Diabetes is the Greek term for "passing through," a phrase used to describe multiple diseases characterized by excessive urination. There are multiple forms of diabetes. The most frequently described is diabetes mellitus, a chronic disorder involving the body's use of blood glucose (blood sugar) and the synthesis, or utility, of the hormone insulin. However, not all forms of diabetes involve glucose or insulin.
Diabetes is a term used to describe multiple distinctive disorders that have the symptom of excessive urination in common. Although there are multiple forms of diabetes, the most common form is diabetes mellitus.
Diabetes mellitus is a chronic disorder of carbohydrate (sugar) metabolism. The word "mellitus" is Latin for "honey." Diabetes mellitus is characterized by abnormal, excessive levels of the sugar glucose in the blood, which is consequently passed through the urine. Most people always have some glucose in the blood to be used by cells for energy. Blood glucose originates from food ingested, the liver, and muscle cells. However, an excessive amount of glucose chronically present in the blood causes a variety of serious health complications.
Diabetics have excessive blood glucose because of a deficiency in the production or utilization of the hormone insulin. Insulin is made by the beta cells of the pancreas in response to the elevated glucose in the blood after a meal. Insulin binds to receptors on the body's cells to allow the passage of glucose into the cell as an energy source. Insulin stimulates cells to remove glucose from the blood, stimulates the liver to metabolize glucose, and thus causes the blood sugar level to return to normal. Diabetics have either a deficiency of insulin or defective insulin receptor binding. As a result, the cells of the body are unable to receive the glucose energy and are essentially starved, despite the energy source present in the blood. Because glucose is not entering the cells, it remains in the blood causing high blood sugar, or hyperglycemia. Chronic diabetes mellitus can lead to serious problems with the eyes, kidneys, nervous system, gums, and teeth. One of the most serious complications caused by diabetes is heart disease. Diabetics are more than twice as likely to develop cardiac disease or a stroke. The risk for diabetics equals that of an individual with a history of heart attacks. The use of cigarettes greatly increases the risk for vascular disease, nerve damage, and limb amputation.
Diabetes mellitus is divided into three main subtypes known as type I diabetes, type II diabetes, and gestational diabetes. Individuals can also develop a condition known as pre-diabetes that may develop into type II diabetes.
Type I diabetes was formerly called juvenile diabetes because it is usually first identified in children or young adults. It was also known as brittle diabetes and insulin-dependent diabetes mellitus (IDDM). Type I diabetes is an autoimmune condition in which the body's immune system has attacked and destroyed the beta cells of the pancreas. As a result there is a shortage of insulin, and glucose cannot enter the cells. Bodily processes involving the storage of glucose as energy and the utilization of glucose are adversely affected. The body is essentially starved of the energy it needs for normal function.
Type II diabetes was formerly called adult-onset diabetes because it usually develops in people over the age of 40 years. However, individuals can develop type II diabetes at any age. Also known as non-insulin-dependent diabetes, type II diabetes is the most common form. Type II diabetes is a condition in which the body's cells become insulin resistant and do not properly utilize the insulin being synthesized and secreted by the pancreas. In the beginning stages, the pancreas increases insulin production in response to the increased demand. However, as the disease progresses, the pancreas loses the ability to secrete sufficient insulin in response to meals.
The third subtype of diabetes mellitus is gestational diabetes. This is a form of glucose intolerance that may develop during the late stages of pregnancy. Pregnancy hormones or an insulin deficiency may cause gestational diabetes. During pregnancy, gestational diabetes requires treatment to normalize maternal blood glucose levels and avoid complications in the infant. Gestational diabetes usually disappears after the infant is born. However, females who have had gestational diabetes are more likely to develop type II diabetes in their later years.
Pre-diabetes is a condition in which blood glucose levels are abnormally elevated, but not enough for a diagnosis of diabetes. This term is used to distinguish individuals who are at increased risk of developing diabetes type II. Individuals with pre-diabetes have impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both. IFG is a condition in which the fasting blood sugar level is elevated to a level between 100 and 125 mg/dL after an overnight fast, a value that is not high enough to be classified as diabetes. IGT is a condition in which the blood sugar level is elevated to between 140 and 199 mg/dL after a two-hour oral glucose tolerance test, a value that is not high enough to be classified as diabetes. Those individuals with pre-diabetes are at increased risk for developing type II diabetes, cardiac disease, and stroke. The risk of progressing into type II diabetes can be significantly lowered with moderate weight loss and physical activity.
Diabetes insipidus is caused when the pituitary gland does not produce enough antidiuretic hormone (ADH), which is responsible for water reabsorption in the kidney. Without sufficient ADH, an abnormal amount of water is secreted in the urine. This results in excessive urination, thirst, weakness, and dry skin. In many cases, the cause of diabetes insipidus is unknown but may involve damage to the pituitary gland by head trauma or a tumor. In some cases, it is treatable with ADH replacement therapy.
Diabetes bronze is a rare disease of iron metabolism that occurs in conjunction with diabetes mellitus and cardiac failure. It usually develops after 40 years. Diabetes bronze is characterized by the usual symptoms of diabetes mellitus with the addition of an enlarged liver and hyperpigmentation of the skin to a bronze color. It occurs 10 times as frequently in males than in females.
Type I and type II diabetes mellitus have different causes, yet both have genetic components. A combination of inheriting a predisposition to diabetes and environmental trigger factors may make the biggest contribution to the development of the disease. A genetic predisposition contributes to, but does not automatically result, in diabetes. Studies of identical twins show that when one twin has type I diabetes mellitus, the other develops the disease about 50% of the time. When one twin has type II diabetes, the other develops the disease about 75% of the time.
Type I diabetes is an autoimmune disorder in which the immune system attacks the insulin-secreting pancreatic beta cells. The onset of type I diabetes is attributed to both inherited risk and external triggers, such as improper diet or an infection. Approximately 18 regions of the genome have been linked with risk for diabetes type I. These regions may each contain several genes that have abnormal variations in some diabetics. They are labeled IDDM1 to IDDM18.
The region, or locus, most well studied is IDDM1. IDDM1 contains genes that encode immune response proteins called the HLA genes. Variations in HLA genes are one of multiple important genetic risk factors. Normal HLA genes encode for proteins called major histocompatibility complex (MHC), which assemble on the cell surface, are viewed by the immune system as "self," and therefore are not attacked. When there are variations in the HLA genes, they encode for variable MHC proteins expressed on the cell surface. The pancreatic beta cells of some diabetics have variable MHC proteins that the immune system does not recognize as self, and attacks as it would a virus or bacteria. The IDDM1 gene locus contains these variations in HLA genes that cause the pancreatic beta cells to be attacked and destroyed by the immune system.
The inheritance of particular HLA gene variations can account for more than 50% of the genetic risk of developing type I diabetes. The genes most strongly linked with diabetes are called HLA-DR, HLA-DQ, and HLA-DP. Half of the general population inherits a copy, called an allele, of the HLA-DR gene called DR3 or DR4. Less than 3% of the general population has both alleles. However, 95% of Caucasians with type I diabetes possesses at least one allele of DR3 or DR4. Individuals with both alleles are at the highest risk of developing type I diabetes mellitus. Conversely, the HLA-DR2 allele has protective effect and lowers the risk of developing diabetes.
As seen with the DR gene, specific alleles of the DQ gene are risk factors for developing type I diabetes, and specific alleles are protective. There is a tendency for individuals who inherit DR3 or DR4 to inherit a variant of DQ that increases their genetic risk of developing type I diabetes. The protective DR and DQ alleles also tend to be inherited together. These combination tendencies are not absolute, a phenomenon known as linkage disequilibrium. The IDDM1 locus contains many diabetes susceptibility genes that exhibit linkage disequilibrium, making it difficult to research the effects of any one gene on diabetes susceptibility.
The IDDM2 locus contains the insulin gene (INS) that is located on chromosome 11. Mutations of INS cause a rare form of diabetes that is similar to MODY. Other variations of the insulin gene may contribute to susceptibility to type I and II diabetes. The IDDM2 locus contributes about 10% toward type I diabetes susceptibility incidence. The type I diabetes risk associated area of this locus is localized to a region flanking the insulin gene that contains a short sequence of DNA that is repeated many times. The repeated sequences follow one behind the other (in tandem) and the number of repeats is variable between individuals, an event called a variable number tandem repeat (VNTR). There are three classes of VNTR in the insulin gene.
Class I has alleles that range 26–63 repeat units, class II has alleles with approximately 80 repeat units, and class III has alleles ranging 141–209 repeat units. In Caucasians, who have the highest rate of type I diabetes, the class-I VNTRs are most common. Class I alleles are responsible for 70% of the VNTR alleles, with nearly all the other alleles being class III. The short class I alleles are associated with a higher risk of developing type I diabetes, whereas the longer class III alleles are protective. The presence of at least one class III allele is associated with a threefold reduction in the risk of type I diabetes. Class III VNTR alleles are associated with higher levels of insulin in the thymus. The thymus gland has an important role in training the immune system to not attack the body's own cells. Immature immune cells called T cells are presented with chains of amino acids, such as insulin, to recognize as self. Any T cells that form a response to them, to attack them, are deleted to prevent autoimmunity. Because the longer VNTRs cause more insulin to be produced in the thymus, the detection and deletion of autoreactive T cells that would attack the body's cells may be more efficient. The resulting improved immune tolerance to insulin would lessen the risk of a future onset of type I diabetes caused by anti-insulin immune responses.
There is conflicting evidence for the role of INS in predisposition to type II diabetes. Certain mutations in INS can result in mutant insulin that results in rare forms of diabetes. One type of mutant insulin, called Chicago insulin, has been found in individuals who have a rare form of diabetes that resembles MODY. This form of diabetes is caused by a single gene mutation and is inherited in an autosomal dominant fashion. The INSR gene encodes the receptor for insulin. Mutations of the insulin receptor can also cause rare forms of diabetes and may play a role in susceptibility to type II diabetes. However, most diabetics have a normal sequence of the insulin receptor, indicating that if insulin receptor mutations contribute to the development of type II diabetes, they will be present only in a minor fraction of the diabetic population.
In determining the risk of developing type II diabetes mellitus, environmental factors such as diet and exercise play an important role. The majority of individuals with type II diabetes are either overweight or obese. Inherited factors are also keys to the development of type II diabetes. However, as of 2004 the multiple genes involved remained poorly defined. Genes that have been implicated may have only subtle variations that are extremely common, known as single nucleotide polymorphisms (SNPs). It is very difficult to link common gene variations with an increased risk of developing diabetes. Many of the links that have been found seem to be important in only select ethnic or geographical populations.
Calpain 10 (CAPN10) is one such gene that maps to chromosome 2. CAPN10 is a calcium-activated enzyme that breaks down proteins. SNPs in part of the CAPN10 gene are associated with a threefold increased risk of type II diabetes in Mexican Americans. It is thought that these genetic variants of CAPN10 may alter pancreatic beta cell survival, insulin production, insulin action, and liver glucose production. CAPN10 may also be involved in development of type II diabetes in Chinese populations. However, in European, Japanese, and Samoan populations, CAPN10 does not appear to play an important role.
