Diabetes is the most common cause of end- stage kidney disease in the United States, patients with diabetes account for two thirds. of all nontraumatic …
12 Complications of Diabetes
Risks for Complications in Diabetes
Persons with diabetes are at increased risk for macrovascular disease; microvascular disease, including retinopathy and nephropathy; peripheral and autonomic neuropathies; and lower extremity disease Diabetic retinopathy is the leading cause of noncongenital blindness among adults Diabetes is the most common cause of endstage kidney disease in the United States, especially among Native American, Hispanic, and African American persons One quarter to one third of patients with type 1 or type 2 diabetes develop some degree of nephropathy Diabetes doubles the risk for cardiovascular disease in men and triples it in women data from the Multiple Risk Factor Intervention Trial [MRFIT] Patients with diabetes are several-fold more likely to have peripheral arterial disease than patients without diabetes Peripheral arterial disease and foot ulcers in patients with diabetes account for two thirds of all nontraumatic amputations performed in the United States Screening for and prevention of these complications are fundamental to the care of patients with diabetes and are important components of quality of care initiatives for
diabetes several years prior to actual diagnosis Indeed, postprandial hyperglycemia, as caused by impaired glucose tolerance, is by itself a risk factor for the development of cardiovascular disease Screening for complications should generally begin 1 year after diagnosis in patients with type 1 diabetes because that is when rates of complications such as retinopathy begin to rise
Preventing Complications
Improved blood pressure control substantially reduces the risks of cardiovascular events and death In addition, for any abnormal serum cholesterol level, patients with diabetes have more coronary disease than do patients without diabetes, so lipid control along with blood pressure control is especially important in this population Lipid control and blood pressure control are discussed in greater detail in Chapter 10 Hyperlipidemia and Hypertension Maintaining excellent glycemic and blood pressure control is essential to protect against the development of progressive nephropathy and retinopathy In the Epidemiology of Diabetes Intervention and Complications EDIC study, the benefits of intensive glycemic control in reducing the risk of microvascular complications continued after 7
years of follow-up, despite the convergence of hemoglobin A1C values in the intensively and the conventionally managed groups
Lifestyle Modifications
When does screening for complications need to begin for patients with a diagnosis of diabetes?
For type 2 diabetes, screening for complications should be initiated at the time of diagnosis because the disease may have been present for
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Weight reduction in the presence of obesity, exercise, and a low-calorie, low-fat, highcomplex carbohydrate diet are all important in preventing or delaying diabetes-related cardiovascular complications In several trials, exercise has been found to improve cardiovascular outcomes and glycemic control among patients with type 2 diabetes A meta-analysis of controlled trials
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that examined the effect of exercise on patients with type 2 diabetes found that exercise training reduced hemoglobin A1C values by 07 percentage point A recent study estimated that one death per year would be prevented for every 61 adults with diabetes who walked at least 2 hours per week Suggestions for helping your patients lose weight and
exercise are discussed in Chapter 5 Helping Patients Make Lifestyle Changes Further, another meta-analysis of cardiovascular risk reduction trials showed that cessation of smoking had a much greater benefit on survival than most other interventions Helping patients who smoke to stop smoking is thus one of the most important aspects of prevention for smokers In some studies, smoking has also been associated with increased progression of retinopathy and peripheral neuropathy
II receptor blockers ARBs have been shown to lower urinary protein excretion and slow the rate of disease progression Randomized controlled trials of intensive therapies that resulted in average A1C values of 7 have found that every percentage point decrease in A1C is associated with significantly decreased rates of retinopathy, nephropathy, and neuropathy, with no threshold effect
Macrovascular Disease
How do I discuss smoking cessation with my patients who smoke?
All patients with diabetes who are older than 40 years should take aspirin 75-162 mg/d for primary prevention of macrovascular disease, unless they have a specific contraindication to aspirin In addition, all patients with diabetes who have a
history of myocardial infarction, vascular bypass, stroke or transient ischemic attack, peripheral vascular disease, claudication, or angina should take a daily aspirin for secondary prevention Statin therapy improves outcomes among patients with diabetes, including those without clinical evidence of coronary artery disease
Ask: Is smoking a problem for you? Are you interested in quitting? Although patients indicate they know that smoking is generally harmful, they rarely know how it specifically relates to them A comment such as the following may be helpful: I am especially concerned about your smoking because you have diabetes, and this greatly increases your risk for other medical complications Offer smoking cessation strategies, such as referrals to smoking cessation programs, medications that help with smoking cessation, and nicotine replacement products
How do I talk to my patients about the complications of diabetes?
