Maturity-Onset Diabetes of The Young Essay
Diabetes, a disease where the blood sugar content is supposed to increase above the normal range. The disease has become quite prevalent in the world today.
Nowadays even adolescents and young children are exhibiting the occurrence of the disease. More commonly, it is the obese children who run a high risk of the disease, children with a positive family history of diabetes are also at an increased risk (CDC.gov, 2014). Thus creating a separate group of diabetes affected individuals, also called as MODY (Maturity Onset Diabetes of the Young) (Diabetes.org.uk, 2014). The symptoms although are quite similar, that are, polydypsia, polyuria or polyphagia(Mayoclinic.org, 2014).
According to International Diabetes Federation, approximately 387 million people in the world are diabetic, with 46.3% undiagnosed cases. The prevalence rate is as high as 8.3% worldwide (International Diabetes Federation, 2014). North America and the Carribean region show the highest percentage of diabetic individuals, followed by Middle East and Africa. In 2013, the country which showed the maximum prevalence of diabetes was Tokelau (37.5%) (Healthintelligence.drupalgardens.com, 2013).
Although random and fasting blood glucose tests are considered the gold standards for the diagnosis of the type 2 diabetes, still another big achievement has been brought about in the field of interventions of diabetes that is the HbA1c test. The use of this test can help the patient and the health care professionals to keep a check on the effectiveness of the provided treatment (American Diabetes Association, 2014), if the patient is abiding by the cautions he was asked to or if there is a chance of any complications related to diabetes, foreseen in the patient (Bonora and Tuomilehto, 2011)Maturity-Onset Diabetes of The Young Essay
Haemoglobin is a protein structure responsible for carrying oxygen to different parts of the body. It is divided into different types, for example, in adults it is called as HbA or adult haemoglobin, in the fetus it is called as fetal haemoglobin or HbF(Wikipedia, 2014). The adult haemoglobin is again divided into different categories, among which the 1c form is taken into consideration while monitoring diabetes (Stoppler, 2014). The HbA1c has an affinity to combine with glucose molecules present in the blood and thus forms glycated or glycosylated haemoglobin(Diabetes.co.uk, 2014). The higher is the blood glucose level, more is the presence of HbA1c in the blood. The test was recommended by WHO in 2011( Diabetes.org.uk., 2014). It is used not as a diagnostic tool, but as a prognostic marker. HbA1c levels can also indicate the risk of possible diabetes in patients with potential chances of diabetes (Rohlfing et al., 2000), like in patients with pre existing pancreatic or hepatic disorders or patients with a positive family history of diabetes, in obese individuals or persons with sedentary lifestyle habits.
HbA1c levels are not indicative of the blood sugar level at a particular point of time but of a time period corresponding to 2-3 months prior to the performance of the test (Science Daily, 2014). Ideally the level of HbA1c should be lower than 6% or 48mmol/mol. Level higher than 7% is considered to run a high risk of diabetes related complications in the patients(Medindia,2014). The levels above 7% do indicate a chance of diabetes in an undiagnosed patient, although it is not a confirmatory test for the diagnosis of diabetes. Any patient exceeding the normal levels of HbA1c but not having any symptoms of diabetes must be repeatedly tested to confirm or refute the diagnosis. If found high repeatedly, the patient should be labelled as a high risk patient and tested again after six months to reassess the levels of HbA1c. A false positive or false negative result can be misleading. Conditions where a false positive level may be obtained are excessive alcohol consumption or renal failure. A false negative result would be present in anaemic patients, as the haemoglobin level is below normal thus the HbA1c level would also remain low( Webmd.boots.com, 2014). The advantage of HbA1c test over blood glucose test is that it does not require an overnight fasting (Tidy, 2012). It can be done at any time of the day irrespective of the intake of meal.Maturity-Onset Diabetes of The Young Essay
Patients should take adequate measures to keep their HbA1c levels below normal, but it should be borne in mind that the control measures should not make the patient hypoglycaemic(, a large number of patients have been found to become hypoglycemic in an attempt to keep the HbA1c levels under check (Lipska et al., 2014). If taken proper care, a correct monitoring of the blood glucose levels may eliminate the risk of any probable diabetic complications.
ROLE OF COMMUNITY NURSE
The community nurses can help by identifying the warning signs in patients who are prone to become diabetic. They can educate the patients about the disease and encourage them to undergo screening test and other intervention programmes. By increasing awareness among the patients they can reduce the chances of life threatening complications in diabetic patients (Perry, 2001). They will be responsible for educating the patient about diabetes, its complications and the relevance of HbA1c test. By keeping a thorough check on the records of the patient they can guide the patients to undergo the test at regular intervals and make sure that they get the test done after every 3 months in case of patients with uncontrolled sugar levels or every 6 months in patients who are at a potential risk of developing diabetes. The nurses can regularly examine the patients to see if there is any development of signs and symptoms pointing towards complications of diabetes. They can insist people in the high risk category to undergo the screening test to eradicate the chances of occurrence of diabetes later on.Maturity-Onset Diabetes of The Young Essay
According to Merriam-Webster dictionary, the meaning of Audit is “a careful check or review of something” (Anon, 2014). Audit gives a clear picture of the ongoing activities being carried out at different levels in an organisation in one go. It sums up the data and forms a collective presentation of the facts in order to give a better understanding and a clear picture of the underlying events.
Auditing in the field of nursing is equally important. Nursing audit is defined as “a review of the patient record designed to identify, examine, or verify the performance of certainspecified aspects of nursing care by using established criteria”(Anon, 2014).It is done by the nurses and other health care professionals. It helps in assessing the quality and efficacy of the nursing care provided in the hospital set up. The nurses study the reports and the documentary evidences of the patients and form an audit depending on which the quality of the nursing care is assessed. The data collected from the patients’ hospital records are taken into consideration for the synthesis of the audit report. The nursing audit can be conducted in two ways, one is the retrospective study and the other is concurrent study ( Jairus and Walia, 2011). In retrospective study the data is studied after the patient has been discharged from the hospital. His reports and progress is observed, if he received proper care, if his medical history was taken appropriately, if the care provided to him was of utmost standard etc., are studied. On the other hand, in concurrent study the data is studied when the patient is still under the hospital set up or is admitted in the hospital during the study period. In this the patient and the staff responsible for providing care are interrogated and a report is formed on that basis about the progress in the condition of the patient and the adequacy of the treatment plan and methods prescribed. The auditing ensures that the quality of care that was required to be provided was actually given. It also helps in keeping a check on the functioning of the staff at all the levels (Currentnursing.com, 2014). In their studies Pinto and Melo took the nurses of a hospital administration as a sample for research. They concluded their role in the auditing as one of the most critical job. The constant efforts put by them into maintenance of the records, knowledge of prescribed medications and correct analysis and interpretation of data were appreciated by them. They interviewed professionals at different strata of the administration and came to a conclusion about the intricate nursing role (Pinto and Melo, 2010).Maturity-Onset Diabetes of The Young Essay
Similarly, auditing is a necessity for the treatment of diabetic patients as it is a disease with lifelong effects. A thorough check on the patients can help in controlling the probability of future complications, if any. The data collected will be helpful in assessing the efficacy of the medications prescribed, recommended dietary changes, lifestyle changes and also if the patient has been following the prescribed guidelines or not can also be determined. The ever increasing number of diabetic individuals in the world is leading to an alarming situation. The need to control the disease has been increasing substantially. According to the data, in 2010 almost 285 million all over the world were found to be diabetic with a percentage of people with type 2 diabetes or diabetes mellitus as high as 90%. The number increased almost up to 100 million within three years span. In 2013, the International Diabetes Federation estimated the number of diabetics as 381 million. Although found all over the world, the prevalence of diabetes is higher in developed countries (Wikipedia, 2014).The cause could be an affluent standard of living, hectic lifestyles with no time for exercises, food habits and sedentary lifestyle. In short it can be said that diabetes and other lifestyle diseases are the price the people are paying for modernisation. Studies reveal that by 2030 a huge population of the western countries will be diabetic individuals, including both adults and adolescents. The tendency to obesity increases the chances of diabetes manifolds. The dietary habits of the western culture play a very important role in that. The increasing dependence of the people on fast foods and processed foods is creating havoc on the health of the people.Maturity-Onset Diabetes of The Young Essay
The aim of the following audit is to observe the number of diabetic patients in a clinical set up, to determine the number of patients undergoing HbA1c test and their outcomes. We will take a sample group of 15 diabetic patients and study the pattern in them. Ideally the patients who are already diagnosed cases of diabetes should undergo the HbA1c test at least once annually. Those with uncontrolled diabetes should take the test every six months to keep an eye over any possible health hazards as a complication of diabetes. The patients were observed for a period of one year, the information was collected from the patients’ records. The nurses were informed about the conduction of the audit and permissions were taken from the concerned authorities and officials.
