Regarding the magnitude of changes in the quantitative measures of DSP, we have shown that over the first decade of type 1 diabetes the mean difference between poorly controlled and well-controlled patients in the annual rate of slowing of peroneal MNCV is 0.6 m/s per year and that of sural sensory NCV (SNCV) is 0.7 m/s per year. After 12 years from the diagnosis of type 1 diabetes, none of the well-controlled patients but 60% of those with long-term poor control developed polyneuropathy [56]. Macleod et al. [57] estimated the annual rate of change for the VPT on the great toe to be 0.4 V in healthy subjects and 2.5 V in those with diabetic neuropathy.
In a mixed cohort of type 1 and type 2 diabetic subjects followed over 9-16 years (mean 10 years) peroneal MNCV was: Progressively reduced with increasing duration of diabetes, but it stabilized once it reached a “plateau” between 36 and 38 m/s [58].
Prevalence
In the Rochester Diabetic Neuropathy Study the prevalence of neuropathies other than DSP was low: symptomatic carpal tunnel syndrome in 9% of type 1 and 4% of type2 patients, proximal asymmetric neuropathy in 1% each (of type 1 and type 2 patients, ulnar neuropathy in 2% each of type 1 and type 2 patients, peroneal neuropathy in one type 2 patient, lateral femoral cutaneous neuropathy of the thigh (meralgia paresthetica) in 1% each of type 1 and type 2 patients. Cranial neuropathy or truncal neuropathy was not present in any of the patients at the time of examination. Approximately 10% of diabetic patients had neurological deficits attributable to nondiabetic causes [21].
In a Japanese survey among 1961 diabetic patients, 19(1%) had cranial nerve palsies: 19 facial nerve, 6 oculomotor nerve, and 2 abducent nerve palsies. Among 3841 nondiabetic subjects only 5 (0.1%) showed cranial nerve palsies, all of which were facial palsies. Only 1 out of 9 patients with facial palsy compared to 7 out of 10 patients with ophthalmoplegia had diabetic complications, suggesting that ophthalmoplegia rather than facial palsy is related to diabetes [59].
Natural History
Proximal motor neuropathy (femoral neuropathy, diabetic amyotrophy) is characterized by pain with or without wasting in one thigh, or, more often, both thighs. It develops over several weeks, and recovery is the rule. The worst pain resolves within 6-12 months, while the remaining discomfort disappears within three years. Function recovers completely, although slight wasting may persist [39].
The onset of cranial nerve palsies is abrupt and oculomotor nerve involvement may be accompanied by supraorbital pain. Cranial nerve palsies resolve completely in three to six months, and relapses are infrequent [39].
Diabetic polyradiculopathy most commonly affects the trunk, where it causes unilateral or bilateral truncal pain and abdominal muscle bulging. It may be accompanied by profound weight loss. Spontaneous recovery within 4-30 months is the rule, but relapses may occur [60].
For the natural history of painful neuropathies see Chapter 5, page 212-213.
Prevalence
Although the impact of autonomic neuropathy is increasingly being recognized, little information exists as to its incidence in representative diabetic populations. The difficulties encountered in epidemiological studies of diabetic neuropathy particularly affect the evaluation of autonomic dysfunction, which involves an even greater variety of nonspecific clinical manifestations that can be explored by numerous diagnostic approaches. Of the manifestations of diabetic autonomic neuropathy, cardiovascular autonomic neuropathy (CAN) has attracted most attention, because it is easily detected at subclinical stages by noninvasive cardiovascular autonomic function tests (AFTs) based on heart rate variability (HRV) and blood pressure responses, before the late sequelae such as resting tachy-cardia or orthostatic hypotension develop.
To date there have been two population-based studies that assessed the prevalence of autonomic dysfunction in diabetic patients. The Oxford Community Diabetes Study [61] included 29 873 adults aged at least 20 years. 412 of whom were known diabetic patients. Autonomic function was assessed in 43 type 1 and 202 type 2 diabetic patients using the standard deviation of HRV at rest, expiration/inhalation (E/l) ratio from a single deep breath, and Valsalva ratio. The overall prevalence of abnormal results in one or more of the three tests was 20.9% in type 1 patients and 15.8% in type 2 patients. Since this study did not include control subjects, the reported prevalence of autonomic dysfunction is difficult to interpret. The definition of one abnormality (<2.5th percentile of normal range) among three tests might yield one abnormal test result in up to 7.5% of a control population. Hence, the specificity of the test battery and the prevalence of CAN in that study were relatively low.
In the Pittsburgh Epidemiology of Diabetes Complications Study [62] autonomic neuropathy was evaluated in 168 type 1 diabetic subjects aged 25-34 years, representing 71% of those who were eligible. Cardiovascular autonomic function tests included the E/l ratio and mean circular resultant (MCR) to deep breathing. 30:15 ratio to standing, and Valsalva ratio. The results of the E/I ratio and MCR were significantly associated with the hypertension status, LDL and HDL cholesterol, and gender. The prevalence of autonomic symptoms, ranging from 0 to 8%, was relatively low except for hypoglycemia unawareness, which was present in 26% of the patients. However, this study neither reported the prevalence of abnormal test results nor did it take into account treatment with drugs that potentially influence autonomic function. Orthostatic hypotension, defined as a systolic blood pressure fall of at least 30 mmHg, was noted in 3.4% of the patients.
In a clinic-based multicenter study (DiaCAN) we have found prevalence rates of borderline CAN (2 out of 7 indices abnormal) or definite CAN (>3 out of 7 indices abnormal) of 8.5% and 16.8% respectively among 647 unselected type 1 diabetic patients, and 12.2% and 22.1% respectively in 524 type 2 diabetic patients [31]. The percentage of type 1 diabetic patients with definite CAN was identical with the 16.6% rate observed in 506 patients randomly selected from four hospital diabetic clinics in Bristol