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Auditory Impairment in Patients with Type 2 Diabetes Mellitus
Archives of Medical Research 36 (2005) 507–510
ORIGINAL ARTICLE
Auditory Impairment in Patients with Type 2 Diabetes Mellitus Luz Vero´nica Dı´az de Leo´n-Morales,a Kathrine Ja´uregui-Renaud,c Marı´a Eugenia Garay-Sevilla,d Jose´ Herna´ndez-Pradob and Juan Manuel Malacara-Herna´ndezc a Servicio de ORL y Audiologı´a and bServicio de Oftalmologia, Hospital de Especialidades T1, Instituto Mexicano del Seguro Social (IMSS), Leo´n Guanajuato, Mexico c Unidad de Investigacio´n Me´dica, Hospital General, Centro Me´dico Nacional (CMN) La Raza, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico d Instituto de Investigaciones Me´dicas, Universidad de Guanajuato, Leo´n, Guanajuato, Mexico
Received for publication October 18, 2004; accepted February 14, 2005 (D-04-00120).
Background. We assessed the auditory function of 94 patients with type 2 diabetes mellitus and 94 age- and sex-matched healthy subjects. Methods. To study the influence of the clinical characteristics of the disease on the auditory function, after a clinical interview with ophthalmological assessment, subjects were evaluated using pure-tone audiometry, speech audiometry, auditory brainstem responses, the Michigan Diabetic Neuropathy Score and albuminuria. The mean age when diabetes was diagnosed was 42.8 ⫾ 6.5 years (mean ⫾ SD) and the time elapsed since diabetes diagnosis was 7.2 ⫾ 5.4 years. Results. Forty-eight patients (62%) had HbA1c ⬎8%; diabetic retinopathy was evident in 14 patients (14%) and microalbuminuria was identified in 12 patients. Compared to healthy subjects, diabetic patients showed an increase of the perception threshold at 8000 Hz (p ⬍0.01), higher hearing levels to discriminate at least 90% of 10 monosyllables (p ⬍0.01), and longer latencies of wave V, interwave I–V and interwave III–V (p ⬍0.01). Significant correlation was found between the hearing threshold at 8 KHz and patient age, and the former and the time elapsed since the diabetes was diagnosed (p ⬍0.001). Conclusions. Patients with type 2 diabetes mellitus can have subclinical hearing loss and impaired auditory brainstem response, independent of peripheral neuropathy, retinopathy or nephropathy. 쑖 2005 IMSS. Published by Elsevier Inc. Key Words: Diabetes mellitus, Hearing loss, Brainstem responses.
Introduction Diabetes mellitus is a common metabolic disease with variable impairment of the body systems. Studies about the relationship between diabetes mellitus and auditory impairment have shown variable results (1–4). The most frequent finding is a high-frequency sensorineural hearing loss (1,5– 8), and the most common abnormality of the brainstem
Address reprint requests to: Dr. Kathrine Ja´uregui-Renaud, Unidad de Investigacio´n Me´dica, Hospital General, CMN La Raza IMSS, Av Vallejo y Jacarandas, Colonia La Raza, 02990 Me´xico, D.F., Me´xico; Phone and FAX: 5782 1976; E-mail: [email protected]
0188-4409/05 $–see front matter. Copyright d o i : 1 0 .1 0 16 / j . a rc m e d .2 00 5 .0 2 .0 02
auditory evoked response is the lengthening of the latency of waves III and V (9–15). Although complications of diabetes have been associated with several factors such as poor diabetes control and time elapsed since diabetes was diagnosed, the influence of these factors on auditory function is not yet understood (2,12,16–18). Comparative studies of auditory function taking into account blood glucose control and other complications of the disease are scarce. The purpose of this study was to assess the auditory function of patients with type 2 diabetes mellitus who were not seeking audiological or otological evaluation, compared to age- and sex-matched healthy subjects and to assess the influence on auditory function of age, time elapsed since diabetes was
쑖 2005 IMSS. Published by Elsevier Inc.
