Otolaryngology http://oto.sagepub.com/ -- Head and Neck Surgery
Hyperglycemia as a Potential Prognostic Factor of Idiopathic Sudden Sensorineural Hearing Loss Ohk Hyun Ryu, Moon Gi Choi, Chan Hum Park, Dong-Kyu Kim, Joong Seob Lee and Jun Ho Lee Otolaryngology -- Head and Neck Surgery published online 30 January 2014 DOI: 10.1177/0194599814521012 The online version of this article can be found at: http://oto.sagepub.com/content/early/2014/01/30/0194599814521012 A more recent version of this article was published on - May 1, 2014
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Original Research
Hyperglycemia as a Potential Prognostic Factor of Idiopathic Sudden Sensorineural Hearing Loss
Otolaryngology– Head and Neck Surgery 1–6 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599814521012 http://otojournal.org
Ohk Hyun Ryu, MD1, Moon Gi Choi, MD, PhD1, Chan Hum Park, MD, PhD2, Dong-Kyu Kim, MD2, Joong Seob Lee, MD2, and Jun Ho Lee, MD, PhD2
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Abstract Objective. Hyperglycemia is not identified as a significant prognostic factor for idiopathic sudden sensorineural hearing loss in any literature. Therefore, we investigated the prognostic value of hyperglycemia in predicting hearing recovery. Study Design. A retrospective cohort study. Setting. Tertiary university hospital. Subjects and Methods. Patients were classified into 3 groups according to their glucose tolerance using the 75-gram oral glucose tolerance test and hemoglobin A1c test as follows: (1) a normal glucose tolerance group, (2) a prediabetes group, which included patients with impaired glucose tolerance and/ or impaired fasting glucose levels, and (3) a diabetes mellitus group. Results. Among 94 patients with idiopathic sudden sensorineural hearing loss, 45 were classified into the normal glucose tolerance group, 28 into the prediabetes group, and 21 into the diabetes mellitus group. The recovery rate of the normal glucose tolerance group was not higher than that of the diabetes mellitus group (P = .140). However, when the prediabetes and diabetes mellitus groups were collectively defined as the impaired glucose regulation (hyperglycemia) group, the hearing recovery rate of the normal glucose tolerance (normoglycemia) group was significantly better than that of the impaired glucose regulation group (P = .038). Conclusion. We suggest that hyperglycemia may be a potential negative prognostic factor for hearing recovery in idiopathic sudden sensorineural hearing loss. Further interventional studies should be followed to determine whether hearing outcomes of the impaired glucose regulation group may be improved to the same extent as those of the normal glucose tolerance group after strict glycemic control.
Keywords sudden hearing loss, glucose intolerance, hyperglycemia
Received September 24, 2013; revised December 3, 2013; accepted January 3, 2014.
Introduction Idiopathic sudden sensorineural hearing loss (ISSHL) is defined as a sensorineural hearing loss of at least 30 dB in 3 consecutive speech frequencies that occurred within the previous 3 days.1,2 Its worldwide incidence has been reported to range from 5 to 20 per 100,000 population.2 The pathogenesis of ISSHL remains controversial. Various causes have been proposed, including viral infection of the labyrinth or cochlear nerve, vascular compromise, intracochlear membrane rupture, perilymphatic fistula, and autoimmune inner ear disease.1,3-8 To date, several studies have reported the prognostic factors for ISSHL such as age, the presence or absence of vertigo, the type and severity of hearing loss, the shape of the audiogram, and the time of treatment initiation.2,9-11 Although several articles on this topic have already been published for tinnitus, the prognostic value has been controversial.12 Recently, the presence of auditory brainstem response and vestibular evoked myogenic potential waveforms might indicate favorable hearing outcomes.13 Hyperglycemia can cause microvascular damages involving sudden increases in blood viscosity and embolic and thrombotic episodes.14 Thus, we hypothesized that these microvascular damages in hyperglycemic patients would affect the prognosis of ISSHL as a negative effect. Some trials have investigated the relationship between diabetes mellitus (DM) and ISSHL or hearing loss; however,
1 Department of Endocrinology and Metabolism, College of Medicine, Hallym University, Chuncheon, Republic of Korea 2 Department of Otorhinolaryngology–Head and Neck Surgery, College of Medicine, Hallym University, Chuncheon, Republic of Korea
Corresponding Author: Jun Ho Lee, MD, PhD, Department of Otorhinolaryngology–Head and Neck Surgery, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, 153, Kyo-Dong, Chuncheon, 200-704, Republic of Korea. Email: [email protected]
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Figure 1. Prediabetes is defined as impaired fasting glucose or impaired fasting glucose/impaired glucose tolerance or impaired glucose tolerance or 5.7 hemoglobin A1c 6.4. Diabetes mellitus is defined as fasting glucose 126 mg/dL or 2 hour plasma glucose 200 mg/dL or HbA1c 6.5% or diabetes mellitus history. The impaired glucose regulation group is the combination of the prediabetes group and diabetes mellitus group.