Out of the 15 patients, 9 patients had good glycemic control whereas 6 had a poor glycemic control. All these 15 patients were asked to undergo the HbA1c test. Among the 9 patients who were considered to have a good glycemic control on the basis of random blood sugar test, 6 patients got the test done, rest 3 did not turn up for the test. 2 of the patients who have undergone the test have shown an increased level of HbA1c which puts them in the risk group. The other 4 showed good results. Out of the high random blood sugar patients group, 4 people came for the test, rest were not available. All of the 4 showed high HbA1c levels, thus requiring an immediate action to be taken. The patient turnover for the recommended test is not satisfactory; the reasons could be lack of awareness among the patients about the importance of the test. It thus becomes the responsibility of the health care professionals to inform the patients about the values of the test and their significance as prognostic markers.Maturity-Onset Diabetes of The Young Essay
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 �“ 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.Maturity-Onset Diabetes of The Young Essay
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.Maturity-Onset Diabetes of The Young Essay
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.Maturity-Onset Diabetes of The Young Essay
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 diabetes�”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.Maturity-Onset Diabetes of The Young Essay 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. Maturity-Onset Diabetes of The Young Essay 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 Maturity-Onset Diabetes of The Young Essay
The HbA1c test can be used as a screening test for high risk individuals, in their study conducted by Rohlfing et al, they showed that levels above the normal values are indicative of risk for development of diabetes. A routine blood sugar test may not be that specific and sensitive but HbA1c levels almost confirm the future chances of diabetes. The study was conducted by them on a sample population who were made to undergo both fasting blood sugar test and HbA1c test. The reports were studied and it was found that the patients who showed a standard deviation of 2 above the normal HbA1c level were at a higher risk of developing diabetes than others. HbA1c levels were more specific and the test was more convenient than fasting blood sugar test (Rohlfing et al., 2000). The nursing professionals can prove to be a great help in spreading awareness among the patients about diabetes and its association with the HbA1c levels. Research conducted by Sanjay et al., depicted that a large number of patients who were diabetic had no knowledge of the test. Thus the lack of knowledge among the patients is making it difficult to fully enforce the utility of the test (Sanjay et al., 2012). They can instill among the patients the need to undergo the test repeatedly for their own well being. A good control over the blood sugar level over a period of 2-3 months will be reflected in the HbA1c values, thus giving a clear prognostic picture of the disease. A good hospital care taken by the nurses and other healthcare professionals can inculcate similar habits in the patients that they will follow after being discharged, thus helping in proper care taking. A proper dietary plan and a physical exercise schedule will help in achieving proper glycemic control. For patients with uncontrolled sugar levels or high HbA1c levels regular physical examinations will be required to be carried out to eliminate the occurrence of any complications like diabetic retinopathy, diabetic ulcers, cardiovascular diseases, renal failure and so on (International Diabetes Federation, 2014). Not just the nursing professionals, personnel at all the levels of the health care departments need to put in their best to reduce the chances of occurrence of the complications in diagnosed patients, to screen the high risk group individuals, and to combat the occurrence of diabetes at the very initial level (Barclay, 2010).Maturity-Onset Diabetes of The Young Essay The occurrence of diabetes can be reduced by creating awareness among the people about healthy eating habits, encouraging the people for physical activities and working towards reduction of obese individuals all over the world (Ndep.nih.gov., 2014). A frequent screening test should be carried out at the health centers, repeated HbA1c testing would be helpful in analyzing not only the complications in diagnosed diabetic individuals, but will also reflect the status of the patients who are at a risk of developing diabetes or in other words, the potential diabetics (Nhs.uk., 2014). Lack of awareness among the patients regarding the test is causing hindrance to its success, a thorough knowledge needs to be provided to the patients so that they will appreciate its importance and take the test when required. It should be made a mandatory practice in health care set ups for diabetes to make the patient undergo the test at least once in every 3 months, especially in the patients who showed an HbA1c level higher than 7 during the initial test (Driskell et al., 2014). In patients with a controlled blood sugar the test can be repeated every 6 months (Diabetes.niddk.nih.gov, 2014). In a study conducted by Higgins et al., they showed that alone HbA1c values cannot confirm the diagnosis of diabetes. Even after obtaining a value of less than 7%, around 12% patients tested positive for diabetes, thus suggesting that the HbA1c levels alone cannot confirm the diagnosis (Higgins et al., 2011).Maturity-Onset Diabetes of The Young Essay
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This review covers the pathophysiology, diagnosis, epidemiology, etiology, clinical presentation, management and complications associated with diabetes mellitus commonly known as diabetes, a disorder that affects more than 385 million people worldwide (idf.org). The long term prognosis and impact on the quality of life are also discussed. Diabetes is defined by the American diabetes association as a group of disorders that are characterized by hyperglycemia stemming from deficiency in the activity of insulin or reduced insulin secretion, or both. There are three main types of diabetes namely type 1, type 2 and gestational diabetes. Diabetes mellitus has no cure. It is a lifelong chronic condition that needs to manage by medication, diet, weight management, and physical activity. The hyperglycemia associated with diabetes can lead to a number of complications affecting multiple organs including, neuropathy, macular degeneration, amputation of limbs, vascular diseases, kidney diseases, etc. The risk for cardiovascular disease also increases with diabetes.Maturity-Onset Diabetes of The Young Essay
The classification of diabetes is based on the physiological process resulting in hyperglycemia. The two main types of DM include the type 1 and type 2 diabetes. The type 1 diabetes occurs as a manifestation of near total or absolute deficiency of insulin by the pancreas. Type 2 diabetes is a more heterogeneous disease in which a deficiency of insulin secretion, insulin resistance or increased glucose production can result in hyperglycemia. Type 2 diabetes occurs to a number of risk factors, including, genetics, environmental factors, and metabolic defects in the patients. It is observed that type 2 diabetes occurs following a period of pre-diabetes. Pre-diabetes, is a critical phase in which while most patients are asymptomatic have an impaired glucose tolerance. If diagnosed and treated many prediabetics can avoid the eventual diagnosis of DM. In the previous system of classification, diabetes was classified as insulin dependent and non- insulin dependent diabetes mellitus. However, it has been shown that many patients with NIDDM require insulin eventually, the use of NIDDM is confusing.
Other types of DM include the gestational diabetes (GDM) and the maturity onset diabetes of the young (MODY). Gestational diabetes is the diabetes that occurs during pregnancy. It is described as increased glucose level in pregnancy or intolerance to the glucose levels. It is usually observed in the second and third trimesters of pregnancy. GD affects 5-7 of all pregnancies (Schoeber, et al., 2006). While most women return back to normal FGL level a substantial 30-50% develop DM later in the life. MODY is diabetes that occurs in young adults due to a number of genetic mutations. The hyperglycemia occurs at < 25 years. The two most commonly identified mutations associated with MODY include the HNF1A and the GCK genes. MODY is very commonly misdiagnosed as either type 1 or type 2.Maturity-Onset Diabetes of The Young Essay
The world health organization and the national diabetes association have developed the diagnosis criteria for diabetes mellitus. The criteria have been developed based on the a). Fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) is different in normal and diabetic adults. b).The level of glycemia has to be defined based on the level at which complications occur in patients (idf.org)Maturity-Onset Diabetes of The Young Essay
The two main diagnostic criteria include
• Fasting blood glucose level is ≥ 7 mmol/L; Two hour plasma glucose is ≥ 11.1 mmol/L at the end of an oral glucose tolerance test.
A third rarely used criteria states that following random sampling blood glucose concentration is 11.1 mmol/L in addition to the presence of various diabetes associated symptoms. According to the ADA protocol, a repeat testing is recommended if an unambiguous result is not obtained. In addition to the diagnostic criteria, the diabetes mellitus patients are also defined based on their glucose tolerance levels. 1. Fasting plasma glucose level of < 5.6 mmol/L is considered healthy and normal. 2. FPG levels between 5.6-6.9 mmol/L is defined as pre-diabetes. 3. FPG level of ≥ 7 mmol/L is diagnosed as diabetes.
Another diagnostic marker that is recommended by some clinicians for DM diagnosis is the Hemoglobin A1C (HbA1C) level at ≥ 6.5%. However, a clear correlation between the HbA1C level and subjects with mild glucose intolerance or normal tolerance to glucose is not established. A conclusive diagnosis of DM results in a major impact on the life of the patient. As a result, various criteria must be satisfactorily satisfied to impart a diagnosis. As has been stated, DM is not a disease it is a way of life (Alberti and Zimmet, 1998).Maturity-Onset Diabetes of The Young Essay
DM is a disease that affects the rich and poor alike. In fact, it is touted as the disease of the rich world. It was demonstrated that an estimated 30 million patients were reported to have DM in 1985. In the year 2014, an estimated 385 million patients have been reported to be suffering from DM (who.org). The number of cases with type 2 diabetes rise at a higher rate than the type 1 as a result of increasing obesity epidemic worldwide and especially as the rate of industrialization increases. It is known that the incidence of DM increases with age. 20.9 % of all adults over the age of 60 had DM. The occurrence of DM is observed to be similar between men and women, with men >60 showing a greater prevalence.
