Diabetes (or Diabetes mellitus) is a complex group of diseases caused by a number of reasons. Individuals suffering from diabetes have hyperglycemia (high blood sugar) either because there is low production of insulin or body cells do not use the produced insulin. About 350 million people suffer from diabetes globally (Danaei et al., 2011). The World Health Organization (1999) has predicted that diabetes will rise to the top seventh cause of death worldwide by 2030. There are three common forms of diabetes: type 1 diabetes, type 2 diabetes and gestational diabetes. This paper mainly discusses these major forms of diabetes considering their causes and consequences.
Type 1 Diabetes
In type 1 diabetes mellitus, body cells fail to produce insulin due to a compromised immune system causing damage to the cells where production of insulin takes place. The cause and prevention of type 1 diabetes are not particularly known; however, it is suspected to be a consequence of certain genetic factors.
Type 2 Diabetes
In type 2 diabetes mellitus, there is low production of insulin by the body cells or the body does not effectively make use of the produced insulin. Type 2 diabetes is known to be the commonest type of diabetes; in fact, 90% of diabetes sufferers have type 2 diabetes (World Health Organization, 1999). The cause and cure of type 2 diabetes remains unknown; however, genetic factors and manner of living take part in its causes, and watching blood sugar level can control the disease.
Gestational diabetes happens when there is a development of high blood sugar level in pregnant women not previously diagnosed of diabetes. For mothers who had gestational diabetes during their first pregnancy, the probability that it will occur in subsequent pregnancies is approximately two-thirds. Furthermore, some patients may subsequently develop type 2 diabetes. After pregnancy, diabetes type 1 or 2 may occur and will require obligatory treatment.
Genetic Factors and Markers
The role of genetic factors as a cause of diabetes has been proven definitively. This is the main etiological factor for diabetes.
IDDM is considered to be a polygenic disease which is based on at least two of the mutant genes in diabetic chromosome 6. They are associated with the HLA system (D-locus), which determines the individual, genetically determined response of the body and B cells to various antigens.
The hypothesis of polygenic inheritance of IDDM suggests that diabetes is caused from two mutant genes (or two groups of genes) that have a recessive inherited predisposition to autoimmune lesions of the insular apparatus or increased sensitivity of B cells to viral antigens or attenuated antiviral immunity.
Genetic susceptibility is linked with particular genes of HLA systems, which are considered markers of such a predisposition.
Patients with a genetic predisposition to IDDM have an altered response to environmental factors. They have weakened antiviral immunity, and they are extremely susceptible to cytotoxic damage to the B cells by viruses and chemical agents.
Viral infection may be a factor that provokes the development of IDDM. The most common occurrence of IDDM clinically is preceded by the following viral infections: measles (rubella virus has a tropism to the islets of the pancreas, accumulates, and can be replicated in them), Coxsackievirus and hepatitis B virus (can be replicated in the insular apparatus), mumps (1-2 years after the epidemic of mumps, the incidence of IDDM in children dramatically increases), infectious mononucleosis, cytomegalovirus, influenza virus, etc. The role of viral infection is confirmed by seasonality in the incidence of IDDM development (often, the first diagnosed cases of IDDM among children occur in autumn and winter months, with a peak incidence in October and January), the detection of high titers of antibodies to the virus in the blood of patients with IDDM, and the detection by immunofluorescent methods for studying viral particles in the islets of Langerhans in people who have died of IDDM. The role of viral infections in the development of IDDM is confirmed in experimental studies. Viral infections among individuals with a genetic predisposition to IDDM are involved in the development of the disease as follows:
- the cause of acute injury to B cells (Coxsackievirus);
- leads to viral persistence (congenital cytomegalovirus infection, rubella) with the development of autoimmune reactions in the islet tissue.
In modern diabetology, the next staging of IDDM is expected.
First stage – a genetic predisposition, due to the presence of certain antigens in the HLA system, as well as genes of chromosomes 11 and 10.
Second stage – the initiation of the autoimmune process in islands of B cells influenced with viruses, cytotoxic agents and any other unknown factors. A crucial point in this step is the expression of B cells HLA-DR-antigen and glutamic acid, and therefore, they become autoantigens that cause the development of autoimmune response reactions.