DM is not stated as a significant prognostic factor in any literature.8,14-19 In previous studies, impaired glucose tolerance patients might be misclassified into a normal glucose tolerance (NGT, normoglycemia) group because impaired glucose tolerance could not be found using the DM history or fasting glucose level.17,18 Thus, we classified patients into 3 groups (NGT, prediabetes [impaired fasting glucose and/or impaired glucose tolerance], and DM) according to the hemoglobin A1c level, oral glucose tolerance test (OGTT), and history of DM (Figure 1). We conducted the present study to assess the prognostic value of hyperglycemia in predicting hearing recovery in ISSHL. The spontaneous recovery rate of ISSHL has varied between 32% and 68% in previous studies.17,20 A high rate of spontaneous recovery has led to diverse opinions regarding the efficacy of treatment modalities; however, systemic corticosteroids are the only treatment for ISSHL that have been shown to be effective in many reports.18,21 In addition, intratympanic steroid injection is another therapeutic modality that has been used as added or salvage treatment.21,22 To minimize the influence of the spontaneous recovery rate on the efficacy of treatment modalities, we used the same therapeutic modality in all the patients in the present study.
Patients and Methods Between August 2010 and October 2012, 94 patients diagnosed with unilateral ISSHL attending the Department of Otorhinolaryngology at the Chuncheon Sacred Heart Medical Center in South Korea were enrolled in this retrospective cohort study. All the patients provided written informed consent in accordance with the Declaration of Helsinki of the World Medical Association. The Chuncheon Sacred Heart Hospital institutional review board approved the following study protocol. All the patients underwent pure-tone audiometry. Auditory brainstem response was
used as a screening test to exclude possible retrocochlear lesions at the first visit. Because various abnormalities may be evident in the auditory brainstem response, we performed magnetic resonance imaging with gadolinium diethylentriamine to exclude vestibular schwannoma. Patients with Me´nie`re’s disease and traumatic history were carefully excluded. All the patients had been treated with oral prednisolone 60 mg for 5 days with dose reductions of 20 mg every 2 days and an intratympanic dexamethasone injection once daily for 6 days. Patients underwent hemoglobin A1c and OGTT testing before starting oral steroid treatment and intratympanic injections.
Criteria of Group Classification Based on the above biochemical testing, we classified patients into 3 groups (NGT, prediabetes, and DM groups) according to the diagnostic criteria of diabetes and prediabetes by the American Diabetes Association (Figure 1).
NGT group. We defined the NGT (normoglycemia) group as having a level of hemoglobin A1c \ 5.7, a fasting (defined as no caloric intake for at least 8 hours) glucose level \ 100 mg/dL, a 2-hour plasma glucose level of 75-g OGTT \ 140 mg/dL, and no history of DM. Prediabetes group. The prediabetes group was divided into the impaired fasting glucose group, which was defined as 100 mg/dL fasting glucose 125 mg/dL, and/or the impaired glucose tolerance group, which was defined as 140 mg/dL 2-hour plasma glucose of 75-g OGTT 199 mg/ dL or 5.7 hemoglobin A1c 6.4. DM group. The DM group was defined as hemoglobin A1c 6.5 or fasting glucose 126 mg/dL or 2-hour plasma glucose 200 mg/dL during an OGTT or history of DM.23 The prediabetes and DM groups were collectively defined as the impaired glucose regulation (hyperglycemia) group. DM patients who were treated by insulin injection or using oral antidiabetic drugs maintained their previous treatment modalities. When the serum glucose level was temporarily greater than 250 mg/dL, the patients were treated with a sliding-scale insulin injection and referred to an endocrinologist to determine whether previous medications should be continued or changed for glycemic control. The ISSHL treatment regimen was the same for all patients irrespective of the glucose tolerance state. Hearing recovery was determined by comparing puretone audiometry at the first visit and 3 months later when hearing was assumed to be fixed completely. Hearing gain represented the absolute value of changes in the averaged hearing levels of 500, 1000, 2000, and 3000 Hz recommended by the Committee on Hearing and Equilibrium.24 Hearing improvement was believed to be a credible parameter for hearing recovery after ISSHL. Hearing outcomes of each group were first categorized into the recovery group and no recovery group by more
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Table 1. Hearing Outcomes by Response Category Based on Greater Than 15 dB Recovery.a Group Normal glucose tolerance Prediabetes Diabetes mellitus
Patients, n (%)
Recovery, n (%)
No recovery, n (%)
45 (100) 28 (100) 21 (100)
28 (62.2) 11 (39.3) 9 (42.9)
17 (37.8) 17 (60.7) 12 (57.1)
a
Comparison of the hearing recovery rates among the 3 groups (P = .113).