508
Dı´az de Leo´n-Morales et al. / Archives of Medical Research 36 (2005) 507–510
diagnosed, age when diabetes was diagnosed, HbAc1 levels and evidence of retinopathy and peripheral neuropathy. Materials and Methods Subjects. Ninety four diabetic patients and 94 healthy subjects gave their informed consent to participate in the study according to the guidelines of the Local Ethics Committee. Patients with type 2 diabetes mellitus were aged 50 ⫾ 6 years (mean ⫾ SD), 77 were females (82%) and 17 males (18%). They had a body mass index of 28.8 ⫾ 4.2 and fasting blood glucose of 170.5 ⫾ 66.6 mg/dL. Healthy subjects were aged 50 ⫾ 6 years, 77 were females (82%) and 17 males (18%). They had a body mass index of 28.6 ⫾ 4.8, fasting blood glucose of 95 ⫾ 12.8 mg/dL and postprandial blood glucose of 89 ⫾ 14.8 mg/dL. Neither normal subjects nor patients had a history of otological, central nervous system or cardiovascular disease or had received ototoxic medication or were exposed to unsafe noise levels. Procedures. After a clinical interview, subjects were evaluated using pure-tone audiometry (Grason-Stadler, Milford, NH) to identify the hearing thresholds at 125–8000 Hz pure tones, using 5-dB nHL steps. Additionally, we calculated the pure tone averages for low (125, 250, 500 Hz), middle (500, 1000, 2000 Hz), and high (2000, 4000, 8000 Hz) frequencies. Speech audiometry (Grason-Stadler) was used to identify the hearing level at which subjects understood and repeated at least 90% of a set of 10 monosyllables. Auditory brainstem responses were used (Audix version 2, Neuronic) to 80 dB SL clicks, at a rate of 11.7 and 67.4 clicks/sec, using 1mV sensitivity, 10 mV gain and 1–3 KHz filters. The responses were recorded using gold disk electrodes placed on the mastoids and high forehead. After the average response to 2000 stimuli was reproduced, we identified the latency of waves I, III and V, the interwave latency of I–III, III–V and I–V and the interaural symmetry of wave V. An ophthalmologic evaluation was performed to identify if there was 1) evidence of diabetic retinopathy, 2) nonproliferative diabetic retinopathy (mild, moderate, severe or very severe) or 3) proliferative diabetic retinopathy (mild, moderate or severe) (19). The Michigan Diabetic Neuropathy Score was administered to evaluate peripheral neuropathy, classified as 1) no evidence of neuropathy, 2) mild neuropathy, 3) moderate neuropathy and 4) severe neuropathy (20). The first morning urine sample was used to measure urine levels of albumin (Boehringer-Mannheim, Lakeside). Results were classified as (21): microalbuminuria ⫽ 22–300 mg/L and macroalbuminuria ⬎300 mg/L. Statistical analysis. Statistical analysis was performed using t test, χ2 and multivariate analysis (CSS, Statsoft, Tulsa, OK). Differences were considered significant when twotailed p values were ⬍0.05.
Results Clinical characteristics of diabetic patients. The mean age for diagnosis of diabetes was 42.8 ⫾ 6.5 years (mean ⫾ SD). Time elapsed since diagnosis of diabetes was 7.2 ⫾ 5.4 years. At the time of evaluation the mean HbA1c was 10.76 ⫾ 2.64%. Forty-eight patients (62%) had HbA1c ⬎8%. Ophthalmologic evaluation showed diabetic retinopathy in 14 patients (14%, 95% CI of 8–20%), which was nonproliferative in 10 patients (severe in two cases) and proliferative in four patients (severe in one case). According to the Michigan Diabetic Neuropathy Score, peripheral neuropathy was identified in 67 patients (71%, 95% CI of 62–80%). In 39 patients (41.4%) the neuropathy was mild, in 21 patients (22.3%) it was moderate and in 7 (7.3%) it was severe. Microalbuminuria was identified in 12 patients and no patient had macroalbuminuria. Auditory function. Auditory symptoms. In both patients and controls, frequency of auditory symptoms was similar. Six (6%) diabetic patients and nine (9%) control subjects reported poor hearing. Thirteen (13%) patients and eight (8%) controls reported tinnitus. Pure tone audiometry. Compared to healthy subjects, diabetic patients showed an increase of the perception threshold at 8000 Hz (p ⬍0.01) (Figure 1), which was related to an increase of the high frequency perception average (p ⬍0.001) (Table 1). Comparison between right and left hearing thresholds within each group did not show any statistical difference. However, individual analysis showed clinical asymmetry between right and left hearing thresholds in
Diabetes Controls
Right Ear
Frequency (Hz) 125
250
500
1000
2000
4000
8000 0 5 10 15 20 25 30 35 40 45 50
Diabetes Controls
Left Ear
Frequency (Hz) 125
250
500
1000
2000
4000
8000 0 5 10 15 20 25 30 35 40 45 50
Figure 1. Mean and 95% confidence interval of the mean of the auditory thresholds to pure tone stimulation of 94 diabetic patients and 94 healthy subjects.
