Distal symmetric diabetic polyneuropathy (DPN) is one of the complications of diabetes. It is the most common presentation of diabetic neuropathy and it presents an insidious and progressive course, resulting in high morbimortality with a negative impact on the patient's quality of life and high social and health care costs.1,2 Epidemiological studies of its prevalence have yielded very different results: from 22.7% to 54%.3–7 This discrepancy may be due to various causes, such as heterogeneity of studied diabetic populations and differences in the diagnostic criteria and in methodologies used in the assessment. While neuropathic clinical symptoms have only a limited value for DPN screening, due to their own intrinsically subjective component, the diagnostic criteria recommended by the San Antonio Conference and other authors8,9 are not always taken in routine practice. On the other hand, the nerve conduction velocity study, despite being the most determinant and reliable test for detecting DPN,10 is not a widely available technique and requires specialized personnel and too much time to perform. Therefore, it is not practical for screening DPN in the clinical routine.

Quantitative sensitive methods allow for the precise determination of the perception thresholds of various sensitivities. They have also proved useful in detecting subclinical DPN and in assessing its severity and progression.11,12 Some studies have used the vibration perception threshold, measured by biothesiometer, as the reference parameter for the assessment of DPN presence.13,14 Other sensitivities such as thermal and tactile sensitivities have scarcely been studied with these quantitative procedures,12 thus limiting our knowledge on the actual prevalence of DPN.

Faced with the above mentioned diagnostic difficulties, as well as the limited epidemiological data available based on objective and quantitative methods, and the less well known associated risk factors for DPN, the present work aims to study this prevalence in a diabetic population with more than 10 years of evolution since the diagnosis of diabetes, using a standardized and homogeneous quantitative methodology, objective and measurable, regarding vibratory, thermal and tactile sensitivities, as well as their relationship with other micro- and macroangiopathic complications and with other associated clinical risk factors . As a result we will be better able to determine the actual prevalence of DPN, which is probably higher than is commonly thought, due to the presence of underdiagnosed subclinical neuropathies.

Although the ADA recommendations15 support the use of simple clinical methods for DPN screening—preferably Semmes–Weinstein monofilaments 10g (1.0g monofilament provides superior diagnostic sensitivity) and 128Hz tuning fork—these methods have certain limitations: considerable inter- and intraanalysis variability, subjective interference, lack of universal agreement in the assessment of outcomes and sensitivity far inferior to the diagnostic standard, which is nerve conduction velocity. Therefore, these simple tests are not sufficient to establish a diagnosis of DPN as an isolated criterion alone and patients with polyneuropathy might go unnoticed. At least another diagnostic information is thus needed apart from nerve conduction velocity or from a quantitative sensitive procedure or from histological studies performed through biopsies in order to confirm the diagnosis according to current recommendations.12,16,17

By using a quantitative sensory testing, the overall prevalence of DPN in our study was 39.6%, a value greater than that published by most of the aforementioned series. The greater prevalence in our study is mainly due to two factors: the studied diabetic population had a longer duration of diabetes, with an average of 19.6 years since they were diagnosed (it is widely known that prevalence of metadiabetic complications increases with disease duration); and our methodology, more sensitive, objective, homogeneous and specific than those normally used in usual care, which allows for the detection of more DPN patients. The same argument can account for the fact that DPN prevalence in our series is higher than that previously shown by Cabezas-Cerrato et al.3 in our country. They used only the ankle reflex and cold, pinprick and vibration perceptions with tuning fork, a limited procedure, which understimates the actual prevalence of polyneuropathy.

In this regard, it is worth pointing out that 58% of our DPN patients had not previously been diagnosed, and more than half of them (33.5%) were exclusively diagnosed with the quantitative sensory testing. This reflects the high rate of DPN underdiagnosis, particularly when it is subclinical and goes unnoticed, as highlighted in other studies.18 The knowledge of vibration perception threshold by means of the biothesiometer is a recognized method for early DPN detection.7,14,16 It provides a positive predictive value for the risk of developing neuropathic ulcers and demonstrates good concordance with nerve conduction studies (77–100% sensitivity and 73–81% specificity).19 Diagnostic accuracy increases with thermal perception threshold, which seems to be affected before vibratory sensitivity or electrophysiological studies are also performed.20,21 The combined assessment of thermal, tactile and vibration perception thresholds, as was determined in our study, is thus more sensitive in the early identification of DPN than the isolated assessment of only one of these three sensitivities.

Another noteworthy outcome in our results is the prevalence of subclinical asymptomatic DPN, which accounted for 36.8% of the DPN diabetic patients. In view of this, DPN screenings should be performed carefully and with the use of some of the quantitative sensory devices. The finding that subclinical DPN is more common among males lacks a convincing explanation and requires more study. However, we can assume that this anomaly is apparent and merely reflects a greater degree of concealment of neuropathic symptoms among males.

Our study confirmed that DPN prevalence increases with disease duration, which coincides with other statistics.6,7,22 For example, Young et al.7 have estimated an average prevalence of 36.8% after 10 years of evolution in their diabetic population. The study by Partanen et al.22 estimated a prevalence of 42% after the same period of time in type 2 diabetic patients. The higher apparent prevalence in type 2 diabetes is probably due to the fact that their disease has a longer actual duration, since it is known that many of these patients have been suffering the disease long before they were diagnosed. The results are similar if the prevalence of the alterations in the three sensitivities is analyzed separately (Figure 1), with a significant loss of thermal and vibratory sensitivities in cases of long-standing diabetes. This loss over time is, however, less outstanding with respect to tactile sensitivity, since, despite the tendency towards greater loss after this period of time, this loss shows no significant differences with shorter evolution times. All this likely reflects a greater fragility of the nerve fibers transporting thermal and vibratory sensitivities as a result of the adverse metabolic effects of diabetes over time.

DPN prevalence also demonstrates a positive relationship with the presence of other macro- and microagiopathic complications, which is not surprising since DPN remains a part of metadiabetic complications. In addition, our study demonstrated a higher prevalence in patients who smoked. In this sense, tobacco could be considered an additional vascular risk factor, since its adverse events on the cardiovascular system are well known. It should not be surprising that in our study DPN prevalence bears no relation to HbA1c blood levels and fructosamine in serum since these analytical parameters express the glycemic control level only at the time the observational study took place, regardless of the degree of glycemic control patients experienced during the previous months and years. However, a diminished DPN prevalence is yielded when a good metabolic control is sustained, which is supported by the finding that DPN is decreased when the patient is intensively treated with insulin. Similarly, dyslipidemia is more common in DPN patients than in those patients with no DPN.

Finally, analysis of the vibratory, thermal and tactile sensitivities reveals interesting results. Losses in the three sensitivities are higher in subclinical DPN, as well as in patients with non-painful clinical DPN (except for tactile sensitivity in the latter group; Figures 2 and 3). Even though these results might seem contradictory, they are not. In fact, it is well known that as DPN worsens its subjective symptoms also decrease. The disappearance of these symptoms and the neuropathic pain in patients who had previously suffered them expresses, frequently, progressive axonal damage of the peripheral nerves and a greater loss of sensitivities,23 regardless of diabetes duration. This would account for the greater prevalence of sensitivity loss in patients with no subjective clinical signs and with no neuropathic pain.

José M. Miralles-García, Pedro de Pablos-Velasco and Lucio Cabrerizo have no conflict-of-interest to disclose. María Pérez and Vanessa López-Gómez are employed by Pfizer Spain, the company funding this study.