Table 2. Siegel’s Criteria (1975): Degree of Hearing Recovery from Sudden Hearing Loss. Type I. Complete recovery II. Partial recovery III. Slight recovery IV. No recovery
Hearing recovery Patients whose final hearing level was better than 25 dB regardless of the size of the gain Patients who showed more than 15 dB of gain and whose final hearing level was between 25 and 45 dB Patients who showed more than 15 dB of gain and whose final hearing level was poorer than 45 dB Patients who showed less than 15 dB of gain or whose final hearing level was poorer than 75 dB
than 15 dB of gain (Table 1). Hearing outcomes were next categorized as complete recovery, partial recovery, slight recovery, or no recovery according to Siegel’s criteria (Table 2).25 Statistical comparisons among groups were based on the chi-square test and the Mann–Whitney U test using SPSS version 12.0. The criterion for statistical significance was set at a P value less than .05.
Results Among 94 patients with ISSHL, 44 males (46.8%) and 50 females (53.2%) were included in our study. The patient ages ranged from 14 to 79 years, with a mean age at the time of presentation of 50.3 years (SD = 16.1 years). Among 94 patients with ISSHL, 45 belonged to the NGT group, 28 belonged to the prediabetes group, and 21 belonged to the DM group (Table 1). No significant differences were found in hearing outcomes among the 3 groups (P = .113). Figure 2 summarizes the hearing outcomes by response category based on greater than 15 dB recovery. The hearing outcomes of the NGT group were not significantly better than those of the DM group (P = .140). However, when the prediabetes and DM groups were collectively defined as the impaired glucose regulation group, the hearing recovery rate of the NGT group was significantly better than the impaired glucose regulation group (P = .038; Figure 3). If the analysis was performed on the supposition that the prediabetes group was undiagnosed and included the NGT group, the NGT plus prediabetes group was not significantly better than the DM group (P = .393; Figure 4). Furthermore, we analyzed the hearing recovery among the groups according to Siegel’s criteria (Table 2). The recovery rate of the NGT group was not significantly higher than that of the DM group (P = .083). However, when the prediabetes group and DM groups were collectively defined as the impaired glucose regulation group, the hearing recovery
Figure 2. Comparison of hearing recovery based on 15 dB for each group after treatment. Normal glucose tolerance group versus diabetes mellitus group (P = .140).
rate of the NGT group was better than that of the IGR group (P = .049). If the prediabetes group was included in the NGT group, the recovery rate of the NGT plus prediabetes group was not better than that of the DM group (P = .206; Figure 5).
Discussion Despite the great advances in otology over the past decades, the etiopathogenesis of ISSHL remains unclear. More than 100 possible causes have been implicated over the years, but most cases remain idiopathic. Many studies of the prognosis of affected patients have demonstrated prognostic factors such as the presence or absence of vertigo, timing of the initiation of treatment, type and severity of hearing loss, and age.2,9-11 Hyperglycemia was believed to be 1 of the
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Figure 3. Comparison of the hearing recovery rates between the normal glucose tolerance group and impaired glucose regulation group (prediabetes 1 diabetes mellitus) (P = .038).
Figure 4. Comparison of hearing recovery rates between the normal glucose tolerance plus prediabetes group and diabetes mellitus group (P = .393).
many causes of ISSHL. Lin et al reported a large populationbased study in which DM was significantly associated with a higher risk of developing ISSHL.8 However, the influence of hyperglycemia on the hearing outcomes of ISSHL remained controversial. Hiraumi et al commented that hyperglycemia (diagnosed using medical history or the fasting glucose level) was not correlated with hearing outcomes.17 Ko¨rpinar et al reported that patients with a DM history were not significantly different in hearing outcomes compared with normal patients.18 Nagaoka et al suggested that ISSHL with hypertension, DM, and dyslipidemia was associated with a slower hearing recovery.19 Otherwise, Orita et al demonstrated that ISSHL with hyperglycemia showed a significantly better hearing recovery rate than the control group.15 Thus,
hyperglycemia was not mentioned as a prognostic factor.19 However, we questioned whether hyperglycemia may be a bad prognostic factor because it can cause microvascular damage and neuropathy.8 Because the cochlea depends on a single terminal branch of the posterior cerebral circulation, vascular occlusion under hyperglycemic conditions has been thought by some authors to be an etiological factor for ISSHL.26 In this occlusive vascular condition, the effectiveness of the therapeutic systemic steroid may be decreased. Thus, the recovering results of the 3 groups in our study might be different according to their vascular condition in different glycemic states. In many previous studies, the differences between the normal and DM groups were analyzed, and most of the results showed no significant differences.17 However, several studies have documented that hyperglycemic vascular status might play an important role in the recovery process in various other diseases.27,28 In other studies, if ISSHL patients were classified according to their medical history (the presence or absence of DM) or fasting blood glucose, we believe that the impaired glucose tolerance group might be misclassified into the NGT group because hemoglobin A1c testing and OGTT were not performed routinely in ISSHL patients. The undiagnosed impaired glucose tolerance patients may have been included in the NGT group based on the initial serum fasting glucose level that was tested on admission in other studies. As a result, many other studies of ISSHL reported various hearing results associated with hyperglycemia or DM.14,15,17-19,29 Therefore, we thought that hyperglycemia was not recognized as a prognostic factor in previous studies. To solve these problems, we divided the glycemic state of the ISSHL patients into the 3 groups (NGT, prediabetes, and DM groups) based on the fasting glucose level, OGTT, and hemoglobin A1c levels. We analyzed the hearing outcomes according to the glucose tolerance state. The comparison of hearing recovery between the NGT and DM groups was not significantly different in our results when the hearing recovery was based on greater than 15 dB (P = .140). However, there were significant differences in the recovery rate when the prediabetes group was integrated into the NGT group (which might be a classification used in previous studies) or DM group (newly classified into the impaired glucose regulation group in our study). The recovery rate of hearing loss was statistically higher in the NGT group than in the impaired glucose regulation group, although no significant differences were noted between the NGT and DM groups.
