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Definition and Classification
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Diabetes is a complex metabolic disease that affects approximately 7% of the population, more than 24 million people, with almost a million and a half new patients annually.61-63 Classically diabetes is characterized by hyperglycemia with polyphagia, polydipsia, polyuria, weight loss, and an increased susceptibility to infections. Severely uncontrolled patients may present with marked hyperglycemia and diabetic ketoacidosis or with the nonketotic hyperosmolar syndrome. The interrelationship between diabetes and other disease processes is vast and includes the metabolic syndrome, infections, heart disease, neuropathy, nephropathy, peripheral vascular disease, and retinopathy.
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Recently the American Diabetes Association62,63 modified its diagnostic criteria for the definition of diabetes to include measuring hemoglobin A1c (HgbA1c). When evaluating an abnormal glucose test, the recommendation is still to have the test repeated another day, unless the patient presents with classic symptoms of diabetes or is in a hyperglycemic crisis, in which case a random plasma glucose of 200 mg/dL (11.1 mmol/L) or higher may be used in conjunction with the classic symptoms (ie, criterion #4). The 4 glucose test criteria used by the American Diabetes Association for the definition of diabetes are as follows: (1) HgbA1c of 6.5% or higher with the test being performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay. If the patient has certain hemoglobinopathies and/or anemias from hemolysis or from nutritional deficiencies, then the use of an HgbA1c of 6.5% or higher alone cannot be used, and other criteria must be used. (An updated list of conditions is available at www.ngsp.org/prog/index3html). (2) A fasting plasma glucose of 126 mg/dL (7.0 mmol/L) or higher, where fasting is defined as no caloric intake for at least 8 hours. (3) A 2-hour plasma glucose of 200 mg/dL (11.1 mmol/L) or higher during an oral glucose tolerance test, which is performed in accordance to World Health Organization standards, with a glucose load containing the equivalent of 75 g of glucose dissolved in water. (4) For patients with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose of 200 mg/dL (11.1 mmol/L) or higher. For a clinical situation in which the test results are discordant, the test that is positive should be repeated, and, if positive, then the definition of diabetes applies.
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Diabetes is a disease that is characterized by hyperglycemia, with defects of insulin secretion, insulin action, or both. The American Diabetes Association classifies diabetes into the following 4 specific categories: (1) type 1 diabetes, which is caused by β-cell destruction and usually results in insulin deficiency; (2) type 2 diabetes, which encompasses a range from insulin resistance with relative insulin deficiency, to insulin secretory defects with insulin resistance; (3) specific types of diabetes, which include genetic defects of β-cell function, defects in insulin action, diseases of the exocrine pancreas, endocrinopathies, drug-induced, and infections; and (4) gestational diabetes mellitus.62,63
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Type 1 diabetes results from β-cell destruction leading to insulin deficiency and accounts for approximately 5% to 10% of patients with diabetes mellitus. Patients with type 1 diabetes have an increased risk of ketoacidosis due to impaired insulin production. Type 1 diabetes is further subdivided into immune-mediated or idiopathic. Immune-mediated type 1 diabetes is characterized by cell-mediated autoimmune destruction of pancreatic β cells with subsequently decreased insulin secretion. The rate of destruction of β cells may vary. Type 1 diabetes often manifests in childhood or adolescence, but may also present at any age, even in elderly patients, including those in their 80s. Markers of autoimmune destruction such as autoantibodies to islet cells, insulin, glutamic acid decarboxylase (GAD65), and tyrosine phosphatases IA-2 and IA-2B are found in approximately 90% of these patients.63 There is a strong human leukocyte antigen (HLA) association with the HLA-DR/DQ alleles. Some patients who present with autoimmune destruction of β cells may be obese, but most tend to be thin. Patients with immune-mediated type 1 diabetes are prone to other autoimmune disease, such as Graves disease, Hashimoto thyroiditis, Addison disease, autoimmune hepatitis, myasthenia gravis, and pernicious anemia.62 In contrast, idiopathic diabetes comprises only a minority of type 1 diabetes, usually in patients of African or Asian descent. Although this form is strongly inherited, there is no HLA association or indication of β-cell autoimmunity, and the requirement for insulin may come and go in affected patients.62-64
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The principal and most common form of diabetes is type 2 diabetes, which comprises 90% to 95% of patients with diabetes. Although the cause or causes of this form of diabetes may be varied, patients who have type 1 diabetes, gestational diabetes, or specific type diabetes cannot be classified as having type 2 diabetics. Patients with type 2 diabetes are characterized by a range and progression of insulin resistance and relative insulin deficiency, and they have a stronger genetic predisposition than those with type 1, but these genetic relationships are complex and ill defined. With increasing age, obesity, lack of exercise, hypertension, dyslipidemia, and gestational diabetes there is an increased risk of developing type 2 diabetes. Although ketoacidosis is more characteristic of type 1 diabetes, it may occur with type 2 diabetes in association with the stress of acute illness or infection. Because type 2 diabetes tends to go undetected for years, there is an increased risk of developing a variety of complications.
