Classification of Diabetes - Essay Example

Diabetes xyz abc Diabetes Diabetes mellitus commonly known as ‘Sugar’ is any of the several metabolic disorders marked by excessive urination and persistent thirst. The Greek word diabetes means to siphon or pass through. The Latin word mellitus means- as sweet as honey. It is a serious lifelong condition which needs constant monitoring and therapy. Around 7% of the US population suffers from this malady (National Diabetes Information Clearinghouse). In 2005, about 1.5 million people aged 20 or older were diagnosed with diabetes in the USA. Most of the food we eat is broken down into glucose, the form of sugar in the blood. Glucose is the main source of fuel for the body. The pancreas, an exocrine gland automatically produces the right amount of insulin to move glucose from blood into the cells. In diabetes, the blood glucose level increases beyond the optimum level which results in a cascade of pathologies in the body. The blood glucose level is normally controlled by the hormone Insulin secreted from the Pancreas. Diabetes has been broadly classified into two categories: Diabetes Type I & II. In Type I diabetes, the body is unable to synthesize enough Insulin hormone and in Type II diabetes, which is more common in occurrence than the former, the body either does not produce enough Insulin or is unable to properly utilize the available Insulin There is a third type known as gestational diabetes which occurs during pregnancy in women. Anatomical and Physiological Aspects Pancreas is a large elongated exocrine gland located behind the stomach and secretes pancreatic juice as well as insulin. Pancreatic juice plays an important role in the digestion of food while the insulin controls the glucose levels of the body. The discovery of insulin was a dramatic event in the history of medicine (Kahn C.R.& Sechter Yoram). In 1869, Paul Langerhans, a German medical student discovered that the pancreas contains two distinct groups of cells. The acinar cells secrete the digestive enzymes while cells clustered in islets had a secondary function. A hint to the functioning of these islets, which were later labeled as ‘Islets of Langerhans’ became somewhat clear when Oskar Minkowski and Joseph von Mering (1889) showed that dogs in whom pancreas was removed suffered from a syndrome similar to diabetes mellitus in man (Kahn C.R.& Sechter Yoram). Banting and Best, two Canadians were successful in extracting insulin from the pancreas in 1922 and treating a patient successfully. The ß cells of pancreatic islets synthesize insulin from a precursor molecule called proinsulin which is converted to insulin by enzymatic action which has a molecular weight of about 5800 (Kahn C.R.& Sechter Yoram). Insulin is a member of a family of related peptides, termed as insulin-like growth factors (IGFs). Insulin secretion is a tightly regulated process, which provides stable concentrations of glucose in blood during both fasting and feeding. This regulation is achieved by a complex and coordinated interplay of nutrients, gastrointestinal hormones, pancreatic hormones and autonomic neurotransmitters. Any condition that activates the autonomic nervous system (such as hypoxia, hypothermia, surgery, etc.) suppresses the secretion of insulin. Vagal nerve stimulation enhances the release of insulin. Glucose is the principal stimulus to insulin secretion. Insulin secretion is also stimulated by gastrin, secretin, cholecystokinin and enteroglucagon. When glucose is the stimulus for insulin secretion, it occurs in a biphasic manner. In the first phase, peak level is achieved within 1 to 2 minutes. This phase is short lived. The second phase has a delayed onset but has a longer duration. Degradation of insulin occurs primarily in liver, kidney and muscle. 50% of the insulin that reaches liver is destroyed. The rest reaches the kidneys where it is filtered by the glomeruli and reabsorbed by the tubules. Classification of Diabetes Diabetes is broadly classified into the following three categories (Bookrags): 1. Insulin dependent diabetes mellitus (IDDM)- Type I: In IDDM, the pancreas does not make enough insulin. Insulin usually signals its target cells -fat, muscle, and liver cells to take glucose from the blood plasma intracellularly for cellular respiration. Individuals with IDDM have to take insulin as a medication to manage their blood glucose levels. Both environmental factors and viral antigens are mostly responsible for IDDM. It is not an inheritable disorder. 2. Non-insulin dependent diabetes mellitus (NIDDM)- Type II: NIDDM is associated with obesity and aging, and has a strong evidence of being a genetic disorder. In this type of diabetes, the glycoprotein receptor sites for insulin on the outer surface of the membrane of target cells do not respond to the presence of insulin and so glucose is not taken up into the cells. Blood glucose levels remain high leading to hyperglycemia and, if untreated, eventually lead to glucose toxicity and death. If diagnosed in the early stages of the disease, NIDDM can be managed with diet and exercise. 