diabetes Flashcards
what is diabetes mellitus?
Diabetes mellitus is a group of metabolic diseases char- acterized by high blood glucose levels (hyperglycemia) and the inability to produce and/or use insulin. The disease is de ned by abnormal blood glucose levels and utilization and is classi ed by the American Diabetes Association into four general types (Box 14-1).1 The four types are determined by the underlying mechanism, each demonstrating different levels of glycemia (Figure 14-1).
Type 1 diabetes is primarily the result of pancreatic beta cell destruction and is characterized by insulin de - ciency. Type 2 diabetes is characterized by insulin resis- tance and relative insulin de ciency. The broad category of other speci c types (see Box 14-1) comprises more than 56 pathologic conditions that are attributed to genetic defects in beta cell function, as well as diseases or infec- tions that cause diabetes. Gestational diabetes is abnor- mal glucose tolerance that rst appears or is detected during pregnancy. In addition, there are two types of prediabetes: impaired glucose tolerance and impaired fasting glucose. Persons who have abnormal blood glucose levels that are not high enough to be classi ed as diabetes are assigned a diagnosis of prediabetes.
what is the etiology of type 1 diabetes?
Diabetes results from several pathogenic processes ranging from autoimmune destruction of pancreatic beta cells in type 1 diabetes to abnormalities that cause insulin resistance (type 2 diabetes). Type 1 diabetes is thought to be the result of genetic, autoimmune, and environmental factors. The genetic component is demonstrated by data showing concordance rates of 30% to 40% amongst identical twins. HLA genes on chromosome 6 are linked to type 1 diabetes. Autoantibodies against beta cell con- stituents are present in 85% to 90% of patients with type 1 diabetes, and destruction of beta cells is modulated by T cells. Viral infections (mumps, rubella, and cox- sackievirus infection) are suggested environmental factors that could trigger the autoimmune response associated with type 1 disease. About 10% to 15% of cases of type 1 diabetes are of unknown etiology (i.e., idiopathic).1,4
what is the etiology of type II diabetes?
Type 2 diabetes has genetic, environmental, and aging components. Positive family history confers a lifetime risk of 38% to the offspring if one parent is affected, and 60% if both parents are affected.13 Identical twin concordance rates approach 100%.4 The peroxisome proliferator-activated receptor γ (PPARγ) gene, which has a key role in regulation of adipogenic differentiation, is a candidate gene of type 2 diabetes, however the disease is likely multigenic. Together the genetic and environmental factors contribute to defects in insulin receptor function, insulin receptor signal transduction,insulin secretion, glucose transport and phosphorylation, glycogen synthesis, glucose oxidation that contribute to insulin resistance, and accelerated endogenous glucose production. Obesity and lack of physical activity are the primary environmental factors involved in the pathogen- esis of type 2 diabetes.1,13,14
what is the pathophysiology of diabetes?
Persistent elevated blood glucose levels put persons at risk for diabetes. In fact, about 11% of people with prediabetes who were followed annually developed overt diabetes each year during the average 3 years of follow-up.17 An overview of the pathophysiologic pro- cesses involved is presented next.
Glucose is rapidly taken up by the pancreatic beta cell and serves as the most important stimulus for insulin secretion. Insulin remains in circulation for only several minutes (half-life [t1/2], 4 to 8 minutes); it then interacts with target tissues (e.g., muscle, liver, fat cells) and binds with cell surface insulin receptors. Secondary intracel- lular messengers are activated and interact with cellular effector systems, including enzymes and glucose trans- port proteins. Lack of insulin or de cient action of insulin leads to abnormalities in carbohydrate, fat, and protein metabolism (i.e, increased production of glucose from glycogen, fat, and protein). This combination of underutilization and overproduction of glucose attained through glycogenolysis and fat metabolism results in glucose accumulation in the tissue uids and in blood18 (Figure 14-2).