Third stage – the stage of the active immunological process with formation of antibodies to B cells, insulin and autoimmune insulitis development.
Fourth stage – the progressive reduction of insulin secretion stimulated by glucose (1-phase secretion of insulin).
Fifth stage – clinical diabetes (the manifestation of diabetes). This step develops during the occurrence of the degradation and death of 85-90% of the B cells.
Many patients after the insulin treatment fall into remission of the disease (the “diabetic honeymoon”). Its length depends on the severity and degree of B cell damage, their ability to regenerate, and the level of residual insulin secretion, as well as the severity and frequency of related viral infections.
Sixth stage – the complete destruction of b-cells, and a complete lack of insulin secretion and C-peptide. Clinical signs of diabetes form and insulin treatment becomes necessary again.
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In the United States, about 16 million people suffer from diabetes mellitus, although only half of these individuals are diagnosed. Every year, about 650,000 people learn they have the disease. Diabetes mellitus is the seventh leading cause of all deaths and the sixth leading cause of all deaths caused by disease. Diabetes is the most common in adults over 45 years of age; in people who are overweight or physically inactive; in individuals who have an immediate family member with diabetes; and in minority populations including African Americans, Hispanics, and Native Americans. The highest rate of diabetes in the world occurs in Native Americans. More women than men have been diagnosed with the disease. Diabetes can develop gradually, often without symptoms, over many years. It may reveal itself too late to prevent damage. In fact, you may first learn you have diabetes when you develop one of its common complications â“ cardiovascular disease, kidney disease, or vision problems. Diabetes is a condition that occurs because of a lack of insulin or because of the presence of factors opposing the actions of insulin. The result of insufficient action of insulin is an increase in blood glucose concentration (hyperglycemia). Hyperglycemia is the unused glucose that builds up in your blood. Many other metabolic abnormalities occur, notably an increase in ketone bodies in the blood when there is a severe lack of insulin.
The condition may also develop if muscle and fat cells responds poorly to insulin. In people with diabetes, glucose levels build up in the blood and urine, causing excessive urination, thirst, hunger, and problems with fat and protein metabolism. Diabetes mellitus differs from the less common diabetes insipidus, which is cause by the lack of the hormone vasopressin that controls the amount of urine secreted.
The earliest known record of diabetes on third dynasty Egyptian papyrus by physician Hesy-ra; mentions polyuria (frequent urination) as a symptom in 1552 B.C. In the 16th century, Paracelsus identifies diabetes as a serious general disorder. In the Early 19th century, the first chemical tests developed to indicate and measure the presence of sugar in the urine. In 1919-20, Allen establishes the first treatment clinic in the USA, the Physiatric Institute in New Jersey, to treat patients with diabetes, high blood pressure, and Bright"s disease; wealthy and desperate patients flock to it. On January 23,1922, one of Dr. Collip"s insulin extracts are first tested on a human being, a 14-year-old boy named Leonard Thompson, in Toronto; the treatment was considered a success by the end of the following February. In 1955, oral drugs are introduced to help lower blood glucose levels, and in 1960, the purity of insulin is improved. Home testing for sugar levels in the urine increases level of control for people with diabetes. The 75th anniversary of the discovery of insulin was celebrated worldwide in 1996.
