Genetic Disorders - Diabetes
type insulin glucose body
Diabetes is a disease that affects the body's use of food, causing blood glucose (sugar levels in the blood) to become too high. Normally, the body converts sugars, fats, starches, and proteins into a form of sugar called glucose. The blood then carries glucose to all the cells throughout the body. In the cells, with the help of the hormone insulin, which facilitates the entry of glucose into the cells, the glucose is either converted into energy for use immediately or stored for the future. Beta cells of the pancreas, a small organ located behind the stomach, manufacture the insulin. The process of turning food into energy via glucose (blood sugar) is important because the body depends on glucose for its energy source.
In a body with diabetes, food is converted to glucose, but there is a problem with insulin. In one type of diabetes the pancreas does not manufacture enough insulin, and in another type the body has insulin but cannot use the insulin effectively (this latter condition is called insulin resistance). When insulin is either absent or ineffective, glucose cannot get into the cells to be converted into energy. Instead, the unused glucose accumulates in the blood. If a person's blood-glucose level rises high enough, the excess glucose "spills over" into the urine, causing frequent urination. This, in turn, leads to an increased feeling of thirst as the body tries to compensate for the fluid lost through urination.
|Type 1 diabetes||Type 2 diabetes|
|Phenotype||Onset primarily in childhood and adolescence||Onset predominantly after 40 years of age*|
|Often thin or normal weight||Often obese|
|Prone to ketoacidosis||No ketoacidosis|
|Insulin administration required for survival||Insulin administration not required for survival|
|Pancreas is damaged by an autoimmune attack||Pancreas is not damaged by an autoimmune attack|
|Absolute insulin deficiency||Relative insulin deficiency and/or insulin resistance|
|Treatment: insulin injections||Treatment: (1) healthy diet and increased exercise; (2) hypoglycemic tablets; (3) insulin injections|
|Genotype||Increased prevalence in relatives||Increased prevalence in relatives|
|Identical twin studies: <50% concordance||Identical twin studies: usually above 70% concordance|
|HLA association: Yes||HLA association: No|
|*Type 2 diabetes is increasingly diagnosed in younger patients.|
|Note: HLA is human leukocyte antigen.|
Types of Diabetes
There are two distinct types of diabetes. Insulin-dependent diabetes (also called Type 1 or juvenile diabetes), the most severe form of the disease, occurs most often in children and young adults. The pancreas stops manufacturing insulin, and the hormone must be injected daily. Non-insulin-dependent diabetes (also known as Type 2) is most often seen in adults. In this type the pancreas produces insulin, but it is not used effectively and the body resists its effects. Table 5.3 compares the phenotype (presentation) and genotype of Type 1 and Type 2 diabetes.
According to the American Diabetes Association (ADA; http://www.diabetes.org/) in early 2005, approximately 18.2 million Americans (6.3% of the population) had diabetes. Of these, approximately one-third had not been diagnosed. The ADA reported that more than thirteen million Americans have Type 2 diabetes. The individuals most at risk for Type 2 diabetes are usually overweight, over forty years old, and have a family history of diabetes. Type 2 patients represent about 90% of diabetes patients. Type 1 accounts for only about 5 to 10% of diabetes cases.
Causes of Diabetes
The causes of both Type 1 and Type 2 diabetes are unknown, but a family history of the disease increases the risk for both types, leading researchers to believe there is a genetic component. Some scientists believe that a flaw in the body's immune system may be a factor in Type 1 diabetes. Poor cardiovascular fitness is another risk factor for developing diabetes.
Mutations in several genes probably contribute to the origin and onset of Type 1 diabetes. For example, an insulin-dependent diabetes mellitus (IDDM1) site on chromosome 6 may harbor at least one susceptibility gene for Type 1 diabetes. The role of this mutation in increasing susceptibility is not yet known; however, since chromosome 6 also contains genes for antigens (the molecules that normally tell the immune system not to attack itself), there may be some interaction between immunity and diabetes. In Type 1 diabetes the body's immune system mounts an immunological assault on its own insulin and the pancreatic cells that manufacture it. Some ten sites in the human genome, including a gene at the locus IDDM2 on chromosome 11 and the gene for glucokinase, an enzyme that is crucial for glucose metabolism, on chromosome 7, appear to increase susceptibility to Type 1 diabetes.
In noninsulin-dependent diabetes, heredity may be a factor, but since the pancreas continues to produce insulin, the disease is considered a problem of insulin resistance, in which the body is not using the hormone efficiently. In people prone to Type 2 diabetes, being overweight can set off the disease because excess fat prevents insulin from working correctly. Maintaining a healthy weight and keeping physically fit can usually prevent noninsulin-dependent diabetes. To date, insulin-dependent diabetes (Type 1) cannot be prevented.
Blacks are somewhat more likely to develop Type 2 diabetes than whites, while Hispanic Americans are much more likely to develop this type of the disease than the general population. Diabetes is also prevalent among many Native Americans. The Pima Indians of southern Arizona, for example, have the highest incidence of Type 2 diabetes in the world (50% of those over age thirty-five).
Complications of Diabetes
Because diabetes deprives body cells of the glucose needed to function properly, several complications can develop to further threaten the lives of victims. The healing process of the body is slowed or impaired and there is increased risk of infection. Complications of diabetes include higher risk and rates of heart disease; circulatory problems, especially in the legs, often severe enough to require surgery or even amputation; diabetic retinopathy, a condition that can cause blindness; kidney disease that may require dialysis; dental problems; and problems of pregnancy.
Failure to follow the proper diet can be particularly dangerous to those who suffer from Type 1 diabetes. People who pay close attention to the roles of diet, exercise, weight management, and pharmacological control (proper use of insulin and other medication) to manage their disease suffer the fewest complications.