Conclusions The present study shows that poor hearing outcome in ISSHL is evident in impaired glucose regulation patients. We suggest that hyperglycemic conditions may affect the prognosis of ISSHL. To investigate the role of hyperglycemia as a potential prognostic factor, further interventional studies should be conducted to determine whether hearing outcomes of the impaired glucose regulation group may be
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Figure 5. Comparison of hearing recovery rates using Siegel’s criteria. Normal glucose tolerance versus diabetes mellitus (P = .083); normal glucose tolerance versus prediabetes (P = .134); normal glucose tolerance 1 prediabetes versus diabetes mellitus (P = .206); normal glucose tolerance versus prediabetes 1 diabetes mellitus (P = .049). Abbreviations: CR, complete recovery; NR, no recovery; PR, partial recovery; SR, slight recovery.
improved to the same extent as those of the NGT group after strict glycemic control. Author Contributions Ohk Hyun Ryu, conception, drafting, final approval; Moon Gi Choi, acquisition of data, drafting, final approval; Chan Hum Park, analysis of data, drafting, final approval; Dong-Kyu Kim, interpretation of data, drafting, final approval; Joong Seob Lee, acquisition of data, drafting, final approval; Jun Ho Lee, conception and design, data acquisition, revision, final approval.
Disclosures Competing interests: None. Sponsorships: None. Funding source: Hallym University Medical Center Research Fund (No. 1-2007-28), no role in study.
References 1. Eisenman D, Arts HA. Effectiveness of treatment for sudden sensorineural hearing loss. Arch Otolaryngol Head Neck Surg. 2000;126:1161-1164. 2. Byl FM Jr.Sudden hearing loss: eight years’ experience and suggested prognosis table. Laryngoscope. 1984;94:647-661. 3. Hughes FB, Freedman MA, Haberkamp TJ, et al. Sudden sensorineural hearing loss. Otolaryngol Clin North Am. 1996;29:393-405. 4. Khetarpal U, Nadol JB, Glynn RJ. Idiopathic sudden sensorineural hearing loss and postnatal viral labyrihthitis: a statistical comparison of temporal bone finding. Ann Otol Rhinol Laryngol. 1990;99:969-976. 5. Plasse HM, Mittleman M, Frost JO. Unilateral sudden hearing loss after open heart surgery: a detailed study of seven cases. Laryngoscope. 1981;91:101-109. 6. Goode RL. Perilymph hypertension and the indirect measurement of cochlear pressure. Laryngoscope. 1981;91:1706-1713.
7. Meyerhoff WL. The management of sudden deafness. Laryngoscope. 1979;89:1867-1868. 8. Lin SW, Lin YS, Weng SF, et al. Risk of developing sudden sensorineural hearing loss in diabetic patients: a populationbased cohort study. Otol Neurotol. 2012;33:1482-1488. 9. Ben-David J, Luntz M, Podoshin L, et al. Vertigo as a prognostic sign in sudden sensorineural hearing loss. Int Tinnitus J. 2002;8:127-128. 10. Shaia FT, Sheehy JL. Sudden sensori-neural hearing impairment: a report of 1220 cases. Laryngoscope. 1976;86:389-398. 11. Saeki N, Kitahara M. Assessment of prognosis in sudden deafness. Acta Otolaryngol Suppl. 1994;510:56-61. 12. Hikita-Watanabe N, Kitahara T, Horri A, et al. Tinnitus as a prognostic factor of sudden deafness. Acta Otolaryngol. 2010; 130:79-83. 13. Wang CT, Huang TW, Kuo SW, et al. Correlation between audiovestibular function tests and hearing outcomes in severe to profound sudden sensorineural hearing loss. Ear Hear. 2009;30:110-114. 14. Fukui M, Kitagawa Y, Nakamura N, et al. Idiopathic sudden hearing loss in patients with type 2 diabetes. Diabetes Res Clin Pract. 2004;63:205-211. 15. Orita S, Fukushima K, Orita Y, et al. Sudden hearing impairment combined with diabetes mellitus or hyperlipidemia. Eur Arch Otorhinolaryngol. 2007;264:359-362. 16. Fowler PD, Jones NS. Diabetes and hearing loss. Clin Otolaryngol Allied Sci. 1999;24:3-8. 17. Hiraumi H, Yamamoto N, Sakamoto T, et al. Multivariate analysis of hearing outcomes in patients with idiopathic sudden sensorineural hearing loss. Acta Otolaryngol Suppl. 2010;563:24-28. 18. Ko¨rpinar S, Alkan Z, Yig˘it O, et al. Factors influencing the outcome of idiopathic sudden sensorineural hearing loss treated with hyperbaric oxygen therapy. Eur Arch Otorhinolaryngol. 2011; 268:41-47.
