Diabetes Type 2 PDF
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Fairleigh Dickinson University
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Summary
This document provides a summary of Type 2 Diabetes, covering its disease summary, symptoms, and complications. It includes information on factors such as insulin resistance and the presence or absence of obesity. The document also highlights the high cost of treatment and management of the disease, and the increased risk for developing complications.
Full Transcript
Type 2 Diabetes Disease summary The term diabetes mellitus refers to a group of clinically heterogeneous endocrine/metabolic disorders with glucose intolerance in common Diabetes mellitus encompasses many causally unrelated disease and is a syndrome characterized by:...
Type 2 Diabetes Disease summary The term diabetes mellitus refers to a group of clinically heterogeneous endocrine/metabolic disorders with glucose intolerance in common Diabetes mellitus encompasses many causally unrelated disease and is a syndrome characterized by: ○ Chronic hyperglycemia (i.e., elevated serum glucose concentrations) abnormalities in carbohydrate, lipid and protein metabolism As many as 30 distinct causes of DM have been identified Although there are a number of different pathophysiologic mechanisms that explain how DM develops, a common feature is that DM is a disorder of insulin availability as a result of defects in how the body produced or utilizes insulin Although the disease can be controlled, DM is a chronic medical condition; that is, it lasts for a lifetime For Type 2 diabetes to be present, both insulin resistance and an inability of the pancreas to secrete enough insulin to compensate for poor utilization of insulin are required 2 subgroups of patients are currently distinguished by the absence or presence of obesity Other terms for T2D that still appear in the medical literature but should no longer be used, include maturity-onset diabetes, stable diabetes, and ketosis-resistant diabetes Especially bothersome symptoms of the disorder may include the following: Lack of energy Excessive thirst Frequent and excessive urination Frequent urination at night resulting in interrupted sleep and daytime drowsiness Slow healing of infections and wounds Generalized pruritus Blurry vision Hypersensitivity to light, touch and occasionally severe and burning pain, especially at night Altered mental status (irritability, confusion, difficulty concentrating) Retinopathy affects 80% of all patients with DM 15 years after diagnosis Diabetes is also the leading cause of end stage renal disease in the US (accounting for approximately 4,000 new cases each year and 36–44% of all cases of end-stage kidney failure) and the leading cause of non-traumatic lower limb amputations. The incidence of gangrene of the feet increases 30-fold in people with diabetes and the risk for a non-traumatic lower limb amputation increases 15-40 fold Approximately half of all non-traumatic amputations in the US are performed on patients with DM Neuropathies are the most common complications of type 2 DM, producing symptoms in up to 70% of diabetics Damage to nerves in the peripheral nervous system can result in sensory impairment with dulled perceptions to vibrations, pain, and temperature and in males often contributes to erectile dysfunction (ED) Approximately half of all males with DM older than age 50 experience ED Damage to nerves in the autonomic nervous system can lead to paralysis of the stomach (i.e., gastroparesis), alternating episodes of diarrhea and constipation, progressive paralysis of the bladder, and loss of control over blood pressure with changes in posture (causing dizziness and fainting spells) Due, in part, to increasing blood pressure and serum lipid concentrations, DM also accelerates the process of atherosclerosis– formation of fatty plaques within arteries and macrovascular disease, which can lead to heart attacks, strokes and decreased circulation in the arms and legs Under the most extreme circumstances, mortality rate from Hyperglycemic hyperosmolar nonketotic syndrome (HHNS) may be as high as 50%. Diabetes mellitus is an especially expensive disease. A recent estimate of the annual cost of DM to the U.S. medical care system was more than $135 billion, with annual increases expected to exceed 11%. The annual per capita cost of healthcare for people with DM was $13,243, compared with a cost of $2,560 for people without diabetes. Furthermore, approximately 20% of all Medicare funds are spent on patients with diabetes. There is a direct relationship between the degree of obesity and the risk for developing type 2 DM– and this relationship holds true for both children and adults It has been estimated that the probability for developing type 2 disease doubles every 20% increase over desirable body weight A new term that is emerging internationally to describe the combination