Diabetes Type 1 PDF

Diabetes Type 1 Disease summary Definitions: Diabetes mellitus is catabolic endocrine diseases characterized by hyperglycemia (i.e., elevated plasma glucose concentrations) and polyuria (i.e., frequent urination) Refers to a heterogeneous group of chronic polydipsia (i.e., ex...

Diabetes Type 1 Disease summary Definitions: Diabetes mellitus is catabolic endocrine diseases characterized by hyperglycemia (i.e., elevated plasma glucose concentrations) and polyuria (i.e., frequent urination) Refers to a heterogeneous group of chronic polydipsia (i.e., excessive drinking of fluids) multiple acute and chronic complications By definition, Type 1 DM is the result of autoimmune process in which pancreatic islet Beta cells are targeted and destroyed by cells of the immune system Circulating insulin is virtually absent and carbohydrate, lipid and protein metabolism is abnormal Patients are susceptible to weight loss and a life-threatening ketoacidosis (i.e., increase in plasma keto acids that lowers blood pH) Patients are typically young and require injections of insulin to manage the disease Type 1 diabetes (the current accepted terminology for this illness) was previously known as juvenile-onset DM and insulin-dependent DM Prevalence: Type 1 DM is the most common metabolic disease of childhood The overall incidence of type 1 diabetes in the US is 15 new cases per 100,000 people younger than age 18 per year Frequencies are higher in states more densely populated with persons of scandinavian descent (e.g., Minnesota) Currently, approximately 1.46 million americans have type 1 diabetes and approximately 10,000 new cases are diagnosed annually The risk in the general population for developing type 1 diabetes is 1 in 300, but increases 15-20 times among people with first-degree relatives with the condition Although it can develop at any age, Type 1 diabetes most commonly has its onset in childhood or adolescence, with an initial peak frequency at 4-6 years and a much greater peak frequency at 11-13 years of age Males and females are affected equally but racial differences clearly exist Caucasians have the highest reported incidence of type 1 dm The rates for developing type 1 diabetes in caucasians are 1.5-2 times higher than for African-americans or hispanics Type 1 dm is uncommon among asian americans Significance The significance of Type 1 DM lies in its chronic and progressive course, multiple clinical manifestations, and many potential life-threatening acute and chronic complications ○ Frequent urination and nocturnal enuresis (i.e., bedwetting) ○ Constant thirst and hunger  ○ Blurred vision ○ Weight loss ○ Pruritus ○ Weakness ○ Fatigue One of the symptoms in diabetes which is most likely caused by peripheral sensory neuropathy due to dysfunction of the somatosensory pathway is known as paresthesias (i.e., burning or tingling sensations in the extremities) are bothersome but not serious manifestations of the disease. Patients are prone to multiple infections, especially foot infections that may progress to gangrene and require limb amputation Infections of the skin, urinary tract and vagina are also common Diabetes Type 1 may be differentiated from diabetes type 2 when the urinalysis is positive for KETONES Ketoacids, one of the most serious acute complications of type 1 diabetes can result in: ○ Anorexia ○ Severe nausea and vomiting ○ Dehydration ○ Dangerously low blood pressure ○ Deteriorating levels of consciousness, occasionally death Acute complications from insulin therapy (e.g., hypoglycemic or insulin shock) can also be very serious Diabetes type 1 Serious chronic complications include: Hypertension Renal failure Blindness Coronary artery disease Cerebrovascular disease Degeneration of autonomic and peripheral nerves results in loss of sensory and motor function Up to 40% of patients develop end stage renal disease ○ Complications from ESRD are a major cause of death Pregnancy in women with type 1 diabetes has been complicated by increased risks for birth defects and perinatal mortality Poor glycemic control during pregnancy can also result in: ○ Miscarriage ○ Stillbirth ○ Macrosomia (i.e., birth weight 9 pounds), neonatal hypoglycemia Macrosomia results, in part, from maternal hyperglycemia and increased glucose delivery to the fetus Causes and risk factors: Type 1 DM is considered a multifactorial disorder in which both environmental factors and heredity play critical roles Immune-mediated type 1A diabetes, the most common subtype of type 1 diabetes, is believed to result from an infectious or toxic insult to persons whose immune systems are genetically predisposed to develop an autoimmune ration Environmental factors that may affect pancreatic B function include: ○ Mumps, rubella, coxsackie B4 viruses, and toxic chemical agents Specific human leukocyte antigen (HLA) immune response genes on chromosome 6 are thought to predispose individuals to a destructive autoimmune process. Pathophysiology Type 1 DM is characterized by an absolute insulin deficiency Tissues dependent on insulin for glucose transport do not have glucose available as a substrate for the generation of energy Production of glucose by the liver is not opposed by insulin and overproduction of glucagon by pancreatic a cells stimulates glycogenolysis and gluconeogenesis Plasma glucose levels rise and hyperglycemia results Immune-mediated type 1A diabetes has an autoimmune