The HFN4A gene encodes a transcription factor that is found in the liver and pancreas. HNF4A maps to a region of chromosome 20 that is linked with type II diabetes. HNF4A mutations cause a rare form of autosomal dominant diabetes. The HNF4A gene is now also being researched for involvement in predisposition to type II diabetes. It is thought that pancreatic beta cells are responsive to the amount of HNF4A present to regulate insulin production. SNPs in HNF4A have an impact on pancreatic beta cell function, increasing or decreasing insulin secretion. In the British population, individuals with SNPs that cause increased insulin secretion capacity have a reduced risk for diabetes. In the Ashkenazi Jewish population and Finnish population, four SNPs near the HNF4A gene have been identified as associated with type II diabetes via an unknown mechanism that may cause pancreatic beta cell malfunction.
In 2004, research began on various other genes that are candidates for type II diabetes predisposition in specific populations, many of which reside on various IDDM loci. The ABCC8 gene encodes the receptor for sulfonylurea. Sulfonylureas are a class of drug used to lower blood glucose levels in type II diabetics by inter-acting with the sulfonylurea receptor of pancreatic beta cells and stimulating insulin release. Genetic variations of ABCC8 may impair the release of insulin in some diabetics. The GCGR gene encodes the hormone glucagon, which regulates glucose levels. A mutation in GCGR has been associated with type II diabetes in the French and Sardinian population. The GCK gene encodes for the enzyme glucokinase, which speeds up glucose metabolism and acts as a glucose detector in pancreatic beta cells. Mutant glucokinase causes a rare form of diabetes and may also play a role in type II diabetes in some populations. Mutations known to activate glucokinase are all clustered in one area of the glucokinase structure that is called the allosteric activator site. These mutations cause an increase in insulin release. Research is being performed to discover pharmacological agents that act as allosteric activators to increase glucokinase activity, increase the release of insulin, and can be used in the treatment of diabetes. Because glucokinase activators also stimulate liver glucose metabolism, they would be doubly effective in reducing the blood sugar of diabetics. The GLUT2 gene encodes a glucose transporter which controls the entry of glucose into pancreatic beta cells and detects blood glucose. Mutations of GLUT2 cause a rare genetic syndrome that disturbs blood glucose control. Common variants of GLUT2 may also be linked with type II diabetes. The KCNJ11 gene encodes a potassium ion channel on the surface of pancreatic beta cells. Closure of potassium channels in these cells triggers insulin release. Pharmacological agents that close the channels are used in the treatment of diabetes.
Variations in KCNJ11 have been linked to both increased and decreased insulin release. A controlled study done in non-diabetic adults with a SNP in KCNJ11 demonstrated that the variation was associated with impaired insulin release in response to glucose and increased body mass index (BMI). Lipoprotein lipase (LPL) is an enzyme that breaks down triglycerides. LPL is functionally impaired or present at low levels in many type II diabetics. Evidence suggests that insulin may help regulate LPL synthesis. A common complication of type II diabetes is protein excreted in the urine because of chronic inflammation and kidney damage. There is a correlation between the severity of this condition and genetic variation in LPL. SNPs in the LPL gene are associated with insulin resistance in Mexican Americans. The same variation is associated with coronary artery disease, and may provide some of the link between diabetes and atherosclerosis.
An important diabetes risk factor and drug target is peroxisome proliferator activated receptor gamma (PPARc). This protein is a transcription factor that regulates fat cell development. Diabetics are prescribed drugs that activate PPARc to increase insulin sensitivity and lower blood sugar. Variations in PPARc influence the risk of developing obesity and type II diabetes. A common variation at position 12 confers a small risk of developing obesity of about 1.3% increase. For the individual, this 1.3% is a small increase of risk, but 75% of the population has this variation, which translates into a large impact on the prevalence of diabetes. The Pima Indians of Arizona, a population known for type II diabetes incidence, contain several SNPs in the gene for PPARc. There are other SNPs in the gene for PPARc that confer a degree of protection against insulin resistance and obesity. Mutations in some of these genes may also lead to a rare form of diabetes known as MODY (maturity-onset diabetes of the young). MODY is inherited in an autosomal dominant fashion. It is similar to non-insulin dependent diabetes, but develops in individuals before the age of 25.
Environmental triggers for type I diabetes are varied. Type I diabetes develops more often in cold climates than warm climates. Type I diabetes is less common in individuals who were breastfed and those whose first solid foods were at later ages. A family history of type II diabetes is only a strong risk factor for individuals living a western lifestyle of high fat diets with little exercise. Individuals who live in areas that do not have westernized lifestyles tend not to develop type II diabetes no matter how high their genetic risk. Obesity is a strong risk factor for type II diabetes; the highest environmental risk is correlated with obesity at early age or for extended periods of time. Women who develop gestational diabetes are likely to have a maternal family history of type II diabetes. The environmental factors that predispose to gestational diabetes are older age and higher weight. The ethnic group in the United States with the highest risk for type I diabetes is Caucasian. The ethnic groups in the United States with the highest risk for type II diabetes are African Americans, Mexican Americans, and Pima Indians.
According to the American Diabetes Association, the number of individuals with diabetes in the United States in the year 2002 reached 6.3% of the population, or 18.2 million. This statistic included 210,000 individuals under the age of 20. The risk for death among individuals with diabetes is approximately two times that of non-diabetics. In 2002 research, cardiac disease and stroke were determined to be the leading cause of diabetes-related mortality, responsible for 65% of deaths. Diabetic adults have two to four times increased risk for both cardiac disease and stroke than non-diabetics. Approximately 73% of adult diabetics have elevated blood pressure or use prescription medication for hypertension. The leading cause of new cases of adult blindness from 20–74 years of age is diabetic retinopathy. Approximately 60–70% of diabetics have some degree of nervous system damage called neuropathy. Severe forms of diabetic neuropathy account for more than 60% of non-traumatic lower-limb amputations in the United States.
Preexisting diabetes that is unsuccessfully controlled before conception and during the first trimester of pregnancy can result in major birth defects in 5–10% of pregnancies and spontaneous abortions in 15–20% of pregnancies. If diabetes is unsuccessfully controlled during the second and third trimesters of pregnancy, it can cause high infant birth weight that poses a risk to both mother and child. Gestational diabetes occurs most frequently in African-American, Hispanic or Latino-American, and Native American populations. It is most common among obese women with a family history of diabetes. Women who have gestational diabetes have a 20–50% chance of developing type II diabetes within 5–10 years.
Type II diabetes is associated with obesity, family history of diabetes, prior history of gestational diabetes, impaired glucose tolerance, physical inactivity, older age, and specific ethnicities. According to the Surgeon General, gaining between 11–18 lbs (4.9–8 kgs) above normal weight doubles the risk of developing type II diabetes. Type II diabetes is increasingly diagnosed in children and adolescents, and is most common in females. African-American, Hispanic or Latino-American, Native American, and some Asian-American, native Hawaiian, or other Pacific Islander populations are particularly at high risk for type II diabetes.
By 2002, 8.4% of non-Hispanic Caucasians (12.5 million) over 20 years of age had diabetes. Regional studies done in 2002 indicated that type II diabetes is becoming more common among Native American, African-American, and Hispanic and Latino children and adolescents. Approximately 11.4% of non-Hispanic blacks (2.7 million) over 20 years of age had diabetes. Generally, non-Hispanic blacks are 1.6 times more likely to develop diabetes than non-Hispanic Caucasians. Approximately 8.2% of Hispanic or Latino Americans (2 million) over 20 years of age had diabetes. Generally, Hispanic or Latino Americans are 1.5 times more likely to have diabetes than non-Hispanic Caucasians. Mexican Americans, the largest Hispanic or Latino subgroup, are more than twice as likely to have diabetes than non-Hispanic Caucasians. Correspondingly, residents of Puerto Rico are 1.8 times more likely to be diagnosed with diabetes than non-Hispanic Caucasians in the United States. Approximately 14.5% of Native Americans and Alaskan natives (107,775) who receive care from the Indian Health Service (IHS) over 20 years of age had diabetes. Within this ethnic group, diabetes is least common among Alaskan natives (6.8%) and most common among Native Americans of the southeastern United States (27%). However, Native Americans and Alaska natives generally have 2.2 times increased risk of developing diabetes than non-Hispanic Caucasians. Native Hawaiians, Japanese, and Filipino residents of Hawaii had approximately two times increased risk to be diagnosed with diabetes than Caucasian residents of Hawaii.
Type I diabetes accounts for 5–10% of diabetes cases, and affects approximately one in every 400–500 children and adolescents. Type II diabetes accounts for 90–95% of all diabetes. This form of diabetes may remain undiagnosed for many years. Increased awareness has led to a rapid rise in the number of cases diagnosed each year, in what has been described as epidemic proportions in the United States. In 1990, 4.9% of the American population was diagnosed with diabetes. In 2001, this proportion increased to 7.9%. In the year 2002, the NIH estimated that diabetes costs more than $130 billion in total health care and was the fifth leading cause of death. According to the CDC, from the year 1980 through 2002, the proportion of diabetic Americans increased from 5.8 million to 13.3 million individuals. Estimates revealed that of the children with birth year 2000, one in three will develop diabetes over their lifetime. According to the CDC, more than 1.3 million adults between 18 and 79 years of age were diagnosed as new cases of diabetes in 2003. The CDC estimates that from 1997 to the year 2003, the number of new cases of diagnosed diabetes increased by 52%. Diabetes is predicted to become one of the most common diseases in the world within decades, affecting at least half a billion individuals.
Type I diabetes may cause the sudden onset of any of the following symptoms:
- increased thirst, especially for sweet beverages
- increased urination
- weight loss, despite increased appetite
- nausea or vomiting
- abdominal pain
- absence of menstruation
Type II diabetes may proceed for long periods of time with no symptoms. When diabetes is present, symptoms include the following:
- increased thirst, especially for sweet beverages
- increased urination
- increased appetite
- blurred vision
- frequent or slow-healing infections (including urinary tract, vaginal, skin)
- dry, itchy skin
- tingling or numbness in hands or feet
- erectile dysfunction in men
Diabetes mellitus impacts many organ systems and can result in many complications. Diabetic ketoacidosis (DKA) is a complication of diabetes caused by the buildup of byproducts of fat metabolism called ketones. Ketone buildup occurs when glucose is not available as a fuel source. Diabetics have a deficiency of the insulin hormone used to metabolize glucose for energy. Because glucose is not being made available for cells to use as energy, body fat is alternatively metabolized. The byproducts of fat metabolism are ketones. The ketones accumulate in the blood and so become present in the urine. DKA develops when ketones are in high enough amounts to cause the blood to acidify. In response, the liver begins releasing glucose to use as an energy source instead of fatty acids. Because the cells cannot take in this glucose in the absence of insulin, it only further elevates the blood glucose level. DKA may be the first symptom that leads to the initial diagnosis of type I diabetes. It may also be a sign that a diagnosed type I diabetic is developing a need for increased insulin. Type I diabetics are more prone to the development of DKA than type II diabetics. In a type I diabetic, DKA can result from infection, trauma, heart attack, or surgery. Type II diabetics usually develop ketoacidosis incidentally under conditions of severe stress. Recurrent episodes of DKA in type II diabetics are usually the result of poor compliance with treatment or diet.