of obesity and type 2 DM is diabesity (youth-onset) Type 2 diabetes While type 2 DM occurs primarily in people older than age 45 years and frequency increases with age, recently there has been an alarming number of individuals diagnosed with type 2 disease who have barely entered their teen years In fact, for the first time in the known history of the disease, type 2 DM is now more common in children than is DM type 1 Most childhood cases of type 2 DM are a direct result of poor eating habits, a lack of exercise, and increasing body weight. Furthermore, when type 2 DM develops in an identical twin older than 40 years of age, it is also diagnosed in the other twin within 1 year more than 70% of the time Attempts to identify genetic markers for type 2 have as yet been unsuccessful, although linkage to a gene on chromosome 2 encoding a cysteine protease–calpain 10–has been reported in a Mexican-american population with type 2 DM Polycystic ovarian syndrome is also a risk factor for type 2 DM Women with POS have a risk that is seven times the average for developing type 2 diabetes later in life Pathophysiology Type 2 DM is characterized initially by a relative insulin deficiency (i.e., insulin is not used effectively), followed ultimately by an absolute lack of insulin The major pathophysiologic process that causes a relative lack of insulin is insulin resistance The major pathophysiologic process that results in an absolute insulin deficiency is pancreatic b-cell dysfunction with impaired production of insulin As a result, individuals with type 2 DM may be predominantly insulin-resistant or predominantly insulin deficient. Impaired storage of glucose in the form of glycogen and continued hepatic gluconeogenesis in response to tissue glucose deprivation may also be significant contributing factors to the pathophysiology of type 2 DM Amylin, a hormone that is co-secreted with insulin by the B cell, is known to inhibit glucagon secretion by a cells, thus promoting storage of glucose as glycogen A number of specific pathophysiologic mechanisms for B-cell dysfunction have been identified 1. A decrease in the number of β cells, which may be related to genetic factors responsible for the maturation of pre-β cells into insulin-secreting cells and environmental factors, such as GDM 2. An increase in the death of β cells with insufficient regeneration of this cell population 3. Long-standing insulin resistance, which leads to “exhaustion” or desensitization of β cells such that they no longer respond to a glucose stimulus 4. An increase in fatty acids secondary to insulin resistance and hyperglycemia that: a. is toxic to β cells—a pathophysiologic phenomenon known as lipid toxicity b. inhibits muscle glycogen synthase and prevents the conversion of glucose to glycogen, and c. reduces insulin sensitivity in the liver and promotes gluconeogenesis 5. An accumulation of an abnormal glycoprotein in the pancreas known as amyloid that 6. impairs β-cell function (occurs in up to 40% of patients with type 2 DM). Diagnosis: clinical manifestations and laboratory tests Onset of type 2 DM is typically slow and progressive Many persons with type 2 DM are completely asymptomatic or have few complaints at the time of diagnosis Although patients may occasionally reveal some of the classic symptoms of DM (e.g., polyuria and increased thirst) Pathophysiologic mechanisms involved: ○ Hyperglycemia and glycosuria ○ Insulin resistance ○ Insulin deficiency ○ Gluconeogenesis insufficient conversion of glucose to glycogen The pathophysiologic sequelae in patients with diabetes mellitus 2 who are experiencing respiratory distress, what may be noted is a high bicarbonate level; K+ shift from intracellular intravascular (ECF) Diabetes Mellitus Type 2 many of the clinical manifestations of T2D are non-specific These include: ○ Recurrent infections (boils, carbuncles, candidal vulvovaginitis with pruritus in women, candidal balanitis in men), blurred vision, lower extremity paresthesias and fatigue ○ The disease is often detected with a random or fasting blood glucose determination ○ Patients who complain of weight loss, increased appetite, and nocturnal enuresis most likely do not have type 2 diabetes ○ Lower extremeity sensory neuropathy may also increase the risk for both a foot infection and amputation ○ A general diagnosis of DM without regard to type of specific cause is simply established if any one of the following three conditions is satisfied 1. Fasting glucose concentration 125 mg/dL (must be confirmed on a subsequent day) 2. Two hours after 75 mg oral glucose (i.e., standard oral glucose tolerance test), plasma glucose concentration 200 mg/dL (must be confirmed on a subsequent day) 3. A random (any time of day without regard to time since last meal) plasma glucose concentration 200 mg/dL combined with symptoms of increased thirst, increased appetite, and complaints of frequent urination and voiding of