Auditory Impairment in Patients with Type 2 Diabetes Mellitus Table 1. Mean and SD of pure tone hearing level on audiometry for low (125, 250 and 500 Hz), middle (500, 1000 and 2000 Hz) and high (2000, 4000 and 8000 Hz) frequencies and for 8000 Hz of 94 patients with type 2 diabetes mellitus and 94 age- and sex-matched non-diabetic subjects Diabetic patients Frequency Low frequencies Right ear Left ear Middle frequencies Right ear Left ear High frequencies* Right ear Left ear 8000 Hz* Right ear Left ear
Mean (dB)
SD
Non-diabetic subjects Mean (dB)
SD
19 20
6 6
18 18
3 4
18 17
6 6
16 15
4 4
24 23
13 12
18 17
7 8
31 32
19 19
22 22
11 12
dB, decibels; SD, standard deviation. *Significant difference between groups (p ⬍0.05).
509
Table 3. Mean and SD of the latency of waves I, III and V and the interwave latency of waves I–III, III–V and I–V of 94 diabetic patients and 94 age- and sex-matched non-diabetic subjects Diabetic patients Component Wave I Right ear Left ear Wave III Right ear Left ear Wave V* Right ear Left ear Interwave I–V* Right ear Left ear Interwave I–III Right ear Left ear Interwave III–V Right ear Left ear*
Non-diabetic subjects
Mean (msec)
SD
Mean (msec)
SD
1.61 1.62
0.24 0.22
1.63 1.61
0.20 0.20
3.85 3.85
0.30 0.20
3.76 3.80
0.21 0.23
5.90 6.00
0.33 0.31
5.76 5.76
0.28 0.31
4.29 4.38
0.35 0.39
4.13 4.15
0.38 0.39
2.22 2.24
0.35 0.25
2.14 2.20
0.31 0.31
2.07 2.14
0.40 0.32
1.99 1.96
0.31 0.37
eight diabetic patients (8%) and four control subjects (4%). An audiometric profile compatible with noise-induced hearing loss was not identified in any of the control subjects but in one diabetic patient, who previously denied noise exposure.
msec, milliseconds; SD, standard deviation. *Significant difference between groups (p ⬍0.05).
Speech audiometry. Speech audiometry results were consistent with the pure tone audiometry. The hearing level needed to discriminate at least 90% of the monosyllables was higher for diabetic patients than for control subjects (p ⬍0.01) (Table 2). No significant difference was found between right and left ear within each group.
for 8 KHz was significantly correlated with patient age and time elapsed since diabetes was diagnosed (p ⬍0.001). However, there was no significant correlation with fasting blood glucose levels, HbA1c, peripheral neuropathy, retinopathy or albuminuria.
Auditory brainstem responses. Absolute latency and interwave latency for waves I, III, and V are shown in Table 3. Compared to control subjects, patients showed an increase of wave V latency and interwave I–V and III–V latencies (p ⬍0.01) (Table 3). Also, right/left asymmetry of the latency of wave V was more frequent in diabetic patients than in control subjects (41%, 95% CI 31–50% vs. 21%, 95% CI 18– 24%; p ⬍0.001).
Discussion
Clinical characteristics of diabetes and auditory function. Multivariate analysis showed that the hearing threshold Table 2. Mean and SD of the hearing level needed to discriminate at least 90% of monosyllables of 94 patients with type 2 diabetes mellitus and 94 age- and sex-matched non-diabetic subjects Diabetic patients Side Right ear* Left ear* Two ears combined*
Non-diabetic subjects
Mean (dB)
SD
Mean (dB)
SD
46 46 46
13 14 12
41 40 41
9 8 8
dB, decibels; SD, standard deviation. *Significant difference between groups (p ⬍0.05).