3. Gestational diabetes: Some women develop gestational diabetes late in pregnancy. Although this form of diabetes usually disappears after the birth of the baby, women who have had gestational diabetes have a 20 to 50 % probability of developing type 2 diabetes within 5 to 10 years. Gestational diabetes is caused by the hormones of pregnancy or a shortage of insulin. Maintaining a reasonable body weight and being physically active may help prevent development of type 2 diabetes. Pathophysiology of Diabetes Type 1: In Type 1 diabetes mellitus, insulin production is absent because of autoimmune pancreatic β-cell destruction possibly triggered by an environmental exposure in genetically susceptible people (Merck Manual online). Destruction progresses sub clinically over months or years until β-cell mass decreases to the point that insulin concentrations are no longer adequate to control plasma glucose levels. Type 1 diabetes mellitus generally develops in childhood or adolescence and until recently was the most common form diagnosed before age 30.The pathogenesis of the autoimmune β-cell destruction is not clearly understood. It involves interactions between genes, autoantigens, and environmental factors. Susceptibility genes are more common in some populations than in others depending on ethnicity. Autoantigens include glutamic acid decarboxylase, insulin, insulinoma-associated protein, and other proteins in β cells. It is thought that these proteins are exposed or released during normal β-cell turnover or β-cell injury (eg, from infection), activating a cell-mediated immune response resulting in β-cell destruction. Glucagon-secreting α cells remain unharmed. Several viral infections (including coxsackievirus, rubella, cytomegalovirus, Epstein-Barr, and retroviruses) have been linked to the onset of type 1 diabetes mellitus. Viruses may directly infect and destroy β cells, or they may cause β-cell destruction indirectly by exposing autoantigens, activating autoreactive lymphocytes, mimicking molecular sequences of autoantigens that stimulate an immune response. Diet may also be a factor. Exposure of infants to dairy products (especially cows milk and the milk protein β casein), high nitrates in drinking water, and low vitamin D consumption have been linked to increased risk of type 1 diabetes mellitus. Type 2: In type 2 diabetes mellitus, insulin secretion is inadequate (Merck manual online). Often insulin levels are very high, especially early in the disease, but peripheral insulin resistance and increased hepatic production of glucose make insulin levels inadequate to normalize plasma glucose levels. Insulin production is gradually reduced resulting in hyperglycemia. The disease generally occurs in adults. Plasma glucose levels reach higher levels after eating in older than in younger adults, when carbohydrate rich diet is taken and take longer to return to normal. There is progressive loss of body weight. Presently type 2 diabetes mellitus is assuming alarming proportions in children as childhood obesity has become epidemic. Genetics has a clear role to play in type 2 diabetes mellitus, however no genes responsible have been identified. Pathogenesis is not clear. Hyperglycemia develops when insulin secretion can no longer compensate for insulin resistance. Although insulin resistance is characteristic in people with type 2 diabetes mellitus, β-cell dysfunction and impaired insulin secretion have also been encountered. Hyperglycemia itself may impair insulin secretion, because high glucose levels desensitize β cells and cause β-cell dysfunction. Obesity and weight gain are the main factors responsible for insulin resistance in type 2 diabetes mellitus. Genetic factors combined with rich diet, lack of exercise, and sedentary lifestyle contribute to its occurrence. Excess adipose tissue increases plasma levels of free fatty acids which impairs insulin-stimulated glucose transport and muscle glycogen synthase activity. Prenatal growth restriction and low birth weight have also been associated with insulin resistance. Signs and Symptoms The most common symptoms of diabetes mellitus are hyperglycemia, polyuria, and polydipsia that may progress to orthostatic hypotension and dehydration (Merck Manual online). . Severe dehydration causes weakness, fatigue, and mental delusions. Symptoms may come and go as plasma glucose levels fluctuate. Polyphagia may accompany symptoms of hyperglycemia. Hyperglycemia can also cause weight loss, nausea and vomiting, and blurred vision, and it may make the patient susceptible to bacterial or fungal infections. Patients with type 1 diabetes typically present with symptomatic hyperglycemia and diabetic ketoacidosis. Some patients experience a long but transient phase of near-normal glucose levels following acute onset of the disease (honeymoon phase) due