Diabetes mellitus is the most common cause of polyneuropathy in general clinical practice, for which reason it is accorded a separate section. We are referring mainly to a generalized, predominantly sensory syndrome, but several focal or regional forms of peripheral nerve disease also result from diabetes and for convenience of exposition, are included here. In recent years, attention has also been directed to a possible association between a nondescript sensory polyneuropathy and impaired glucose tolerance, even without manifest diabetes, persistent hyperglycemia, or an elevation of hemoglobin A1c. The survey by Sumner and colleagues makes a case for such an association, but we remain uncertain about the relationship between glucose intolerance alone and polyneuropathy. By statistically adjusting for relevant factors such as glycemic control and glycosylated hemoglobin, Tesfaye and colleagues have suggested that some cardiovascular risk factors subsumed under the term “metabolic syndrome” (triglyceride levels, body mass, hypertension) are themselves risk factors for diabetic polyneuropathy.
Approximately 15 percent of patients with diabetes have symptoms and signs of polyneuropathy, but nearly 50 percent of cross-sectional population samples have evidence of peripheral nerve damage as judged by nerve conduction abnormalities. The duration of diabetes is perhaps the most important factor. Fewer than 10 percent of patients have clinically evident polyneuropathy at the time of discovery of diabetes, but this figure rises to 50 percent after 25 years. The presence of diabetic retinopathy is associated with higher incidences of neuropathy. It is not surprising, therefore, that neuropathy is most common in diabetics older than 50 years; it is infrequent in those younger than age 30 years and is rare in childhood. Dyck and colleagues (1993) studied diabetics in Rochester, Minnesota, and found that 54 percent with type 1 (insulin-deficient) and 45 percent with type 2 (insulin-resistant) had polyneuropathy. The percentages were lower when patients were selected on the basis of clinical symptoms alone rather than on the presence of changes in nerve conduction; close to 15 percent at the time of diagnosis in both groups. In the syndromes described further on, both type 1 and type 2 diabetic patients are susceptible, the duration of diabetes being a major factor.
Several fairly distinct clinical syndromes of diabetic neuropathy have been delineated: (1) the most common as noted is a distal, symmetrical, primarily sensory polyneuropathy affecting feet and legs in a chronic, slowly progressive manner; the others are (2) acute ophthalmoplegia that affects the third, and less often the sixth, cranial nerve on one side; (3) acute mononeuropathy of limbs or trunk including a painful thoracolumbar radiculopathy; (4) an acute or subacute painful, asymmetrical, predominantly motor, multiple neuropathy affecting the upper lumbar roots and the proximal leg muscles (“diabetic amyotrophy”); (5) a more symmetrical, proximal motor weakness and wasting, usually without pain and with variable sensory loss, pursuing a subacute or chronic course; and (6) an autonomic neuropathy involving bowel, bladder, sweating and circulatory reflexes. These forms of neuropathy often coexist or overlap, particularly the autonomic and distal symmetrical types and the subacute proximal neuropathies.