In order to assess the peripheral and central auditory function, in this study we evaluated pure tone perception thresholds, speech audiometry and brainstem responses. Selection criteria were applied to control for several factors that could have influenced the results. Our findings are in agreement with previous reports showing that type 2 diabetes mellitus is related to high-frequency sensorineural hearing loss (1,5,6–8,22,23) and impaired auditory brainstem responses (9,13,24). These results are in support of the fact that diabetes mellitus may have a complex repercussion on the auditory pathways. The finding of hearing loss in 50 patients when only 6 reported hearing impairment is consistent with previous reports suggesting that patients with diabetes mellitus may have progressive hearing loss (7), which could be subclinical (14). The brainstem responses suggested normal VIII nerve function but impaired neural conduction time within the brainstem. Bayazit et al. (2000), in 59 diabetic patients, showed a lengthening of the latencies of the main components of the brainstem responses (25), suggesting microangiopathy of the central nervous system. Although the findings
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were similar, our study does not support the theory suggested by Bayazit et al., because the brainstem responses were independent from the evidence of retinopathy, peripheral neuropathy and nephropathy. Another explanation for the auditory impairment could be a metabolic compromise. The high metabolic demands of the inner ear and the auditory pathway could make them a target of the disease, even before evidence of microvascular complications (12,16,26,27). Lisowska et al. evaluated 42 patients with type 1 diabetes mellitus. The main finding was an impairment of the cochlear micromechanics, with no relationship to microangiopathy (23). We observed that hearing impairment in diabetes is related with patient age and time elapsed since diabetes was diagnosed but not with other clinical characteristics of the disease. This correlation is consistent with the findings of Rozanska et al. (2002), who compared the hearing thresholds of 20 patients with type 2 diabetes mellitus and 20 healthy subjects (7). The main finding was a progressive highfrequency hearing loss related to patient age and with the duration of the disease. In the two studies, the hearing loss affected the high frequencies, which are also the frequencies most frequently affected by age-related hearing loss. However, the finding of an influence of the time elapsed since diabetes was diagnosed and the comparison to ageand sex-matched controls support that the hearing loss was related to the disease and suggest that diabetes mellitus could aggravate the hearing loss related to age. In conclusion, patients with type 2 diabetes mellitus can have subclinical hearing loss and impaired auditory brainstem response. This auditory dysfunction can be independent of peripheral neuropathy, retinopathy or nephropathy.
Acknowledgments The study was supported by Fondo para el Fomento de la Investigacio´n del Instituto Mexicano del Seguro Social.
References 1. Ravecca F, Berretini S, Bruschini L, Segnini G, Sellari-Franceschini S. Progressive sensorineural hearing loss: metabolic, hormonal and vascular etiology. Acta Otorhinolaryngol Ital 1998;18:42–50. 2. deEspana R, Biurrun O, Lorente J, Traserra J. Hearing and diabetes. ORL J Otorhinolaryngol Relat Spec 1995;57:325–327. 3. Taylor IG, Irwin J. Some audiological aspects of diabetes mellitus. J Laryngol Otol 1972;92:99–113. 4. Cullen JR, Cinnamond MJ. Hearing loss in diabetics. J Laryngol Otol 1993;107:179–182. 5. Parving A, Elberling C, Balle V, Parbo J, Dejgaard A, Parving HH. Hearing disorders in patients with insuline-dependent diabetes mellitus. Audiology 1990;29:113–121.
6. Ravi KV, Henderson A. Sudden deafness as the sole presenting symptom of diabetes mellitus—a case report. J Laryngol Otol 1996;110: 59–61. 7. Rozanska-Kudelska M. Hearing loss in patients with diabetes mellitus type II. Otolaryngol Pol 2002;5:607–610. 8. Kakarlapudi V, Sawyer R, Staecker H. The effect of diabetes on sensorineural hearing loss. Otol Neurotol 2003;24:382–386. 9. Celik O, Yalcin S, Selebi H, Ozturk A. Hearing loss in insulin-dependent diabetes mellitus. Auris Nasus Larynx 1996;23:127–132. 10. Dalton DS, Cruickshanks KJ, Klein R, Klein BE, Wiley TL. Association of NIDDM and hearing loss. Diabetes Care 1998;21:1540–1544. 11. Comi G. Evoked potentials in diabetes mellitus. Clin Neurosci 1997;4: 374–379. 12. Obrebowski A, Pruszewicz A, Gawlinski M, Swidzinski P. Electrophysiological hearing examination in children and teenagers with insulindependent diabetes mellitus. Otolaryngol Pol 1999;53:595–598. 