Type 1 and type 2 diabetes demonstrate a difference based on the location. The Scandinavia region has been reported to have the highest type 1 incidence while the Pacific rim including Japan and parts of China report to have lowest worldwide occurrence of type 1 diabetes. The occurrence of pre-diabetes and type 2 diabetes is greatest in a few Pacific islands. Nations like US and India demonstrate a medium to high occurrence, and most of the African nations demonstrate a low type 2 DM incidence (idf.org).Maturity-Onset Diabetes of The Young Essay
Insulin is the hormone that is secreted by the cells (islets of Langerhans) of the pancreas in response to elevated blood glucose levels following a meal. While glucose is the key modulator of insulin secretion, amino acids, other nutrients, ketones and some neurotransmitters can affect the secretion of insulin. A blood sugar level of >4 mmol /L followed by the transport of glucose by glucose transporter 2 to the islet cells results in increased production of insulin and subsequent release. Glucose gets phosphorylated by the glucokinase that can regulate secretion of insulin. Glucose -6 phosphate is further metabolized by glycolysis that inhibits the activity of ATP sensitive K+ channel. Inhibition of the K+ channel results in opening of voltage dependent Ca2+ channels inducing secretion of insulin (Butler et al., 2006). Incretin are proteins released by neuroendocrine cells, and they stimulate the insulin secretion following food consumption. Following the release of insulin, it binds to insulin receptor and activates tyrosine kinase activity of the receptor. The insulin receptor undergoes auto-phosphorylation resulting in recruitment and activation of a number of signaling pathways. One event associated with the activation of insulin receptor involves glucose transporter 4 (GLTU4). GLUT4 gets translocated to the cellular surface resulting in the uptake and absorption of glucose in skeletal muscle and fat (Tisch & McDevitt, 1996). The homeostasis of glucose involves uptake of glucose by muscle and fat cells and production of glucose in the liver. Insulin is the primary regulator of maintaining this homeostasis in humans. In most cells the glucose uptake and release in under the control of insulin except cells such as in the brain.Maturity-Onset Diabetes of The Young Essay
Type 1 diabetes occurs as a result of genetic and immunological factors that result in the destruction pancreatic beta cells. In most type 1 patients, an autoimmune mediated destruction of the islet cells of pancreas is observed. Individuals have a genetic mutation are born predisposed to developing autoimmunity. They exhibit normal pancreatic function at the time of birth, however, following a certain trigger the functioning beta cells decrease and the beta cell mass gets reduced also. This results in a progressive decrease in the production and secretion of insulin. Unfortunately most type 1 patients remain asymptomatic for a long time, and clinical symptoms become evident when 80% or more of the beta cells are damaged. The remaining functioning beta cells can produce some insulin that is inadequate to maintain a proper balance of glucose level. The remaining beta cells are destroyed eventually making the patient completely insulin deficient.
The genes most commonly responsible for predisposition to type 1 are located on the HLA region of chromosome 6. This cluster of genes is responsible for the synthesis of major histocompatibility (MHC) II molecules. These MHC II molecules are involved in initiating an immune response resulting in the islet cell death. In addition to the HLA region genes, certain other genes such as the IF1H1, PTPN22, CTLA-4, etc. are responsible for increasing susceptibility to developing type 1 ( Davies et al., 1994). The beta cells are infiltrated by T lymphocytes and attacked a number of cytokines resulting in beta cell death (Daneman, 2006).Maturity-Onset Diabetes of The Young Essay
Type 2 diabetes progression carries a greater genetic component. A person with both parents’ diagnosed with type 2 diabetes has a 40% likelihood of developing type 2 diabetes. Identical twins bear a greater degree of co-occurrence. There are a few genes that have been identified as being responsible for increasing susceptibility to type 2. Genetic polymorphism is also associated with increased risk for type 2 diabetes development. However, in addition to the genetic component environmental factors play a vital role too. Obesity, presence/absence of physical activity and diet contribute to the risk for type 2 diabetes. Pre-diabetes is usually identified in obese patients especially centrally or viscerally obese people. Many pre-diabetics present insulin resistance which is compensated by increased insulin production by the beta cells. The beta cells, however, fail to keep up with the demand and hyperglycemia develops. This state of pre-diabetes is followed by further reduction in insulin secretion and increased glucose production in the liver resulting in type 2 diabetes.Maturity-Onset Diabetes of The Young Essay
The occurrence of type 2 diabetes is a follow up to an event called “insulin resistance”. In this condition, the cells are not receptive to the plasma glucose level and cannot utilize the glucose adequately resulting in hyperglycemia. Obesity has been identified as a critical driver for insulin resistance. A greater fat content and fatty acids inhibit the signaling molecules driving the insulin receptor activity (Muoio & Newgard, 2011). Free fatty acids also inhibit the utilization of glucose in skeletal muscle cells and impair the activity of pancreatic beta cells. Insulin resistance is also an indicator of metabolic syndrome. Metabolic syndrome is a term used to describe a number of metabolic deficiencies including hyperglycemia, dyslipidemia, and hypertension. Pre-diabetes is one of the conditions of metabolic syndrome. It has been reported that if identified, pre-diabetes can be treated, and progression to diabetes prevented.
Some of the classical symptoms of diabetes ae frequent urination, increased thirst and increased hunger. These symptoms are commonly presented in patients with type 1 diabetes. Many type 2 patients do not show any of these symptoms. Diabetes affects the blood flow and often leads to a number of microvascular and macro-vascular complications. Diabetes leads to damage to blood vessels. This vascular damage can lead to retinopathy or eye damage, nephropathy or kidney damage. Damage to nerves is also observed in an ineffective hyperglycemia control. Diabetic neuropathy leads to wasting of nerve cells. As diabetes affects the circulation, the lower extremities including toes and feet can suffer damage and require amputation in uncontrolled cases. Diabetes also increases the risk for peripheral vascular disease, stroke and cardiovascular disease.Maturity-Onset Diabetes of The Young Essay
Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic nonketotic syndrome (HHNS) are two of the severe complications of diabetes. DKA can induce coma and be life threating. DKA manifests as due to inadequate glucose metabolism fat cells are metabolized to derive energy. Excessive breakdown of fat causes production of ketone bodies that are toxic to the human body. HHNS occurs when the body tries to remove all of the excess sugar resulting in excessive urination. This excessive urination can lead to coma and death if not treated in a timely manner (Olokaba, Obateru & Olokaba, 2012).
Treatment and Management
The aim of diabetes treatment is to maintain ‘normal’ blood glucose level or achieve a state of euglycemia. The maintenance of normal glucose level can be attained by a combination of medication, physical activity, diet, and weight loss. Metformin, a biguanide is the first line of treatment against type 2 diabetes. Metformin induces activation of AMP activated protein kinase responsible for regulating expression of gluconeogenesis genes.Maturity-Onset Diabetes of The Young Essay It inhibits gluconeogenesis that is the production of glucose from the liver. It has also been shown to increase the sensitivity to insulin by phosphorylating GLUT 4 enhancer receptor. Sulfonylureas are also used to treat hyperglycemia in patients with type 2 diabetes. They bind to the ATP dependent K+ channel in the beta cells and stimulate the secretion of insulin. These agents are well tolerated but have been associated with hypoglycemia. In addition to sulfonylurea, Meglitinides also act on the ATP dependent K+ channel and induce insulin secretion. Meglitinides have a short duration of action and therefore exhibit a lower risk of hypoglycemia. Thiazolidinedione are the third group of drugs used in the management of type 2 diabetes. They bind to and activate the peroxisome proliferator activated gamma (PPAR- ) receptor. Alpha-glucosidase analogues such as Acarbose, Miglitol, incretin based agents, DPP-IV inhibitors are other agents used in the treatment of type 2 diabetes (Tehrani, Bailey, Del Parto & Barnett, 2011)
Patients with type 1 diabetes are treated with insulin. Insulin replacement therapy is carried out by using insulin or insulin analogues. The insulin administered to the patients can differ based on the onset of effect. The insulin can be differentiated based on the onset and duration of action (Migdalis, 2001). A fast acting insulin (lyspro) preparation works rapidly and is used to manage glucose levels between meals. A long acting insulin (NPH, lente and ultralente insulin) is absorbed at a slower rate and has longer duration of action. Insulin can be administered as injection or infusion. The insulin syringe is the most common method of insulin administration. However, in recent years insulin pen is becoming more popular. The insulin pen contains a ‘cartridge’, a replaceable reservoir with needle to puncture the skin for delivery.Maturity-Onset Diabetes of The Young Essay
In addition to physiological effects, diabetes can cause depression, anxiety and feeling of helplessness in patients due to the lack of cure. Weight gain can occur due to environmental factors. In addition to diabetes treatment, the care should involve proper education, especially among the poor and the elderly. The importance of physical activity, maintaining healthy diet, controlling alcohol consumption should be imparted in all diabetics. Tobacco intake should be stopped in patients with diabetes. While there is no cure for this disease, novel drugs are being developed. A wholesome approach to the management of this lifestyle can result in patients leading happy and fulfilling lives.