The symptoms of DKA may include the following:
- fruity breath odor
- appetite loss, nausea, or vomiting
- rapid deep breathing
- difficulty breathing, especially when lying down
- decreased consciousness
- mental stupor that may progress to coma
- muscular stiffness or aching
- low blood pressure
Diabetics may endure periods of hypoglycemia if their blood sugar is unsuccessfully controlled or if they imbibe even small amounts of alcohol. Hypoglycemia is a low level of blood glucose that occurs when the balance between insulin, food intake, and physical exertion is disturbed. Symptoms of mild hypoglycemia include hunger, sweating, anxiety, and increased heart rate. Severe hypoglycemia can lead to a confused mental state, slurred speech, weakness, lack of coordination, dizziness, drowsiness, and loss of consciousness. The loss of consciousness due to low levels of blood sugar is called a hypoglycemic coma.
Diabetics are prone to infections from even simple lacerations. Damage to the peripheral nervous system, called diabetic peripheral neuropathy, may result in decreased blood flow and loss of sensation to the limbs. When there is loss of sensation to the feet, an infection developing from a laceration may go unnoticed and therefore not be properly cared for. Diabetics also have decreased immune defenses with which to fight infection. Because of lack of peripheral sensation, deficient oxygen supply from decreased blood flow, and reduced immune defense, diabetics are prone to developing peripheral gangrene. Small cuts with infections can rapidly progress to death of the tissue, which may require amputation of the affected limb to preserve the life of the patient. Gangrene is responsible for many limb amputations in diabetics. Diabetic individuals are advised to keep their feet clean and dry, and to thoroughly inspect daily for any sign of injury or infection.
Poorly controlled blood sugar also predisposes diabetics to fungal infections of the skin, nails, female genital tract, and urinary tract. Diabetic nephropathy is kidney disease that may occur early in diabetes. Diabetics tend to have severe urinary tract infections and are prone to kidney damage as a result. Diabetics also have an increased vulnerability to kidney damage from high blood pressure. Late-stage kidney disease may display symptoms that result from excessive protein in the urine. These symptoms include swelling around the eyes in the morning, swelling of the legs, unintentional weight gain from fluid accumulation, poor appetite, fatigue, headache, and frequent hiccups.
Diabetic retinopathy develops in 80% of diabetics after 15 years with the disease. Diabetic retinopathy is damage to capillary blood vessels that nourish the retina of the eye due to the effects of poorly controlled blood
sugar. Signs of diabetic retinopathy include decreased visual acuity and floating spots within the field of vision. Diabetics may also develop cataracts, which are clouding of the lens of the eye that develop slowly and painlessly with increasing visual difficulty. The signs of cataracts include cloudy vision and difficulty with night driving due to glare from bright lights. Initially, most diabetics experience only mild vision problems. However, both diabetic neuropathy and cataracts can progress into blindness. Diabetic retinopathy is a leading cause of legal blindness among adults in the United States. The best defense against severe vision loss is early detection and treatment via annual eye examinations, and steps to maintain control over blood sugar, blood pressure, and blood cholesterol.
Type II diabetes is diagnosed with the following blood tests:
- Fasting blood glucose test (FGT): positive diagnosis of diabetes or pre-diabetes requires values higher than 126 mg/dL after eight hours of fasting on two separate occasions.
- Random (non-fasting) blood glucose: values higher than 200 mg/dL, accompanied by increased thirst, urination, and fatigue, cause suspicion of diabetes that must be confirmed with a fasting blood glucose test.
- Oral glucose tolerance test (OGTT): positive diagnosis of diabetes or pre-diabetes requires values higher than 200 mg/dL two hours after consuming a glucose solution.
A positive diagnosis of diabetes requires positive results on any one of the three listed tests, with confirmation from a second positive test on a different day. The fasting plasma glucose test is preferred for diagnosing type I and type II diabetes, and pre-diabetes. This convenient test is most reliably performed in the morning after eight hours of fasting, on two separate occasions. FGT values from 70–99 mg/dL are considered normal. Fasting glucose levels of 100–125 mg/dL may indicate a form of pre-diabetes called impaired fasting glucose (IFG). Individuals with IFG have an increased probability of developing type II diabetes in the future. A fasting glucose level 126 mg/dL, in conjunction with a positive OGTT on a separate testing occasion, indicates diabetes.
The random (non-fasting) glucose test can be performed at any time of day, regardless of previous food intake. Diabetes is suspected when blood glucose levels above 200 mg/dL are present in combination with classic diabetic symptoms such as increased thirst and urination, and fatigue. Diagnosis of diabetes requires a positive fasting blood glucose test or oral glucose tolerance test to be performed on a different occasion.
The oral glucose tolerance test can be used to diagnose diabetes or pre-diabetes. The patient is required to fast for eight hours and then drink a solution containing 2.6 oz (75 g) of glucose dissolved in water. Blood glucose levels are then measured at separate points over a three-hour time interval. A value less than 140 mg/dL is considered normal. Values from 140–200 mg/dL may indicate pre-diabetes. A value over 200 mg/dL, in conjunction with a positive FGT on a separate testing occasion, indicates diabetes.
Gestational diabetes is diagnosed with the OGTT. Glucose levels are normally lower during pregnancy, so the threshold values for diagnosis are proportionally lower. The presence of two plasma glucose values meeting or exceeding any of the following levels results in a diagnosis of gestational diabetes: a fasting plasma glucose level of 95 mg/dL, a one-hour level of 180 mg/dL, a two-hour level of 155 mg/dL, or a three-hour level of 140 mg/dL. Some practices deem a 1.7 oz (50 g) glucose solution with one-hour testing to be acceptable.
The hemoglobin A1c (HbA1c) test is used primarily to monitor the quality of glucose control over several weeks. Controlled blood glucose helps to minimize the development of complications caused by chronically elevated glucose levels, such as progressive damage to body organs. The HbA1c test is an overall picture of the average amount of glucose in the blood over the previous few months. HbA1c is the term for glycosylated (glucose-carrying)
hemoglobin in red blood cells. It is a measurement of how successful the employed treatments are at controlling blood sugar values. The HbA1c test can determine how severe blood sugar fluctuations have been in newly diagnosed diabetics and indicate the need for treatment adjustments in the medication or diets of known diabetics. Physicians may perform HbA1c tests on a patient several times a year to verify that good control is being maintained. The HbA1c test will not reflect temporary, acute fluctuations in blood glucose. A 1% change in HbA1c reflects a fluctuation of approximately 30 mg/dL in average blood glucose. An HbA1c value of 6% corresponds to an average blood glucose value of 135 mg/dL, while an HbA1c of 9% corresponds to an average blood glucose value of 240 mg/dL. The closer the HbA1c can be kept to 5% or 6%, the better diabetic control. Risk of diabetic complications increases with increased values of HbA1c.
A urinalysis followed by a blood test for ketones and pH is used in diagnosing ketoacidosis. Type I diabetes may also require a test for insulin level to determine whether it is very low or absent. A test for C-peptide levels, a byproduct of insulin production, is also often performed.
After a diagnosis of type I diabetes, the immediate goals of treatment are to control blood glucose levels and control diabetic ketoacidosis, if present. Type I diabetics often have a sudden onset of severe symptoms that may require hospitalization. The ongoing goals of treatment are to prolong life, reduce symptoms, and prevent diabetes-related complications. Medication, education, weight control, exercise, foot care, and self-testing of blood glucose levels are key to a good prognosis.
Insulin lowers blood sugar by allowing it to leave the blood and enter the cells to be used as energy. Type I diabetics are insulin deficient and so must take insulin every day. Insulin is either injected under the skin at set times using a syringe, or administered by an infusion pump that delivers the insulin continuously. Insulin is not available as an oral medication. There are different types of insulin that vary in how quickly they work and the duration of their effect. More than one type of insulin is sometimes mixed together in an injection. Injections are usually self-administered from one to three times daily. Type I diabetes requires that food intake is balanced by insulin intake to prevent extreme fluctuations in blood glucose.
In March of 2005, the FDA approved Symlin, the first non-insulin drug for the treatment of adult type I diabetes. Symlin is intended as an addition to insulin therapy for three hours after meals when blood glucose control is not tight enough on insulin alone. Symlin is injectable and can be used to augment treatment of both type I and type II diabetes. Appropriate use of Symlin involves close monitoring by a physician to prevent hypoglycemic attacks. However, the addition of Symlin to the therapeutic environment is hoped to result in much tighter overall control in diabetics for whom current therapies are inadequate.
After a diagnosis of type II diabetes, the immediate goals are to eliminate symptoms and stabilize blood glucose levels. The ongoing goals are to prevent complications and prolong life. The primary treatment for type II diabetes is physical activity, weight control, and diet. Non-insulin oral medication is sometimes indicated to assist in lowering blood sugar when diet and exercise are not enough. These oral medications are effective in type II diabetics, but not type I diabetics.
There are multiple classes of medication available for treatment of type II diabetes. Oral sulfonylureas trigger the pancreas to increase insulin production. Biguanides (metformin) cause a decrease in liver glucose production to bring down blood glucose levels, while alpha-glucosidase inhibitors (acarbose) decrease the absorption of carbohydrates from the digestive tract, thereby lowering blood glucose levels after meals. Thiazolidinediones (rosiglitazone) assist insulin functioning at the cell surface by increasing the responsiveness to insulin. Meglitinides (repaglinide and nateglinide) trigger the pancreas to increase the proportion of insulin released in response to blood glucose. Type II diabetics who continue to have poor blood glucose control despite lifestyle changes and the use of oral medicines may be prescribed insulin treatment. Type II diabetics are also sometimes prescribed insulin treatment if they cannot tolerate the oral medications. Insulin must be injected under the skin using a syringe and cannot be taken orally.
For all types of diabetes, planning balanced meals and dietary control requires education. Regular physical activity is important to help control blood glucose and weight. However, diabetics must take special precautions before engaging in intense physical activity that may alter blood glucose levels too rapidly. Blood glucose monitoring is done with specialized home kits called glucometers. A glucometer is a small device that provides an exact reading of blood glucose. A test strip is used to collect a small drop of blood obtained by pricking the finger with a small needle called a lancet. The test strip is placed in the meter and results are available within 30–45 seconds. Testing is done on a regular basis to monitor the balance between food intake, medication, and physical activity. Test results may are used to adjust meals, activity, and medications to keep blood glucose under control. Diabetes causes damage to the blood vessels and nervous system that often results in a loss of sensation to the foot. Foot injuries may go unnoticed until severe infection develops due to lack of care and a depressed immune system. A daily foot care routine involves washing and inspecting the feet, and generally keeping them clean and dry.
Hypoglycemia, or low blood glucose, can occur in diabetics when they use too much insulin, drink alcohol, exercise too much, or eat too little food. Symptoms of low blood sugar typically appear when blood glucose levels fall below 70. Treatment involves eating something with sugar such as fruit juice. Sugar intake should be continued until blood glucose control is achieved. Only after blood glucose has returned to normal should more substantial food be eaten. Severe hypoglycemia may require a shot of glucagon at a hospital emergency room.