13. Akinci A, Deda G, Karagol U, Tezi T. Brainstem auditory evoked potential, visual evoked potential and nerve conduction velocity and their relation with HbA1c and beta 2 microglobulin in children with insulin dependent diabetes mellitus. Turk J Pediatr 1994;36:279–287. 14. Jauregui-Renaud K, Dominguez-Rubio B, Ibarra-Olmos A, GonzalezBarcena D. Otoneurologic abnormalities in insulin-dependent diabetes. Rev Invest Clin 1998;50:137–138. 15. Ma F, Gomez-Marin O, Lee DJ, Balkany T. Diabetes and hearing impairment in Mexican American adults: a population-based study. J Laryngol Otol 1998;112:835–839. 16. Tay HL, Ohri R, Frootko NJ. Diabetes mellitus and hearing loss. Clin Otolaryngol 1995;20:130–134. 17. Sasso FC, Salvatore T, Tranchino G, Cozzolino D, Carusso A, Persico M, Torella D, Torella R. Cochlear dysfunction in type 2 diabetes: a complication independent of neuropathy and acute hyperglicemia. Metabolism 1999;48:1346–1350. 18. Bonafonte S, Garcı´a ChA, Davis M. Clasificacio´n de la retinopatı´a diabe´tica. En: Retinopatı´a Diabe´tica. Harcourt Brace 1998;4:63–90. 19. Emancipator K. Laboratory diagnosis and monitoring of diabetes mellitus. Am J Clin Pathol 1999;112:665–674. 20. Feldman EL, Stevens MJ, Thomas PK, Brown MB, Canal N, Greene A. A practical two-step quantitative clinical and electrophysiological assessment for the diagnosis and staging of diabetic neuropathy. Diabetes Care 1994;17:1281–1289. 21. Acun˜a Garcı´a M, Herrero Laso JL, Dura´n Diez C, Mene´ndez Argu¨elles ME, Vallejo Valdezate LA, Diaz Suarez I, Pomar Blanco P, Alvarez Iscar N. Diabetic complications and hypoacusia. An Otorrinolaringol Ibero Am 1997;24:465–476. 22. Boomsma LJ, Stolk RP. The frequency of hearing impairment in patients with diabetes mellitus type 2. Ned Tijdschr Geneeskd 1998;14: 1823–1825. 23. Bayazit Y, Bekir N, Gungor K, Kepekci Y, Mumbuc S, Kanlikama M. The predictive value of auditory brainstem responses for diabetic retinopathy. Auris Nasus Larynx 2000;27:219–222. 24. Lisowska G, Namyslowski G, Morawski K, Strojek K. Early identification of hearing impairment in patients with type 1 diabetes mellitus. Otol Neurotol 2001;22:316–320. 25. Bayazit Y, Yilmaz M, Kepekci Y, Mumbuc S, Kanlikama M. Use of the auditory brainstem response testing in the clinical evaluation of the patients with diabetes mellitus. J Neurol Sci 2000;181:29–32. 26. Lisowska G, Namyslowski G, Morawski K, Strojek K. Cochlear dysfunction and diabetic microangiopathy. Scand Audiol Suppl 2001;52: 199–203. 27. Alam SA, Oshima T, Suzuki M, Kawase T, Takasaka T, Ikeda K. The expression of apoptosis-related proteins in the aged cochlea of mongolian gerbils. Laryngoscope 2001;111:528–534.
ORIGINAL ARTICLE
Auditory Impairment in Patients with Type 2 Diabetes Mellitus Luz Vero´nica Dı´az de Leo´n-Morales,a Kathrine Ja´uregui-Renaud,c Marı´a Eugenia Garay-Sevilla,d Jose´ Herna´ndez-Pradob and Juan Manuel Malacara-Herna´ndezc a Servicio de ORL y Audiologı´a and bServicio de Oftalmologia, Hospital de Especialidades T1, Instituto Mexicano del Seguro Social (IMSS), Leo´n Guanajuato, Mexico c Unidad de Investigacio´n Me´dica, Hospital General, Centro Me´dico Nacional (CMN) La Raza, Instituto Mexicano del Seguro Social (IMSS), Mexico City, Mexico d Instituto de Investigaciones Me´dicas, Universidad de Guanajuato, Leo´n, Guanajuato, Mexico
Received for publication October 18, 2004; accepted February 14, 2005 (D-04-00120).
Background. We assessed the auditory function of 94 patients with type 2 diabetes mellitus and 94 age- and sex-matched healthy subjects. Methods. To study the influence of the clinical characteristics of the disease on the auditory function, after a clinical interview with ophthalmological assessment, subjects were evaluated using pure-tone audiometry, speech audiometry, auditory brainstem responses, the Michigan Diabetic Neuropathy Score and albuminuria. The mean age when diabetes was diagnosed was 42.8 ⫾ 6.5 years (mean ⫾ SD) and the time elapsed since diabetes diagnosis was 7.2 ⫾ 5.4 years. Results. Forty-eight patients (62%) had HbA1c ⬎8%; diabetic retinopathy was evident in 14 patients (14%) and microalbuminuria was identified in 12 patients. Compared to healthy subjects, diabetic patients showed an increase of the perception threshold at 8000 Hz (p ⬍0.01), higher hearing levels to discriminate at least 90% of 10 monosyllables (p ⬍0.01), and longer latencies of wave V, interwave I–V and interwave III–V (p ⬍0.01). Significant correlation was found between the hearing threshold at 8 KHz and patient age, and the former and the time elapsed since the diabetes was diagnosed (p ⬍0.001). Conclusions. Patients with type 2 diabetes mellitus can have subclinical hearing loss and impaired auditory brainstem response, independent of peripheral neuropathy, retinopathy or nephropathy. 쑖 2005 IMSS. Published by Elsevier Inc. Key Words: Diabetes mellitus, Hearing loss, Brainstem responses.