Read more at: https://www.wowessays.com/free-samples/free-diabetes-a-review-essay-example/
Diabetes mellitus is a disorder that affects the body’s
ability to make or use insulin. Insulin is a hormone produced in the pancreas that helps transport glucose (blood
sugar) from the bloodstream into the cells so they can
break it down and use it for fuel. People cannot live
without insulin (ADA, 2007).Maturity-Onset Diabetes of The Young Essay
Diabetes results in abnormal levels of glucose in the
bloodstream. This can cause severe short-term and longterm consequences ranging from brain damage to amputations and heart disease (ADA, 2007).
Root causes of diabetes mellitus (DM)
The root causes of diabetes are complex. Most cases
begin with one of two processes:
Metabolic: Unhealthy lifestyle factors such as overeating, physical inactivity and obesity can impair the
body’s ability to use insulin. This is called insulin resistance. Uncontrollable risk factors including genetics, family history and age can also be involved. Metabolic
forms of diabetes include:
Type 2 diabetes: This accounts for 90 – 95% of diabetic
cases, according to the U.S. National Institutes of Health
(NIH). Some of these patients have had prediabetes that
went uncontrolled. Once considered a disease of middle
and old age, type 2 is also becoming more common in
youths as the incidence of childhood obesity grows.
Gestational diabetes: Hormonal changes contribute to
this condition which can develop in any previously nondiabetic woman during pregnancy, especially those who
are overweight.Maturity-Onset Diabetes of The Young Essay
The body’s immune system can mistakenly destroy the
insulin-producing beta cells of the pancreas. The causes
of autoimmune diabetes are poorly understood, but
genetics and family history play a role, and viruses or
other environmental factors are believed to figure in.
Autoimmune forms of diabetes include:
Type 1 diabetes: Formerly known as juvenile diabetes,
this form generally develops in children and young adults.
Latent autoimmune diabetes of adulthood: This variation of type 1 can occur later in life. Individuals with autoimmune diabetes who overeat, are sedentary, gain
weight or have certain genes can, like people with metabolic forms of diabetes, develop insulin resistance. This
state is known as double diabetes.
Diabetes can also result from another disease, such as
pancreatitis, or even from a medical treatment, including
pancreatectomy (surgical removal of the pancreas) or certain medications. This is known as secondary diabetes. In
addition, there are uncommon inherited disorders that
cause diabetes, such as maturity-onset diabetes of the
young and Wolfram syndrome. Most cases of diabetes
368 Sci. Res. Essays
last the rest of a person’s life. However, gestational diabetes generally ends when the pregnancy does, and
some cases of secondary diabetes are also temporary
(Cefalu et al., 2007).Maturity-Onset Diabetes of The Young Essay
Factors contribute in DM
Diabetes involves chronic levels of abnormally high
glucose (hyperglycemia). Many patients, especially those
with type 2 diabetes, also have elevated blood pressure
(hypertension), chronic high levels of insulin (hyperinsulinemia) and unhealthy levels of cholesterol and other
blood fats (hyperlipidemia). All of these factors contribute
to the long-term complications of diabetes, which include:
Vascular disease (diabetic angiopathy), atherosclerosis, heart conditions and stroke: These cardiovascular disorders are the leading cause of death in people
Kidney disease (diabetic nephropathy): Diabetes is
the chief cause of end-stage renal disease, which requires treatment with dialysis or a kidney transplant.
Eye diseases: These include diabetic retinopathy,
glaucoma and cataracts. Diabetes is a leading cause of
visual impairment and blindness.
Nerve damage (diabetic neuropathy): This includes
peripheral neuropathy, which often causes pain or numbness in the limbs, and autonomic neuropathy, which can
impede digestion (gastroparesis) and contribute to sexual
dysfunction and incontinence. Neuropathy may also
impair hearing and other senses.Maturity-Onset Diabetes of The Young Essay
Impaired thinking: Many studies have linked diabetes to
increased risk of memory loss, dementia, Alzheimer’s disease and other cognitive deficits. Recently some researchers have suggested that Alzheimer’s disease might be
“type 3 diabetes,” involving insulin resistance in the brain.
Infections and wounds: Foot conditions and skin disorders, such as ulcers, make diabetes the leading cause
of nontraumatic foot and leg amputations. People with
diabetes are also prone to infections including periodontal
disease, thrush, urinary tract infections and yeast infections.
Cancer: Diabetes increases the risk of malignant tumors
in the colon, pancreas, liver and several other organs.
Musculoskeletal disorders: Conditions ranging from
gout to osteoporosis to restless legs syndrome to myofascial pain syndrome are more common in diabetic patients than nondiabetics.
Pregnancy complications: Diabetes increases the risk
of preeclampsia, miscarriage, stillbirth and birth defects.
Emotional difficulties: Many but not all of the studies
exploring connections between diabetes and mental
illness have found increased rates of depression, anxiety
and other psychological disorders in diabetic patients. In
addition to chronic hyperglycemia, diabetic patients can
experience acute episodes of hyperglycemia as well as
hypoglycemia (low glucose). Severe cases can cause
seizures, brain damage and a potentially fatal diabetic
coma. Acute glucose emergencies include:
Insulin shock: This advanced stage of hypoglycemia is
typically due to excessive amounts of insulin medication
or certain antidiabetic agents.
Diabetic ketoacidosis: A lack of insulin can force the
body to burn fats instead of glucose for energy. The
result is a toxic byproduct called ketones, along with severe hyperglycemia.Maturity-Onset Diabetes of The Young Essay
Hyperosmolar hyperglycemic nonketotic state: This
involves severe hyperglycemia and dehydration.
These dangerous glucose complications are most common in patients with unstable diabetes, but they can develop even in individuals who do not realize they have
diabetes. About one-third of the estimated 20.8 million
Americans with diabetes have not yet been diagnosed,
according to the U.S. Centers for Disease Control and
Prevention (CDCP, 2005).
Incidence of Diabetes Mellitus
The incidence of diabetes has soared worldwide in recent
years and is expected to keep growing, with the greatest
increase seen in metabolic forms of diabetes, notably
type 2. This is blamed largely on the rise of obesity and
the global spread of Western-style habits: physical inactivity along with a diet that is high in calories, processed
carbohydrates and saturated fats and insufficient in fiberrich whole foods. The aging of the population is also a
factor. However, other factors, such as environment may
also be contributing, because cases of autoimmune diabetes (type 1) are also becoming more common.
The estimated number of people with diabetes has
jumped from 30 million in 1985 to 150 million in 2000 and
then to 246 million in 2007, according to the International
Diabetes Federation. It expects this number to hit 380
million by 2025. Seven percent of Americans have diabetes, according to the CDC, which predicts that one in
three Americans born in 2000 will eventually become
diabetic. Health agencies are warning that diabetes is becoming an unprecedented epidemic even as other major
diseases including cancer and nondiabetic heart disease
are being controlled.Maturity-Onset Diabetes of The Young Essay
Diabetes is ranked as the sixth-leading cause of death
in the United States, but the actual ranking may be higher
because it is underreported as a cause of death, according to the NIH. Diabetes kills more than 1 million people
a year, the World Health Organization reports. It predicts
life expectancy to decline worldwide for the first time in
two centuries because of diabetes. Experts are urging
people to help stem this epidemic by getting regular exercise and controlling their diet and weight.
Humans are not the only species that can develop diabetes. This disease also occurs in dogs, cats and other
animals, as increasing numbers of pet owners are discovering.
The word “diabetes” stems from a Greek term for passing through, a reference to increased urination (polyuria), a common symptom of the disease. “Mellitus” is the
Latin word for honeyed, a reference to glucose noted in
the urine of diabetic patients.
Diabetes mellitus is sometimes referred to as sugar
diabetes but usually is simply called diabetes. There is
also a rare disease called diabetes insipidus (water diabetes) in which the kidneys release too much water. Like
diabetes mellitus, it has excessive urination as a symptom, but these two endocrine disorders are otherwise
unrelated (DCCT, 1993).
Types and differences of diabetes
There are several forms of diabetes. Scientists are still
defining and categorizing some of these variations and
establishing their prevalence in the population. Types of
diabetes include:Maturity-Onset Diabetes of The Young Essay
Type 1 diabetes: An autoimmune disease in which the
immune system mistakenly destroys the insulin-making
beta cells of the pancreas. It typically develops more
quickly than other forms of diabetes. It is usually diagnosed in children and adolescents, and sometimes in
young adults. To survive, patients must administer insulin
Type 1 diabetes used to be called juvenile diabetes and
insulin-dependent diabetes mellitus (IDDM). However,
those terms are not accurate because children can develop other forms of diabetes, adults sometimes develop
type 1, and other forms of diabetes can require insulin
A variation of type 1 that develops later in life, usually
after age 30, is called latent autoimmune diabetes of
Sometimes patients with autoimmune diabetes develop
insulin resistance because of weight gain or genetic
factors. This condition is known as double diabetes.
Type 2 diabetes: A disorder of metabolism, usually
involving excess weight and insulin resistance. In these
patients, the pancreas makes insulin initially, but the body
has trouble using this glucose-controlling hormone.
Eventually the pancreas cannot produce enough insulin
to respond to the body’s need for it.Maturity-Onset Diabetes of The Young Essay
Type 2 diabetes is by far the most common form of
diabetes, accounting for 85 to 95% of cases in developed
nations and an even higher percentage in developing
nations, according to the International Diabetes Federation.