Ketones can be monitored using a simple urine test available at pharmacies. Warning signs for ketoacidosis include flushed face, dry skin and mouth, nausea or vomiting, stomach pain, deep, rapid breathing, or fruity breath odor. If left untreated, the condition can worsen and lead to death. Treatment of DKA involves lowering the blood glucose level to normal, and to replacing fluids lost through excessive urination and vomiting. It is often possible to recognize the early warning signs of DKA and make appropriate corrections at home before the condition progresses. If severe DKA develops, hospitalization is often required to control the condition. immunizations. Diabetes education is critical to the treatment plan.
Diabetes is a chronic disease for which there is not yet a cure. The prognosis for diabetics is varied based on blood glucose control. Tight control of blood glucose can delay or even prevent the progression of complications and secondary illnesses caused by diabetes. However, complications may occur even when good control is achieved. Diabetics with high control of blood glucose and blood pressure significantly reduce their risk of death, stroke, and heart failure. A reduction of HbA1c by one percentage point can improve prognosis and cause a decrease in the risk for complications by 25%. Prognosis is greatly improved by a normal BMI, which uses individuals' height and weight to rate them as normal, overweight, or obese. A score of 18–24.9 is considered normal and improves the prognosis for diabetes. A score of 25–29.9 indicating overweight, or a score of 30 or more indicating obesity, results in a poorer prognosis. Diabetics have increased susceptibility to illness such as influenza. Once a diabetic has an illness, they often have a worse prognosis than non-diabetics. Smoking cigarettes drastically worsens the prognosis for diabetes, greatly increasing the risk of vascular complications, gangrene, and amputations.
Champe, P. C., and R. A. Harvey. Lippincott's Illustrated Review of Biochemistry, Second Edition. Philadelphia, PA: Lippincott, 1994.
Thompson & Thompson Genetics in Medicine, Sixth Edition. St. Louis, MO: Elsevier Science, 2004.
All About Diabetes. American Diabetes Association. (April 2, 2005.) <http://www.diabetes.org/genetics.jsp>.
Diabetes. MedlinePlus. (April 2, 2005.) <http://www.nlm.nih.gov/medlineplus/diabetes.html>.
Diabetes. National Diabetes Information Clearinghouse. (April 2, 2005.) <http://diabetes.niddk.nih.gov/dm/a-z.asp>.
Diabetes Data and Trends. Centers for Disease Control and Prevention. (April 2, 2005.) <http://www.cdc.gov/diabetes/statistics/index.htm>.
Diabetes Health Topics. Centers for Disease Control and Prevention. (April 2, 2005.) <http://www.cdc.gov/doc.do/id/0900f3ec802723eb>.
The Genetic Landscape of Diabetes. National Institutes of Health. (April 2, 2005.) <http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=diabetes.TOC&depth=1>.
American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. 800-DIABETES, (800) 342-2383. (April 2, 2005.) <http://www.diabetes.org>.
National Diabetes Education Program. (800) 438-5383. (April 2, 2005.) <http://www.cdc.gov/diabetes/ndep/index.htm>.
National Diabetes Information Clearinghouse. 1 Information Way, Bethesda, MD 20892-3560. (800) 860-8747. (April 2, 2005.) <http://diabetes.niddk.nih.gov/about/index.htm>.
Maria Basile, PhD
Diabetes mellitus is a condition that results when the pancreas produces little or no insulin, or when the cells of the body cannot use the insulin produced effectively. When insulin is absent or ineffective, the cells of the body cannot absorb glucose (sugar) from blood to provide the body with energy.
for searching the Internet and other reference sources
Melinda had just turned twelve and felt hungry all the time. Her stomach growled in class and her after-school snack no longer held her until dinner. No matter how many trips she made to the school water fountain, she was always thirsty. Even worse, she could not believe how often she needed to go to the bathroom. One of her teachers, after signing Melinda’s seventh bathroom pass for the day, suggested that Melinda ask her parents to take her to the doctor. She thought that Melinda might have diabetes, and she was right.
Diabetes is a group of related diseases characterized by elevated levels of glucose (sugar) in the blood. It is caused by the failure of the pancreas to produce sufficient insulin, or any insulin at all. It can also be caused by the failure of the body’s cells to make proper use of the insulin that is produced.
The pancreas, the site of insulin production, is a large gland near the stomach. It contains groups of cells that function like tiny factories, producing different hormones* at exactly the right time and in the right amount. These groups (or “islands”) of cells are called islet (EYE-let) cells.
- * hormones
- are chemicals that are produced by different glands in the body. Hormones are like the body’s ambassadors: they are created in one place but are sent through the body to have specific regulatory effects in different places.
One type of islet cell is called a beta (BAY-ta) cell. Beta cells are responsible for producing a hormone called insulin. The human body needs insulin to function, because insulin helps the body use food for energy.
When people eat, their bodies break food down and convert it into sugars and other fuels. The main fuel is a sugar called glucose (GLOO-kose). When it is in the blood, it is called “blood glucose” or sometimes “blood sugar.” Glucose provides the energy people need to carry out almost every task, from pumping blood to walking to reading a book. But glucose cannot get too far on its own—insulin must be there to allow it to pass into the body’s cells.
Insulin works like a key, “unlocking” the door to cells. When insulin production stops or slows down in the beta cell factory, the body’s cells cannot take in the glucose they need for energy. People with diabetes get glucose from their food, but no matter how much they eat, if the insulin “key” is absent or not working properly, their glucose fuel is “locked out” of the body’s cells.
More than fifteen million people in the United States have diabetes, but fewer than one million of those people (about 750,000) have the type that Melinda has. This type is known as Type 1 diabetes. It is also called immune-mediated diabetes or insulin-dependent diabetes mellitus (IDDM).
Type 1 diabetes is usually diagnosed before a person turns 19, and is therefore also referred to as “juvenile” diabetes. About 125,000 children and teenagers in the United States today have Type 1 diabetes. They make little or no insulin of their own, so they depend on injections of insulin to stay healthy. They also need to make lifestyle changes, such as when and what they eat.
The other fourteen-plus million Americans with diabetes have what is called Type 2 diabetes. Other names for this kind of diabetes include non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes. Type 2 diabetes occurs when the cells of the body do not respond to insulin the way they should. This type of diabetes usually affects people who are over 40 years old. Extra body fat often contributes to this condition and, many times, weight loss can help remedy it. A person with Type 2 diabetes is not necessarily dependent on insulin injections the way a person with Type 1 diabetes is. Type 2 diabetes can also be treated with pills in addition to a change in diet.
Type 1 diabetes
Type 1 diabetes is not contagious like a cold or chickenpox: people cannot catch it from one another. Nor do people get Type 1 diabetes suddenly. It usually takes months or years to develop in a person’s body. Despite what many people think, Type 1 diabetes isn’t caused by eating too many sweets.
Although scientists do not know exactly what causes Type 1 diabetes, they have enough evidence to suggest that there are at least a couple of different reasons why one person might develop it while another would not: genes and environmental triggers.
- Genes. People with Type 1 diabetes are born with certain genes for the illness, just as they are born with genes for blue eyes or brown eyes. Genes are something people inherit from their parents before they are born. In some families, the genes for Type 1 diabetes are passed from parents to more than one child; a sibling of someone with Type 1 diabetes has about a 5 percent chance of also developing it.
- Environmental triggers. Some people have Type 1 diabetes set in motion by an environmental trigger, like a virus. The trigger will make the person’s immune system attack and destroy the beta cells, with the result that insulin can no longer be produced. However, for an environmental trigger to have this effect, people probably have to have a genetic predisposition to it. Most people do not just suddenly develop diabetes because they get the flu.
Type 2 diabetes
Just as with Type 1 diabetes, people with Type 2 diabetes are not contagious. Two major factors seem to play a role in why people develop Type 2 diabetes: genes and obesity (or being overweight).
- Genes. Just as certain genes may mean that a person may be more likely to develop Type 1 diabetes, other genes play an important part in people who develop Type 2 diabetes.
- Obesity. Many people who have Type 2 diabetes are obese. Scientists think that this extra weight may impair the body’s ability to use insulin effectively.
When the body does not have adequate amounts of insulin, symptoms like Melinda’s result. Frequent urination is very common in a person with Type 1 diabetes. This happens because glucose cannot get into the body’s cells and builds up in the blood instead. Normally, the kidneys do not allow glucose to get into the urine. But in the case of diabetes, the high level of blood glucose spills into the urine, pulling extra water out of the body along with it.
Feeling very thirsty is also common, because the body needs to make up for all the liquid lost through urination. Feeling hungry and eating a lot are also common symptoms; the body is looking for a way to get the energy that it is missing. But even with all the extra eating, people with undiagnosed diabetes may lose weight, because their bodies start to use fat for energy instead of sugar. In the case of growing children and teenagers, the fact that they are not gaining weight at a time in their lives when they should be may be a sign that diabetes may be present.
These symptoms are common to both Type 1 and Type 2 diabetes, although usually less severe in the latter. Type 2 diabetes may sometimes present with other symptoms, such as repeated or hard-to-heal infections, blurred vision, and dry, itchy skin. But often these symptoms are quite mild, and due attention is not paid to them.
Diabetes at a Glance
|Type 1||insulin||babies to adults|
|Type 2||diet, exercise, pills; in some cases insulin||most common in overweight adults over 40, but increasing among children and young adults|
If a doctor suspects that a patient has diabetes, usually he or she will first do a urine test. The test is simple: it involves a small sample of the patient s urine and special strips of paper that are treated with a chemical to detect glucose. If the immersed strip shows that glucose is present, the doctor will want to confirm the test by checking the patient’s blood sugar with a blood test. If the doctor feels sure that there is too much glucose in the patient’s blood, further evaluation and testing will be done, and treatment will be started if the diagnosis of diabetes is confirmed.
Because people with Type 2 diabetes continue to make insulin that is functioning to a certain extent, they may develop symptoms over a period of months or years without facing immediate danger. They may
Two Millennia of Medicine
The ancient Greek physician Aretaeus (ar-e-TE-us) of Cappadocia (c. 81-c. 138) described diabetes as a “melting down of the flesh and limbs into urine.” Throughout history, many people with the disease died at an early age by wasting away, although the disease was probably not as prevalent in ancient times as it is now.
Treatments frequently involved dietary changes. Aretaeus recommended milks, cereals, and starches. In 1797, John Rollo recommended a meat diet high in proteins. These diets were not cures for diabetes, but they did allow people with diabetes to live longer than if they had remained on standard diets.
The first truly successful treatment for diabetes was finally made available in the 1920s when Frederick Banting, Charles Best, and John James Macleod first isolated insulin for use through therapeutic injections.
feel tired, worn out, or thirsty much of the time, without thinking that it could be diabetes. In many cases, Type 2 diabetes is actually discovered by accident, during a routine physical exam or screening blood or urine test.
Sports Stars with Type 1 Diabetes
These outstanding athletes were all diagnosed with Type 1 diabetes at an early age:
- Jackie Robinson Robinson was the baseball immortal who broke the color barrier in 1947. In his 10-year career with the Brooklyn Dodgers, Robinson was a batting champion, the League MVP, and a member of six championship teams. He was elected to the Hall of Fame in 1962, his first year of eligibility.