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19. Nagaoka J, Anjos MF, Takata TT, et al. Idiopathic sudden sensorineural hearing loss: evolution in the presence of hypertension, diabetes mellitus and dyslipidemias. Braz J Otorhinolaryngol. 2010;76:363-369. 20. Labus J, Breil J, Stu¨tzer H, et al. Meta-analysis for the effect of medical therapy vs. placebo on recovery of idiopathic sudden hearing loss. Laryngoscope. 2010;120:1863-1871. 21. Choung YH, Park K, Shin YR, et al. Intratympanic dexamethasone injection for refractory sudden sensorineural hearing loss. Laryngoscope. 2006;116:747-752. 22. Lim HJ, Kim YT, Choi SJ, et al. Efficacy of 3 different steroid treatments for sudden sensorineural hearing loss: a prospective, randomized trial. Otolaryngol Head Neck Surg. 2013;148:121-127. 23. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33:S62-S69. 24. Committee on Hearing and Equilibrium. Committee on hearing and equilibrium guidelines for the evaluation of results of
25. 26.
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treatment of conductive hearing loss. Otolaryngol Head Neck Surg. 1995;113:186-187. Siegel LG. The treatment of idiopathic sudden sensorineural hearing loss. Otolaryngol Clin North Am. 1975;8:467-473. Arts HA. Sensorineural hearing loss in adults. In: Flint PW, Haughey BH, Lund VJ, Niparko JK, Richardson MA, Robbins KT, Thomas JR, eds. Otolaryngology Head and Neck Surgery. 5th ed.St. Louis, MO: Mosby; 2010:2116-2130. Advani A, Gilbert RE. The endothelium in diabetic nephropathy. Semin Nephrol. 2012;32:199-207. Costa PZ, Soares R. Neovascularization in diabetes and its complication. Unraveling the angiogenic paradox. Life Sci. 2013;92:1037-1045. Wilson WR, Laird N, Moo-Young G, et al. The relationship of idiopathic sudden hearing loss to diabetes mellitus. Laryngoscope. 1982;92:155-160.
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Hyperglycemia as a Potential Prognostic Factor of Idiopathic Sudden Sensorineural Hearing Loss Ohk Hyun Ryu, Moon Gi Choi, Chan Hum Park, Dong-Kyu Kim, Joong Seob Lee and Jun Ho Lee Otolaryngology -- Head and Neck Surgery published online 30 January 2014 DOI: 10.1177/0194599814521012 The online version of this article can be found at: http://oto.sagepub.com/content/early/2014/01/30/0194599814521012 A more recent version of this article was published on - May 1, 2014
Published by: http://www.sagepublications.com
On behalf of:
American Academy of Otolaryngology- Head and Neck Surgery
Additional services and information for Otolaryngology -- Head and Neck Surgery can be found at:
P> OnlineFirst Version of Record - Jan 30, 2014 What is This?
Downloaded from oto.sagepub.com at The University of Iowa Libraries on November 13, 2014
Original Research
Hyperglycemia as a Potential Prognostic Factor of Idiopathic Sudden Sensorineural Hearing Loss
Otolaryngology– Head and Neck Surgery 1–6 Ó American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0194599814521012 http://otojournal.org
Ohk Hyun Ryu, MD1, Moon Gi Choi, MD, PhD1, Chan Hum Park, MD, PhD2, Dong-Kyu Kim, MD2, Joong Seob Lee, MD2, and Jun Ho Lee, MD, PhD2
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Abstract Objective. Hyperglycemia is not identified as a significant prognostic factor for idiopathic sudden sensorineural hearing loss in any literature. Therefore, we investigated the prognostic value of hyperglycemia in predicting hearing recovery. Study Design. A retrospective cohort study. Setting. Tertiary university hospital. Subjects and Methods. Patients were classified into 3 groups according to their glucose tolerance using the 75-gram oral glucose tolerance test and hemoglobin A1c test as follows: (1) a normal glucose tolerance group, (2) a prediabetes group, which included patients with impaired glucose tolerance and/ or impaired fasting glucose levels, and (3) a diabetes mellitus group. Results. Among 94 patients with idiopathic sudden sensorineural hearing loss, 45 were classified into the normal glucose tolerance group, 28 into the prediabetes group, and 21 into the diabetes mellitus group. The recovery rate of the normal glucose tolerance group was not higher than that of the diabetes mellitus group (P = .140). However, when the prediabetes and diabetes mellitus groups were collectively defined as the impaired glucose regulation (hyperglycemia) group, the hearing recovery rate of the normal glucose tolerance (normoglycemia) group was significantly better than that of the impaired glucose regulation group (P = .038). Conclusion. We suggest that hyperglycemia may be a potential negative prognostic factor for hearing recovery in idiopathic sudden sensorineural hearing loss. Further interventional studies should be followed to determine whether hearing outcomes of the impaired glucose regulation group may be improved to the same extent as those of the normal glucose tolerance group after strict glycemic control.