This disease may take years or decades to develop. It
is usually preceded by prediabetes, in which levels of
glucose (blood sugar) are above normal but not high
enough yet for a diagnosis of diabetes. People with prediabetes can often delay or prevent the escalation to type
2 diabetes by losing weight through improvements in
exercise and diet, as the Diabetes Prevention Program
and other research projects have demonstrated.
Type 2 diabetes used to be called adult-onset diabetes
and non-insulin-dependent diabetes mellitus (NIDDM).
Those terms are not accurate because children can also
develop this disease, and some patients require insulin
Gestational diabetes: A temporary metabolic disorder
that any previously nondiabetic woman can develop during pregnancy, usually the third trimester. Hormonal
changes contribute to this disease, along with excess
weight and family history of diabetes. About 4% of pregnant women develop gestational diabetes, according to
the American Diabetes Association.
Gestational diabetes can cause problems for the mother
and baby, including preeclampsia, premature deli-very,
macrosomia (oversized infant), and jaundice and
breathing difficulties in the infant. This disease typically
ends when the pregnancy does, but it increases the risk
of type 2 diabetes later in life for the mother and the child.
Secondary diabetes: Diabetes caused by another condition. The many potential sources of secondary diabetes
range from diseases such as pancreatitis, cystic fibrosis,
Down syndrome and hemochromatosis to medical treatments including corticosteroids, other immunosuppressives, diuretics and pancreatectomy.Maturity-Onset Diabetes of The Young Essay
Maturity-onset diabetes of the young (MODY). An uncommon disease caused by a genetic defect inherited
from a parent. It is usually diagnosed before age 25 in
people of normal weight. MODY is sometimes classified
as a form of type 2 or secondary diabetes but is often
considered a separate condition.
There are also rare syndromes (clusters of conditions)
that include diabetes, notably:
Wolfram syndrome: A genetic disorder that involves
insulin-dependent diabetes, vision problems, deafness
and diabetes insipidus.
Autoimmune polyglandular syndrome (APS): Group of
autoimmune endocrine diseases. Two of the three forms
of APS feature type 1 diabetes.
Unstable diabetes, also known as brittle or labile diabetes, is a term that may be used to describe any case of
poorly controlled diabetes regardless of the type.
All of these conditions involve diabetes mellitus (“sugar
370 Sci. Res. Essays
diabetes”). Diabetes insipidus (“water diabetes”) is an
unrelated endocrine system disorder in which the kidneys
release too much water (Frank, 2004; Jawa et al., 2004).
Risk factors and causes of diabetes
The causes of diabetes are complex and only partly
understood. This disease is generally considered multifactorial, involving several predisposing conditions and
risk factors. In many cases genetics, habits and environment may all contribute to a person’s diabetes.
To complicate matters, there can be contrary risk
factors for the various forms of the disease. For example,
autoimmune diabetes (type 1 and latent autoimmune
diabetes of adulthood, LADA) is more common in white
people, but metabolic diabetes (type 2 and gestational
diabetes) is more common in people of other races and
ethnicities. Type 1 is usually diagnosed in children, but
advancing age is a risk factor for type 2 and gestational
diabetes.Maturity-Onset Diabetes of The Young Essay
Insulin resistance, prediabetes and metabolic syndrome are strong risk factors for type 2 diabetes. Other
diabetic risk factors and causes include:
Genetics and family history: Certain genes are known
to cause maturity-onset diabetes of the young (MODY)
and Wolfram syndrome. Genes also contribute to other
forms of diabetes, including types 1 and 2.
Family medical history is also influential to varying
degrees: For example, a person whose parents both
have type 1 diabetes has a 10 to 25% chance of developing that disease, according to the American Diabetes
Association, and someone whose parents both have type
2 diabetes has a 50% chance of developing that disease.
Weight and body type: Overweight and obesity are
leading factors in type 2 diabetes and gestational diabetes. Excess fat, especially around the abdomen
(central obesity), promotes insulin resistance and metabolic syndrome.
Most people with autoimmune diabetes (type 1 and
LADA) are of normal weight, and excess weight has not
traditionally been considered to be related to these
conditions. However, recent research indicates that obesity may hasten the development of type 1 diabetes and
that the increasing rate of type 1 diabetes may be at least
partly due to the rise of childhood obesity. Furthermore,
patients with autoimmune diabetes who gain weight are
susceptible to insulin resistance and double diabetes.
Sex: Though men make up less than 49% of the U.S.Maturity-Onset Diabetes of The Young Essay
adult population, they account for 53% of the adult cases
of diabetes, according to the National Institutes of Health
(NIH). The prevalence of diabetes in American men and
women was similar until 1999, when a growing disparity
began, according to an analysis of statistics published by
the U.S. Centers for Disease Control and Prevention
(CDC). Little or no research has been conducted to
explain this trend. One factor may be the documented
increase in recent years of low testosterone levels (male
hypogonadism), which scientists have linked to insulin
Level of physical activity: Lack of regular exercise is
blamed for much of the twin global epidemics of obesity
Diet: The effect of diet in the development of diabetes is
controversial. Some studies have linked heavy consumption of soft drinks and other simple carbohydrates to risk
of metabolic diabetes, and foods low in the glycemic
index, such as whole grains, to reduced risk. Yet the ADA
states that eating foods containing sugar does not cause
the disease. The culprit, rather, is the weight gain due to
sedentary habits and excess intake of calories, according
to the ADA.Maturity-Onset Diabetes of The Young Essay
Another dispute centers around whether being fed cow’s
milk early in life might be linked to type 1 diabetes. Some
researchers have noted a connection, but others have
not. Further scientific research is likely on this topic.
Other diseases: Medical conditions including high blood
pressure, hyperlipidemia (unhealthy levels of cholesterol),
polycystic ovarian syndrome, asthma and sleep apnea
have been linked to type 2 diabetes. Celiac disease
(gluten intolerance) and other autoimmune diseases have
been linked to type 1. The many conditions that may
cause secondary diabetes include pancreatitis, hemochromatosis, endocrine disorders including hyperthyroiddism, Cushing’s disease and acromegaly, and genetic
conditions including cystic fibrosis, Down syndrome and
some forms of muscular dystrophy, Diabetic foot and
urinary tract infection (Lipsky et al., 2004; Mokabberi and
Hormones: These chemical messengers can contribute
to diabetes in various ways. For example, stress hormones such as cortisol have been linked to fluctuating
glucose levels in type 2 diabetes, and stress hormones in
women during pregnancy have been linked to risk of type
1 diabetes in the child. The release of growth and sex
hormones during adolescence may make some teens
more susceptible to diabetes. A wide range of hormonal
treatments including anabolic steroids, growth hormone,
estrogens, injected contraceptives, androgen deprivation
therapy for prostate cancer and corticosteroids have
been linked to secondary diabetes.
Medical treatments: In addition to hormonal therapies,
medications including diuretics, beta blockers (another
class of antihypertensives), immunosuppressives, antiretrovirals (AIDS/HIV drugs) antipsychotics, lithium, and
some antidepressants, anticonvulsants and chemotherapy drugs have been linked to an increased risk of
secondary diabetes. Pancreatectomy and radiation therapy may also result in secondary diabetes. Drugs including
pentamidine (used to treat pneumonia) and L–asparaginase (used to treat leukemia) have been linked to type
1 diabetes.Maturity-Onset Diabetes of The Young Essay
Other chemicals: In addition to these pharmaceuticals,
some studies have linked PCBs, other pollutants and
certain pesticides including the defoliant Agent Orange
and dioxin (its active ingredient) to insulin resistance and
type 2 diabetes. Common consumer plastics and plastics
ingredients including phthalates and bisphenol A have
also been linked to insulin resistance in some cases.
Exposure to agricultural pesticides during pregnancy has
been tentatively linked to gestational diabetes. A rat poison called pyriminal has been linked to type 1 diabetes.
Other environmental factors: Some researchers theorize that free radicals may contribute to the development
of type 1 and possibly other forms of diabetes. Free radicals are formed as a result of chemical reactions in the
body. Smoke, air pollution and even genetics contribute
to the formation of free radicals. When these radicals
build up, they can destroy cells, including those involved
in the production of insulin.
Cold weather is another possible environmental factor
in type 1 diabetes. This disease occurs more commonly
in cold climates and develops more frequently in the winter than the summer.
Viruses: Some people are diagnosed with type 1 diabetes after a viral infection. Viruses thought to be related
to type 1 diabetes include mumps, rubella and coxsackie
virus (related to the virus family that causes polio and
Smoking: Cigarette smoking is a risk factor for type 2
diabetes and possibly other forms of diabetes.
Alcohol: Excessive use of alcohol is a risk factor for
diabetes. For example, it can cause pancreatitis. However, some research has found that light drinking may
decrease the risk of becoming diabetic.