Diabetes is classified into two types. In Type I, or insulin-dependent diabetes mellitus (IDDM), formerly called juvenile-onset diabetes, the body does not produce insulin or produces it only in very small quantities. Symptoms usually appear suddenly and in individuals under 20 years of age. Most cases occur before or around puberty. In the United States, about 5 to 10 percent of all diagnosed cases of diabetes, up to 800,000 persons, suffer from Type I diabetes. About 30,000 new cases are diagnosed every year. Type I diabetes is considered an autoimmune disease because the immune system (system of organs, tissues, and cells that rid the body of disease-causing organisms or substances) attacks and destroys cells in the pancreas, known as beta cells, that produce insulin. Scientists believe that genetic and environmental factors, such as viruses or food proteins, may somehow trigger the immune system to destroy these cells. Untreated Type I diabetes affects the metabolism of fat. Because the body cannot convert glucose into energy, it begins to break down stored fat for fuel. This produces increasing amounts of acidic compounds called ketone bodies in the blood, which interfere with respiration. In Type II, or non-insulin-dependent diabetes mellitus (NIDDM), formerly called adult-onset diabetes, the body either makes insufficient amounts of insulin or is unable to use it. Symptoms characteristic of Type II diabetes include repeated infections or skin sores that heal slowly or not at all, generalized tiredness, tingling or numbness in the hands or feet, and itching. The most common form of diabetes, Type II accounts for 90 to 95 percent of all cases of diagnosed diabetes in the United States. Each year 595,000 new cases are diagnosed. The onset of Type II diabetes usually occurs after the age of 40, and often after the age of 55. Because symptoms develop slowly, individuals with the disease may not immediately recognize that they are sick. Scientists believe that in some persons weight gain or obesity triggers diabetesâ”about 80 percent of diabetics with this form of the disease are overweight. Diabetes is detected by measuring the amount of glucose in the blood after the individual has fasted (abstained from food) for several hours, either overnight or several hours after breakfast. In some cases, physicians diagnose diabetes by administering an oral glucose tolerance test, the measurement of glucose levels before and after a specific amount of sugar is ingested. Another test being developed for Type I diabetes looks for specific antibodies (proteins of the immune system that attack foreign substances called antigens) present only in persons with diabetes. This test may detect Type I diabetes at an early stage, reducing the risk for complications from the disease. Once diabetes is diagnosed, treatment consists of controlling the amount of glucose in the blood and preventing complications. Depending on the type of diabetes, this can be accomplished through regular physical exercise, a carefully controlled diet, and medication. Individuals with Type I diabetes require insulin injections, often two to four times a day, to provide the body with the insulin it does not produce. The amount of insulin needed varies from person to person. Typically, several times a day, individuals with Type I diabetes measure the level of glucose in a drop of their blood obtained by pricking a fingertip. They can then adjust the amount of insulin injected, physical exercise, or food intake to maintain the blood sugar at a normal level. People with Type I diabetes must carefully control their diets by distributing meals and snacks throughout the day so the insulin supply is not overwhelmed and by eating foods that contain complex sugars, which break down slowly and cause a slower rise in blood sugar levels.
Although most persons with Type I diabetes strive to lower the amount of glucose in their blood, levels are too low can also cause health problems. For example, low blood sugar levels can cause hypoglycemia, a condition characterized by shakiness, confusion, and anxiety. The treatment for hypoglycemia is to eat or drink something that contains sugar. One third of type 2 diabetics can control their condition with diet and exercise alone, which benefits both glucose levels and blood pressure. The remainders of diabetics, however, need oral medications that stimulate residual insulin secretion or increase sensitivity to it. Such as the sulfonylurea drugs or metformin. Eventually, natural insulin fails and insulin replacement is needed. Studies are now indicating that, as in type 1 patients, rigorous control of blood glucose levels can help reduce the risk for complications of diabetes, particularly retinopathy, but also kidney and nerve damage. Controlling glucose levels is not enough. Intensive insulin producing or sensitizing treatments needed for strict control put patients at increased risk for weight gain and arteriosclerosis and offer no protection against heart problems and stroke. For type 2 diabetes, many lifestyle measures can be used to treat and prevent the disease. For most diet is the key to managing this complicated disease. It is also extremely difficult to do so. All people with diabetes should aim for healthy lipid (cholesterol and triglyceride) levels and control of blood pressure. For overweight type 2 diabetics, both weight loss and blood glucose control are important. Health benefits are highest with the first pounds lost, and losing only 10% body weight can control progression of diabetes. For obese patients who cannot control weight using dietary measures, medication may be needed. A new drug orlistat (Xenical) appears not only to reduce weight but also to have benefits on glucose control and cholesterol and lipid levels has proven to work in one study. Long-term side effects are unknown at this time. People taking oral medications should focus on coordinating calorie intake with insulin administration, exercise, and other variables. Adequate calories must be maintained for normal growth in children, for increased needs during pregnancy, and after illness. For overweight type2 diabetics who are not taking medication, both weight loss and blood sugar control are important. A reasonable weight is usually defined as what is achievable and sustainable, rather than one that is culturally defined as desirable or ideal. Some general rules for healthy eating apply to everyone; limit fats (particularly saturated fats) and consume plenty of fiber and vegetables. Some general guidelines for treating type 2 diabetes. Exercise helps to lower the blood glucose level and increase insulin sensitivity; it also helps to lower blood pressure, improve cholesterol levels, decrease body fat, and reduce the risk of cardiovascular disease. Aerobic exercise is best. Regular exercise, even moderate intensity, improves insulin sensitivity. Unlike type 1 diabetes, in type 2 diabetes some insulin is still produced, although not in the amounts necessary to overcome insulin resistance. Patients, then, who need medications usually, start out with drugs that enhance residual insulin production or the sensitivity rather than replacing the insulin by the standard treatment for type 1 diabetics.