Keywords sudden hearing loss, glucose intolerance, hyperglycemia
Received September 24, 2013; revised December 3, 2013; accepted January 3, 2014.
Introduction Idiopathic sudden sensorineural hearing loss (ISSHL) is defined as a sensorineural hearing loss of at least 30 dB in 3 consecutive speech frequencies that occurred within the previous 3 days.1,2 Its worldwide incidence has been reported to range from 5 to 20 per 100,000 population.2 The pathogenesis of ISSHL remains controversial. Various causes have been proposed, including viral infection of the labyrinth or cochlear nerve, vascular compromise, intracochlear membrane rupture, perilymphatic fistula, and autoimmune inner ear disease.1,3-8 To date, several studies have reported the prognostic factors for ISSHL such as age, the presence or absence of vertigo, the type and severity of hearing loss, the shape of the audiogram, and the time of treatment initiation.2,9-11 Although several articles on this topic have already been published for tinnitus, the prognostic value has been controversial.12 Recently, the presence of auditory brainstem response and vestibular evoked myogenic potential waveforms might indicate favorable hearing outcomes.13 Hyperglycemia can cause microvascular damages involving sudden increases in blood viscosity and embolic and thrombotic episodes.14 Thus, we hypothesized that these microvascular damages in hyperglycemic patients would affect the prognosis of ISSHL as a negative effect. Some trials have investigated the relationship between diabetes mellitus (DM) and ISSHL or hearing loss; however,
1 Department of Endocrinology and Metabolism, College of Medicine, Hallym University, Chuncheon, Republic of Korea 2 Department of Otorhinolaryngology–Head and Neck Surgery, College of Medicine, Hallym University, Chuncheon, Republic of Korea
Corresponding Author: Jun Ho Lee, MD, PhD, Department of Otorhinolaryngology–Head and Neck Surgery, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, 153, Kyo-Dong, Chuncheon, 200-704, Republic of Korea. Email: [email protected]
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Figure 1. Prediabetes is defined as impaired fasting glucose or impaired fasting glucose/impaired glucose tolerance or impaired glucose tolerance or 5.7 hemoglobin A1c 6.4. Diabetes mellitus is defined as fasting glucose 126 mg/dL or 2 hour plasma glucose 200 mg/dL or HbA1c 6.5% or diabetes mellitus history. The impaired glucose regulation group is the combination of the prediabetes group and diabetes mellitus group.
DM is not stated as a significant prognostic factor in any literature.8,14-19 In previous studies, impaired glucose tolerance patients might be misclassified into a normal glucose tolerance (NGT, normoglycemia) group because impaired glucose tolerance could not be found using the DM history or fasting glucose level.17,18 Thus, we classified patients into 3 groups (NGT, prediabetes [impaired fasting glucose and/or impaired glucose tolerance], and DM) according to the hemoglobin A1c level, oral glucose tolerance test (OGTT), and history of DM (Figure 1). We conducted the present study to assess the prognostic value of hyperglycemia in predicting hearing recovery in ISSHL. The spontaneous recovery rate of ISSHL has varied between 32% and 68% in previous studies.17,20 A high rate of spontaneous recovery has led to diverse opinions regarding the efficacy of treatment modalities; however, systemic corticosteroids are the only treatment for ISSHL that have been shown to be effective in many reports.18,21 In addition, intratympanic steroid injection is another therapeutic modality that has been used as added or salvage treatment.21,22 To minimize the influence of the spontaneous recovery rate on the efficacy of treatment modalities, we used the same therapeutic modality in all the patients in the present study.
Patients and Methods Between August 2010 and October 2012, 94 patients diagnosed with unilateral ISSHL attending the Department of Otorhinolaryngology at the Chuncheon Sacred Heart Medical Center in South Korea were enrolled in this retrospective cohort study. All the patients provided written informed consent in accordance with the Declaration of Helsinki of the World Medical Association. The Chuncheon Sacred Heart Hospital institutional review board approved the following study protocol. All the patients underwent pure-tone audiometry. Auditory brainstem response was
used as a screening test to exclude possible retrocochlear lesions at the first visit. Because various abnormalities may be evident in the auditory brainstem response, we performed magnetic resonance imaging with gadolinium diethylentriamine to exclude vestibular schwannoma. Patients with Me´nie`re’s disease and traumatic history were carefully excluded. All the patients had been treated with oral prednisolone 60 mg for 5 days with dose reductions of 20 mg every 2 days and an intratympanic dexamethasone injection once daily for 6 days. Patients underwent hemoglobin A1c and OGTT testing before starting oral steroid treatment and intratympanic injections.