Pharmaceutical Measures
Microvascular Disease
Discussing diabetes complications requires both sensitivity and honesty It is important to offer hope by providing information about what can be done to prevent and treat these devastating problems, including
concrete actions that patients can implement One way to present the information is as a bad news/good news situation The bad news is that complications can and do occur The good news is that we know more about preventing and treating these complications than ever before Most patients with type 2 diabetes are aware of the complications because of what they have been told by friends or family members
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For patients who have microalbuminuria or overt nephropathy, both angiotensin-converting enzyme ACE inhibitors and angiotensin
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with diabetes Early in the course of their diabetes, ask patients what they know or have experienced in terms of the complications and what concerns or questions they have Reassure patients that what happened to people with diabetes in the past is no longer inevitable It is important to review the results of annual screenings with patients and explain what the findings mean in terms of their treatment and future health Your Diabetes Test Record in Chapter 10 of the Diabetes Care Guide Toolkit can help patients focus on the importance of these findings Patients should be
encouraged to bring the form to their next visit and remind you when tests are due An example of this tool, partially filled out, is shown in Figure 12-1 Use the professional education resources available on the Internet, such as the Diabetes Complications Risk Profile from the Michigan Diabetes Research and Training Center http://medumichedu/mdrtc/ education/profeduhtm, to help patients understand the meaning of their screening results and adopt behaviors that may improve these results While stressing the importance of glucose and blood pressure control to prevent complications, remember to point out that there are no guarantees Let patients know, however, that they are increasing their odds and lowering their risks by doing all they can to care for their diabetes and their health Provide patients with The ABCs to Better Diabetes Care from Chapter 10 of the Diabetes Care Guide Toolkit, which can help them achieve their goals At the same time, avoid using the threat of complications as a method for encouraging behavior change Scare tactics are ineffective for long-term behavior change
Diabetic Retinopathy
Diabetic retinopathy is classified as nonproliferative mild, moderate, or
severe and proliferative Changes in retinal blood flow occur after several years of diabetes These changes cause retinal ischemia, which in turn promotes growth factors that stimulate proliferation of new blood vessels that are more prone to leak blood This process leads to scarring and fibrosis As fibrous tissue contracts with time, it may put traction on the retina, causing retinal detachment with resultant vision loss New vessels can also become more permeable and leak serum, which causes macular edema Primary and secondary prevention of retinopathy involves optimal control of hyperglycemia, blood pressure, and lipids, as well as regularly scheduled dilated eye examinations
Eye Examinations
All adults with diabetes should undergo an initial comprehensive, dilated eye examination by an ophthalmologist knowledgeable and experienced in diagnosing retinopathy and its management Type 1 diabetes: Initial eye examination should occur within 1 year after the onset of diabetes Type 2 diabetes: Initial eye examination should occur shortly after diagnosis All patients with diabetes should receive annual follow-up eye examinations by an ophthalmologist More frequent evaluation is indicated
if retinopathy is progressive If the results of an examination are normal, the next examination may be scheduled less frequently 2 to 3 years on the advice of an eye care professional Women with diabetes who are planning a pregnancy should receive a comprehensive eye
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Name: Mary Jones ________________ Year ______________ 20072008
Dates of Tests Tests Weight Blood pressure A1C LDL HDL Triglycerides Eye exam Foot exam My Goal 200 130/80 Less than 70 Less than 100 Greater than 50 Less than 150 Yearly Yearly 3/15 225 140/98 95 140 60 140 — – Schedule my next exam for Dec 2007 Schedule my next exam for Jan 2008 4/30 217 138/80 86 — 6/15 220 140/80 82 — My Notes
Figure 12-1 Diabetes Test Record This figure shows a sample Diabetes Test Record first tool in Chapter 10 of the toolkit on which a patient has been recording her test results
Ocular Telemedicine for Diabetic Retinopathy
Nearly half of adults with diabetes in the United States do not have eye examinations at the recommended frequency, which greatly limits early intervention To reduce barriers to treatment, nonmydriatic digital retinal