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Other Types of Diabetes62,63
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Genetic defects of β-cell function are due to specific monogenetic defects or specific point mutations. Maturity-onset diabetes of the young (MODY) has been associated with at least 6 different abnormal gene products (ie, MODY 1, Chr 20–HNF4α; MODY 2, Chr 7, glucokinase; MODY 3, Chr 12, HNF-1α; MODY 4, Chr 13, 1PF-1; MODY 5, Chr 17, HNF–1β; MODY6, Chr 2, neuro D1). Point mutations of mitochondrial DNA may also lead to diabetes. Gene defects in insulin action are found in type A insulin resistance, leprechaunism, Rabson-Mendenhall syndrome, and insulin-resistant lipodystrophy. Diseases of the exocrine pancreas, such as severe pancreatitis, trauma, pancreatectomy, pancreatic carcinoma, cystic fibrosis, hemochromatosis, and fibrocalculous pancreatopathy, can cause diabetes. Endocrinopathies such as acromegaly, Cushing syndrome, glucagonoma, pheochromocytoma, hyperthyroidism, somatostatinoma, and primary hyperaldosteronism cause diabetes, and with the treatment of the primary disease, the diabetes resolves. Certain drugs may precipitate diabetes in patients with underlying insulin resistance and include IV pentamidine, nicotinic acid, glucocorticoids, thyroid hormone, diazoxide, β-adrenergic agents, thiazides, dilantin, and interferon. Certain viruses such as congenital rubella may result in B-cell destruction. Other viruses such as coxsackievirus B, cytomegalovirus, adenovirus, and mumps can cause diabetes. Uncommon forms of immune-mediated diabetes include "stiff man syndrome" with GAD (glutamic acid decarboxylase) autoantibodies and anti-insulin receptor antibodies found in patients with lupus and other autoimmune diseases. Genetic syndromes such as Down syndrome, Klinefelter syndrome, Turner syndrome, Wolfram syndrome, Fredreich ataxia, Huntington disease, Laurence-Moon Biedl syndrome, myotonic dystrophy, porphyria, and Prader-Willi syndrome are associated with diabetes.
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Gestational diabetes occurs in at least 200,000 US pregnancies each year and carries with it a host of other risks. Patients with gestational diabetes are at increased risk for fetal macrosomia, maternal hypertension, cesarean section, neonatal hypoglycemia, and neonatal jaundice and hypocalcemia. The American Diabetes Association is currently working with the obstetrical societies to adopt International Association of Diabetes and Pregnancy Study Group (IADPSG) recommendations.62,63
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The American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) has recently established an algorithm for glycemic control (Fig. 13-1.). The guiding principle is to use an individualized stepwise approach to achieve an HgbA1c level of 6.5% or less. This should be done with lifestyle modifications, medications including insulin, the use of HgbA1c to guide therapy, and education and compliance on the part of both patients and caregivers.63,64 Table 13-20 lists the current classes of medications used for diabetes control.