Most of these risk factors can be described as either
uncontrollable, such as genetics and age, or controllable,
such as exercise and diet. Some, such as obesity, may
involve genetics and lifestyle choices. People cannot alter
their uncontrollable risk factors, but they can lower their
risk of developing diabetes by reducing controllable risk
factors through improved health habits.Maturity-Onset Diabetes of The Young Essay
Signs and symptoms of diabetes
Diabetes often goes undetected because symptoms can
be attributed to many other causes and some patients
experience no symptoms or fail to heed warning signs.
Possible indicators of diabetes include:
– Excessive thirst (polydipsia)
– Excessive urination (polyuria) and dehydration
– Excessive hunger or appetite (polyphagia)
– Unexplained weight loss
– Blurred vision, nearsightedness or other vision problems
– Frequent infections, including skin infections, thrush,
gingivitis, urinary tract infections and yeast infections
– Slow healing of sores
– Skin problems, such as itchiness or acanthosis
– Fatigue, lethargy or drowsiness
– Shakiness or trembling
– Mood swings or irritability
– Dizziness or fainting
– Numbness, tingling or pain in the feet, legs or hands
Type 1 diabetes can develop rapidly and often occurs
after an illness, but symptoms may be mistaken for the flu
or other common conditions. Type 2 diabetes can take
many years to develop and sometimes becomes apparent only after long-term complications occur, such as
sexual dysfunction or leg pain that is due to diabetic
neuropathy or claudication (caused by peripheral artery
disease).Maturity-Onset Diabetes of The Young Essay
Some people, especially young people with type 1
diabetes, go undiagnosed until they are brought to a hospital with an emergency condition called diabetic ketoacidosis. Indicators of diabetic ketoacidosis include sweet
fruity-smelling or wine-smelling breath, confusion and
heavy labored breathing (Kussmaul breathing). Sometimes patients are diagnosed with diabetes only after
suffering other serious complications including insulin
shock, hyperosmolar hyperglycemic nonketotic syndrome
or diabetic coma.
To help prevent such complications, people are advised to undergo periodic screening for diabetes with glucose tests, especially if they have risk factors.
Diagnosis methods for diabetes
Physicians use glucose tests to diagnose diabetes.
These blood tests measure the level of glucose (blood
sugar) in a person’s bloodstream.
Often when people have a physical examination they
are screened for diabetes with a fasting plasma glucose
test (FPG). An FPG is usually performed in the morning
because this makes it easier for the patient to fast for the
required eight hours.
Glucose is measured in milligrams per deciliter (mg/dl)
of blood. FPG results below 100 mg/dl are normal. Glucose between 100 and 125 mg/dl is considered prediabetes. Glucose above 125 mg/dl indicates diabetes.
To confirm diagnosis, another glucose test should be
performed on another day, according to the National
Institute of Diabetes and Digestive and Kidney Disorders.
If glucose testing determines that a patient has
diabetes, additional tests may be offered to establish the
type. For example, a C-peptide test can distinguish
372 Sci. Res. Essays
autoimmune from metabolic diabetes. People with type 2
diabetes have C-peptide, which is a byproduct of insulin
production, but people with type 1 diabetes and latent
autoimmune diabetes of adulthood do not nor have a
very low level.
Autoantibody testing can reveal misguided antibodies
present in autoimmune but not metabolic diabetes.
Genetic tests can help diagnose conditions such as
maturity-onset diabetes of the young and Wolfram
Other tests, such as thyroid blood tests, may be ordered to find the cause of secondary diabetes.
During pregnancy, usually during the 24th to the 28th
week, women may be screened for gestational diabetes
with a glucose challenge test, which evaluates the body’s
ability to metabolize sugar. Blood is drawn an hour after
the patient drinks a solution containing 50 g of glucose. If
results are abnormal, an additional, more complicated
blood test called an oral glucose tolerance test (OGTT) is
used to confirm diabetes (Peters et al., 1996).Maturity-Onset Diabetes of The Young Essay
Treatment options for diabetes
Patients who are diagnosed with diabetes usually require
regular monitoring by various healthcare providers to
manage their condition and reduce the risk of complications. For example, endocrinologists are physicians
who specialize in diabetes and other endocrine disorders.
In locations where an endocrinologist is not available, an
internist or other physician may treat diabetic patients.
Diabetes care teams also include certified diabetes
educators and registered dietitians. Patients need to see
an ophthalmologist and a dentist regularly and may be
referred as needed to other specialists such as a podiatrist, athletic trainer, cardiologist, nephrologist (kidney
specialist) or neurologist.
Diet and exercise are crucial in managing diabetes,
especially type 2 diabetes and gestational diabetes.
Some patients with metabolic forms of diabetes are able
to control their disease using only these lifestyle interventions, which help the body use glucose (blood sugar)
and prevent or reduce hyperglycemia. It is also important
to avoid smoking, drink enough water to avoid dehydration, and drink alcohol only in moderation and only if
approved by the physician.
All people with type 1 diabetes and Wolfram syndrome
and eventually all people with latent autoimmune diabetes of adulthood require regular insulin therapy to live.
Some people with other forms of diabetes, including
gestational diabetes, type 2 diabetes, secondary diabetes
and maturity-onset diabetes of the young, also are prescribed insulin. Forms of insulin administration include
syringe injections, insulin pumps, insulin pens, jet injectors and inhaled insulin.
Many patients are prescribed antidiabetic agents. The
U.S. Food and Drug Administration has approved oral
diabetes drugs only to treat type 2 diabetes, but
physicians sometimes use them to treat other conditions
including prediabetes, insulin resistance and polycystic
ovarian syndrome. Oral diabetes medications include:
i.) Alpha-glucosidase inhibitors Maturity-Onset Diabetes of The Young Essay
vi.) A new group called DPP-4 inhibitors
There are also injected medications known as incretin
mimetics and synthetic amylin. Synthetic amylin is the
only drug other than insulin approved to treat type 1
In addition, patients may be prescribed a glucagon kit.
Glucagon is a hormone that acts against insulin and can
be injected in cases of severe hypoglycemia or insulin
Diabetes mellitus is a heterogeneous group of disorders characterized by persistent hyperglycemia.
The two most common forms of diabetes are type 1 diabetes (T1D, previously known as insulindependent diabetes or IDDM) and type 2 diabetes (T2D, previously known as non-insulin-dependent
diabetes or NIDDM). Both are caused by a combination of genetic and environmental risk factors.
However, there are other rare forms of diabetes that are directly inherited. These include maturity
onset diabetes in the young (MODY), and diabetes due to mutations in mitochondrial DNA.
All forms of diabetes have very serious effects on health. In addition to the consequences of abnormal
metabolism of glucose (e.g., hyperlipidemia, glycosylation of proteins, etc.), there are a number of
long-term complications associated with the disease. These include cardiovascular, peripheral
vascular, ocular, neurologic and renal abnormalities, which are responsible for morbidity, disability and
premature death in young adults. Furthermore, the disease is associated with reproductive Maturity-Onset Diabetes of The Young Essay
complications causing problems for both mothers and their children. Although improved glycemic
control may decrease the risk of developing these complications, diabetes remains a very significant
cause of social, psychological and financial burdens in populations worldwide.
Type 1 Diabetes
Epidemiology. T1D is caused by the autoimmune destruction of the beta cells of the pancreas, and
represents approximately 10% of all cases with diabetes. At present, lifelong insulin therapy is the only
treatment for the disease. Without exogenous insulin injections, individuals with T1D will not survive.
Although the prevalence of T1D is <1% in most populations, the geographic variation in incidence is
enormous, ranging from <1/100,000 per year in China to approximately 40/100,000 per year in Finland
(Figure 1) (Karvonen et al., 1993). The only chronic childhood disorder more prevalent than T1D is
asthma. It has been estimated that approximately 20 million people worldwide, mostly children and
young adults, have T1D (Holt, 2004).
FIN SAR SWE NOR US-WI US-PA ITA ISR JAP CHI
FIN = Finland, SAR = Sardinia, SWE = Sweden, NOR = Norway, US-WI = US-Wisconsin, US-PA =
US-Pennsylvania, ITA = Italy, ISR = Israel, JAP = Japan, CHI = China
The incidence of T1D is increasing worldwide at a rate of about 3% per year (Onkamo et al., 1999).
This trend appears to be most dramatic in the youngest age groups, and is completely unrelated to the
current increase in T2D in children. More children with beta cell autoantibodies, a hallmark of T1D,
are being diagnosed with the T1D around the world each year. Although the peak age at onset is at
puberty, T1D can also develop in adults. Epidemiologic studies have revealed no significant gender
differences in incidence among individuals diagnosed before age 15 (Kyvik et al., 2004). However,
after age 25, the male to female incidence ratio is approximately 1.5. There is also a notable seasonal Maturity-Onset Diabetes of The Young Essay
variation in the incidence of T1D in many countries, with lower rates in the warm summer months, and
higher rates during the cold winter (Dorman et al., 2003).