imaging telemedicine systems are being developed These systems allow remote diagnosis of the clinical level of diabetic retinopathy and diabetic macular edema in a nonophthalmologic setting, which aids appropriate triage for eye care One such system is the Joslin Vision Network, a digital teleophthalmology system designed by the Joslin Diabetes Center in Boston, Massachusetts Nonmydriatic digital color images of the retina and pertinent health information are forwarded to an image reading center for diagnosis and development of a treatment plan In eyes that can be graded by this technique, the technique offers a very high correlation with dilated clinical examination by an ophthalmologist who specializes in retinal disease When the Joslin Vision Network was implemented in a primary care setting to supplement an existing referral program for diabetes eye care, the annual diabetic retinopathy surveillance rate increased by nearly 50
examination and should be counseled on the risk of the development or progression of retinopathy Transient retinopathy progression has been associated with intensification of glycemic control For women with diabetes who are pregnant, a comprehensive eye
examination is indicated during the first trimester Close follow-up is indicated throughout pregnancy and up to 1 year postpartum In addition, patients with pre-existing
proteinuria need to be monitored closely because of the risk of worsening retinopathy A patient with any level of macular edema or severe nonproliferative or proliferative retinopathy should be referred to a retina specialist knowledgeable and experienced in the management of diabetic retinopathy For a discussion of digital retinal imaging telemedicine systems, see Ocular Telemedicine for Diabetic Retinopathy
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Diabetic Nephropathy
Screening for Kidney Disease
Table 12-1 Classification of Urine Albumin Excretion
Category
Normal
Spot Collection g/mg creatinine
30 30299 300
Microalbuminuria–the presence of trace levels of albumin in the urine–is an indicator of early nephropathy Albuminuria is also associated with a several-fold increase in cardiovascular disease in diabetes Patients with diabetes should be screened annually for the presence of microalbuminuria Type 1 diabetes: Annual screening should begin 5 years after
the onset of diabetes Type 2 diabetes: Annual screening should begin at diagnosis Screening can be initiated with a standard dipstick urinalysis; if no protein is detected, however, a more sensitive test for microalbuminuria should be performed A random spot urine collection to determine the albumin-to-creatinine ratio is convenient and cost-effective and is the screening method preferred by the American Diabetes Association ADA; a timed urine collection or 24-hour collection is rarely necessary Table 12-1 shows the classification of urine albumin excretion Because of variability in albumin excretion, two of three specimens collected over 3 to 6 months should be abnormal before a patient is designated as having microalbuminuria Febrile illness, exercise within the past 24 hours, infection, hematuria, menstruation, marked hyperglycemia, and marked hypertension can lead to elevations above baseline and false-positive results If a patient tests positive for microalbuminuria or macroalbuminuria, a 24-hour urine sample for measurement of creatinine clearance and protein loss offers the most precise quantification of nephropathy On a 24-hour urine sample, microalbuminuria is defined as a
urinary albumin excretion of 30 mg/24 h or 20 g/min Overt nephropathy is diagnosed at a urine albumin excretion of greater than 300 mg/24 h; thereafter, the disease tends to progress, with a decline in the glomerular filtration rate GFR of
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Microalbuminuria Macroalbuminuria clinical albuminuria
Reprinted with permission from: American Diabetes Association Standards of medical care in diabetes—2006 Diabetes Care 2006;29 Suppl 1:S4-42
about 1 mL/min/173 m2 each month However, this course of progression can be reduced by optimal blood pressure control In addition to screening for microalbuminuria, the ADA recommends that all patients with diabetes–regardless of their degree of albumin excretion–have their serum creatinine levels measured for the estimation of GFR and the staging of chronic kidney disease Table 12-2 Up to 30 of patients with type 2 diabetes may have a low GFR in the absence of significant microalbuminuria A GFR below 60 mL/min/173 m2 is a risk factor for the progression of renal disease and for cardiovascular events, even in the absence of albuminuria The Cockcroft-Gault and the Modification of Diet in Renal Disease MDRD study group equations calculate GFR
