Hyperglycemia as a Potential Prognostic Factor of Idiopathic Sudden Sensorineural Hearing Loss

Original ResearchOtology and Neurotology

Hyperglycemia as a Potential PrognosticFactor of Idiopathic Sudden SensorineuralHearing Loss

OtolaryngologyHead and Neck Surgery2014, Vol. 150(5) 853858 American Academy ofOtolaryngologyHead and NeckSurgery Foundation 2014Reprints and permission:sagepub.com/journalsPermissions.navDOI: 10.1177/0194599814521012http://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 dis-

closed at the end of this article.

Abstract

Objective. Hyperglycemia is not identified as a significant prog-nostic factor for idiopathic sudden sensorineural hearing lossin any literature. Therefore, we investigated the prognosticvalue of hyperglycemia in predicting hearing recovery.

Study Design. A retrospective cohort study.

Setting. Tertiary university hospital.

Subjects and Methods. Patients were classified into 3 groupsaccording to their glucose tolerance using the 75-gram oral glu-cose 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 mellitusgroup.

Results. Among 94 patients with idiopathic sudden sensori-neural hearing loss, 45 were classified into the normal glu-cose tolerance group, 28 into the prediabetes group, and 21into the diabetes mellitus group. The recovery rate of thenormal glucose tolerance group was not higher than that ofthe diabetes mellitus group (P = .140). However, when theprediabetes and diabetes mellitus groups were collectivelydefined as the impaired glucose regulation (hyperglycemia)group, the hearing recovery rate of the normal glucose tol-erance (normoglycemia) group was significantly better thanthat of the impaired glucose regulation group (P = .038).

Conclusion. We suggest that hyperglycemia may be a potentialnegative prognostic factor for hearing recovery in idiopathicsudden sensorineural hearing loss. Further interventionalstudies should be followed to determine whether hearingoutcomes of the impaired glucose regulation group may beimproved to the same extent as those of the normal glucosetolerance 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 previ-

ous 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 arti-

cles on this topic have already been published for tinnitus, the

prognostic value has been controversial.12 Recently, the pres-

ence of auditory brainstem response and vestibular evoked

myogenic potential waveforms might indicate favorable hear-

ing 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 dia-

betes mellitus (DM) and ISSHL or hearing loss; however,

1Department of Endocrinology and Metabolism, College of Medicine,

Hallym University, Chuncheon, Republic of Korea2Department of OtorhinolaryngologyHead and Neck Surgery, College of

Medicine, Hallym University, Chuncheon, Republic of Korea

Corresponding Author:

Jun Ho Lee, MD, PhD, Department of OtorhinolaryngologyHead and

Neck Surgery, Chuncheon Sacred Heart Hospital, Hallym University

College of Medicine, 153, Kyo-Dong, Chuncheon, 200-704, Republic of

Korea.

Email: [email protected]

at IMSS on May 26, 2015oto.sagepub.comDownloaded from

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 tol-

erance 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 assessthe 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, sys-

temic corticosteroids are the only treatment for ISSHL that

have been shown to be effective in many reports.18,21 In addi-

tion, intratympanic steroid injection is another therapeutic

modality that has been used as added or salvage treat-

ment.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 diag-

nosed with unilateral ISSHL attending the Department of

Otorhinolaryngology at the Chuncheon Sacred Heart

Medical Center in South Korea were enrolled in this retro-

spective 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 diethylentria-

mine to exclude vestibular schwannoma. Patients with

Menie`res 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 predia-

betes by the American Diabetes Association (Figure 1).

NGT group. We defined the NGT (normoglycemia) group ashaving a level of hemoglobin A1c\ 5.7, a fasting (definedas 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 intothe impaired fasting glucose group, which was defined as

100 mg/dL fasting glucose 125 mg/dL, and/or theimpaired 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 plasmaglucose 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 treat-

ment modalities. When the serum glucose level was tempo-

rarily greater than 250 mg/dL, the patients were treated with

a sliding-scale insulin injection and referred to an endocri-

nologist 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 pure-

tone 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 recom-

mended by the Committee on Hearing and Equilibrium.24

Hearing improvement was believed to be a credible para-

meter for hearing recovery after ISSHL.