Environmental Risk Factors. The epidemiological patterns described above suggest that environmental
factors contribute to the etiology of the T1D. In particular, the recent temporal increase in T1D
incidence points to a changing global environment rather than variation in the gene pool, which require
the passage of multiple generations. Twin studies also provide evidence for the importance of
environmental risk factors for T1D. T1D concordance rates for monozygous twins are higher than
those for dizygous twins (approximately 30% vs. 10%, respectively) (Hirschhorn, 2003). However,
most monozygous twin pairs remain discordant. Thus, T1D cannot be completely genetically
Environmental risk factors are thought to act as either ‘initiators’ or ‘accelerators’ of beta cell
autoimmunity, or ‘precipitators’ of overt symptoms in individuals who already have evidence of beta
cell destruction. They also may function by mechanisms that are directly harmful to the pancreas, or
by indirect methods that produce an abnormal immune response to proteins normally present in cells.
The T1D environmental risk factors that have received most attention are viruses and infant nutrition.
Enteroviruses, especially Coxsackie virus B (CVB), have been the focus of numerous ecologic and
case-control studies (Dahlquist et al., 1998). CVB infections are frequent during childhood and are
known to have systemic effects on the pancreas. Recent prospective studies are helping to elucidate the
role of viruses to the etiology of T1D. For example, enteroviral infections occurring as early as in
utero appear to increase a child’s subsequent risk of developing the disease (Dahlquist et al., 1995,
Hyoty et al., 1995). Other viruses, including mumps (Hyoty et al., 1993), cytomegalovirus (Pak et al.,
1988), rotavirus (Honeyman et al., 2000) and rubella, (McIntosh and Menser, 1992) have also been
associated with the disease.Maturity-Onset Diabetes of The Young Essay
Another hypothesis that has been the subject of considerable interest relates to early exposure to cow’s
milk protein and the subsequent development of T1D. The first epidemiologic observation of such a
relationship was by Borch-Johnsen et al., who found that T1D children were breast-fed for shorter
periods of time than their non-diabetic siblings or children from the general population (Borsh-Johnsen
et al., 1984). The authors postulated that the lack of immunologic protection from insufficient breastfeeding may increase risk for T1D later during childhood. It was also postulated that shorter duration
of breast feeding may indirectly reflect early exposure to dietary proteins that stimulate an abnormal
immune response in newborns. Most recently it has been hypothesized that the protective effect of
breast-feeding may be due, in part, to its role in gut maturation (Kolb and Pozzilli, 1999; Harrison and
Honeyman, 1999; Vaarala, 1999). Breast milk contains growth factors, cytokines, and other substances
necessary for the maturation of the intestinal mucosa. Breast-feeding also protects against enteric
infections during infancy, and promotes proper colonization of the gut. Interestingly, enteroviral
infections can also interfere with gut immunoregulation, which may explain the epidemiologic
associations between viral infections and T1D.
The role of hygiene in the etiology of T1D is also currently being explored (McKinney et al., 1997;
Marshall et al., 2004). It has been hypothesized that delayed exposure to microorganisms due to
improvements in standard of living hinders the development of the immune system, such that it is more
likely to respond inappropriately when introduced to such agents at older (compared to younger) ages.
This explanation is consistent with recent reports indicating that factors such as day care attendance
(McKinney et al. 2000), sharing a bedroom with a sibling, and contact with pets are protective against
T1D (Marshall et al., 2004). Further studies are needed to determine if improved hygiene can explain
the temporal increase in the incidence of T1D worldwide.Maturity-Onset Diabetes of The Young Essay
Type 2 Diabetes
Epidemiology. T2D is the most common form of the disease, accounting for approximately 90% of all
affected individuals. A diagnosis of T2D is made if a fasting plasma glucose concentration is > 7.0
mmol/L (> 126 mg/dl) or plasma glucose 2 hours after a standard glucose challenge is > 11.1 mmol/L
(> 200 mg/dl) (WHO, 1999) T2D is caused by relative impaired insulin secretion and peripheral
insulin resistance. Typically, T2D is managed with diet, exercise, oral hypoglycemic agents and
sometimes exogenous insulin. However, it is associated with the same long-term complications as
The highest rates of T2D are found among Native Americans, particularly the Pima Indians who reside
in Arizona in the US, and in natives of the South Pacific islands, such as Nauru (Wild et al., 2004).
T2D is also known to be more predominant in Hispanic and African American populations than in
Caucasians. In 2000, it is estimated that 171 million people (2.8% of the worlds population) had
diabetes and that by 2030 this number will be 366 million (4.4% of the world’s population). The vast
majority of this increase will occur in men and women aged 45 to 64 years living in developing
countries. According to Wild et al.(2004), the ‘top’ three countries in terms of the number of T2D
individuals with diabetes are India (31.7 million in 2000; 79.4 million in 2030), China (20.8 million in
2000; 42.3 million in 2030) and the US (17.7 million in 2000; 30.3 million in 2030). Clearly, T2D has
become an epidemic in the 21st century.
In addition to the burden of T2D there is an even larger number of people with raised levels of blood
glucose but below the level for diabetes. The World Health Organization defines impaired fasting
glucose as a fasting plasma glucose level of > 6.1 mmoll-1 and less than 7 mmoll-1, and impaired
glucose tolerance as 2 hour plasma glucose, post glucose challenge, of 7.8 to less than 11.1 mmoll Maturity-Onset Diabetes of The Young Essay
The prevalence of T2D increases with age of population (Wild et al., 2004). In developing countries,
the largest number of people with diabetes are in the age group 45 to 64 years, while in developed the
largest number is found in those aged 65 years and over. These differences largely reflected differences
in population age structure between developed and developing countries. Worldwide rates are similar
in men and women, although they are slightly higher in men < 60 years of age and in women > age 65
Of great concern is the recent increase in T2D in children (Bloomgarden, 2004). A report based on the
Pima Indians in Arizona noted that between 1967-76 and 1987-96, the prevalence of T2D increased 6-
fold in adolescents (Fagot-Campagna et al., 2000). In the US, the incidence of T2D increased from
0.3-1.2/100,000/yr before 1992 to 2.4/100,000/yr in 1994 (Weill et al., 2004). Most T2D children
diagnosed during this period were females from minority populations, with a mean age of onset at
around puberty. They were also likely to have a positive family history of the disease, particularly
maternal diabetes.Maturity-Onset Diabetes of The Young Essay
Environmental Risk Factors. As early as 1962, Neel hypothesized that T2D represented a ‘thrifty
genotype’, which had a selective advantage (Neel, 1962). He postulated that in primitive times,
individuals who were ‘metabolically thrifty’ and able to store a high proportion of energy as fat when
food was plentiful were more likely to survive times of famine. However, in recent years, most
populations experience a continuous supply of calorie-dense processed foods, as well as a decrease in
physical activity. This likely explains the rise in T2D prevalence worldwide.
The major environmental risk factors for T2D are obesity (> 120% ideal body weight or a body mass
index > 30 k/m2
) and a sedentary lifestyle (van Dam, 2003; Shaw and Chisholm, 2003). Thus, the
tremendous increase in the rates of T2D in recent years has been attributed, primarily, to the dramatic
rise in obesity worldwide (Zimmet et al., 2001). It has been estimated that approximately 80% of all
new T2D cases are due to obesity (Lean, 2000). This is true for adults and children. In the Pima
Indians, 85% of the T2D children were either overweight or obese (Fagot-Campagna et al., 2000).
Another study in the US reported that IGT was detected in 25% of obese children age 4-10 years, and
in 21% of obese adolescents (Sinha et al., 2002). Undiagnosed T2D was detected in 4% of the
adolescents.Maturity-Onset Diabetes of The Young Essay
In addition to general obesity, the distribution of body fat, estimated by the ratio of waist-to-hip
circumference (WHR), also has an impact on T2D risk. WHR is a reflection of abdominal (central)
obesity, which is more strongly associated with T2D than the standard measures of obesity, such as
those based on body mass index.
The other major T2D risk factor is physical inactivity. In addition to controlling weight, exercise
improves glucose and lipid metabolism, which decreases T2D risk. Physical activity, such as daily
walking or cycling for more than 30 minutes, has been shown to significantly reduce the risk of T2D
(Hu et al., 2003). Physical activity has also been inversely related to body mass index and IGT.
Recently, intervention studies in China (Pan et al., 1997), Finland (Tuomilehto J et al., 2001) and the
US (Diabetes Prevention Program Study Group, 2002) have shown that lifestyle interventions targeting
diet and exercise decreased the risk of progression from IGT to T2D by approximately 60% . In
contrast, oral hypoglycemic medication only reduced the risk of progression by about 30%.
There is also considerable evidence suggesting that the intrauterine environment is an important
predictor of T2D risk (Hales and Barker, 2001; Sobngwi et al., 2003), Numerous studies have shown
that low birth weight, which is an indicator of fetal malnutrition, is associated with IGT and T2D later
in life. However, it is unclear whether low birth weight is causal or related to potential confounding
factors that contribute to both poor fetal growth and T2D (Frayling and Hattersley, 2001).