Criteria of Group Classification Based on the above biochemical testing, we classified patients into 3 groups (NGT, prediabetes, and DM groups) according to the diagnostic criteria of diabetes and prediabetes by the American Diabetes Association (Figure 1).
NGT group. We defined the NGT (normoglycemia) group as having a level of hemoglobin A1c \ 5.7, a fasting (defined as no caloric intake for at least 8 hours) glucose level \ 100 mg/dL, a 2-hour plasma glucose level of 75-g OGTT \ 140 mg/dL, and no history of DM. Prediabetes group. The prediabetes group was divided into the impaired fasting glucose group, which was defined as 100 mg/dL fasting glucose 125 mg/dL, and/or the impaired glucose tolerance group, which was defined as 140 mg/dL 2-hour plasma glucose of 75-g OGTT 199 mg/ dL or 5.7 hemoglobin A1c 6.4. DM group. The DM group was defined as hemoglobin A1c 6.5 or fasting glucose 126 mg/dL or 2-hour plasma glucose 200 mg/dL during an OGTT or history of DM.23 The prediabetes and DM groups were collectively defined as the impaired glucose regulation (hyperglycemia) group. DM patients who were treated by insulin injection or using oral antidiabetic drugs maintained their previous treatment modalities. When the serum glucose level was temporarily greater than 250 mg/dL, the patients were treated with a sliding-scale insulin injection and referred to an endocrinologist to determine whether previous medications should be continued or changed for glycemic control. The ISSHL treatment regimen was the same for all patients irrespective of the glucose tolerance state. Hearing recovery was determined by comparing puretone audiometry at the first visit and 3 months later when hearing was assumed to be fixed completely. Hearing gain represented the absolute value of changes in the averaged hearing levels of 500, 1000, 2000, and 3000 Hz recommended by the Committee on Hearing and Equilibrium.24 Hearing improvement was believed to be a credible parameter for hearing recovery after ISSHL. Hearing outcomes of each group were first categorized into the recovery group and no recovery group by more
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Table 1. Hearing Outcomes by Response Category Based on Greater Than 15 dB Recovery.a Group Normal glucose tolerance Prediabetes Diabetes mellitus
Patients, n (%)
Recovery, n (%)
No recovery, n (%)
45 (100) 28 (100) 21 (100)
28 (62.2) 11 (39.3) 9 (42.9)
17 (37.8) 17 (60.7) 12 (57.1)
a
Comparison of the hearing recovery rates among the 3 groups (P = .113).
Table 2. Siegel’s Criteria (1975): Degree of Hearing Recovery from Sudden Hearing Loss. Type I. Complete recovery II. Partial recovery III. Slight recovery IV. No recovery
Hearing recovery Patients whose final hearing level was better than 25 dB regardless of the size of the gain Patients who showed more than 15 dB of gain and whose final hearing level was between 25 and 45 dB Patients who showed more than 15 dB of gain and whose final hearing level was poorer than 45 dB Patients who showed less than 15 dB of gain or whose final hearing level was poorer than 75 dB
than 15 dB of gain (Table 1). Hearing outcomes were next categorized as complete recovery, partial recovery, slight recovery, or no recovery according to Siegel’s criteria (Table 2).25 Statistical comparisons among groups were based on the chi-square test and the Mann–Whitney U test using SPSS version 12.0. The criterion for statistical significance was set at a P value less than .05.
Results Among 94 patients with ISSHL, 44 males (46.8%) and 50 females (53.2%) were included in our study. The patient ages ranged from 14 to 79 years, with a mean age at the time of presentation of 50.3 years (SD = 16.1 years). Among 94 patients with ISSHL, 45 belonged to the NGT group, 28 belonged to the prediabetes group, and 21 belonged to the DM group (Table 1). No significant differences were found in hearing outcomes among the 3 groups (P = .113). Figure 2 summarizes the hearing outcomes by response category based on greater than 15 dB recovery. The hearing outcomes of the NGT group were not significantly better than those of the DM group (P = .140). However, when the prediabetes and DM groups were collectively defined as the impaired glucose regulation group, the hearing recovery rate of the NGT group was significantly better than the impaired glucose regulation group (P = .038; Figure 3). If the analysis was performed on the supposition that the prediabetes group was undiagnosed and included the NGT group, the NGT plus prediabetes group was not significantly better than the DM group (P = .393; Figure 4). Furthermore, we analyzed the hearing recovery among the groups according to Siegel’s criteria (Table 2). The recovery rate of the NGT group was not significantly higher than that of the DM group (P = .083). However, when the prediabetes group and DM groups were collectively defined as the impaired glucose regulation group, the hearing recovery
Figure 2. Comparison of hearing recovery based on 15 dB for each group after treatment. Normal glucose tolerance group versus diabetes mellitus group (P = .140).
rate of the NGT group was better than that of the IGR group (P = .049). If the prediabetes group was included in the NGT group, the recovery rate of the NGT plus prediabetes group was not better than that of the DM group (P = .206; Figure 5).