based on serum creatinine, age, race, and gender Either equation can be used Laboratories often provide a calculated GFR with the creatinine level A GFR calculator is available on the accompanying CD-ROM and on the ACP Diabetes Portal http://diabetes acponlineorg Patients with a GFR below 60 mL/min/173 m2 and patients with hypertension or hyperkalemia that is difficult to manage should be referred to a renal specialist
Slowing the Progression of Kidney Disease
Several large-scale clinical trials have shown that nephropathy can be prevented or its progression delayed by interventions that provide
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Table 12-2 Stages of Chronic Kidney Disease
Stage
Description
GFR mL/min/ 173 m2
90 6089 3059 1529 15 or dialysis
Peripheral Vascular Disease and Diabetic Foot Ulcers
Peripheral vascular disease PVD disproportionately affects the elderly as well as nonHispanic blacks and Mexican-Americans Diabetic vascular disease is often complicated by the presence of peripheral neuropathy, which increases the risk for developing traumatic foot ulcers The cost of managing foot ulcers in patients with diabetes is
estimated to approach 28,000 for the 2 years after the onset of the diagnosis of the foot ulcer In addition, survival is significantly reduced in patients with diabetic foot ulcers
1 2 3 4 5
Kidney damage with normal or increased GFR Kidney damage with mildly decreased GFR Moderately decreased GFR Severely decreased GFR Kidney failure
GFR glomerular filtration rate Adapted with permission from: National Kidney Foundation Kidney Disease Outcome Quality Initiative K/DOQI Advisory Board K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification Available at: wwwkidneyorg/professionals/KDOQI/guidelines_ckd/tochtm Accessed 3 October 2006
Foot Examinations
tight control of blood pressure and glucose levels Much attention is therefore given to early detection and aggressive intervention in diabetic nephropathy Tight glycemic control should be initiated at the onset of type 1 and type 2 diabetes Elevated blood pressure may have the greatest effect on the development of proteinuria and nephropathy Whether specific antihypertensive agents improve proteinuria to a greater degree than the decrease in blood pressure alone remains
controversial Currently, the use of an ACE inhibitor or ARB is favored However, studies of beta-blockers, thiazides, and other classes of antihypertension drugs have also shown favorable responses Whether all patients with diabetes, regardless of whether they have hypertension, should begin therapy with an ACE inhibitor or an ARB before the onset of microalbuminuria requires further study Decreasing dietary protein to less than 08 g/kg of body weight daily has been shown to have a salutary effect on creatinine clearance and proteinuria However, dietary protein restriction is one of the most difficult strategies for treating nephropathy Such regimens are complex, are difficult for most patients to implement, and may decrease overall adherence to the meal plan In addition, the higher amounts of carbohydrates and fat that a protein-restricted diet requires may be a concern A comprehensive foot examination should be performed annually in all patients with diabetes to identify high-risk foot problems Signs in patient examination rooms reminding those with diabetes to remove their shoes can greatly facilitate this examination The foot examination should include: Visual inspection for
deformities of the toes, arch, and nails Skin examination to detect calluses, fungal infection, ulcers, or wounds Neuropathy assessmen 
t using a tuning fork to test vibratory sensation and a SemmesWeinstein 507 10-g monofilament to test light touch Assessment of pedal pulses Foot Sensory Exam Findings is an illustrated worksheet in Chapter 12 of the Diabetes Care Guide Toolkit that enables you to mark up the results of filament tests for 10 visits An illustrated tutorial on how to use a monofilament is available on the ACP Diabetes Portal at http://diabetesacponlineorg Early recognition of PVD and peripheral neuropathy are the best tools to prevent amputations Signs of diabetic vascular disease include claudication, loss of foot hair, delayed capillary
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filling, dependent rubor, and absence of peripheral pulses The ankle to brachial index ABI correlates well with the presence of arterial occlusive disease The ABI should be measured in patients with symptoms of PVD and in asymptomatic patients with diminished pedal pulses on palpation and other physical signs of vascular insufficiency The ABI is