to partial recovery of insulin secretion. Patients with type 2 diabetes are often asymptomatic and their condition is detected only on routine testing. In some patients, hyperosmotic coma occurs initially, especially during a period of stress or when glucose metabolism is further impaired by drugs, such as corticosteroids. Diagnosis Diabetes is diagnosed by typical symptoms and signs and confirmed by measurement of plasma glucose. Measurement after an 8- to 12-h fast (fasting plasma glucose [FPG]) or 2 h after ingestion of a concentrated glucose solution (oral glucose tolerance testing) are used (Merck Manual online). Treatment Treatment involves control of hyperglycemia to improve symptoms and prevent complications while minimizing hypoglycemic episodes (Merck Manual online). Goals for treatment are maintenance of plasma glucose between 80 and 120 mg/dL (4.4 and 6.7 mmol/L) during the day and between 100 and 140 mg/dL (5.6 and 7.8 mmol/L) at bedtime (as determined by home monitoring and maintenance of HbA1c levels < 7% (Merck manual online). These goals may be adjusted for patients in whom strict glucose control may be inadvisable, such as the frail elderly and young children. Patient education, dietary and exercise counseling, and monitoring of glucose control are important. All type 1 diabetics require insulin treatment. Diet adjusted to individual circumstances can help patients control fluctuations in their glucose level and, for type 2 patients to lose weight In general, all diabetics need to be educated about a diet that is low in saturated fat and cholesterol and contains moderate amounts of carbohydrate, preferably from whole grain sources with higher fiber content. Dietary protein restriction to ≤ 0.8 g/kg/day to prevent progression of early nephropathy is also recommended. Injectable as well as prefilled pens of insulin are available. Oral forms and transmucosal (e.g., intranasal, oral spray) or transdermal delivery systems are also being developed. Hypoglycemia is the most common complication of insulin treatment, occurring more often as patients try to achieve strict glucose control and approach near-normoglycemia. Symptoms of mild or moderate hypoglycemia include headache, palpitations, light-headedness, blurred vision, agitation, and confusion. In older patients, hypoglycemia may produce stroke like symptoms, myocardial infarction and sudden death. Patients should be taught to recognize symptoms of hypoglycemia, which usually respond rapidly to the ingestion of sugar, including candy, juice, and glucose tablets.10 to 15 g of glucose or sucrose should be ingested. For patients who are unconscious or unable to swallow, hypoglycemia can be treated immediately with glucagon 1 mg sc or IM or a 50% dextrose solution 50 mL IV (25 g), followed, if necessary, by IV infusion of a 5 or 10% dextrose solution to maintain adequate plasma glucose levels. Insulin resistance occurs mostly in type 2 diabetics. The causes are usually obesity and genetic factors. Circulating anti-insulin antibodies are a rare cause; it can sometimes be treated by changing insulin preparations (eg, from animal to human insulin) and by administering corticosteroids if necessary. Oral antihyperglycemic drugs: Oral antihyperglycemic drugs are the primary treatment for type 2 diabetics, although insulin is often added when ≥ 2 oral drugs fail to provide adequate glycemic control. Oral antihyperglycemic drugs may enhance pancreatic insulin secretion (secretagogues), sensitize peripheral tissues to insulin (sensitizers), or impair GI absorption of glucose. Drugs with different mechanisms of action may be synergistic.Some examples are Sulfonylureas, Short-acting insulin secretagogues, Biguanides like Metformin, Thiazolidinediones, α-Glucosidase inhibitors (AGIs), Glucagon-like peptide-1 (GLP-1) agonists and Dipeptidyl peptidase-4 inhibitors. Other antihyperglycemic treatments: Transplantation of pancreatic or islet cells is an alternative means of insulin delivery; both techniques effectively transplant insulin-producing β-cells into insulin-deficient (type 1) patients. Finally, all diabetics should be vaccinated against Streptococcus pneumoniae (once) and influenza virus (annually) (Merck manual online). References Bookrags, Avaialble at: http://www.bookrags.com/research/diabetes-mellitus-wap/ http://www.nlm.nih.gov/medlineplus/diabetes.html http://www.diabetes.org/about-diabetes.jsp http://www.ijddc.com/article.asp?issn=0973-3930;year=2007;volume=27;issue=4;spage=122;epage=128;aulast=Attili Kahn C.Ronald & Shechter Yoram, Insulin, Oral Hypoglycemic Agents, and the Pharmacology of the Endocrine Pancreas, Chapter 61, Pgs. 1463-1473, Goodman & Gilmans The Pharmacological Basis of Therapeutics, Eighth Edition, Volume II, 1991,Pergamon Press, USA Merck Manual online, Available at: http://www.merck.com/mmpe/sec12/ch158/ch158b.html National Diabetes Information Clearinghouse, Available at: http://diabetes.niddk.nih.gov/dm/pubs/overview/ Read More