an important factor in diabetic neuropathy (see below), and the considerably younger age of the subjects in the DCCT probably accounts for the differences seen. Indeed, when age has been corrected for, the prevalence of neuropathy does not differ between type 1 and type 2 diabetes [8,11].
In the EURODIAB Prospective Complications Study, which included 986 type 1 diabetic subjects without DSP at baseline, the cumulative prevalence after an average follow-up of 7.3 years was 25% [50].
Several clinic-based prospective studies examined the relationship between the natural history of abnormalities in nerve function tests and the degree of longterm glycemic control. Hillson et al [51], followed 71 patients who showed a slight deterioration in mean pedal VPT during the first five years after diagnosis of type 2 diabetes, which correlated significantly with increased mean fasting blood glucose. A more pronounced deterioration in sensory nerve function as assessed by thermal, vibration, and pressure perception thresholds has been observed over 1-3.5 years and two years in newly diagnosed and longer-term type 2 diabetic patients, respectively [35,52]. There was a correlation between the changes in the various sensory thresholds. [52], suggesting that small and large nerve fiber dysfunction may develop in parallel in type 2 diabetic patients.
Young et al. [53,54] studied 75 type 1 diabetic patients aged 16-19 years over an average of 2.4 years, 70 of whom were reassessed again after six years. During the first study period the deterioration in motor and sensory NCV was associated with poor glycemic control, but no patient had symptoms and only seven had minor signs, of neuropathy [53]. After six years 16 patients had Symptoms, 12 had “major signs,” 15 had “minor signs”, and 27 showed no symptoms of neuropathy. Baseline HbA1 was significantly higher in patients who developed symptoms or major signs compared win hi those showing minor signs or no symptoms. In addition, peroneal motor NCV (MNCV) deteriorated if the symptomatic but not in the asymptomatic group [54]. On the other hand, it has been demonstrated that neuropathic pain may improve and resolve completely within three to four years of follow-up despite persistent poor glycemic control, but thermal perception thresholds continue to deteriorate [55]. Thus, small-fiber function tests do not seem to predict the evolution of painful symptoms.
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]
