Diabetic nephropathy is a leading cause of end-stage renal disease in the United States. The earliest manifestation of diabetic nephropathy is the appearance of small amounts of albumin in the urine (>30 but <300 mg/ day). Without specific interventions, approximately 80% of patients with type 1 diabetes and 20% to 40% of those with type 2 diabetes will develop overt nephropathy with macroalbuminuria (excretion of >300 mg/day) over the ensuing 10 to 15 years, usually accompanied by the appearance of hypertension. The progression from overt nephropathy to end-stage renal disease is highly variable and is evidenced by a progressive drop in glomerular filtration rate. By 20 years after diagnosis, more than 75% of individuals with type 1 diabetes and about 20% of those with type 2 diabetes with overt nephropathy will develop end-stage renal disease, necessitating dialysis or renal transplantation.
Visual impairment, sometimes even total blindness, is one of the more feared consequences of long-standing diabetes. Diabetes is the fourth leading cause of acquired blindness in the United States. Approximately 60% to 80% of patients develop some form of diabetic retinopathy approximately 15 to 20 years after diagnosis. The fundamental lesion of retinopathy—neovascularization—is attributable to hypoxia-induced overexpression of VEGF in the retina. Current treatment for this condition includes intravitreous injection of anti-angiogenic agents. In addition to retinopathy, diabetic patients also have an increased propensity for glaucoma and cataract formation, both of which contribute to visual impairment in diabetes.
Diabetic neuropathy can produce a variety of clinical syndromes, afflicting the central nervous system, peripheral sensorimotor nerves, and autonomic nervous system. The most frequent pattern of nerve involvement is a distal symmetric polyneuropathy of the lower extremities that affects both motor and sensory function, particularly the latter (Chapter 22). Over time, the upper extremities may be involved as well, thus approximating a “glove and stocking” pattern of polyneuropathy. Other forms include autonomic neuropathy, which produces disturbances in bowel and bladder function and sometimes sexual impotence, and diabetic mononeuropathy, which may manifest as sudden footdrop, wristdrop, or isolated cranial nerve palsies.
• Diabetic patients are plagued by an increased susceptibility to infections of the skin, tuberculosis, pneumonia, and pyelonephritis. Infections cause about 5% of diabetes-related deaths. In an individual with diabetic neuropathy, a trivial infection in a toe may be the first event in a long succession of complications (gangrene, bacteremia, pneumonia) that may ultimately lead to death.