- Bobby Clarke The tenacious leader of hockey’s Philadelphia Flyers for 15 seasons, Bobby Clarke was first diagnosed with diabetes at the age of 15. Undeterred, he went on to win three Hart Trophies as league MVP.
- Wade Wilson An NFL quarterback for over 16 years, beginning in 1981, Wilson led the Minnesota Vikings to three playoffs and the 1987 NFC Championship game.
A person who has been diagnosed with Type 1 diabetes needs to do a number of things to function well. These include taking insulin, following a food plan, exercising, monitoring blood glucose levels, and taking urine tests. All of these things contribute toward achieving the major goal: keeping the amount of glucose in the blood as close to normal as possible, so the person with diabetes stays healthy and feels good, now and in the future.
People with Type 1 diabetes must get the correct amount of insulin into their blood. Different sources of insulin have been used to treat diabetes. Pork insulin is extracted from the pancreas of a pig, but human insulin does not come from the pancreas of a human. Instead, human insulin is synthetic. It is made in a laboratory, and is the type most commonly used to treat diabetes today.
Insulin comes in liquid form (dissolved in water) in a bottle and must be injected into the body. Unlike a lot of medications, insulin cannot be swallowed in pill form because the hormone insulin is a protein. Like other proteins, it would be digested and broken apart in the stomach, just like the protein contained in food.
Most people take insulin by using a needle to inject it into the layer of fat beneath the skin. The most common places where people take insulin are in their arms, legs, stomach, and hips—all places where people have some fat. The injection does not hurt very much, since the needle is very thin. Usually, a person needs to inject insulin this way two or more times a day, on a set schedule, coordinated with meals.
Some people with Type 1 diabetes use an insulin pump. It is about the same size as a beeper, with a small container filled with insulin. The insulin gets automatically “pumped” into the person’s body through a small tube attached to a needle inserted into the skin. The insulin is pumped in at a slow rate all the time, with an extra “boost” pumped in before meals to prepare the body for the incoming sugar.
However people with Type 1 diabetes take insulin, one thing stays constant: they must take insulin every single day to allow the body’s cells to take in and use glucose properly. They cannot take a break or decide to stop taking it, or they will become ill.
Proper nutrition is a very important part of staying healthy—for everyone—and especially for a person with Type 1 diabetes. Since food affects how much glucose is in the blood, people with Type 1 diabetes must pay careful attention to the food they eat, how much they eat, and when they eat it. In particular, since carbohydrates are the body’s main source of glucose, many people with diabetes estimate the amount of carbohydrates in each meal to determine if they are getting the right amount of sugar.
All that does not mean that the eating habits of someone with diabetes are so very different from other people. The food itself can be the same as that eaten by most people. But in most cases, their meal plans must be on some sort of schedule, include snacks, and limit sweets because of the large amount of sugar they contain.
Just like healthy eating, exercise is something that is important for everyone and especially for people with Type 1 diabetes. It was not too long ago that some doctors thought people with Type 1 diabetes should not exercise, but that opinion has changed. Exercise helps insulin work better to control the level of glucose in the blood. Exercise also helps keep people with diabetes at the right weight, and it helps maintain a healthy heart and blood vessels. In addition, exercise helps people feel good about themselves.
When people with Type 1 diabetes exercise, they use glucose at a faster-than-normal rate, so they must pay special attention to ensure that their blood glucose level does not drop too low. This may mean taking less insulin, eating more before exercise, or having snacks during and after exercise.
Blood glucose and urine testing
People who have Type 1 diabetes usually test their blood glucose three or more times a day. This involves pricking the finger with a tiny, sharp device to get a drop of blood. The blood drop is put on a chemical strip and inserted into a testing meter that “reads” the amount of sugar in the blood. The person then records the blood glucose numbers in a diary. This monitoring helps to determine if the level of glucose in the blood is where it should be and guides adjustment in the treatment plan.
Urine testing is another helpful form of monitoring. It is especially important when a person with Type 1 diabetes is sick (with the flu, for example). Any kind of physical stress, such as an infection, tends to interfere with the body’s cells taking in and using glucose properly. When this happens, the cells begin to break down fat for energy. A potentially harmful byproduct of this process is the production of ketones*. Urine testing is an effective means of determining if ketones are building up in the blood.
- * ketones
- (KEE-tones) are the chemicals produced when the body breaks down fat for energy. In large amounts, ketones are poisonous; as they build up in the blood, they become increasingly toxic.
Sometimes, even with insulin, proper nutrition, and exercise, it can be difficult to control diabetes completely. Blood glucose levels can become either too high or too low in some cases, and blood levels of ketones can rise to toxic levels.
If the level of glucose in the blood is too low, this is called hypoglycemia (hy-po-gly-SEE-mee-a). This can result when someone takes too much insulin, misses a meal or snack, or exercises too hard without taking special precautions. In its beginning stages, hypoglycemia can make someone weak, shaky, dizzy, and sweaty. A person with diabetes learns to be very aware of these warning signs and almost always takes action
to treat them, by drinking some juice or taking glucose tablets, before they become severe. If left untreated, a person may become disoriented, sleepy, or have a hard time talking. Eventually, he may become very confused and uncoordinated and, in extreme cases, go into a coma*. The treatment for an extreme case of hypoglycemia is to give the person sugar as soon as possible, by intravenous* injection if necessary.
- * coma
- is an unconscious state, like a very deep sleep. A person in a coma cannot be awakened, and cannot move, see, speak, or hear.
- * intravenous
- (in-tra-VEE-nus) means injected directly into the veins
Clinical trials are research projects undertaken by scientists, pharmaceutical companies, and government researchers to investigate whether medications and treatment plans are safe and effective.
To evaluate the effectiveness of careful self-management in reducing the long-term complications of diabetes, in 1983 the U.S. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) undertook a large ten-year study, called the Diabetes Control and Complications Trial (DCCT for short).
People with diabetes took part in the DCCT and followed instructions for testing their blood glucose three or four times a day, taking more frequent insulin injections or using an insulin pump, and following a healthy meal plan. The test results showed that the people who maintained near-normal blood glucose levels had fewer long-term complications, such as problems with their hearts, eyes, or kidneys. It proved that for a person with diabetes, paying close attention to small things on a daily basis has a big payoff later on.
Another problem that people with Type 1 diabetes can have is too much glucose in the blood, called hyperglycemia (hy-per-gly-SEE-mee-a). When there is too much sugar in the blood, it is often because the person has taken too little insulin, has eaten too much high-sugar food, or is ill with an infection or stressed for other reasons. Symptoms include very frequent urination, extreme thirst, weakness, and tiredness.
In uncontrolled diabetes, when the blood becomes too acidic because of high levels of ketones in it, the condition that results is called ketoacidosis (ke-to-a-si-DO-sis). A person in ketoacidosis may be nauseated or vomiting and breathing very deeply. If he does not get treatment, he will become dehydrated and go into a coma. Emergency treatment involves insulin and lots of fluids, usually by intravenous injection. Fortunately, ketoacidosis is almost always preventable in people whose diabetes has been diagnosed, and who take care to manage their diabetes properly.
People who have Type 2 diabetes are often able to treat their diabetes with dietary changes and a weight-control program, if needed. This consists of balancing a healthy combination of foods and exercise.
In some cases, people with Type 2 diabetes are treated with pills. These pills do not contain insulin, but they help the body to make more insulin or respond to insulin more normally. Sometimes, a person with Type 2 diabetes will need to take insulin injections, like a person with Type 1 diabetes.
There are many similarities in the treatments for Type 1 and Type 2 diabetes, but the main difference is the role of insulin. If a person with Type 2 diabetes forgets to take his insulin, he will not go into ketoacidosis. And while a doctor might say it is all right for a person with Type 2 diabetes to stop taking insulin completely and just take pills, this would not be possible for a person with Type 1 diabetes.
The U.S. and the World
Globally, there were approximately 135 million adults with diabetes in 1995. By the year 2025, that number is expected to rise to 300 million.
- By the year 2025, it is estimated that the number of person’s with diabetes will be over 57 million in India, 37 million in China, and 22 million in the United States.
- In 1997, there were more than 15 million people with diabetes in the U.S. Of those, more than 5 million had not been diagnosed.
- Over 90 percent of diabetes cases are Type 2 diabetes. While Type 1 (the type that affects most children and teenagers with diabetes) is most common in Americans of European descent, the prevalence of Type 2 diabetes is 2 to 4 times higher in Americans of African, Hispanic, and Asian heritage. The highest incidence of all is among Native Americans.
- In 1997, the average cost of health care for each American with diabetes was over $10,000 per year, compared to approximately $2,500 per year for Americans without diabetes.
Between taking insulin, following a meal plan, testing blood sugar levels, and the rest, living with Type 1 diabetes can sound like a big job—and it can be—especially in the beginning. Luckily, many people who have been diagnosed with Type 1 diabetes have an entire diabetes treatment team to help them along. This team usually includes a doctor, a diabetes nurse, a dietician, a psychologist, and a social worker. Ideally, the entire team works to become partners with the patient and the patient’s family, so that they can maintain as normal a life as possible.
People with diabetes can do almost everything that people without diabetes can. They can:
- go to school
- play sports
- spend time with friends
- eat food at parties
- do almost every kind of job
- go to college
- get married
A person with diabetes may have to eat an extra snack before competing in a track meet, or duck out of a party for a minute to take insulin, or have only a small bit of ice cream when everyone else is going for the Super Sundae. But people who control their diabetes lead normal lives. And women with diabetes who want to have babies can usually do so, with the support of their diabetes treatment team.
Both Type 1 and Type 2 diabetes can have negative long-term effects on a person’s health. These effects tend to develop very slowly and gradually. Because a person with diabetes may not process fat properly, there tends to be damage to the blood vessels in the body, which increases the chances for high blood pressure, heart attacks, and strokes. Diabetes can also have long-term effects on the eyes, because tiny blood vessels in the retina* become weakened. If these blood vessels burst, they can cause bleeding and scarring in the eye, or even blindness. The chance of nerve damage, and of developing kidney disease, is also increased in a person with diabetes. Finally, foot health can become an issue for people with diabetes: because the condition can affect circulation to the feet, small cuts or wounds can turn into serious infections without proper care.
- * retina
- is the back inner surface of the eyeball that plays a key role in vision. This surface contains millions of light-sensitive cells that change light into nerve signals that the brain can interpret.
People with diabetes can take steps to help prevent or lessen the effects of these long-term problems. Recent research has shown that blood sugar control is a key factor. It is very important for people with diabetes to have regular physical checkups, when a doctor can monitor blood pressure and foot health, check fat levels in the blood, and look for problems with the kidneys. Annual trips to the eye doctor are crucial for people with diabetes. If the ophthalmologist* discovers problems with the blood vessels in the retina, vision problems often can be prevented or lessened with laser surgery.
- * ophthalmologist
- is a medical doctor who specializes in treating diseases of the eye.
Medic Alert Tags
People with diabetes often wear metal tags or bracelets imprinted or inscribed with important medical information. In the event of an accident or diabetic coma, the information on the tag can alert medical personnel about the patient’s condition.
Some companies offer medical alert tags that have an identification number that is unique to the individual so that a doctor who doesn’t know the person can retrieve the patient’s medical history in the event of emergency.