calculated by measuring systolic blood pressure in the posterior tibial and dorsalis pedis arteries of both lower extremities The highest of these four measurements is used for the ankle pressure Pressure is also measured in both brachial arteries, with the highest of the two used as the brachial pressure The ratio is then calculated as: ABI ankle pressure/brachial pressure The interpretation of ABI results is shown in Table 12-3 In patients with values above 09 but in whom PVD is still suspected, an ABI can be calculated after a treadmill test If the ABI decreases 20 or more following exercise, PVD is very likely present Patients with abnormal ABIs should be further assessed and treated for cardiovascular risk factors Those with moderate or advanced ischemia should be referred to a vascular specialist for further evaluation The classification of diabetic foot ulcers is shown in Table 12-4 For patients with foot ulcers or high-risk foot conditions or with a history of ulcers or amputation, a multidisciplinary team approach is beneficial, including infectious disease, podiatry and/or orthopedic surgery, vascular surgery, endocrinology, and rehabilitation specialists
Table 12-3
Interpretation of Ankle-Brachial Index
Ankle-Brachial Index
13 1013 0409 04
Interpretation
Noncompressible calcified arteries Normal Moderate arterial obstruction, often with claudication Advanced ischemia
Table 12-4 Classification of Diabetic Foot Ulcers
Grade
Grade 0 Grade 1 Grade 2
Description
No ulcer in a high-risk foot Superficial ulcer involving a full skin thickness but not underlying tissues Deep ulcer penetrating down to ligaments and muscle but no bone involvement or abscess formation Deep ulcer with cellulitis or abscess formation, often with osteomyelitis Localized gangrene Extensive gangrene involving the whole foot
Grade 3 Grade 4 Grade 5
the need to protect the feet by wearing appropriate footwear Offer a podiatry referral for patients who have difficulty caring for their toenails or who have corns or calluses that need treatment Patients with signs of nerve damage need more specific information During the examination, point out areas of decreased sensation that the patient needs to inspect closely on a daily basis Patients may benefit from a referral for podiatry services for routine foot care services or orthotics One pair of shoes per year is generally a
covered benefit for patients with neuropathy Taking Care of Your Feet in Chapter 12 of the Diabetes Care Guide Toolkit provides instructions for proper foot care that all patients with diabetes should follow
Foot Care Education
All patients with diabetes need education regarding routine self-care practices and the avoidance of smoking Emphasize that caring for their feet is one of the least expensive and easiest things they can do in caring for their diabetes and that it can have a very real benefit in preventing amputations Basic foot care education includes the importance of looking at the feet daily after a shower or when getting undressed for signs of injury, blisters, or damage from poorly fitting shoes and
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Coronary Artery Disease in Diabetes
Persons with diabetes have a greatly increased risk of cardiovascular disease The increased risk seen in the MRFIT trial was present even after adjusting for age and other cardiovascular risk
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factors, such as smoking, hypertension, and hypercholesterolemia In those with multiple risk factors, the increase in cardiovascular risk was even greater In a
study carried out in Finland, the risk of death from coronary artery disease for persons with diabetes who had not had a prior myocardial infarction was comparable to that of persons without diabetes who had already had a prior myocardial infarction These results provided the rationale for considering the presence of diabetes to be a coronary artery disease equivalent in the National Cholesterol Education Program Persons with diabetes are thus classified in the highest cardiovascular risk category, regardless of the presence of established coronary artery disease
intervention In addition, all patients should begin aspirin therapy if they are not already on it Patients should be reinterviewed for atypical symptoms and referred to a cardiologist for consideration of invasive studies if noninvasive studies reveal major abnormalities
Diabetic Peripheral Neuropathy
Up to 50 of patients with peripheral neuropathy experience symptoms, with pain being the most common Peripheral sensory neuropathies vary in their presentation, but they typically begin with dysesthesias distally and symmetrically They then progress to varying degrees of discomfort and numbness as they ascend symmetrically
