diabetes, go to sections of Preserved Specimen Photos and to Microscope Slides.

For Internet images of the effects and complications from diabetes, search the Images section of http://www.google.com/ for specific items (e.g., diabetic cataract, diabetic retinopathy, diabetic gangrene, diabetic kidney). For diseases, I highly recommend searching WebPath: The Internet Pathology Laboratory , the excellent complete version of which can be purchased on a CD.

Excess Glucose

One outcome of high blood glucose levels is excess conversion of glucose to a sugar-like molecule (i.e., sugar alcohol) called sorbitol, which accumulates in certain areas. Within the eye, sorbitol causes cataracts in the lens and initiates diabetic retinopathy. These conditions are, respectively, the leading eye disease and the leading cause of blindness among the elderly. Within nerves, sorbitol causes degeneration of neurons and the Schwann cells that surround them, resulting in deterioration of sensory and motor neuron functioning and leading to diminished reflex response, conscious sensation, and voluntary muscle control. Effects include reduced sweating, increased traumatic injury, gangrene of the feet, abnormal GI tract peristalsis, and fecal and urinary incontinence.

A second outcome of high blood glucose levels is the formation of glucose cross-links between protein molecules both inside and outside cells. No enzymes are needed to initiate this process, which is called nonenzymatic glycosylation. Furthermore, once started, the process continues even if glucose levels return to normal. Since the cross-links formed by glucose are strong and permanent, the movement of protein molecules and the passage of materials between proteins, such as collagen fibers, are restricted. Harmful consequences of nonenzymatic glycosylation in the circulatory system adversely affect all parts of the body. The most frequent serious complications of circulatory system changes are heart attacks, strokes, and gangrene of the feet and legs. Non-enzymatic glycosylation promotes free radical formation, and it can also lead to degeneration and failure of the kidneys.

A third effect of high blood glucose levels is high osmotic pressure. A high concentration of glucose in the blood causes some dehydration of cells because water moves from the cells into the blood, causing the cells to malfunction. The situation is compounded because the extra glucose prevents the collecting ducts in the kidneys from reabsorbing enough water, leading to excess water loss in urine.

The consequences of altered kidney functioning caused by high blood glucose levels are revealed by three classic signs and symptoms of diabetes mellitus: an increase in urine production (polyuria), the presence of glucose in the urine (glycosuria), and an increase in appetite and eating (polyphagia). An abnormally high loss of water in the urine tends to lower blood pressure while further increasing blood osmotic pressure and cell dehydration. This is indicated by the fourth classical sign and symptom of DM: increased thirst and drinking (polydipsia). Finally, as more water leaves the body and dehydration worsens, additional minerals (e.g., sodium, potassium) are lost and mineral deficiencies develop. Outcomes may include circulatory failure, brain malfunction, coma, and death.

Two other effects of high blood glucose levels include; (a) increased risk of infection. This occurs because the glucose provides abundant nutrients for microbes, encouraging their rapid proliferation, and because the glucose inhibits defense functions by WBCs; (b) reduced oxygen carrying capacity by RBCs, because hemoglobin is distorted when glucose binds to it.

Ketoacidosis

In all cases of IDDM and some cases of NIDDM, insulin levels are so low that very little glucose enters liver, muscle, and fat cells. These cells then attempt to obtain energy from the breakdown of fats and amino acids. However, this requires the use of some glucose because glucose provides the substance that channels fatty acid fragments and amino acid fragments into the Krebs cycle. With inadequate insulin to assist the entry and use of glucose, the fragments from the fat and amino acids cannot be broken down but are converted into substances called ketoacids (ketones). Ketoacids enter and accumulate in the blood, producing a condition called ketoacidosis. The resulting disturbance in acid/base balance causes cells to malfunction, especially in the brain.

Excess ketones leave the body in exhaled breath and in the urine (ketonuria). The ketones are noticed as a sweet fruity aroma, which indicates the presence of ketoacidosis. When ketoacids are eliminated in the urine, they carry minerals (e.g., sodium, potassium, zinc, magnesium) out of the body, causing increased mineral deficiencies.

Prevention

There are no preventive measures for IDDM. However, the development over a period of weeks of polyuria, polydipsia, and polyphagia, which are usually accompanied by rapid weight loss, is a clear warning sign that this disease has developed. The intensity of these conditions forces affected individuals to seek medical attention. Failure to obtain treatment results in serious acute illness and death.

NIDDM develops subtly and insidiously over a period of years. The classic warning signs and symptoms may not be apparent or may develop gradually and be ignored or attributed to other conditions. Therefore, the first indication of NIDDM to be noticed is often a complication it causes, such as eye diseases, heart attack, stroke, and foot infections. At this stage many other complications are also well established. Therefore, early prevention of NIDDM by avoiding modifiable risk factors is very important, especially for blacks and anyone with close relatives who have NIDDM.

Perhaps the most important modifiable risk factor for NIDDM is having an abundance of body fat, particularly when it reaches the level of obesity. Obesity accompanied by a diet high in carbohydrates creates an especially high risk of developing NIDDM. Furthermore, the greater the amount of body fat, obesity, and carbohydrate intake, the greater the risk. Therefore, one of the best ways to prevent NIDDM is to maintain a desirable body weight and avoid excess body fat. The other important modifiable risk factor for NIDDM is having a low level of physical activity. Exercise reduces the risk of NIDDM by helping to increase insulin sensitivity, improve glucose tolerance, and prevent obesity by increasing energy use and influencing appetite (Chapter 8).

Treatments

The goals for treating DM include maintaining homeostasis of blood glucose levels and avoiding ketoacidosis. One key to achieving these goals is dietary regulation. Careful planning includes controlling the times food is consumed; the amounts of sugar, fiber, and other carbohydrates consumed; and the total intake of kilocalories.

A second aspect of these treatment plans is regulating the amount of physical activity. Exercise tends to lower glucose levels by causing cells to consume glucose and glycogen and to have increased insulin sensitivity. Sedentary periods have the opposite effects. Exercise that is accompanied by reductions in body fat can cure some cases of NIDDM. However, exercise programs must be tailored to individual needs to maximize the benefits while minimizing the adverse effects.

Treatment plans may include the administration of insulin or medications that stimulate insulin production. Various types, doses, and schedules of insulin administration are used in different individuals. Furthermore, the administration of insulin and other medications is adjusted frequently to compensate for fluctuations in diet, exercise, and other aspects of daily living.

In spite of all efforts at planning, numerous factors militate against maintaining glucose homeostasis and preventing ketoacidosis at all times. These factors include an inability to adequately regulate diet and exercise; age changes; the presence of abnormal conditions or diseases; other medications; physical and mental limitations and disabilities; and a host of social, psychological, and economic factors. Furthermore, the number and severity of these factors and the complexity of interactions among them increase with age. Therefore, it is likely that an elderly person with diabetes mellitus will develop at least some complications. However, the adverse effects can be minimized by regularly checking for complications and promptly treating any that appear.