Role of Genetics in the Development of Diabetes
Type 1 Diabetes
First degree relatives have a higher risk of developing T1D than unrelated individuals from the general
population (approximately 6% vs. <1%, respectively) (Dorman and Bunker, 2000). These data suggest
that genetic factors are involved with the development of the disease. At present, there is evidence that
more than 20 regions of the genome may be involved in genetic susceptibility to T1D. However, none
of the candidates identified have a greater influence on T1D risk than that conferred by genes in the
HLA region of chromosome 6. This region contains several hundred genes known to be involved in
immune response. Those most strongly associated with the disease are the HLA class II genes (i.e.,Maturity-Onset Diabetes of The Young Essay
HLA-DR, DQ, DP).
IDDM1. The HLA class II genes, also referred to as IDDM1, contribute approximately 40-50% of the
heritable risk for T1D (Hirschhorn et al., 2003). When evaluated as haplotypes, DQA1*0501-
DQB1*0201 and DQA1*0301-DQB1*0302 are most strongly associated T1D in Caucasian
populations. They are in linkage disequilibrium with DRB1*03 and DRB1*04, respectively. Specific
DRB1*04 alleles also modify the risk associated with the DQA1*0301-DQB1*0302 haplotype. Other
reported high risk haplotypes for T1D include DRB1*07-DQA1*0301-DQB1*0201 among African
Americans, DRB1*09-DQA1*0301-DQB1*0303 among Japanese, and DRB1*04-DQA1*0401-
DQB1*0302 among Chinese. DRB1*15-DQA1*0602-DQB1*0102 is protective and associated with a
reduced risk of T1D in most populations. Recent reports suggest that other genes in the central, class I
and extended class I regions may also increase T1D risk independent of HLA class II genes (Nejentsev
et al., 1997; Lie et al., 1999).
Individuals with two high risk DRB1-DQA1-DQB1 haplotypes have a significantly higher T1D risk
than individuals with no high risk haplotype. The T1D risk among those with only one susceptibility
haplotype is also increased, but effect is more modest. Relative risk estimates range from 10 – 45 and
3-7, respectively, for these groups, depending on race (Dorman and Bunker, 2000). In terms of
absolute risk, Caucasian individuals with two susceptibility haplotypes have an approximately 6%
chance of developing T1D through age 35 years. However, this figure is substantially lower in
populations where T1D is rare (i.e., < 1% among Asians). In addition to IDDM1, two other genes are
now known to influence T1D risk (Anjos and Polychronakos, 2004). These include INS and CTLA-4.
Table 1. Several T1D Susceptibility Genes
Gene Locus Variant Estimated
HLA-DQB1 6p21.3 *0201 & *0302 3 – 45
INS 11p15. 5 Class I 1 – 2
CTLA4 2q31-35 Thr17Ala 1 – 2 Maturity-Onset Diabetes of The Young Essay
RR = relative risk
INS (insulin). The INS gene, located on chromosome 11p15.5, has been designated as IDDM2.
Positive associations have been observed with a non-transcribed variable number of tandem repeat
(VNTR) in the 5’ flanking region (Bennett et al., 1997; Pugliese et al., 1997) . There are two common
variants. The shorter class I variant predisposes to T1D (relative increase: 1 – 2), whereas the longer
class III variant appears to be dominantly protective. The biological plausibility of these associations
may relate to the expression of insulin mRNA in the thymus. Class III variants appear to generate
higher levels of insulin mRNA than class I variants. Such differences could contribute to a better
immune tolerance for class III positive individuals by increasing the likelihood of negative selection for
autoreactive T-cell clones. The effect of INS appears to vary by ethnicity, with lesser effects in nonCaucasian populations (Undlien et al. 1994).
CTLA-4 (cytotoxic T lymphocyte-associated 4). The CTLA-4 gene is located on chromosome 2q31-35
(Anjos and Polychronakos, 2004), where multiple T1D genes may be located. CTLA-4 variants have
been associated with T1D, as well as other autoimmune disease. CTLA-4 negatively regulates T-cell
function. However, impaired activity, which has been associated with the Thr17Ala variant, may
increase T1D risk. Overall, the relative increase in risk for the CTLA-4Ala17 variant has been
estimated as ~ 1.5.Maturity-Onset Diabetes of The Young Essay
Type 2 Diabetes
It has long been known that T2D is, in part, inherited. Family studies have revealed that first degree
relatives of individuals with T2D are about 3 times more likely to develop the disease than individuals
without a positive family history of the disease (Flores et al., 2003; Hansen 2003; Gloyn 2003). It has
also been shown that concordance rates for monozygotic twins, which have ranged from 60-90%, are
significantly higher than those for dizygotic twins. Thus, it is clear that T2D has a strong genetic
One approach that is used to identify disease susceptibility genes is based on the identification of
candidate genes (Barroso et al., 2003; Stumvoll, 2004). Candidate genes are selected because they are
thought to be involved in pancreatic β cell function, insulin action / glucose metabolism, or other
metabolic conditions that increase T2D risk (e.g., energy intake / expenditure, lipid metabolism). To
date, more than 50 candidate genes for T2D have been studied in various populations worldwide.
However, results for essentially all candidate genes have been conflicting. Possible explanations for
the divergent findings include small sample sizes, differences in T2D susceptibility across ethnic
groups, variation in environmental exposures, and gene-environmental interactions. Because of current
controversy, this review will focus only on a few of the most promising candidate genes. These
include PPARγ, ABCC8, KCNJ11, and CALPN10.
Table 2. Several T2D Susceptibility Genes
Gene Locus Variant Estimated RRP
PPARγ 3p25 Pro12Ala 1 – 3
ABCC8 11p15.1 Ser1369Ala 2 – 4
KCNJ11 11p15.1 Glu23Lys 1 – 2
CALPN10 2q37.3 A43G 1 – 4
PRR = relative risk
UPPARγ (peroxisome proliferator-activated receptor-γ)U. This gene has been widely studied because it is
important in adipocyte and lipid metabolism. In addition, it is a target for the hypoglycemic drugs
known as thiazolidinediones. One form of the PPARγ gene (Pro) decreases insulin sensitivity and
increases T2D risk by several fold. Perhaps more importantly is that this variant is very common in
most populations. Approximately 98% of Europeans carry at least one copy of the Pro allele. Thus, it
likely contributes to a considerable proportion (~25%) of T2D that occurs, particularly among Maturity-Onset Diabetes of The Young Essay
UABCC8 (ATP binding cassette, subfamily C, member 8)U. This gene encodes the high-affinity
sulfonylurea receptor (SUR1) subunit that is coupled to the Kir6.2 subunit (encoded by UKCNJ11U, also
known as the potassium channel, inwardly rectifying subfamily J, member 11). Both genes are part of
the ATP-sensitive potassium channel, which plays a key role in regulating the release of hormones,
such as insulin and glucagon, in the beta cell. Mutations in either gene can affect the potassium
channel’s activity and insulin secretion, ultimately leading to the development of T2D. Interestingly,
ABCC8 and KCNJ11 are only 4.5 kb apart, and not far from the INS gene. Variant forms of KCNJ11
(Lys) and ABCC8 (Ala) genes have been associated with T2D, as well as other diabetes-related traits.
Because of the close proximity of these genes, current studies are evaluating whether they work in
concert with each other, or rather have an independent effect on T2D susceptibility.
Since PPARγ, ABCC8 and KCNJ11 are the targets of drugs used routinely in the treatment of T2D,
there are pharmacogenetic implications for maintaining good glycemic control. Response to
hypoglycemic therapy may actually be related one’s genotype. Thus, genetic testing may not only help
determine who is at high risk for developing T2D, but may also be useful in guiding treatment
regimens for T2D.
UCAPN10 (calpain 10)U. CAPN10 encodes an intracellular calcium-dependent cysteine protease that is
ubiquitously expressed (Cox et al., 2004). A haplotype that was initially linked to T2D included an
intronic A to G mutation at position 43, which appears to be involved in CAPN10 transcription. Two
amino acid polymorphisms (Thr504Ala and Phe200Thr) have also been associated with T2D risk.
However, it has been suggested that the coding and noncoding polymorphisms do not independently
influence T2D risk, but instead contribute to an earlier age at diagnosis. Physiological studies suggest
that variations in calpain 10 activity effects insulin secretion, and therefore, susceptibility to T2D.
Studies from different ethnic groups indicate that the contribution of this locus to increased T2D risk
may be much larger in Mexican-American than Caucasian populations.
Maturity-Onset Diabetes of the Young
An uncommon form of T2D (accounting for <5% of all T2D cases) that generally occurs before age 25
years is MODY. MODY is characterized by a slow onset of symptoms, the absence of obesity, no
ketosis, and no evidence of beta cell autoimmunity. It is most often managed without the need for
exogenous insulin. MODY displays an autosomal dominant pattern inheritance, generally spanning
three generations (Stride and Hattersley, 2002). Because of advances in molecular genetics, it is now
known that there are at least six forms of MODY, each of which caused by a mutation in a different
gene that is directly involved with beta cell function (Winter, 2003). Table 3 lists the MODY genes
that have been identified to date. Because ~15% of MODY patients do not carry mutations in one of
these genes, it is anticipated that other genes that cause MODY will be discovered in the near future
(Demenais et al., 2003; Frayling et al., 2003; Kim et al., 2004). Maturity-Onset Diabetes of The Young Essay
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