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Non-Insulin Medications
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The biguanides suppress hepatic glucose production by decreasing gluconeogenesis and glycogenolysis. There is also decreased absorption of glucose, increased insulin sensitivity, and increased synthesis of GLP-1. Metformin, the principal agent used, is recommended as initial therapy, in combination with other classes of drugs, and may be given in combination with insulin. Nausea and gastrointestinal distress is minimized by a gradual increase in dosage. Metformin is renally excreted and impaired renal function (indicated by a plasma creatinine ≥1.5 or a creatinine clearance of <60 mL/min) may lead to metformin accumulation and lactic acidosis. Metformin therapy is contraindicated in the presence of heart failure, liver disease, alcoholism, sepsis, hypoxemia, and during the administration of intravenous contrast agents. Metformin also decreases the absorption of vitamin B12 and may lead to a megaloblastic anemia without vitamin B12 supplementation. The insulin secretagogues comprise 2 classes of medicine: the sulfonylureas and the meglitinides. The sulfonylureas bind to receptors on the β cell to increase insulin secretion. They can have a hypoglycemic effect, which is more pronounced in the elderly, and they can be associated with weight gain and edema. The meglitinides are rapid-acting and short-duration insulin secretagogues. They are tightly bound and metabolized in the liver by cytochrome P450. Thiazolidinediones (TZDs) are insulin-sensitizing agents that act on muscle, adipose tissue, and the liver to increase insulin-mediated glucose uptake. Side effects include weight gain and edema, which is not responsive to loop diuretics. TZDs are contraindicated in New York Heart Association functional class III or IV heart failure. TZDs cause patients to be at risk for bone fractures. In addition, a "black box warning" has been issued for rosiglitazone because of its possible association with increased ischemic heart disease. The α-glucosidase inhibitors acarbose and miglitol act on the brush border of the intestine to inhibit the breakdown of carbohydrates. Their main side effects are gastrointestinal discomfort, diarrhea, and, in rare instance, cholestatic jaundice. The dipeptidyl C-peptidase-4 inhibitors sitagliptin and saxagliptin inhibit DPP-4, an enzyme that metabolizes GLP-1 and gastric inhibitory polypeptide. The incretin hormones cause increased insulin secretion, increased peripheral glucose uptake, and suppression of glucose production in the liver. Allergic reactions may occur. Because these medications are renally excreted, caution must be used in the presence of renal insufficiency. The GLP-1 agonists, exenatide and liraglutide, bind to GLP-1 receptors, resulting in increased glucose-dependent insulin secretion and suppression of glucagon secretion. This results in increased satiety, reduced appetite, and weight loss, with the principal side effects being gastrointestinal, although renal insufficiency and pancreatitis have been reported, as well as hypoglycemia when used with sulfonylureas. Pramlintide is a synthetic amylin that decreases glucagon secretion, promotes satiety, decreases gastric emptying, and causes weight loss but is associated with nausea and hypoglycemia. Colesevelam is a bile acid sequestrant that decreases glucose, but whose precise mechanism of action is unknown.
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The American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) consensus panel no longer recommends the use of either regular insulin or NPH insulin for the treatment of type 2 diabetes.63,64 Regular insulin has an onset of action that is too slow and persists for too long, so that effective glucose control is not achieved, and the risk of delayed hypoglycemia is increased. NPH insulin does not have a consistent absorption pattern from day to day, nor does it persist long enough to provide a basal insulin level, and this increases the risk of hypoglycemia. The AACE/ACE recommends a basal insulin supply, such as provided by glargine or detemir, and treatment with rapid-acting insulins, such as aspart, lispro, or glulisine, to cover postprandial glucose elevations. This more closely mimics normal physiology and minimizes the risk of hypoglycemia.63,64 The use of continuous insulin infusions requires frequent blood glucose monitoring in order to provide optimal control.
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Perioperative Changes in Glucose Metabolism
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The surgical stress response65-71 is characterized by increases in sympathetic tone, glucagon levels, pituitary hormone levels (notably corticotropin and growth hormone), and interleukin-1. During the perioperative period, increases in plasma norepinephrine and epinephrine also occur. Epinephrine and norepinephrine stimulate liver glycogenolysis and gluconeogenesis68,70 and inhibit glucose uptake by insulin-dependent tissues. The α and β effects of the catecholamines may influence glucose metabolism. For instance, epinephrine increases the metabolic rate through its β effects.69,70 The α and β effects also have profound influences on pancreatic function. β-Receptor stimulation enhances insulin and glucagon release, whereas α-receptor stimulation inhibits the release of insulin. During the intraoperative and immediate postoperative course, α effects predominate, causing suppression of insulin secretion. Decreased insulin levels coupled with increased gluconeogenesis and insulin resistance cause hyperglycemia and glucose intolerance, prompting the term "the diabetes of injury."
