Peripheral and Autonomic Neuropathy in Diabetes

Excerpt

Diabetes is the most common cause of neuropathy in the United States. Of hospital discharges between 2005 and 2010 among those age ≥18 years, 7.8% had an International Classification of Diseases, Ninth Revision (ICD-9), code of Diabetes with Neurological Manifestations, and 4.6% of discharges had a code of Polyneuropathy in Diabetes. This far exceeds hospital discharges coded for any other cause of neuropathy.

Classification systems have been developed for a number of manifestations of neuropathy. Among these various forms, the most common is distal symmetrical polyneuropathy (DSPN). The reported incidence and prevalence vary widely from study to study. These differences are likely attributable to several factors, including the population studied, the criteria used to diagnose DSPN, and the modalities used to detect the condition. Among type 1 diabetes patients, one prospective study found a 29% cumulative incidence after approximately 5 years of follow-up, while another found a cumulative incidence of 35% over a follow-up of 13–14 years.

DSPN is associated with several risk factors, of which glucose levels and the duration of diabetes appear to be the most influential. However, associations have been found with other characteristics, including height, blood pressure, and lipid levels.

Autonomic neuropathy is another troubling complication of diabetes. Of its multiple manifestations, cardiovascular autonomic neuropathy (CAN) has been the most studied. Similar to DSPN, incidence and prevalence estimates vary. In a large study of patients with type 1 diabetes who had normal autonomic function at baseline, less than 10% were found to have CAN after approximately 5 years of follow-up. CAN increases substantially with diabetes duration to rates as high as 35% after 22 years in individuals with type 1 diabetes and to 60% in patients with type 2 diabetes. Differences in prevalence and incidence estimates of CAN also could be attributable to differences in study populations, diagnostic criteria, and tests utilized for detection.

Risk factors have been identified for autonomic neuropathy. Although glycemia is a risk factor among individuals with type 1 diabetes, it has not clearly been identified as such for individuals with type 2 diabetes. Autonomic neuropathy has also been associated with cardiovascular risk factors.

In an analysis performed for Diabetes in America, 3rd edition, heart rate (beats/minute) was significantly higher in adults with diagnosed diabetes (mean 75.8) compared with those with normal glucose levels (mean 68.9). Heart rate was also higher in those who were diagnosed at the study visit with diabetes (mean 73.9) or prediabetes (mean 70.5) than in those with normal glucose levels. Of those with diabetes, the heart rate was significantly higher among diabetic individuals with glycosylated hemoglobin (A1c) ≥11.0% (mean 85.0) than among those with A1c <7.0% (mean 74.1). The basis for the higher heart rate among diabetic patients and the relation of heart rate to A1c are unknown. However, it is possible that heart rate, even within the normal range, is related to autonomic dysfunction.

A number of questions need to be answered with regard to diabetic neuropathy, such as whether glucose variability influences its development beyond the effects of the degree and duration of hyperglycemia. Such information should ultimately lead to a better understanding of how to treat and prevent the disorder.