Introduction Diabetes mellitus is a common metabolic disease with variable impairment of the body systems. Studies about the relationship between diabetes mellitus and auditory impairment have shown variable results (1–4). The most frequent finding is a high-frequency sensorineural hearing loss (1,5– 8), and the most common abnormality of the brainstem
Address reprint requests to: Dr. Kathrine Ja´uregui-Renaud, Unidad de Investigacio´n Me´dica, Hospital General, CMN La Raza IMSS, Av Vallejo y Jacarandas, Colonia La Raza, 02990 Me´xico, D.F., Me´xico; Phone and FAX: 5782 1976; E-mail: [email protected]
0188-4409/05 $–see front matter. Copyright d o i : 1 0 .1 0 16 / j . a rc m e d .2 00 5 .0 2 .0 02
auditory evoked response is the lengthening of the latency of waves III and V (9–15). Although complications of diabetes have been associated with several factors such as poor diabetes control and time elapsed since diabetes was diagnosed, the influence of these factors on auditory function is not yet understood (2,12,16–18). Comparative studies of auditory function taking into account blood glucose control and other complications of the disease are scarce. The purpose of this study was to assess the auditory function of patients with type 2 diabetes mellitus who were not seeking audiological or otological evaluation, compared to age- and sex-matched healthy subjects and to assess the influence on auditory function of age, time elapsed since diabetes was
쑖 2005 IMSS. Published by Elsevier Inc.
508
Dı´az de Leo´n-Morales et al. / Archives of Medical Research 36 (2005) 507–510
diagnosed, age when diabetes was diagnosed, HbAc1 levels and evidence of retinopathy and peripheral neuropathy. Materials and Methods Subjects. Ninety four diabetic patients and 94 healthy subjects gave their informed consent to participate in the study according to the guidelines of the Local Ethics Committee. Patients with type 2 diabetes mellitus were aged 50 ⫾ 6 years (mean ⫾ SD), 77 were females (82%) and 17 males (18%). They had a body mass index of 28.8 ⫾ 4.2 and fasting blood glucose of 170.5 ⫾ 66.6 mg/dL. Healthy subjects were aged 50 ⫾ 6 years, 77 were females (82%) and 17 males (18%). They had a body mass index of 28.6 ⫾ 4.8, fasting blood glucose of 95 ⫾ 12.8 mg/dL and postprandial blood glucose of 89 ⫾ 14.8 mg/dL. Neither normal subjects nor patients had a history of otological, central nervous system or cardiovascular disease or had received ototoxic medication or were exposed to unsafe noise levels. Procedures. After a clinical interview, subjects were evaluated using pure-tone audiometry (Grason-Stadler, Milford, NH) to identify the hearing thresholds at 125–8000 Hz pure tones, using 5-dB nHL steps. Additionally, we calculated the pure tone averages for low (125, 250, 500 Hz), middle (500, 1000, 2000 Hz), and high (2000, 4000, 8000 Hz) frequencies. Speech audiometry (Grason-Stadler) was used to identify the hearing level at which subjects understood and repeated at least 90% of a set of 10 monosyllables. Auditory brainstem responses were used (Audix version 2, Neuronic) to 80 dB SL clicks, at a rate of 11.7 and 67.4 clicks/sec, using 1mV sensitivity, 10 mV gain and 1–3 KHz filters. The responses were recorded using gold disk electrodes placed on the mastoids and high forehead. After the average response to 2000 stimuli was reproduced, we identified the latency of waves I, III and V, the interwave latency of I–III, III–V and I–V and the interaural symmetry of wave V. An ophthalmologic evaluation was performed to identify if there was 1) evidence of diabetic retinopathy, 2) nonproliferative diabetic retinopathy (mild, moderate, severe or very severe) or 3) proliferative diabetic retinopathy (mild, moderate or severe) (19). The Michigan Diabetic Neuropathy Score was administered to evaluate peripheral neuropathy, classified as 1) no evidence of neuropathy, 2) mild neuropathy, 3) moderate neuropathy and 4) severe neuropathy (20). The first morning urine sample was used to measure urine levels of albumin (Boehringer-Mannheim, Lakeside). Results were classified as (21): microalbuminuria ⫽ 22–300 mg/L and macroalbuminuria ⬎300 mg/L. Statistical analysis. Statistical analysis was performed using t test, χ2 and multivariate analysis (CSS, Statsoft, Tulsa, OK). Differences were considered significant when twotailed p values were ⬍0.05.