from the lower extremities The sensory neuropathies can involve the upper extremities as well, but typically only after involvement in the lower extremities is severe, often up to the knee or above Sensory neuropathies are detected by testing vibration sense, pinprick, light touch, proprioception, and position sense Use of the 10-g monofilament test is additionally recommended because an abnormal response to this test also identifies a foot at risk of ulceration Patients must be informed about the degree of their neuropathic impairment, especially if it includes significant loss of vibratory or pain sensation, because they may not respond rapidly to burn or skin-breaking injury Pointing out specific areas during the examination is a particularly useful educational strategy Painful peripheral sensory neuropathy is an exceptionally difficult problem for which there are no consistently effective therapies Approximately 10 of patients with diabetic peripheral neuropathy experience persistent pain Diabetic neuropathic pain can interfere with quality of life by affecting mood, coordination, walking, the ability to work, and the ability to manage other aspects of diabetes and health It is
often worse at night If pain persists for more than 3 months,
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Screening Cardiac Stress Tests
Guidelines on screening cardiac stress tests vary, and no consensus currently exists The ADA currently recommends screening cardiac stress testing in patients with diabetes who also have any of the characteristics below: A history of peripheral or carotid occlusive disease A sedentary lifestyle, age 35 years or older, and the intention of beginning a vigorous exercise program Two or more of the following cardiovascular risk factors: dyslipidemia, hypertension, smoking, a positive family history of premature coronary disease, and the presence of microalbuminuria or macroalbuminuria Remember that sudden exercise in sedentary subjects can precipitate myocardial infarction Most experts agree that a complete physical examination and an exercise stress test should be performed in patients with type 1 diabetes who are older than 35 years and have had diabetes for more than 10 years Abnormal results on a stress test in an asymptomatic patient need to be evaluated on an individual basis All patients should be treated for risk factors of coronary artery disease according to currently established
guidelines for high-risk patients, including lipid and blood pressure
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it is unlikely to resolve spontaneously Pain that lasts more than 6 months is classified as chronic
gain No known drug interactions are associated with the use of pregabalin Other antiepileptic drugs used to treat painful neuropathy include carbamazepine, gabapentin, lamotrigine, sodium valproate, and topiramate Studies evaluating the efficacy of these drugs have been small and not always conclusive; hence, these drugs have not been officially approved by the FDA for this use
Opioid or Opioid-like Drugs
Management of Painful Neuropathy
Treatment of diabetic neuropathic pain is largely symptomatic Modification of risk factors glycemia, hypertension, hyperlipidemia, obesity, and smoking may help prevent neuropathy The ADA recommends a stepwise approach to the symptomatic treatment of painful neuropathy: Stabilization of glycemic control First-line treatment: tricyclic antidepressants Second-line treatment: antiepileptic drugs Third-line treatment: opioid or opioid-like drugs Fourth-line treatment: possible referral to a pain
clinic
Antidepressants
Third-line treatment for diabetic painful neuropathy includes the use of opioid or opioid-like drugs, such as oxycodone and tramadol Referral to a pain clinic is recommended before prescribing these medications Combinations of medications–for example, morphine and gabapentin–sometimes help to reduce the pain
Other Agents
Duloxetine is the only antidepressant officially approved by the US Food and Drug Administration FDA for use in diabetic peripheral neuropathy It is a selective serotonin and norepinephrine reuptake inhibitor Common side effects include nausea, somnolence, dizziness, constipation, dry mouth, increased sweating, decreased appetite, and asthenia Tricyclic antidepressants are not officially approved by the FDA for diabetic peripheral neuropathy, but they may help some patients However, the side effect profile of these drugs including orthostatic hypotension, drowsiness, constipation, urinary retention, and dry mouth needs to be considered when prescribing these medications
Antiepileptic Agents
Alpha-lipoic acid 600 mg/d for periods ranging from weeks to months has been associated with an improvement in symptoms and in neurologic deficits,
but this drug has not been approved by the FDA It is sold in health food stores and on the Internet as a dietary supplement This agent appears to be safe
Mononeuropathies and Multifocal Neuropathies
Some mononeuropathies are not specific to diabetes and are not thought to be related to the duration of diabetes Their primary symptom is usually acute local discomfort, with abnormal conduction that corresponds to the distribution of a single nerve, multiple peripheral nerves, the brachial or lumbosacral plexus, or nerve roots Focal neuropathies, such as lateral femoral cutaneous nerve palsy, are more common in middle-aged patients or those with sensorimotor polyneuropathy No specific strategies detect or prevent focal neuropathies Diabetic mononeuropathies can involve the median carpal tunnel syndrome and ulnar wrist drop nerves, the sciatic or femoral nerves