While people with diabetes must depend on doctors and other medical professionals to help them, they can also do quite a bit to help themselves. Continued education about proper diabetes management is a key part of helping people with diabetes stay healthy.
Diabetes research is an active field. Much of the scientific work is concerned with insulin: how to get it into the body, or how to get the body to produce it on its own. Since insulin cannot be swallowed, researchers
Banting, Best, and the Dog With Diabetes
Two scientists and a dog may sound like characters in a movie, but it was just such a threesome who were involved in discovering insulin. Shortly after World War I had ended, a Canadian surgeon named Frederick Banting (1891–1941) became very interested in diabetes and how the pancreas functions in a person with diabetes. A neighborhood child had died from diabetes, and this helped pique Banting’s interest in making discoveries about the condition.
In his University of Toronto laboratory, assisted by a graduate student named Charles Best, Banting took out the pancreas glands of several dogs (which caused the dogs to develop diabetes), extracted their insulin, and began investigating the properties of insulin. Banting and Best discovered that insulin brought down the level of blood glucose in the dogs’ blood; the dogs who had their pancreas glands removed could now survive, as long as they had insulin injections. A famous photo was taken of the two scientists in 1921, and between them stands the very first dog with diabetes that was kept alive with insulin.
In 1923, Sir Frederick Banting and the Scottish scientist John James Macleod (1876–1935) were awarded the Nobel Prize for medicine and physiology for their discovery of insulin.
have been investigating other ways to get it into the bloodstream without an injection, such as eye drops, nasal sprays, and inhalers. They have also experimented with pancreas transplantation, as well as transplantation of the islet cells that make insulin. Until there is a cure for diabetes, however, people must live with it and control it using the information and equipment available to them now.
Greek Speak: A Diabetes Dictionary
Many English words come from Greek. These include many of the words used to describe diabetes, as well as the word “diabetes” itself.
Diabetes Greek for “passing through,” because Greek doctors noticed how much liquid people with diabetes drank, and how often they needed to urinate.
Mellitus Greek for “honey-like” or “sweet,” because it was noticed that the urine of people with diabetes smelled sweet, due to its high sugar content.
Insulin Greek for “island.” The groups of islet cells in the pancreas that are responsible for making insulin and other hormones look like tiny islands under a microscope.
Hypo Greek for “below,” and thus “too little.”
Hyper Greek for “above,” and thus “too much.”
Glyk Greek for “sugar.”
Emia Greek for “blood.”
Betschart, Jean, and Susan Thorn. In Control: A Guide for Teens with Diabetes. Minneapolis: Chronimed Publishing, 1995.
Chase, H. Peter. Understanding Insulin Dependent Diabetes. Denver: The Guild of the Children’s Diabetes Foundation, 1995. Also available online at the website for the Barbara Davis Center for Childhood Diabetes.
Silverstein, Alvin, Virginia B. Silverstein, and Robert A Silverstein. Diabetes. Springfield, New Jersey: Enslow Publishing, 1994.
Diabetes Forecast. A magazine published by the American Diabetes Association.
Diabetes Self-Management. A magazine published by R.A. Rapaport Publishing, Inc. Available online at
American Diabetes Association, 1660 Duke Street, Alexandria, VA 22314. The American Diabetes Association website offers trustworthy reviews of many other diabetes-related sites on the web.
Children With Diabetes. Produced by the Juvenile Diabetes Foundation, this site is an online community for children and young adults with Type I diabetes.
Juvenile Diabetes Foundation, 120 Watts Street, New York, NY 10005.
Information about Frederick Banting and Charles Best may be found at the website devoted to the work of Frederick Banting.
Starting in the second half of the twentieth century, the prevalence of non-insulin-dependent (type 2) diabetes increased substantially in many populations and ethnic groups, including African Americans, Native Americans, Mexicans Americans, and Pacific Islanders. Diabetes is a metabolic disorder characterized by an inability to regulate blood sugar. The increase in this disease is clearly related to shifts in diet and lifestyle. While some researchers have proposed that it is related to genetic factors, other researchers point to stressful and challenging life conditions resulting from poverty and social inequality.
More than 90 percent of all diabetics have type 2 diabetes. Unlike the more rare form of the disease, type 1 diabetes, people with type 2 diabetes produce insulin and therefore seldom need therapeutic insulin at the initial onset of the disease. Type 2 diabetes is considered a late-onset chronic disease and is associated with risk factors such as increased obesity, dietary fat intake, smoking, and low physical activity. Racism, stress, and socioeconomic status have also been implicated in the development of diabetes. Diabetes is diagnosed by measuring the percentage of red blood cells that are bound with glucose. There is no cure for diabetes, but the traditional treatment includes alterations in diet, exercise, and drug therapies to control glucose metabolism.
Prevalence rates follow a strikingly similar pattern in varied populations. For First Nations Canadian men and women, age-adjusted prevalence rates are 3.6 and 5.5 times higher, respectively, than among the general Canadian population. Among Indigenous Australians, the prevalence rates are almost four times higher than the rate for the non-Indigenous population. Researchers comparing age-adjusted prevalence rates for Nigerians and people of African origin living elsewhere found diabetes rates were
2.5 to 5 times higher for those living in the Caribbean and United Kingdom. In the United States, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) estimates that at least 8 to 10 percent of all Latinos, African Americans, and Native Americans aged twenty years or older have diabetes. The comparable prevalence rates for non-Hispanic whites is 4.8 percent.
According to the U.S. Centers for Disease Control and Prevention (CDC), diabetes is the seventh leading cause of death in the United States. The World Health Organization (WHO) has called diabetes an emerging epidemic, with more than 16 million people affected in the United States and millions more in the rapidly urbanizing Southern Hemisphere and China. According to the WHO, approximately 366 million people worldwide will have diabetes by 2025. The very similar epidemiological patterns that exist for U.S. minorities, First Nations Canadians, Indigenous Australians, peoples of the African diaspora, and peoples of the Pacific Islands strongly indicate that diabetes disproportionately affects subordinated groups around the world.
Type 2 diabetes (hereafter referred to simply as diabetes), like heart disease, hypertension, and asthma, is a complex disease because its putative risks lay in both environmental and biological domains. That is, diabetes is caused by an as yet unknown combination of factors such as lifestyle, diet, physical activity, and an array of physiological triggers. The relative overburden of diabetes on people whose social histories contain violent and radical disruptions of their lifeways has not resulted in any real agreement about its cause. Rather, diabetes has engendered competing etiological hypotheses. For simplicity, these three competing theories will be named the social conditions, the fetal origins, and the thrifty genotype hypothesis respectively.
Research into the social conditions that impact diabetogenesis has generated considerable evidence for the link between stress and glucose metabolic impairment. Life conditions such as experiences of racism, poverty, and job insecurity have all been associated with measured levels of elevated blood glucose. These findings clearly suggest that the epidemiological patterns of diabetes reflect sociocultural conditions in nonrandom ways. For example, the increased prevalence of diabetes within Native American, Latino, and African-American groups can be attributed to the differential experiences of social inequality these groups endure compared to nonwhite Hispanics. Similarly, the increasing rates of diabetes in geographic areas where human populations are rapidly moving to urban areas suggests that the disease may be an index of the stressors of rural-to-urban migration and lifeways disruptions resulting from the profound political and economic dislocations required for flexible labor markets.
Researchers looking for physiological causes of diabetes investigate conditions during fetal development as primarily responsible for the disease. This hypothesis, also called the thrifty phenotype hypothesis, the developmental hypothesis, or the fetal origins hypothesis, proposes that poor fetal conditions, such as those that cause low birth weight, impair the in-utero development of the glucose-insulin physiological systems. Research in a number of populations and animal studies suggests that the fetus adapts itself to its developmental environment as a preparatory response to postnatal life conditions. Because low birth weight is also associated with the deprivations often linked to social inequality, the fetal origins hypothesis implicates historical and contemporary systems of social stratification as causally linked to disease outcomes in groups with these experiences. Fetal origins research offers physiological evidence that social and environmental conditions related to social inequality can impact developmental gene expression and lead to impaired health in adult life.
The other dominant theory for the pronounced differences in the prevalence of diabetes, and perhaps the oldest, is the thrifty genotype hypothesis. Research into this hypothesis attempts to explain disparities in disease patterns between human groups as a function of evolutionary pressures. One of the oldest gene-based theories of chronic disease causation, the thrifty genotype hypothesis postulates the existence of an evolutionarily and advantageous genetic predisposition to the efficient metabolic storage and utilization of caloric energy— a predisposition rendered “maladaptive” by the contemporary widespread overabundance of food. The thrifty genotype hypothesis has enjoyed more than four decades of concerted research attention, coinciding with, and in many respects developing alongside, the molecular revolution.
In this model, disparities in diabetes between various ethnoracial groups are often attributed to the genetic triggering of the “thrifty genes” that are presumed to result from the transition to urban, sedentary lifestyles. The original proponent of the thrifty genotype hypothesis, geneticist James Neel (1915–2000), considered diabetes a condition of environmental origins. In his final statement on diabetes, Neel found “no support to the notion that high frequency of NIDDM [non-insulin-dependent diabetes mellitus] in reservation Amerindians might be due simply to an ethnic predisposition—rather, it must predominantly reflect lifestyle changes” (Neel 1999, p. S3). Still, the thrifty genotype model has widespread allegiance and fuels millions of dollars in research activity.
The technical, methodological, and conceptual premises of the gene-based hypothesis have engendered considerable ethical debates surrounding the use of socially labeled populations for studies of complex diseases like diabetes. Underlying these current debates are laudable goals of disease prevention and harm reduction for all persons, especially descendants of the formerly enslaved or colonized. Yet the persistence of these concerns, in and out of academe, signals a fundamentally sociocultural phenomenon that will not be resolved by attention to analytical considerations alone and will involve complex sociological and cultural factors.
First, owing to advances in genomic biology, genetics-based models of diabetes causation now have considerable advantages in competition for research attention. Researchers claim that finding genetic contributions to complex diseases is the first step to understanding physiology and subsequent drug interventions. In nations where public health infrastructures are already suffering from neglect, the policy impulse to advance a gene-based research that promises drug therapies for the most costly diseases is understandable. Yet while public health interventions to prevent tobacco use, require seat belts, provide prenatal care, and make vaccinations widely available have been proven to be cost effective, no such proof exists for gene-based research into complex diseases such as diabetes. Thus, there is reason to dispute the high investment in capital and human talent for scientific hypotheses that have little translatable application toward disease prevention and treatment.
Second, the use of genetic variation hypotheses to explain ethnoracial differences in complex diseases is a particular form of racialization, which is “a dialectical process by which meaning is attributed to particular biological features of human beings, as a result of which individuals may be assigned to a general category of persons that reproduces itself biologically” (Miles and Brown 2003, p. 102). In other words, racialization is the attribution of innate fixed biological differences between human groups labeled with ethnic, cultural, national, political, or geographical taxonomies. It does not refer to descriptive taxonomic structures, which are the labels humans use to identify themselves or others. Rather, racialization occurs when these descriptions are used in a manner that ascribes a somatic innate and fixed difference between the labeled groups. In the descriptive mode, the labels black, African American, Latino, Mexicano, or white are labels used as identifiers. Yet these identifiers have been shown time and again to be historically and situationally determined, unreliable, and invalid proxies for biological human differences.