Results Clinical characteristics of diabetic patients. The mean age for diagnosis of diabetes was 42.8 ⫾ 6.5 years (mean ⫾ SD). Time elapsed since diagnosis of diabetes was 7.2 ⫾ 5.4 years. At the time of evaluation the mean HbA1c was 10.76 ⫾ 2.64%. Forty-eight patients (62%) had HbA1c ⬎8%. Ophthalmologic evaluation showed diabetic retinopathy in 14 patients (14%, 95% CI of 8–20%), which was nonproliferative in 10 patients (severe in two cases) and proliferative in four patients (severe in one case). According to the Michigan Diabetic Neuropathy Score, peripheral neuropathy was identified in 67 patients (71%, 95% CI of 62–80%). In 39 patients (41.4%) the neuropathy was mild, in 21 patients (22.3%) it was moderate and in 7 (7.3%) it was severe. Microalbuminuria was identified in 12 patients and no patient had macroalbuminuria. Auditory function. Auditory symptoms. In both patients and controls, frequency of auditory symptoms was similar. Six (6%) diabetic patients and nine (9%) control subjects reported poor hearing. Thirteen (13%) patients and eight (8%) controls reported tinnitus. Pure tone audiometry. Compared to healthy subjects, diabetic patients showed an increase of the perception threshold at 8000 Hz (p ⬍0.01) (Figure 1), which was related to an increase of the high frequency perception average (p ⬍0.001) (Table 1). Comparison between right and left hearing thresholds within each group did not show any statistical difference. However, individual analysis showed clinical asymmetry between right and left hearing thresholds in
Diabetes Controls
Right Ear
Frequency (Hz) 125
250
500
1000
2000
4000
8000 0 5 10 15 20 25 30 35 40 45 50
Diabetes Controls
Left Ear
Frequency (Hz) 125
250
500
1000
2000
4000
8000 0 5 10 15 20 25 30 35 40 45 50
Figure 1. Mean and 95% confidence interval of the mean of the auditory thresholds to pure tone stimulation of 94 diabetic patients and 94 healthy subjects.
Auditory Impairment in Patients with Type 2 Diabetes Mellitus Table 1. Mean and SD of pure tone hearing level on audiometry for low (125, 250 and 500 Hz), middle (500, 1000 and 2000 Hz) and high (2000, 4000 and 8000 Hz) frequencies and for 8000 Hz of 94 patients with type 2 diabetes mellitus and 94 age- and sex-matched non-diabetic subjects Diabetic patients Frequency Low frequencies Right ear Left ear Middle frequencies Right ear Left ear High frequencies* Right ear Left ear 8000 Hz* Right ear Left ear
Mean (dB)
SD
Non-diabetic subjects Mean (dB)
SD
19 20
6 6
18 18
3 4
18 17
6 6
16 15
4 4
24 23
13 12
18 17
7 8
31 32
19 19
22 22
11 12
dB, decibels; SD, standard deviation. *Significant difference between groups (p ⬍0.05).
509
Table 3. Mean and SD of the latency of waves I, III and V and the interwave latency of waves I–III, III–V and I–V of 94 diabetic patients and 94 age- and sex-matched non-diabetic subjects Diabetic patients Component Wave I Right ear Left ear Wave III Right ear Left ear Wave V* Right ear Left ear Interwave I–V* Right ear Left ear Interwave I–III Right ear Left ear Interwave III–V Right ear Left ear*
Non-diabetic subjects
Mean (msec)
SD
Mean (msec)
SD
1.61 1.62
0.24 0.22
1.63 1.61
0.20 0.20
3.85 3.85
0.30 0.20
3.76 3.80
0.21 0.23
5.90 6.00
0.33 0.31
5.76 5.76
0.28 0.31
4.29 4.38
0.35 0.39
4.13 4.15
0.38 0.39
2.22 2.24
0.35 0.25
2.14 2.20
0.31 0.31
2.07 2.14
0.40 0.32
1.99 1.96
0.31 0.37
eight diabetic patients (8%) and four control subjects (4%). An audiometric profile compatible with noise-induced hearing loss was not identified in any of the control subjects but in one diabetic patient, who previously denied noise exposure.
msec, milliseconds; SD, standard deviation. *Significant difference between groups (p ⬍0.05).