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During the convalescent stage after surgery, there is increased gluconeogenesis, and glucose uptake by the peripheral tissues is normal and insulin secretion is increased. The normal pancreas is able to respond normally to the increased glucose loads. A contributing factor to this metabolic change in glucose kinetics is the hormonal shift from α- to β-adrenergic catecholamine effects.71 Plasma glucagon levels increase after surgery and promote hepatic amino acid uptake, gluconeogenesis, and glycogenolysis.70,71 Nonetheless, the increase in splanchnic glucose production with glucagon is a transient phenomenon, and it is only with the combined effects of all the stress hormones that hepatic gluconeogenesis is maintained.70,71 Increased pituitary release of corticotropin leads to increased glucocorticoid levels, which can produce a moderate glycemic response.67,68 Postoperative increases in growth hormone have an anabolic effect, causing nitrogen retention, protein synthesis, lipolysis, and decreased peripheral glucose uptake.72 The net effects of the neuroendocrine response on metabolism during the convalescent stage after acute tissue injury include an increased rate of gluconeogenesis, increased blood glucose level, and stimulation of lipolysis.
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During surgery, blood glucose concentrations in nondiabetic patients may increase to as much as 60 mg/dL above preoperative levels.73 The extent of operative stress is the primary determinant of the absolute increase in glucose values. Inadequate insulin secretion, coupled to the stress hormone milieu and the preoperative fasting state, makes the diabetic patient more susceptible to hyperglycemia, osmotic diuresis, hypovolemia, ketosis, and possible changes in acid–base balance. Hyperglycemia may have detrimental effects if it is unmanaged. Osmotic diuresis resulting from the osmotic activity of glucose occurs when the patient's blood glucose level exceeds the renal glucose threshold (approximately 180-250 mg/dL). This osmotic diuresis can result in dehydration, acidosis, and electrolyte abnormalities. Although hyperglycemia per se does not have direct effects on the patient's acid–base status, the ketone bodies that result from inadequate insulin therapy can elicit such effects. Acetoacetic acid and β-hydroxybutyric acid lower serum pH by dissociation of hydrogen ions.
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Complications of Diabetes
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Diabetes reduces the overall life span75 and produces multisystem complications. Table 13-21 summarizes the principal complications of diabetes.
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Cardiovascular Disease and Diabetes
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The relationship between diabetes and cardiovascular disease is complex. Not only is cardiovascular disease a major complication of diabetes, but diabetes is a major risk factor for cardiovascular disease. Diabetes patients have a higher incidence of cardiovascular disease than the general population.76-78 Diabetes patients are at increased risk of myocardial infarction and exhibit a greater risk of both pre-hospital and in-hospital mortality after a myocardial infarct.79 The National Cholesterol Education Program has defined diabetes as a coronary risk equivalent because a higher mortality is associated with diabetes and coronary artery disease.80 With intensive focus, the risk as a consequence of cardiovascular disease has decreased, but there has not been a decrease in the number of patients with diabetes.81 Thus risk factor modification assumes greater significance in diabetics.
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Similarly, the relationship between diabetes and hypertension is complex and interrelated. Not only should diabetes be aggressively treated, but hypertension should be aggressively treated, as revealed in 2 key studies—the United Kingdom Prospective Diabetes Study (UKPDS) and the Hypertension Optimal Treatment (HOT) trial.82-84 The UKPDS study found that although intensive glucose therapy was beneficial in reducing cardiovascular risk, there was an even more significant effect of reducing blood pressure, not only for cardiovascular events but also for cerebrovascular events. The HOT study demonstrated that aggressive diastolic blood pressure reduction reduced cardiovascular mortality. These findings have been incorporated into the Joint National Committee on Prevention, Detection, Evaluation, Treatment of High Blood Pressure 7th Report (JNC-7) guidelines.85 In high-risk cardiovascular patients, angiotensin-converting enzyme (ACE) inhibitors improve cardiovascular morbidity and mortality.86,87 Despite all the recommendations and the higher prevalence of hypertension among diabetes patients, unfortunately hypertension remains, for many patients, uncontrolled.88,89
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Dyslipidemias are widely prevalent among diabetes patients and are part of the complex relationship between diabetes and the associated cardiovascular and cerebrovascular events leading to increased morbidity and mortality. Multiple studies—the Heart Protection Study,89 the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group,90 the Scandinavian Simvastatin Survival Study,91 and the MRC/BHF Heart Protection Study92—show a clear benefit of aggressive lipid management. The American Diabetes Association used this information to help set its lipid goal recommendations63,93: low-density lipoprotein (LDL) cholesterol in diabetes patients should be less than 100 mg/dL. The National Cholesterol Education Program (NCEP) has set a more aggressive goal in high-risk patients: LDL less than 70 mg/dL, triglycerides less than 150 mg/dL, and high-density lipoprotein greater than 40 mg/dL.63,93 The Lescol Intervention Prevention Study found a marked reduction of more than 50% in major adverse cardiac events such as death or nonfatal myocardial infarction with the use of statin therapy.94
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Diabetes is associated with a prothrombotic state that contributes to the increased risk of mortality from cardiovascular disease.95,96 One of the early studies to show the benefits of aspirin was the Physicians Health Study,97 which noted a marked reduction in myocardial infarctions among diabetic physicians taking aspirin. Subsequent work, such as the HOT trial, continued to show a significant reduction in cardiovascular events, as well as myocardial infarction for patients taking aspirin. The benefits of aspirin plus clopidogrel, as well as aspirin plus glycoprotein 2b/3a inhibitors, has been noted,95 although the risk of bleeding is increased with these combinations versus aspirin alone.