Socially derived group labels, at best, work like pronouns, always requiring specification and never defining the person or thing to which the pronoun refers. In the attributive mode, these labels are used to ascribe fixed, innate attributes to the bodies of human groups. This occurs, for example, when geneticists studying diabetes use “Mexicano” as a label and attach to it the meanings of biological features that differentiate Mexicanos from other human groups. When inequalities of morbidity and mortality of a disease such as diabetes are explained or hypothesized as a condition of innate and fixed biological differences among groups, the existence of sociopolitical inequalities between human groups are effectively overlooked, and the related embodied health outcomes are, by default, attributed to biological differences.
Racialization must be distinguished from the descriptions of humans used in studies that measure different health outcomes not attributed to evolution or to the discovery of biogenetic characteristics of one human group. These studies use ethnoracial labels to describe the social histories of health phenomena, the social epidemiology of disease, and the health consequences of sociopolitical phenomena—or to simply socially identify those human groups most impacted by a disease. A nonracialized understanding of disease patterns avoids the biological determinism that is inherent in racialization.
As a racializing practice, gene-based approaches to diabetes advance the myth that biology can explain social phenomena. In fact, considerable evidence suggests that biology and social phenomena are co-produced, that biological and social phenomena develop in mutually interdependent ways. In its most crude form, this is evident when genetic researchers use social labels to describe human groups, which renders their findings both biological and social in origin. Similarly, researchers using evolutionary models for complex diseases require genetic samples of the populations most impacted by diabetes. They are thus investigating the physiological impact of social stratification and the radical lifestyle transformation required of advanced capitalism.
Viewing complex disease through a genetic lens is a long-established sociocultural phenomenon, one that has been applied to diseases such as sickle-cell anemia, hypertension, and diabetes. For diabetes, the alleged metabolic adaptation within the thrifty genotype hypothesis presumes that hunter-gatherers experienced severe episodes of feast and famine. Selective evolutionary pressures would therefore favor those whose metabolism would best convert glucose to fat for use during periods of food scarcity. Contemporary human groups impacted by diabetes are viewed as genetically predis-posed to the disease by virtue of their current similarity to the lifeways of earlier humans. However, both the extent of the feast-and-famine cycles of hunter-gatherers and the association of contemporary human groups with early human life-ways are unsubstantiated premises, relying on presumed rather than empirically supported benefits of modernity. The widespread adherence to the evolutionary hypothesis of diabetes (and the considerable resources directed toward such studies) is another iteration of a race theory that advances the cultural notion that diabetes affects human groups differently because of innate genetic differences.
Examining diabetes as an evolutionary trait denies the impact of the social dislocation, dispossession, colonization, slavery, racism, and other sociohistorical impact on those groups affected by diabetes. For example, the groups most disproportionately impacted by diabetes, Native Americans, experienced extreme deprivations during the violent dispossession of their lands and subsequent attempts by white settlers to eradicate them. It is the children and grandchildren of those born during this period who now suffer disproportionately from diabetes. These conditions support the fetal origins hypotheses and do not require the logical leap that such recent experiences could have evolutionary significance, and thus result in genotypic human variation. Thus, the widespread adherence to the genetic predisposition thesis for diabetes reflects a dominant cultural way of making sense of relations between groups impacted by the disease.
In order to understand the causes of diabetes, its evolutionary hypothesis must be seen as fitting not the natural history of the disease, but rather the ideological premise of a subordinating majority whose scientists refuse to seriously account for the social history of those peoples most impacted by the disease. Researchers seriously interested in preventing diabetes would greatly benefit by approaching the disease in ethnoracial groups as a biocultural phenomenon. To avoid merely reproducing another unprovable evolutionary genetic predisposition claim, researchers must carefully investigate diabetes as the biological impact of economic and sociocultural changes for human life. This requires uncommon multi-disciplinary methods spanning the biological and social sciences and humanities. More importantly, researchers must actively counter the racialized hypothesis of genetic predisposition, especially in research into health inequalities among minority and emerging majority groups in parts of the world with high levels of ethnoracial stratification and an unequal distribution of resources. In short, researchers must recognize the link between diabetes and institutional racism.
SEE ALSO Diseases, Racial.
Australian Bureau of Statistics. 2002. National Health Survey: Aboriginal and Torres Strait Islander Results, Australia, 2001. Canberra: Australian Bureau of Statistics. Available from http://www.abs.gov.au.
Barker, David. J. 2005. “The Developmental Origins of Insulin Resistance.” Hormone Research 64 (Suppl. 3): 2–7. Available from http://content.karger.com.
Benyshek, Daniel C., John F. Martin, and Carol S. Johnston. 2001. “A Reconsideration of the Origins of the Type 2 Diabetes Epidemic among Native Americans and the Implications for Intervention Policy.” Medical Anthropology 20 (1): 25–44.
Cooper, Richard S., et al. 1997. “Prevalence of NIDDM among Populations of the African Diaspora.” Diabetes Care 20 (3): 343–348.
Foliaki, Sunai, and Neil Pearce. 2003. “Prevention and Control of Diabetes in Pacific People.” British Medical Journal 327: 437–439.
Hales, C. Nicholas, and David J. Barker. 2001. “The Thrifty Phenotype Hypothesis.” British Medical Bulletin 60 (1): 5–20.
Karlsen, Saffron, and James Y. Nazroo. 2002. “Relation between Racial Discrimination, Social Class, and Health among Ethnic Minority Groups.” American Journal of Public Health 92 (4): 624–631.
Kaufman, Jay, and Richard Cooper. 2001. “Commentary: Considerations for Use of Racial/Ethnic Classification in Etiologic Research.” American Journal of Epidemiology 154 (4): 291–298.
Krieger, Nancy, ed. 2005. Embodying Inequality: Epidemiologic Perspectives. Amityville, NY: Baywood.
Maty, S. M., et al. 2002. “Interaction between Childhood Socioeconomic Position, Adult Body Mass Index and 34-year Incidence of Type 2 Diabetes Mellitus.” Annals of Epidemiology 12 (7): 501–502.
Miles, Robert, and Malcolm Brown. 2003. Racism. New York: Routledge.
———. 1999. “The ‘Thrifty Genotype’ in 1998.” Nutrition Reviews 57 (5): S2-S9.
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Michael J. Montoya
Diabetes mellitus is a group of diseases characterized by elevated levels of glucose in the blood. Diabetes is caused by problems producing or responding to the hormone insulin. Insulin is produced in the pancreas by specialized cells called beta cells, in response to the presence of glucose absorbed through the gastrointestinal tract following a meal. Insulin promotes the uptake of glucose into muscle and fat cells, and it promotes the storage of excess glucose in the liver.
Excess blood glucose over time damages organs, particularly the eyes, kidneys, nerves, heart, and blood vessels. It is the leading cause of adult blindness, end-stage kidney disease, and lower limb amputations, and it is a major risk factor for heart attacks and strokes. Diabetes is classified into four major groups: type 1 diabetes (T1DM), type 2 diabetes (T2DM), other specific types, and gestational diabetes (GDM), occurring during pregnancy. Approximately 5 percent to 8 percent of the people of the industrialized world have diabetes, mostly (approximately 90 percent) type 2, which at least 16 million Americans have.
Type 1 Diabetes
Type 1 diabetes is caused by beta cell destruction, leading to insulin deficiency. T1DM was previously called insulin-dependent diabetes mellitus (IDDM), because patients who have it require insulin for survival. It was also called juvenile-onset diabetes mellitus, because most type 1 diabetics are children or young adults. At the time of diagnosis, about 85 percent to 90 percent of people with type 1 diabetes have antibodies directed against components of their beta cells, indicating that the immune system is responsible for the progressive and irreversible beta cell destruction.
Current evidence indicates a genetic component to T1DM. HLA (histocompatibility leukocyte antigen) genes are a group of genes on chromosome 6 that encode proteins that are part of the immune system. Normally the immune system defends the body against disease by destroying foreign cells, but in the case of type 1 diabetes, the body's immune system destroys its own beta cells.
Certain types of HLA genes are strongly associated with type 1 diabetes, and other types protect against its development. However, these HLA genes are neither necessary nor sufficient to cause or protect from type 1 diabetes. T1DM is therefore a "complex" genetic disorder, in which several genes interact with the environment to result in the disease. Scientists are currently working to identify these other genes, as well as environmental factors (e.g., toxins and viruses) that provoke the development of T1DM.
Type 2 Diabetes
Type 2 diabetes is itself a group of disorders caused by some combination of insulin resistance—which occurs when cells' ability to respond to insulin is compromised—and insulin deficiency, which occurs when the beta cells' ability to make insulin is compromised. T2DM has, in the past, been called adult-onset diabetes, because most people with T2DM were adults. It was also called non-insulin-dependent diabetes mellitus (NIDDM), because people with type 2 diabetes usually do not require insulin injections. In the Unites States, T2DM is especially prevalent among certain ethnic minorities, including African Americans, Mexican Americans, Asian Americans, and Native Americans.
Obesity is a potent risk factor for T2DM. In the last thirty years, due to increased caloric intake and physical inactivity, both of which contribute to obesity, there was an explosion in the prevalence of T2DM, and it started occurring at younger ages—even in children. In addition to its association with an unhealthy lifestyle, T2DM is known to have a strong genetic component.
Scientists have been searching throughout the genome for T2DM-susceptibility genes. One such gene, calpain 10 protease, was identified on chromosome 2. A common variant of this gene may predispose certain individuals to T2DM; however, the true significance of this gene variant remains to be determined. In addition, several candidate genes have shown some evidence of being involved in T2DM. However, the effect of any single candidate gene variant on the risk of developing T2DM is modest. A candidate gene is a gene for which prior knowledge of its function leads researchers to assess whether chemical variation in it is associated with a disease.
As of 2002 there was no clinically available genetic test to predict the onset of type 2 diabetes, but it is anticipated that with a better understanding of the roles of various genes in T2DM, it will eventually be possible to use multiple genetic tests to identify individuals at risk for T2DM and to predict which treatments will be most helpful in specific patients. Although genetic susceptibility plays an important role in determining the risk of developing T2DM, studies have shown that the disease can often be prevented through diet, physical activity, and weight loss.
Other Specific Types of Diabetes
The third category of diabetes, containing other specific types, includes nongenetic forms as well as single-gene forms of diabetes. One group of single-gene diabetes disorders are genetic defects in beta cell function. The most common of the genetic beta cell defects are the disorders known as MODY, or maturity onset diabetes of the young. MODY constitutes no more than 2 percent to 5 percent of all cases of diabetes. It often occurs in children and young adults and is characterized by decreased but not absent insulin production. It is inherited in an autosomal dominant manner, which means that an affected person has a 50 percent chance of passing on the disease-version of the gene with each pregnancy. Most, but not all, people receiving a MODY gene do develop diabetes.