Speech audiometry. Speech audiometry results were consistent with the pure tone audiometry. The hearing level needed to discriminate at least 90% of the monosyllables was higher for diabetic patients than for control subjects (p ⬍0.01) (Table 2). No significant difference was found between right and left ear within each group.
for 8 KHz was significantly correlated with patient age and time elapsed since diabetes was diagnosed (p ⬍0.001). However, there was no significant correlation with fasting blood glucose levels, HbA1c, peripheral neuropathy, retinopathy or albuminuria.
Auditory brainstem responses. Absolute latency and interwave latency for waves I, III, and V are shown in Table 3. Compared to control subjects, patients showed an increase of wave V latency and interwave I–V and III–V latencies (p ⬍0.01) (Table 3). Also, right/left asymmetry of the latency of wave V was more frequent in diabetic patients than in control subjects (41%, 95% CI 31–50% vs. 21%, 95% CI 18– 24%; p ⬍0.001).
Discussion
Clinical characteristics of diabetes and auditory function. Multivariate analysis showed that the hearing threshold Table 2. Mean and SD of the hearing level needed to discriminate at least 90% of monosyllables of 94 patients with type 2 diabetes mellitus and 94 age- and sex-matched non-diabetic subjects Diabetic patients Side Right ear* Left ear* Two ears combined*
Non-diabetic subjects
Mean (dB)
SD
Mean (dB)
SD
46 46 46
13 14 12
41 40 41
9 8 8
dB, decibels; SD, standard deviation. *Significant difference between groups (p ⬍0.05).
In order to assess the peripheral and central auditory function, in this study we evaluated pure tone perception thresholds, speech audiometry and brainstem responses. Selection criteria were applied to control for several factors that could have influenced the results. Our findings are in agreement with previous reports showing that type 2 diabetes mellitus is related to high-frequency sensorineural hearing loss (1,5,6–8,22,23) and impaired auditory brainstem responses (9,13,24). These results are in support of the fact that diabetes mellitus may have a complex repercussion on the auditory pathways. The finding of hearing loss in 50 patients when only 6 reported hearing impairment is consistent with previous reports suggesting that patients with diabetes mellitus may have progressive hearing loss (7), which could be subclinical (14). The brainstem responses suggested normal VIII nerve function but impaired neural conduction time within the brainstem. Bayazit et al. (2000), in 59 diabetic patients, showed a lengthening of the latencies of the main components of the brainstem responses (25), suggesting microangiopathy of the central nervous system. Although the findings
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were similar, our study does not support the theory suggested by Bayazit et al., because the brainstem responses were independent from the evidence of retinopathy, peripheral neuropathy and nephropathy. Another explanation for the auditory impairment could be a metabolic compromise. The high metabolic demands of the inner ear and the auditory pathway could make them a target of the disease, even before evidence of microvascular complications (12,16,26,27). Lisowska et al. evaluated 42 patients with type 1 diabetes mellitus. The main finding was an impairment of the cochlear micromechanics, with no relationship to microangiopathy (23). We observed that hearing impairment in diabetes is related with patient age and time elapsed since diabetes was diagnosed but not with other clinical characteristics of the disease. This correlation is consistent with the findings of Rozanska et al. (2002), who compared the hearing thresholds of 20 patients with type 2 diabetes mellitus and 20 healthy subjects (7). The main finding was a progressive highfrequency hearing loss related to patient age and with the duration of the disease. In the two studies, the hearing loss affected the high frequencies, which are also the frequencies most frequently affected by age-related hearing loss. However, the finding of an influence of the time elapsed since diabetes was diagnosed and the comparison to ageand sex-matched controls support that the hearing loss was related to the disease and suggest that diabetes mellitus could aggravate the hearing loss related to age. In conclusion, patients with type 2 diabetes mellitus can have subclinical hearing loss and impaired auditory brainstem response. This auditory dysfunction can be independent of peripheral neuropathy, retinopathy or nephropathy.
Acknowledgments The study was supported by Fondo para el Fomento de la Investigacio´n del Instituto Mexicano del Seguro Social.
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