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Although recent studies98 indicate that current assessment guidelines may miss patients with silent ischemia, there is still no well-established data in asymptomatic patients demonstrating that advanced testing with nuclear stress tests or stress echocardiography can lead to better outcomes. The emphasis should rather be on risk reduction and adopting proven beneficial therapies—lipid reduction, blood pressure control, smoking cessation, weight reduction, increasing physical activity, and aspirin therapy. A detailed history and physical examination including laboratory and electrocardiogram (ECG) analysis should be done. Exercise capacity should be determined in accordance with the American College of Cardiologists/American Heart Association preoperative assessment guidelines.
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Diabetic neuropathy is common, varied, and affects between 75% and 90% of all diabetes patients, with the elderly having more pronounced effects. There are many classification systems for diabetic neuropathy.99,100 The American Diabetes Association63 classifies neuropathies as (1) sensory neuropathies—acute sensory neuropathy and chronic distal symmetric polyneuropathy; (2) focal and multifocal neuropathies; and (3) autonomic neuropathy. The classification system used by Vinik and Mehrabyan102,103—small-fiber neuropathies, large-fiber neuropathies, and autonomic neuropathy—is somewhat more intuitive. A key point emphasized by the American Diabetes Association63 is that early recognition and treatment of neuropathy is important; it is equally important to determine which neuropathies are not attributable to diabetes and to correctly diagnose and exclude them.
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The small-fiber neuropathies63,102 are characterized by being electrophysiologically silent with preservation of reflexes and motor strength, but with loss of cutaneous nerve fibers on tissue staining. Allodynia with burning superficial pain of the c-fiber type is a characteristic, but later there is hypoalgesia. There is decreased thermal sensation with impaired vasomotor and blood flow and decreased autonomic function, leading to decreased sweating, dry skin, and an increased risk of foot ulceration and gangrene.
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The large-fiber neuropathies encompass both sensory and motor nerves and are more amenable to diagnosis with electromyography, nerve conduction velocity studies, and quantitative sensory tests.99,101,103 Clinical manifestations include changes in perception presenting with impaired vibratory perception and position sense. There is depression of the deep tendon reflexes, sensory ataxia, and a deep-seated, dull, aching pain in the feet. Initially there may be a feeling of warmth in the feet because of increased blood flow. There is a shortening of the Achilles tendon and wasting of the small muscles of the feet, with hammertoes and subsequent weakening of the hands and feet. Distal muscle weakness can been seen as leading to an inability to stand on the heels or toes. Distal symmetric neuropathy, diffuse motor neuropathy, and distal motor neuropathy are part of the large-fiber neuropathy syndrome. It is important to exclude other causes of these types of neuropathies, such as familial B12 deficiency, folate deficiency, Lyme disease, heavy-metal poisoning, reaction to cytotoxins, and the neuropathies caused by malignancy. In the elderly, there is an increase in proximal muscle neuropathy. These can present as pain in the buttocks, thighs, and hips that can be either abrupt or gradual in onset. Symptoms can progress to weakness with inability to get up from a sitting position and can coexist with distal symmetric polyneuropathy. Fasciculations may be provoked by percussion or may occur spontaneously with electrophysiologic studies indicating a lumbosacral plexopathy. The elderly are also at greater risk for mononeuropathies. These tend to occur spontaneously, acutely, and with pain. They tend to affect the ulnar, median, peroneal nerves, and cranial nerves III, VI, and VII and are characterized by a spontaneous remission and lack progression. These mononeuropathies must be distinguished from nerve-entrapment syndromes such as carpal tunnel, which are more frequent in diabetes patients but which tend to be gradual in onset and progressive in nature.63,99,101