unusually large volumes of urine (must be confirmed on a subsequent day) 4. Individuals with a fasting plasma glucose concentration of 100–125 mg/dL or those with an abnormal plasma glucose measurement of 140–199 mg/dL 2 hours after initiating an oral glucose tolerance test are currently labeled as having prediabetes. Approximately 3-7% of people with prediabetes progress to DM each year Serious complications and prognosis: The most common, serious, acute (i.e., rapid onset) complications of type 2 DM include: ○ Medication- or exercise-induced hypoglycemia that may rapidly progress to seizure and coma ○ Infections of the bone and bone marrow (i.e., osteomyeltitis) and kidney (i.e., pyelonephritis) ○ Hyperosmolar hyperglycemic nonketotic syndrome (HHNS) that may render the patient comatose ○ The most common, serious chronic (i.e, slowly progressive) complications of type 2 DM are Eye disease (cataracts, retinopathy, and glaucoma), which may significantly impair vision and progress to blindness Coronary artery disease and cerebrovascular disease, which increase risk for heart attacks and strokes, respectively Renal disease which may progress to end-stage kidney failure A reduction in glycosylated hemoglobin levels by even 1% can decrease the risk for developing complications by 25% ○ However, recent studies suggest that a broad based focus on treatment (with attention to glucose control, nutrition, exercise, lipids, hypertension, smoking cessation) is much more likely to reduce the burden of complications ○ For example, when hypertension and dyslipidemia are treated aggressively, risks for heart attack, stroke, and PVD in the diabetic patient also decrease ○ The life expectancy in people who are diagnosed with type 2 diabetes in their 40s decreases by 5-10 years ○ Cardiovascular disease is the leading cause of death ○ When evaluating patients for metabolic syndrome one of the diagnostic criteria are triglycerides greater than 150 Medications that provide more than one benefit (lower both blood sugar and low-density lipoprotein concentrations) are preferred Furthermore, the cost of drug therapy is relatively low compared with the cost of managing the long-term complications of poorly controlled type 2 DM Treatment of the obese type 2 patient is initially directed at achieving weight reduction Mild to moderate weight loss (5-10% of total body weight) has been shown to improve control of diabetes, even if desirable weight is not achieved Monotherapy with metformin or an a-glucosidase inhibitor is first-line therapy for the obese patient with mild type 2 diabetes when medication is required. Neither agent causes weight gain or drug-induced hypoglycemia. If metformin therapy and weight reduction are inadequate to control blood glucose levels, then a thiazolidinedione (TZD) or sulfonylurea (SFU) is added. Some patients may require metformin, a TZD, and an SFU to achieve adequate glycemic control. Exenatide is indicated as adjunctive therapy to improve glycemic control in patients with type 2 DM who are taking metformin, an SFU, or a combination of metformin and an SFU but who have not achieved adequate sugar control Insulin therapy is instituted when combinations of the medications described above fail to restore normal blood glucose levels. Weight reduction interventions are continued. Treatment of the non-obese type 2 patient depends on whether hyperglycemia is mild or severe (in which case the patient is positive for ketoacidosis). If hyperglycemia is mild, a normoglycemic state occasionally can be restored with a diet limited in simple sugars and a calorie content sufficient to maintain ideal weight. Restriction of saturated fats and cholesterol is also strongly promoted. When diet therapy in non-obese patients with type 2 diabetes is insufficient to correct hyperglycemia, a trial of an SFU is often successful Once the dosage of one of the more potent SFUs reaches the upper recommended limit without maintaining a fasting blood glucose concentration below 140 mg/dL during the day, addition of metformin or a TZD—or both—is tried. Examples of specific primary action of medication Class of agents medications increases insulin output by pancreas ○ Sulfonylureas ○ (SFUs) Chlorpropamide ○ Meglitinide ○ Glipizide ○ D-phenylalanine derivatives Glyburide ○ Glimepiride A recently available advance in insulin delivery is the insulin pump, which is the closest device on the market to an artificial pancreas and delivers insulin continuously. However, only patients who are highly motivated to perform frequent blood glucose tests and make daily insulin adjustments are good candidates for this method of treatment. Insulin pumps provide tight control of blood sugar and lifestyle flexibility, while minimizing hypoglycemic episodes. The instrument is composed of a pump reservoir, a battery-powered pump, and a computer chip that allows the user to program the precise dose of insulin that is delivered