Hyperglycemia leads to glucose excretion in the urine, which results in increased urinary volume. The increase in uid lost through urine may lead to dehydration and loss of electrolytes. With type 2 diabetes, prolonged hyperglycemia can lead to signi cant losses of uid in the urine. When this type of severe dehydration occurs, urinary output drops, and a hyperosmolar nonketotic coma may result. This condition is seen most often in elderly persons with type 2 diabetes.18
Lack of glucose utilization by many cells of the body leads to cellular starvation. The patient often increases intake of food but in many cases still loses weight. If these events continue to progress, the person with type 1 diabetes develops metabolic acidosis. For a time, the body may be able to maintain the pH at nearly normal levels, but as the buffer system and respiratory and renal regulators fail to compensate, body uids become more acidic (i.e., pH falls). Severe acidosis will lead to coma and death if it is not identi ed and treated. The primary manifestations of diabetes—hyperglycemia, ketoacido- sis, and vascular wall disease—contribute to the inability of patients with uncontrolled diabetes to ght infection and to characteristic poor wound healing. The end results of these effects, as well as others yet to be identi- ed, are that the patient with uncontrolled diabetes is rendered much more susceptible to infection, the patient’s ability to deal with an infection once it has been estab- lished is reduced, and healing of traumatic and surgical wounds is delayed.18,19
Complications of diabetes are related to the level of hyperglycemia and pathologic changes that occur withinthe vascular system and the peripheral nervous system (Box 14-2). The vascular complications result from microangiopathy and atherosclerosis. The mechanisms by which hyperglycemia may lead to microvascular and atherosclerotic complications include increased accumu- lation of polyols through the aldose reductase pathway, advanced glycation end products, and increased produc- tion of vascular endothelial cell growth factor (VEGF).23 Vessel changes include thickening of the intima, endo- thelial proliferation, lipid deposition, and accumulation of para-aminosalicylic acid–positive material. These changes can be seen throughout the body but have par- ticular clinical importance when they occur within the retina and the small vessels of the kidney.4,24
Retinopathy occurs in all forms of diabetes. It consists of nonproliferative changes (microaneurysms, retinal hemorrhages, retinal edema, and retinal exudates) and proliferative changes (neovascularization, glial prolifera- tion, and vitreoretinal traction) and is the leading cause of blindness in the United States. The incidence of blind- ness in all persons with diabetes is 0.2% per year; it is 0.6% per year for diabetic patients with retinopathy. Proliferative retinopathy is most common among patients with type 1 diabetes; a much lower incidence is seen among those with type 2 diabetes. Cataracts occur at an earlier age and with greater frequency in those with type 1 diabetes. The typical cataract, senile cataract, is identi- ed in 59% of persons with diabetes aged 35 to 55 years but in only 12% of those without the disease. Young people with diabetes are prone to the development of metabolic cataracts. The risk that a person with diabetes will become blind is 20 times greater than that for the general population.4,25
Diabetics are 25 times more likely to acquire end- stage renal disease than persons without diabetes.12 Dia- betic nephropathy leads to end-stage renal disease in 30% to 40% of patients with type 1 diabetes (Figure 14-3) and in 5% of patients with type 2 diabetes. However, because type 2 diabetes is much more common than type 1, the number of persons with renal failure is the same for the two types of diabetes. Renal failure is the leading cause of death in patients with type 1 diabe- tes. Of all patients who undergo dialysis, 37% have diabetes. Microangiopathy in the kidney usually involves the capillaries of the glomerulus.8,26,27
Macrovascular disease (atherosclerosis) occurs earlier and is more widespread and more severe in persons with diabetes. In patients with type 1 diabetes, atherosclerosis seems to develop independent of microvascular disease (microangiopathy). Hyperglycemia plays a role in the evolution of atherosclerotic plaques. Persons with uncon- trolled diabetes have increased levels of low-density lipoprotein (LDL) cholesterol and reduced levels of high-density lipoprotein (HDL) cholesterol. Attainment of normal glycemia often improves the LDL-to-HDL ratio.2
A major determinant of the morbidity associated with poor glycemic control in diabetes is accelerated athero- sclerosis. Atherosclerosis increases the risks of ulceration and gangrene of the feet (Figure 14-4), hypertension, renal failure, coronary insuf ciency, myocardial infarc- tion, and stroke. The most common cause of death in patients with type 2 diabetes is myocardial infarction. By age 60, a third of all persons with diabetes die of com- plications from coronary heart disease (CHD). Women with diabetes treated with insulin are at higher risk for CHD than non–insulin-treated women. This is not true for insulin-treated men. Also, diabetics are at a two- to four-fold greater risk for myocardial infarction and stroke than in persons without the disease, and a person with diabetes has less chance of surviving a myocardial infarction than that typical for a nondiabetic person.2,7,28
In the extremities, diabetic neuropathy may lead to muscle weakness, muscle cramps, a deep burning pain, tingling sensations, and numbness. In addition, tendon re exes, two-point discrimination, and position sense may be lost. Some cases of oral paresthesia and burning tongue are caused by this complication.4,29-31
Diabetic neuropathy also may involve the autonomic nervous system. Esophageal dysfunction may cause dys- phagia, stomach involvement may cause a loss of motil- ity with massive gastric distention, and involvement of the small intestine may result in nocturnal diabetic diar- rhea. Sexual impotence and bladder dysfunction also may occur. Diabetic neuropathy is common with type 1 and type 2 diabetes and may occur in more than 50% of patients. Neuropathy progresses over time in type 2 diabetes, and this increase may be greater in patients with hypoinsulinemia.4,29-31
Diabetes is associated with skin rashes, deposits of fat in the skin (xanthoma diabeticorum), decubitus ulcer- ations, poor wound healing, and gangrenous extremities. The relative risk that patients with diabetes will require amputation of an extremity because of diabetic compli- cations is more than 40 times that of normal persons. Recent data show that more than 65,000 amputations are performed annually in patients with diabetes melli- tus. This number represents more than 60% of all non- traumatic amputations.8
The severity of complications of diabetes is largely dependent on the level of glycemic control.32 In one longitudinal study conducted over a period of more than 17 years, scientists demonstrated that diabetic patients with good glycemic control (hemoglobin A1c levels below 7%) had 42% fewer systemic complications and 57% fewer deaths than those reported for patients with dia- betes and poorly controlled hyperglycemia (HbA1c levels above 8%).2 Thus, a strong case can be made for early diagnosis and appropriate glycemic control to prevent or reduce progression of complications.