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Autonomic neuropathy99-103 has many clinical manifestations and involves multiple physiologic systems. Cardiovascular manifestations include a resting tachycardia, exercise intolerance, orthostatic hypotension, cardiac degeneration and silent myocardial infarction, alterations in blood flow to skin and extremities, and temperature intolerance. The gastrointestinal system is affected by a variety of changes, including esophageal dysmotility, diarrhea, constipation, incontinence, and diabetic gastroparesis. Genitourinary syndromes include cystopathy, neurogenic bladder, and sexual dysfunction in women and erectile dysfunction in men. Besides temperature intolerance, there are abnormalities of sweating. There is decreased lower-body sweating, with resulting skin dryness and cracking contributing to increased infections and ulcerations of the diabetic foot. Autonomic neuropathy affects the metabolic response to glucose regulation with both a decreased ability to detect and respond to hypoglycemia. Ocular manifestations of autonomic neuropathy include Argyll-Robertson–like pupil and a decreased diameter of a dark-adapted pupil.102
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As pointed out by Luukinen and Airaksinen,104 orthostatic hypotension for older diabetes patients portends a higher risk of vascular death. The increase in morbidity and mortality associated with autonomic neuropathy is one of the reasons the American Diabetes Association63,102 advocates the performance of standard examinations to diagnose autonomic neuropathy. Examination of the resting heart rate is key, because a resting heart rate greater than 100 beats per minute is abnormal. Next, an examination of fasting, nonhypoglycemic heart rate with a study of heart rate variability is done with a patient monitored by an ECG breathing at 6 breaths per minute; the difference in heart rate between resting and supine should be greater than 15 beats per minute, and if the heart rate variability is less than 10 beats per minute, and the R-R interval ratio is not greater than 1.17, then the heart rate variability is considered abnormal.
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As noted by Cox et al,105 hyperglycemia impairs cognitive performance in diabetes patients. Arvanitakis et al106 notes that diabetes, in addition to aging, contributes to the progression and worsening of rigidity and gait disturbance in the elderly. The DCCT trial107,108 demonstrated the beneficial effect of tight glucose control on limiting the microvascular complications of diabetes; the goal advocated is an HgbA1c level less than 7%. In addressing the pain and discomfort associated with diabetic neuropathy, the American Diabetes Association63,102 recommends a stepwise approach starting with exclusion of nondiabetic causes, stabilizing the blood sugar, and then attempting to achieve an HgbA1c level of less than 7%. Tricyclics are the first-line drugs for pain control, then anticonvulsants, and finally opiates. However, Gilron et al109 recently demonstrated that the lower-dose combination of opiates and anticonvulsants achieves better analgesia than higher doses of either drug alone. The EURODIAB Study Group,110 in addition to the findings of the UKPDS, emphasizes the importance of addressing all modifiable risk factors to minimize diabetic neuropathy.
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Nephropathy and Urologic Complications
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Diabetic effects on the urologic system encompass diabetic nephropathy, urologic cystopathy, erectile dysfunction, and infection. Diabetic nephropathy affects more than 40% of patients with type 1 diabetes and more than 20% of those with type 2 diabetes.63,111,112 The National Kidney Foundation112 defines diabetes as a risk factor for chronic kidney disease and recommends screening and risk factor reduction. The effects of diabetes in leading to end-stage renal disease are worse for certain ethnic groups, namely Native Americans, Hispanics, and African Americans.63 It appears that aggressive risk-factor reduction and tight blood pressure and glucose control113 can decrease both the rate of progression to end-stage kidney disease and the renal complications of diabetes. The American Diabetes Association recommends the early diagnosis and treatment of microalbuminuria along with aggressive risk-factor reduction and blood glucose control to prevent the albuminuria, blood pressure elevation, and persistent decline in glomerular filtration rate (GFR) that is characteristic of diabetic nephropathy and which ultimately contributes to increased mortality and morbidity.