Hearing outcomes of each group were first categorized

into the recovery group and no recovery group by more

Figure 1. Prediabetes is defined as impaired fasting glucose orimpaired fasting glucose/impaired glucose tolerance or impairedglucose tolerance or 5.7 hemoglobin A1c 6.4. Diabetes melli-tus is defined as fasting glucose 126 mg/dL or 2 hour plasma glu-cose 200 mg/dL or HbA1c 6.5% or diabetes mellitus history.The impaired glucose regulation group is the combination of theprediabetes group and diabetes mellitus group.

854 OtolaryngologyHead and Neck Surgery 150(5)


than 15 dB of gain (Table 1). Hearing outcomes were nextcategorized as complete recovery, partial recovery, slight

recovery, or no recovery according to Siegels criteria

(Table 2).25

Statistical comparisons among groups were based on the

chi-square test and the MannWhitney 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 differ-ences were found in hearing outcomes among the 3 groups

(P = .113). Figure 2 summarizes the hearing outcomes byresponse category based on greater than 15 dB recovery.

The hearing outcomes of the NGT group were not signifi-

cantly better than those of the DM group (P = .140).

However, when the prediabetes and DM groups were collec-

tively 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 suppositionthat 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; Figure4). Furthermore, we analyzed the hearing recovery amongthe groups according to Siegels criteria (Table 2). Therecovery 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

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 prog-

nosis of affected patients have demonstrated prognostic fac-

tors 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

Figure 2. Comparison of hearing recovery based on 15 dB foreach group after treatment. Normal glucose tolerance groupversus diabetes mellitus group (P = .140).

Table 2. Siegels Criteria (1975): Degree of Hearing Recovery from Sudden Hearing Loss.

Type Hearing recovery

I. Complete recovery Patients whose final hearing level was better than 25 dB regardless of the size of the gain

II. Partial recovery Patients who showed more than 15 dB of gain and whose final hearing level was between 25 and 45 dB

III. Slight recovery Patients who showed more than 15 dB of gain and whose final hearing level was poorer than 45 dB

IV. No recovery Patients who showed less than 15 dB of gain or whose final hearing level was poorer than 75 dB

Table 1. Hearing Outcomes by Response Category Based on Greater Than 15 dB Recovery.a

Group Patients, n (%) Recovery, n (%) No recovery, n (%)

Normal glucose tolerance 45 (100) 28 (62.2) 17 (37.8)

Prediabetes 28 (100) 11 (39.3) 17 (60.7)

Diabetes mellitus 21 (100) 9 (42.9) 12 (57.1)

aComparison of the hearing recovery rates among the 3 groups (P = .113).

Ryu et al 855


many causes of ISSHL. Lin et al reported a large population-

based 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 Korpinar et al

reported that patients with a DM history were not signifi-

cantly different in hearing outcomes compared with normal

patients.18 Nagaoka et al suggested that ISSHL with hyper-

tension, 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 effective-

ness 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, sev-

eral 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 accord-

ing 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 per-

formed 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 out-

comes according to the glucose tolerance state. The compar-

ison of hearing recovery between the NGT and DM groups

was not significantly different in our results when the hear-

ing 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 previ-

ous studies) or DM group (newly classified into the

impaired glucose regulation group in our study). The recov-

ery 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 hyperglyce-

mia as a potential prognostic factor, further interventional

studies should be conducted to determine whether hearing

outcomes of the impaired glucose regulation group may be

Figure 3. Comparison of the hearing recovery rates between thenormal glucose tolerance group and impaired glucose regulationgroup (prediabetes 1 diabetes mellitus) (P = .038).

Figure 4. Comparison of hearing recovery rates between thenormal glucose tolerance plus prediabetes group and diabetes mel-litus group (P = .393).



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, concep-

tion 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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Hyperglycemia as a Potential Prognostic Factor of Idiopathic Sudden Sensorineural Hearing Loss