There are at least six different genetic forms of MODY. MODY2 is caused by a mutation in a gene on chromosome 7 that makes a protein called glucokinase, which is an enzyme in beta cells that helps to provide a chemical signal needed for insulin release. The other MODYs involve mutations in genes that encode proteins called transcription factors, which allow beta cells to develop and function properly. These are hepatocyte nuclear factor 4-alpha (HNF4-alpha, causing MODY1, on chromosome 20), HNF1-alpha (causing MODY3, on chromosome 12), insulin promoter factor 1 (IPF1, causing MODY4, on chromosome 13), HNF1-beta (causing MODY5, on chromosome 17) and NeuroD1/beta2 (causing MODY6, on chromosome 2).
A very rare genetic insulin secretion disorder is maternally inherited diabetes and deafness (MIDD), caused by changes in the DNA of the mitochondria. The mitochondria are the energy powerhouses of the cell and the only part of the cell to contain DNA other than the nucleus, where most DNA is contained. MIDD and other mitochondrial disorders are maternally inherited because the fertilized egg has only mitochondria derived from the mother. The clinical features of MIDD can be similar to type 2 diabetes, and the hearing loss can be mild or even undetectable, except by special tests.
Another group of rare genetic diabetes types is characterized by extreme insulin resistance, which is defined as occurring when the ability of the body's cells to respond to insulin is severely compromised. Disorders of extreme insulin resistance include type A syndrome, leprechaunism, and Rabson-Mendenhall syndrome, and they are caused by inherited defects in the gene on chromosome 19 that makes the insulin receptor, a protein that allows cells to respond to insulin. Without properly functioning insulin receptors, insulin cannot work effectively. In addition to diabetes, individuals with insulin receptor defects may also have dental, genital, skin, and growth abnormalities. Most insulin receptor gene defects manifest in an autosomal recessive manner. That is, two defective copies of the gene are required for disease expression, and couples in which each partner has one defective copy (and in which neither is therefore affected) have a 25 percent chance of having an affected child, with each pregnancy.
Familial partial lipodystrophic diabetes (FPLD) is a rare condition in which children develop an unusual fat distribution at puberty, with little or no fat on their arms, legs, and trunk. They also develop insulin-resistant diabetes. FPLD is an autosomal dominant condition caused by mutations in the lamin A/C gene on chromosome 1. Another rare form of lipodystrophic diabetes is congenital (i.e., present at birth) generalized lipodystrophic (CGL) diabetes, which is autosomal recessive, and in about half of cases is due to mutations in the gamma-3-like gene (GNG3 ; also called the seipin gene), on chromosome 11.
Wolfram syndrome is a rare autosomal recessive condition presenting in childhood that includes diabetes mellitus as well as other problems, including deafness and deficiency of antidiuretic hormone. Mutations in the wolframin gene on chromosome 4 are responsible for some cases, but other cases appear to be caused by a gene in a different area of chromosome 4.
Another rare autosomal recessive childhood condition, thiamine-responsive megaloblastic anemia syndrome (TRMA), consists of several features, including blood abnormalities, deafness, and diabetes. TRMA, which responds to treatment with thiamine (a form of vitamin B), is a disorder caused by mutations in the thiamine transporter gene SLC19A2, on chromosome 1.
Transient neonatal diabetes (TNDM) is a condition in which infants are born requiring injected insulin but are able to make sufficient insulin later in infancy. Later in childhood or in adulthood, they may again develop diabetes, which may or may not require insulin treatment. Most cases of transient neonatal diabetes appear to be caused by the inheritance of an extra copy of a region of chromosome 6 from the father.
Many known genetic disorders other than those mentioned previously are associated with an increased risk of diabetes. Among those most strongly associated are Friedreich's ataxia, cystic fibrosis, and hemochromatosis.
Gestational Diabetes Mellitus
Hormones associated with pregnancy may cause diabetes in susceptible individuals. Although the diabetes goes away after the pregnancy, individuals who have had GDM are at increased risk of developing T2DM. Currently very little is known about the genetic basis of GDM. It is possible that some of the same genes responsible for T2DM are also involved in GDM.
Genetic Susceptibility to Complications
As mentioned above, diabetes is associated with complications involving the eyes, kidneys, blood vessels, and heart. However, not all individuals with diabetes develop these complications. There is increasing evidence that there are genes other than those that increase susceptibility to developing the disease that may influence susceptibility to developing its complications. These genes are not yet identified, but they are likely to interact with other known risk factors for complications, including poor blood-sugar control and increased blood-pressure and blood-cholesterol levels.
see also Complex Traits; Disease, Genetics of; Gene and Environment; Gene Discovery; Immune System Genetics; Mitochondrial Diseases.
Toni I. Pollin
and Alan R. Shuldiner
American Diabetes Association. <http://www.diabetes.org>.
Joslin Diabetes Center. <http://www.joslin.org>.
Juvenile Diabetes Research Foundation International. <http://www.jdrf.org>.
National Institute of Diabetes and Digestive and Kidney Diseases. <http://www.niddk.nih.gov>.
diabetes or diabetes mellitus (məlī´təs), chronic disorder of glucose (sugar) metabolism caused by inadequate production or use of insulin, a hormone produced in specialized cells (beta cells in the islets of Langerhans) in the pancreas that allows the body to use and store glucose. It is a leading cause of death in the United States and is especially prevalent among African Americans. The treatment of diabetes was revolutionized when F. G. Banting and C. H. Best isolated insulin in 1921.
The lack of insulin results in an inability to metabolize glucose, and the capacity to store glycogen (a form of glucose) in the liver and the active transport of glucose across cell membranes are impaired. The symptoms are elevated sugar levels in the urine and blood, increased urination, thirst, hunger, weakness, weight loss, and itching. Prolonged hyperglycemia (excess blood glucose) leads to increased protein and fat catabolism, a condition that can cause premature vascular degeneration and atherosclerosis (see arteriosclerosis). Uncontrolled diabetes leads to diabetic acidosis, in which ketones build up in the blood. Patients have sweet-smelling breath, and may suffer confusion, unconsciousness, and death. There are two distinct types of diabetes mellitus: insulin-dependent and noninsulin-dependent.
Insulin-dependent diabetes (Type I), also called juvenile-onset diabetes, is the more serious form of the disease; about 10% of diabetics have this form. It is caused by destruction of pancreatic cells that make insulin and usually develops before age 30. Type I diabetics have a genetic predisposition to the disease. There is some evidence that it is triggered by a virus that changes the pancreatic cells in a way that prompts the immune system to attack them. The symptoms are the same as in the non-insulin-dependent variant, but they develop more rapidly and with more severity. Treatment includes a diet limited in carbohydrates and saturated fat, exercise to burn glucose, and regular insulin injections, sometimes administered via a portable insulin pump. Transplantation of islet cells has also proved somewhat successful since 1999, after new transplant procedures were developed, but the number of pancreases available for extraction of the islet cells is far smaller than the number of Type I diabetics. Patients receiving a transplant must take immunosuppressive drugs to prevent rejection of the cells, and many ultimately need to resume insulin injections, but despite that transplants provide real benefits for some whose diabetes has become difficult to control.
Noninsulin-dependent diabetes (Type 2), also called adult-onset diabetes, results from the inability of the cells in the body to respond to insulin. About 90% of diabetics have this form, which is more prevalent in minorities and usually occurs after age 40. Although the cause is not completely understood, there is a genetic factor and 90% of those affected are obese. As in Type I diabetes, treatment includes exercise and weight loss and a diet low in total carbohydrates and saturated fat. Some individuals require insulin injections; many rely on oral drugs, such as sulphonylureas, metformin, acarbose or another alpha-glucosidase inhibitor, thiazolidinediones, or dipeptidyl peptidase–4 (DPP-4) inhibitors.
Diabetes affects the way the body handles fats, leading to fat accumulation in the arteries and potential damage to the kidneys, eyes, heart, and brain, and statins (cholesterol-lowering drugs) may be prescribed to prevent heart disease. It is the leading cause of kidney disease. Many patients require dialysis or kidney transplants (see transplantation, medical). Most cases of acquired blindness in the United States are caused by diabetes. Diabetes can also affect the nerves, causing numbness or pain in the face and extremities. A complication of insulin therapy is insulin shock, a hypoglycemic condition that results from an oversupply of insulin in relation to the glucose level in the blood (see hyperinsulinism).
See A. Bloom, Diabetes Explained (1973); Portland Area Diabetes Program, Diabetes and Insulin (1988); M. Davidson, Diabetes Mellitus: Diagnosis and Treatment (1991).
Diabetes insipidus is a metabolic disorder characterized by extreme thirst, excessive consumption of liquids and excessive urination, due to failure of secretion of the antidiuretic hormone.
Diabetes mellitus is a metabolic disorder involving impaired metabolism of glucose due to either failure of secretion of the hormone insulin (insulin‐dependent diabetes) or impaired responses of tissues to insulin (non‐insulin‐dependent diabetes). If untreated, the blood concentration of glucose rises to abnormally high levels (hyperglycaemia) after a meal and glucose is excreted in the urine (glucosuria). Prolonged hyperglycaemia may damage nerves, blood vessels, and kidneys, and lead to development of cataracts, so effective control of blood glucose levels is important.
Type I diabetes mellitus develops in childhood (juvenile‐onset diabetes) and is due to failure to secrete insulin, and hence is called insulin‐dependent diabetes. Treatment is by injection of insulin (originally purified from beef or pig pancreas, now biosynthetic human insulin), together with restriction of the intake of sugars.
Type II diabetes mellitus generally arises in middle age (maturity‐onset diabetes) and is due to resistance of the tissues to insulin action; secretion of insulin by the pancreas may be normal or higher than normal. It is referred to as non‐insulin‐dependent diabetes and can sometimes be treated by restricting the consumption of sugars and reducing weight, or by the use of oral drugs which stimulate insulin secretion and/or enhance the insulin responsiveness of tissues (sulphonylureas and biguanides). It is also treated by injection of insulin to supplement secretion from the pancreas and overcome the resistance. Impairment of glucose tolerance similar to that seen in diabetes mellitus sometimes occurs in late pregnancy, when it is known as gestational diabetes. Sometimes pregnancy is the stress that precipitates diabetes, but more commonly the condition resolves when the child is born.
Renal diabetes is the excretion of glucose in the urine without undue elevation of the blood glucose concentration. It is due to a reduction of the renal threshold which allows the blood glucose to be excreted. See also glucose tolerance.
The illness with ‘the passing of too much urine’ was known in 1500 bc to the Egyptians; Aretaeus wrote of it in the second century ad as ‘diabetes … a melting down of the flesh and limbs into urine’; Paracelsus described it in the sixteenth century; but it was the English physician Thomas Willis who first reported in 1679 that the urine was ‘so wonderfully sweet’.
A much rarer condition, diabetes insipidus (with copious urine which is not ‘sweet’), is caused by deficiency of antidiuretic hormone (ADH) (also known as vasopressin) from the pituitary gland. ADH normally acts in the kidneys to prevent any greater escape of water in the urine than is necessary to maintain constancy of the salt concentration and volume of the body fluids. When ADH is lacking, due to disease or injury in or near the pituitary gland, the daily output of dilute urine can be 25–30 litres, with extreme thirst to match.
See blood sugar; body fluids; insulin; pancreas; pituitary gland.
—diabetic (dy-ă-bet-ik) adj., n.www.diabetes.org.uk Website of Diabetes UK