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Diabetic cystopathy affects almost 50% of diabetes patients and increases with age.102 In diabetic cystopathy there is impaired sensation of bladder fullness, an increase in bladder capacity, a reduction in bladder contractility, and increased residual urine volume. Residual urine increases the risk for urinary tract infections, urethral reflux, hydronephrosis, pyelonephritis, and urosepsis. A urologic evaluation for cystopathy may include cystometry, sphincter electromyography, uroflowmetry, and urethral pressure profile. Both cystopathy and erectile dysfunction result from microvascular changes of diabetes and the polyneuropathy associated with diabetes.114
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Diabetic Ketoacidosis and Nonketotic Hyperglycemic Hyperosmolar Syndrome
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Poorly controlled diabetes may cause severe metabolic abnormalities, including diabetic ketoacidosis or a hyperglycemic hyperosmolar nonketotic state. The hyperosmolar nonketotic state is characterized by marked hyperglycemia, dehydration, and hyperosmolarity, but severe ketosis is absent. Patients unable to compensate for hyperglycemia and dehydration are often elderly type 2 diabetes patients. The presence of diabetic ketoacidosis is suggested strongly by the history and physical examination, along with a high blood sugar level and positive urine ketones, although a definitive diagnosis of diabetic ketoacidosis must be verified with arterial blood gases and consists of (1) hyperglycemia (>250 mg/dL), (2) decreased bicarbonate (<15 mEq/L), and (3) a decreased arterial pH (<7.3) with ketonemia (positive at 1:2 dilution) and moderate ketonuria. The principal therapy includes hydration, IV insulin, and frequent monitoring of electrolytes, glucose, and acid–base status. The details of therapy are addressed in Chapter 60.
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Diabetes Preoperative Evaluation
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Diabetes is a disease with enormous physiologic impact, and the preoperative evaluation should be done in accordance with current American College of Cardiologists/American Heart Association guidelines. The preoperative evaluation should include assessment of the systemic manifestations noted previously. The ECG should be analyzed, bearing in mind the greater incidence of silent myocardial infarctions among diabetes patients. Because diabetic patients tend to receive multiple medications, obtaining a metabolic profile may be worthwhile. The levels of key electrolytes, sodium, and potassium should be determined. Current glucose level both in reference to a patient's baseline and also as a baseline for subsequent comparisons is useful. An HgbA1c level is useful to indicate overall glycemic control, with current American Diabetes Association recommendations being below 7% and values above 10% corresponding to poor glycemic control.63 A fasting lipid profile provides information regarding concomitant cardiovascular risk. The serum creatinine, along with blood urea nitrogen level, helps to provide information on volume status and renal function. It must be borne in mind that as patients age, their muscle mass diminishes, as does the creatinine that one measures. Because urinary tract infections tend to be common among diabetic patients, a urinalysis can provide insight regarding the presence of infection, ketones, protein, and sediment.
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Laryngoscopy and Intubation
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Diabetes may be associated with a greater incidence of difficult laryngoscopy and intubation. In patients with diabetes, stiff joint syndrome can occur, affecting all joints, including those of the cervical and thoracic spine. The incidence of difficult laryngoscopy in long-term type 1 diabetic patients is reported to be 30% to 40%.117-119 The diagnosis of stiff-joint syndrome is relatively easy. Besides evaluation of spine mobility, the wrists and elbows should be observed for incomplete extension and flexion. The hands should be assessed for thick, waxy skin and an inability to oppose the interphalangeal joints of the fingers assessed in the "prayer" position.119
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Patients with the metabolic syndrome are at an increased risk for cardiovascular disease, cerebrovascular disease, and diabetes. This may be a result of dyslipidemia, vascular dysregulation, a proinflammatory state, prothrombotic state, insulin resistance, or some other mechanism. The recent consensus definition of the metabolic syndrome120,121 uses in large part the International Diabetes Foundations definition. Currently the consensus conference considers the metabolic syndrome present when any 3 of the following 5 criteria are present: (1) elevated waist circumference that is ethnically and country specific; (2) elevated triglycerides with a value of 150 mg/dL (1.7 mmol/L), or higher, or undergoing drug treatment; (3) reduced high-density lipoprotein cholesterol (<40 mg/dL [1.7 mmol/L] in men and 50 mg/dL [1.3 mmol/L] in women) or undergoing drug treatment; (4) an elevated blood pressure (systolic ≥130, or diastolic ≥85) or undergoing drug treatment; (5) elevated fasting glucose of 100 mg/dL, or higher, or undergoing drug treatment.121 Whether the metabolic syndrome is a clustering of risk factors or a specific disease itself remains to be determined.
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Acknowledgment: The author thanks F.E. Sieber for his work on this chapter in the previous edition.