Porth's Essentials of Pathophysiology, 4e

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Endocrine System

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glycemic control, maintenance of blood pressure control (<140/80 mm Hg), prevention or reduction in the level of proteinuria (using angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, or protein restriction in selected patients), treatment of hyperlipid- emia, and smoking cessation in people who smoke. 11,57 Smoking increases the risk of CKD in both persons with and without diabetes. People with type 2 diabetes who smoke have a greater risk of increased urinary albu- min excretion, and their rate of progression to CKD is approximately twice as rapid as in those who do not smoke. 11 Diabetic Retinopathies Diabetes is the leading cause of acquired blindness in the United States. 58,59 Although people with diabetes are at increased risk for development of cataracts and glau- coma, retinopathy is the most common pattern of eye disease. Diabetic retinopathy is estimated to be the most frequent cause of newly diagnosed blindness among Americans between the ages of 20 and 74 years. 59 Diabetic retinopathy is characterized by abnormal retinal vascular permeability, microaneurysm forma- tion, neovascularization and associated hemorrhage, scarring, diabetic macular edema, and retinal detach- ment 59 (see Chapter 38). Twenty years after the onset of diabetes, nearly all people with type 1 diabetes and more than 60% of people with type 2 diabetes have some degree of retinopathy. Pregnancy, puberty, and cataract surgery can accelerate these changes. 59 Risk fac- tors associated with diabetic retinopathy are similar to those for other complications. Among the suggested risk factors associated with diabetic retinopathy are poor glycemic control, elevated blood pressure, dyslipidemia, and smoking. The strongest case for control of blood glucose comes from the DCCT/EDIC and UKPDS stud- ies, which demonstrated a reduction in retinopathy with improved glucose control. 49,50 Because of the risk of retinopathy, it is important that people with diabetes have regular dilated eye examina- tions. The recommendation for follow-up examinations is based on the type of examination that was done and the findings of that examination. People with persis- tently elevated glucose levels or proteinuria should be examined yearly. 59 Women who are planning a preg- nancy should be counseled on the risk of development or progression of diabetic retinopathy. Women with dia- betes who become pregnant should be followed closely throughout pregnancy. This does not apply to women in whom GDM develops because such women are not at risk for development of diabetic retinopathy. People with macular edema, moderate to severe non- proliferative retinopathy, or any proliferative retinopa- thy should receive the care of an ophthalmologist who is knowledgeable and experienced in the management and treatment of diabetic retinopathy. Methods used in the treatment of diabetic retinopathy include the destruction and scarring of the proliferative lesions with laser pho- tocoagulation. The use of antagonists to growth factors (e.g., vascular endothelial growth factor) administered

by intra-vitreal injections also play an important role in the management of diabetic retinopathy, and are con- sidered the gold-standard therapy in diabetic macular edema. Macrovascular Complications Diabetes mellitus is a major risk factor for atheroscle- rotic coronary artery disease, cerebrovascular disease, and peripheral vascular disease. The prevalence of these macrovascular complications is increased two- to four- fold in people with diabetes. Multiple risk factors for macrovascular disease, including obesity, hypertension, hyperglycemia, hyper- insulinemia, hyperlipidemia, altered platelet function, endothelial dysfunction, systemic inflammation (as evidenced by increased CRP), and elevated fibrinogen levels, frequently are found in people with diabetes. There appear to be differences between type 1 and type 2 diabetes in terms of duration and development of macrovascular disease, with type 2 diabetics more com- monly manifesting macrovascular disease at the time of diagnosis. This greater prevalence has been attributed to the associated cardiovascular risk factors that are part of the metabolic syndrome and which may have been present for many years before the diagnosis of type 2 diabetes. 19,20 Aggressive management of cardiovascular risk fac- tors should include smoking cessation, lifestyle changes including weight loss, and measures to control blood lipids, hypertension, and blood glucose, as appropri- ate. 19 Antiplatelet agents (aspirin or clopidogrel) may be prescribed to reduce the threat of blood clots. If treatment is warranted for peripheral arterial disease, the peroneal arteries between the knees and ankles commonly are involved in diabetes, making revascular- ization difficult. Diabetic Foot Ulcers Foot problems are common among people with diabetes and may become severe enough to cause ulceration, infec- tion, and, eventually, the need for amputation. 60,61 Foot problems have been reported as the most common com- plication leading to hospitalization among people with diabetes. They represent the effects of neuropathy and vascular insufficiency. Approximately 60% to 70% of people with diabetic foot ulcers have neuropathy without vascular disease, 15% to 20% have vascular disease, and 15% to 20% have neuropathy and vascular disease. 60 Distal symmetric neuropathy is a major risk factor for foot ulcers. People with sensory neuropathies have impaired pain sensation and often are unaware of the constant trauma to the feet caused by poorly fitting shoes, improper weight bearing, hard objects or peb- bles in the shoes, or infections such as athlete’s foot. Neuropathy may prevent people from detecting pain; they are unable to adjust their gait to avoid walking on an area of the foot where pressure is causing trauma and necrosis. Motor neuropathy with weakness of the intrinsic muscles of the foot may result in foot deformi- ties, which lead to focal areas of high pressure. When