Discussion Despite the great advances in otology over the past decades, the etiopathogenesis of ISSHL remains unclear. More than 100 possible causes have been implicated over the years, but most cases remain idiopathic. Many studies of the prognosis of affected patients have demonstrated prognostic factors such as the presence or absence of vertigo, timing of the initiation of treatment, type and severity of hearing loss, and age.2,9-11 Hyperglycemia was believed to be 1 of the
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Figure 3. Comparison of the hearing recovery rates between the normal glucose tolerance group and impaired glucose regulation group (prediabetes 1 diabetes mellitus) (P = .038).
Figure 4. Comparison of hearing recovery rates between the normal glucose tolerance plus prediabetes group and diabetes mellitus group (P = .393).
many causes of ISSHL. Lin et al reported a large populationbased study in which DM was significantly associated with a higher risk of developing ISSHL.8 However, the influence of hyperglycemia on the hearing outcomes of ISSHL remained controversial. Hiraumi et al commented that hyperglycemia (diagnosed using medical history or the fasting glucose level) was not correlated with hearing outcomes.17 Ko¨rpinar et al reported that patients with a DM history were not significantly different in hearing outcomes compared with normal patients.18 Nagaoka et al suggested that ISSHL with hypertension, DM, and dyslipidemia was associated with a slower hearing recovery.19 Otherwise, Orita et al demonstrated that ISSHL with hyperglycemia showed a significantly better hearing recovery rate than the control group.15 Thus,
hyperglycemia was not mentioned as a prognostic factor.19 However, we questioned whether hyperglycemia may be a bad prognostic factor because it can cause microvascular damage and neuropathy.8 Because the cochlea depends on a single terminal branch of the posterior cerebral circulation, vascular occlusion under hyperglycemic conditions has been thought by some authors to be an etiological factor for ISSHL.26 In this occlusive vascular condition, the effectiveness of the therapeutic systemic steroid may be decreased. Thus, the recovering results of the 3 groups in our study might be different according to their vascular condition in different glycemic states. In many previous studies, the differences between the normal and DM groups were analyzed, and most of the results showed no significant differences.17 However, several studies have documented that hyperglycemic vascular status might play an important role in the recovery process in various other diseases.27,28 In other studies, if ISSHL patients were classified according to their medical history (the presence or absence of DM) or fasting blood glucose, we believe that the impaired glucose tolerance group might be misclassified into the NGT group because hemoglobin A1c testing and OGTT were not performed routinely in ISSHL patients. The undiagnosed impaired glucose tolerance patients may have been included in the NGT group based on the initial serum fasting glucose level that was tested on admission in other studies. As a result, many other studies of ISSHL reported various hearing results associated with hyperglycemia or DM.14,15,17-19,29 Therefore, we thought that hyperglycemia was not recognized as a prognostic factor in previous studies. To solve these problems, we divided the glycemic state of the ISSHL patients into the 3 groups (NGT, prediabetes, and DM groups) based on the fasting glucose level, OGTT, and hemoglobin A1c levels. We analyzed the hearing outcomes according to the glucose tolerance state. The comparison of hearing recovery between the NGT and DM groups was not significantly different in our results when the hearing recovery was based on greater than 15 dB (P = .140). However, there were significant differences in the recovery rate when the prediabetes group was integrated into the NGT group (which might be a classification used in previous studies) or DM group (newly classified into the impaired glucose regulation group in our study). The recovery rate of hearing loss was statistically higher in the NGT group than in the impaired glucose regulation group, although no significant differences were noted between the NGT and DM groups.
Conclusions The present study shows that poor hearing outcome in ISSHL is evident in impaired glucose regulation patients. We suggest that hyperglycemic conditions may affect the prognosis of ISSHL. To investigate the role of hyperglycemia as a potential prognostic factor, further interventional studies should be conducted to determine whether hearing outcomes of the impaired glucose regulation group may be
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Figure 5. Comparison of hearing recovery rates using Siegel’s criteria. Normal glucose tolerance versus diabetes mellitus (P = .083); normal glucose tolerance versus prediabetes (P = .134); normal glucose tolerance 1 prediabetes versus diabetes mellitus (P = .206); normal glucose tolerance versus prediabetes 1 diabetes mellitus (P = .049). Abbreviations: CR, complete recovery; NR, no recovery; PR, partial recovery; SR, slight recovery.
improved to the same extent as those of the NGT group after strict glycemic control. Author Contributions Ohk Hyun Ryu, conception, drafting, final approval; Moon Gi Choi, acquisition of data, drafting, final approval; Chan Hum Park, analysis of data, drafting, final approval; Dong-Kyu Kim, interpretation of data, drafting, final approval; Joong Seob Lee, acquisition of data, drafting, final approval; Jun Ho Lee, conception and design, data acquisition, revision, final approval.
Disclosures Competing interests: None. Sponsorships: None. Funding source: Hallym University Medical Center Research Fund (No. 1-2007-28), no role in study.
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