Original
Prevalence of distal diabetic polyneuropathy using quantitative sensory methods in a population with diabetes of more than 10 years’ disease durationPrevalencia de polineuropatía diabética distal según métodos sensoriales cuantitativos en una populación con diabetes mellitus de más de 10 años de duración

https://doi.org/10.1016/j.endonu.2010.05.006Get rights and content

Abstract

Objectives

Results of studies on the prevalence of distal diabetic polyneuropathy (DPN) are contradictory. Conventional methods used for the diagnosis of DPN in clinical practice have limited effectiveness. The present study aimed to assess the prevalence of DPN in a population with long-standing diabetes (more than 10 years disease duration) by measuring vibratory, thermal and tactile sensitivities with quantitative sensory devices, as well as their relationship with associated clinical risk factors.

Patients and methods

A total of 1011 diabetic patients were evaluated in a multicenter, cross-sectional, observational study. The three sensitivities were assessed by ultrabiothesiometer, aesthesiometer and thermoskin devices, respectively. The prevalence of neuropathic pain was validated by the DN4 questionnaire.

Results

Of the 1011 cases included, 400 (39.6%) met the diagnostic criteria of DPN, while no DPN was found in the remaining 611 (60.4%). Of the 400 patients with DPN, 253 (63.2%) showed clinical manifestations, while 147 (36.8%) were diagnosed as subclinical DPN. The prevalence of DPN increased with disease duration. There was a progressive loss of the three sensitivities with increased disease duration, particularly thermal and vibratory sensitivities. This loss was statistically significant for the latter two sensitivities. Among patients with clinical DPN, 84.2% had painful neuropathic symptoms. The prevalence of DPN was positively related to micro- and macroangiopathic complications and with dyslipidemia.

Conclusion

This study reveals a high degree of underdiagnosis of DPN, most likely due to the asymptomatic nature of the disease in a considerable proportion of patients. Our observations provide evidence of the usefulness of specific equipment for quantitative and objective assessment of polyneuropathy.

Resumen

Objetivos

Los resultados de los estudios sobre la prevalencia de la polineuropatía distal diabética (DPN) son discrepantes. Los métodos convencionales para su diagnóstico tienen una eficacia limitada. Por ello, el presente trabajo pretende estudiar su prevalencia en una población diabética con más de 10 años de evolución de la enfermedad, valorando las sensibilidades vibratoria, térmica y táctil con dispositivos que cuantifican el grado de sensibilidad, a la vez que su relación con los factores de riesgo asociados.

Pacientes y métodos

Se evaluaron 1.011 diabéticos en un estudio multicéntrico, transversal y observacional. Se valoraron las tres sensibilidades con un ultrabiotesiómetro, un estesiómetro y un termoskin. Se validó la prevalencia de dolor neuropático con el cuestionario DN4.

Resultados

Del total de 1011 casos, 400 (39,6%) cumplían criterios de DPN, mientras que los 611 restantes (60,4%) no los cumplían. De los 400 enfermos con DPN, 253 (63,2%) presentaban manifestaciones clínicas, mientras que los 147 restantes (36,8%) fueron diagnosticados de DPN subclínica. La prevalencia de DPN aumentaba al avanzar la enfermedad. Había una pérdida progresiva de las tres sensibilidades con el tiempo, sobre todo de la térmica y táctil, cuya pérdida era estadísticamente significativa. Un 84,2% de los casos con DPN clínica aquejaban dolor neuropático. La prevalencia de DPN guardaba una relación positiva con las complicaciones micro y macroangiopáticas, y con la dislipidemia.

Conclusiones

El presente estudio revela que hay un alto porcentaje de DPN sin diagnosticar, lo más probable por la ausencia de síntomas en buena parte de los pacientes. Los resultados muestran la utilidad de dispositivos específicos que valoren de manera objetiva y cuantitativa la presencia de polineuropatía.

Introduction

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, 4, 5, 6, 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.

Section snippets

Subjects

One thousand one hundred and fifty-nine ambulatory patients suffering from diabetes mellitus were studied. They were recruited from hospital outpatient clinics in 20 endocrinology units in Spain, during a 6-month period in 2007. These patients met the following inclusion criteria: age ranging from 16 to 70, diagnosis of type 1 or type 2 diabetes mellitus according to the American Diabetes Association (ADA) recommendations, more than 10 years of disease duration, absence of any known

Prevalence of clinical and subclinical DPN

The average age of patients was 49.7±14.8 (SD) years and the average duration of diabetes was 19.6±8.2 (SD) years. From the total of 1011 cases included, 400 met the diagnostic criteria of DPN, while the other 611 had no DPN, which represents 39.6% and 60.4%, respectively. Of the 400 patients with DPN, 253 (63.2%) presented clinical manifestations, while 147 (36.8%) were diagnosed with subclinical DPN as they presented no symptoms.

Variables associated with DPN

When comparing the group of DPN patients (clinical+subclinical)

Discussion

Although the ADA recommendations15 support the use of simple clinical methods for DPN screening—preferably Semmes–Weinstein monofilaments 10 g (1.0 g monofilament provides superior diagnostic sensitivity) and 128 Hz 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.

Conflict of interest

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.

Acknowledgements

This study has been funded by an unrestricted grant from Pfizer Spain that covered the costs of the devices used in the study. The authors want to acknowledge Inmaculada Vilardaga (employed by European Biometric Institute, an independent company contracted by Pfizer to collaborate in data analysis and logistic of the study) for her role in study analysis and statistics interpretation, and to all participating investigators (see Appendices 1), whose collaboration was essential for the conduct of

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