Pregabalin is the only antiepileptic drug approved for use in diabetic peripheral neuropathy Adverse effects include dizziness, somnolence, peripheral edema, nausea, and weight
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foot drop, or the third, fourth, or sixth cranial nerves paralysis
They have no clear precipitant or treatment, and they usually resolve spontaneously in weeks Radiculopathy of the chest or abdomen can mimic herpes zoster In rare cases, when more than one nerve is involved simultaneously, the condition is termed mononeuropathy multiplex, indicating that each affected nerve is independently involved Patients with long-standing diabetes and vasculopathy may develop diabetic amyotrophy, which involves pain, atrophy, and fasciculations of the limb girdle muscles
Screening for Autonomic Neuropathies
All patients with type 2 diabetes and those who have had type 1 diabetes for more than 5 years should be screened for autonomic neuropathy by history and physical examination directed at the cardiovascular and gastrointestinal systems Postural changes in blood pressure should be monitored yearly Any patients with unexplained postural symptoms, such as dizziness on standing and syncope, can be referred for additional laboratory studies and testing for autonomic neuropathy
Autonomic Neuropathies
Cardiovascular Autonomic Neuropathy
The development of diabetic autonomic neuropathy is clinically challenging to treat and an important indicator of patients who
are at very high risk for cardiovascular disease and sudden death Cardiovascular neuropathies may result in orthostatic hypotension, a lack of normal variation of the heart rate with breathing, tachycardia, and sudden death To treat orthostatic hypotension, fludrocortisone and midodrine are the drugs of first choice Patients being treated with these drugs should be closely monitored for supine hypertension, abnormal potassium levels, and fluid retention
Erectile Dysfunction
Erectile dysfunction is one of the more common autonomic neuropathies of diabetes and has historically tended to be underdiagnosed More than 50 of men with diabetes are believed to have some degree of erectile dysfunction after 10 years with the disease Furthermore, erectile dysfunction may be a marker for other, more serious vascular disease or neurologic dysfunction In the erectile dysfunction of diabetes, nocturnal and morning erections are characteristically absent Oral therapies for erectile dysfunction, which help sustain a normal erection in many men with diabetes, include the phosphodiesterase type 5 PDE-5 inhibitors sildenafil, vardenafil, and tadalafil These drugs are nearly as effective in the
presence of diabetes as in its absence Before they are prescribed for patients with diabetes, however, other causes of erectile dysfunction, including hypogonadism, depression, and advanced vascular disease, should be ruled out No side effects are specific to diabetes However, these agents should be avoided in patients with significant cardiovascular disease They can potentiate the hypotensive effects of nitrate, and they are contraindicated in patients who are using organic nitrates in any form–whether regularly or intermittently–or alpha-adrenergic receptor blockers In patients with more
Gastrointestinal Autonomic Neuropathy
Gastrointestinal autonomic neuropathy includes gastroparesis and diarrhea Gastroparesis may present with bloating, early satiety, vomiting, or symptoms of gastroesophageal reflux disease Diabetic diarrhea is characteristically nocturnal but can occur at any time of the day and may alternate with constipation Treatment is largely targeted at symptoms and includes the use of metoclopramide for gastroparesis
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Comorbidities and Complications
advanced erectile dysfunction or those failing to respond to
PDE-5 inhibitors, intracavernosal injections of vasodilators or penile implants offer the best hope
Screening for Erectile Dysfunction
ing sexual relationships, including depression; and possible use of drugs that adversely affect sexual function
Sexual Dysfunction in Women
Several small studies have evaluated sexual function in women with type 1 diabetes Most have found a higher risk of sexual dysfunction eg, decreased sexual arousal and the need for further study in these patients
Screening for erectile dysfunction should include taking a thorough history to detect loss of libido or other signs and symptoms of hormonal deficiency; underlying psychological issues affect-
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