Metformin (Glucophage) is a biguanide drug, which appears to work by reducing glucose production in the liver and by making tissues more sensitive to insulin. Combinations with other insulin-secreting or insulin-sensitizing drugs, such as repaglinide and acarbose, are proving to be particularly effective. Sulfonylureas are oral drugs that stimulate that pancreas to release insulin. A number of brands are available, including chlorpropamide (diabinese), tolazamide (tolinase), glimepiride (amaryl), and glyburide (diabeta, micronase). Other new drugs include glibenclamide and gliclazide. Gliclazide may have specific benefits for the heart. For adequate control of blood glucose levels, the drugs should only be taken 20 to 30 minutes before a meal. Eventually oral drugs usually fail, and patients need insulin injections. In patients being treated with insulin or insulin-producing or sensitizing drugs, it is important to monitor blood glucose levels carefully to avoid hypoglycemia. Patients should aim for premeal glucose levels of between 80 and 120 and bedtime levels of between 100 and 140. Blood glucose levels are generally more stable in type 2 diabetes than in type 1, so experts usually recommend measuring blood levels only once or twice a day. Usually, a drop of blood obtained by pricking the finger is applied to a chemically treated strip. The glucose level is read on a standard meter or a small, portable digital display device. New methods for accurately measuring blood glucose levels may improve the quality of life for many individuals with diabetes. Techniques being developed include the use of laser beams and infrared technology. At present, no cure exists for diabetes and scientists are unsure of the exact cause. Researchers in England have identified up to 18 genes involved in Type I diabetes and are working to determine each gene"s role in causing the disease. Other scientists hope to identify the environmental factors that trigger Type I diabetes. If they can determine what causes the immune system to attack the cells that produce insulin, they may discover how to prevent the condition from developing. In 1996, researchers discovered the first genetic link to Type II diabetes. The gene, which controls storage of sugar in muscle tissue, has been found in one-third of people with Type II diabetes and may indicate susceptibility to adult-onset diabetes. Recent findings indicate that a pair of genes causes a variation of Type II diabetes called maturity onset diabetes of the young (MODY), which develops in persons under the age of 25. While scientists do not yet understand how these genes cause the disease, the genes are known to be active in the liver, intestine, kidney, and pancreas. Today, improved methods of diabetes control, new medications, and easier ways to take insulin enable most people who develop type 1 or 2 diabetes to live a long and healthy life. A diagnosis of diabetes is not a sentence of premature death, as it often used to be
"Diabetes mellitus," Diabetes Timeline, http://www.diabetes.ca/atoz/diatime.htm,
"Diabetes," Treatment, http://members.aol.com/m4ynk/treatment.html,
Metabolic control and prevalent cardiovascular disease in non-insulin dependant diabetes mellitus (NIDDDM); The American Journal of Medicine, January 1997
Don"t let diabetes go undetected, Consumer Reports on Health, February 1997.
Milchovich, Dunn-long, Diabetes Mellitus, A Practical Handbook, Palo Alto, California: Bull Publishing Company, 1995.
Krall, Beaser, Joslin Diabetes Manual, Pennsylvania: Lea & Febiger, 1988.
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