pathogenesis and is believed to result when pancreatic B cells are targeted for destruction by cytotoxic T lymphocytes The development of paresthesias reflects temporary dysfunction of peripheral sensory nerves Paresthesias resolves when blood glucose concentrations are normalized, suggesting that neurotoxicity may result from sustained hyperglycemia An absence of insulin in association with elevated levels of growth hormone, catecholamines, and glucagon increase lipolysis, and fatty acids are converted to keto acids in the liver Keto Acids can cause a low blood pH (i.e., acidosis) and are toxic in high concentrations Hepatic gluconeogenesis in response to glucose deprivation also enhances production of ketoacids Furthermore, there is evidence that reduced ketolysis by insulin-deficient peripheral tissues also promotes ketoacidosis The development of coronary artery disease, Cerebrovascular disease, and peripheral vascular disease is often related to a poor lipid profile when plasma glucose is not tightly controlled, to renal dysfunction, and to hypertension secondary to renal disease Gangrene of the feet is caused by occlusive vascular disease (both arteriolosclerosis and atherosclerosis), leading to ischemia, peripheral neuropathy causing insensitivity of the feet, repeated injuries without pain, and secondary infection Loss of both sensory and motor function is due to localized demyelination, degeneration of axons, and loss of nerve function, which, at least in some cases is the result of ischemia  Furthermore, myoinositol, a cell membrane component normally found in abundance in nerve tissues, is deficient in diabetics with neuropathy Although the exact level of plasma glucose above which leukocyte function is impaired has not been firmly established, in vitro data suggest that blood glucose concentrations 250 mg/dL cause white cell dysfunction Microalbuminuria, an early sign of kidney complications from diabetes, can be attributed to hypertension and, more specifically an increase in intraglomerular pressure Microalbuminuria refers to urinary excretion of small amounts of albumin– below the level of routine dipstick analysis Microalbuminuria has also been defined as urine protein loss of 30-300 mg/day A chronic elevation in intraglomerular pressure can injure the glomerular filtration apparatus and cause a loss of selective filtration. Clinical manifestations and lab tests The patient with type 1 diabetes is typically young, lean and has a parent or sibling with DM A relatively mild and slowly progressive form of immune mediated type 1A diabetes known as latent autoimmune diabetes in adults (LADA) is known to develop in people older than 30 years of age Early symptoms of type 1 DM are related to elevated blood glucose levels and a significant loss of water through the urinary tract Major symptoms of type 1 diabetes include: ○ Increased thirst, increased urination, weight loss despite an increased appetite, fatigue, nausea and vomiting Many primary care provider periodically test for HbA1C to determine glycemic control during the preceding 3 months Determination of HbA1c is not a routine test initially used for diagnosing DM However, increased HbA1c suggests a persistently elevated plasma glucose concentration and is used to monitor glycemic control with time and make adjustments in therapy Furthermore, an elevated HbA1c is highly predictive of DM-induced microvascular complications The American Diabetes association currently recommends that HbA1c be maintained below 7.0% In a similar manner, fructosamine is formed by a chemical reaction of glucose with plasma proteins and also reflects glycemic control over the previous 3 months. To distinguish Type 1 from type 2 diabetes, subnormal plasma insulin and/or C-peptide concentrations suggest type 1 disease C-peptide is formed during the conversion of proinsulin to insulin An elevated titer of glutamic acid decarboxylase antibodies also suggests type 1 diabetes Sensitivity of this test may be as high as 90% with a specificity of 99%  Islet cell and anti-insulin antibodies are present in early type 1 diabetes but cannot be detected after the disease has progressed for 6 months Serious complications and prognosis: The most serious acute complications of type 1 dm includes: ○ Ketoacidosis, hypoglycemic coma secondary to insulin overdose or insufficient caloric intake, dehydration, infections of the ears, nose, throat, urinary tract, and skin are especially common ○ Even the smallest wound of the feet can be rapidly complicated by a serious staphylococcal or streptococcal infection and result in a bone infection (i.e., osteomyelitis), sepsis, or amputation of the lower extremity Pancreatic transplantation has been performed in individuals with diabetes since 1966 and has resulted in consistent improvement in patient outcomes Pancreatic transplantation is performed most commonly with simultaneous kidney transplantation for ESRD Patients undergoing simultaneous pancreas and kidney transplantation have an 85% probability for pancreatic graft survival and a 92% chance of renal graft survival after 1 year Both the surgery itself and the use of potent immunosuppressive drugs to prevent organ rejection pose significant hazards to the post transplant patient In a 2007 brazilian study, a small number of people with type 1 diabetes were able to stop using insulin after being treated with stem cells from their own blood