This study aimed to evaluate the clinical features and the clinical factors associated with prognosis of sudden sensorineural hearing loss (SSNHL) in diabetic patients.
Forty-nine diabetic with unilateral SSNHL were retrospectively included. All patients received systemic high dose steroid therapy within one month after onset and had more than one month of follow-up audiogram. The basic characteristics of the patients, initial and follow-up audiograms, laboratory data, and methods of steroid treatment were collected.
Compared to reference values in healthy subjects, 79%, 55%, and 45% of the patients had higher values of mean neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), respectively. Older patients had significantly less degree of hearing loss, but they also had significantly worse hearing thresholds in the unaffected ear. After steroid treatment, less than half patients (47%) showed hearing recovery. Simultaneous intratympanic dexamethasone (ITD) injections with systemic steroid did not confer an additional hearing gain or an earlier recovery rate in diabetic patients with SSNHL. In the multivariate analysis, initial hearing thresholds of affected ear and timing of steroid treatment were significantly associated with hearing prognosis in diabetic patients with SSNHL.
Diabetic patients with SSNHL tended to have increased NLR, LMR, and PLR, which are reported to be associated with microvascular angiopathy. Simultaneous ITD injections to improve hearing recovery in diabetic patients with SSNHL seems unnecessary.
Sudden sensorineural hearing loss (SSNHL) is defined as a sudden onset of sensorineural hearing loss of 30 dB or more over at least three contiguous audiometric frequencies [
With associated microangiopathy or inflammatory processes, diabetes mellitus (DM) could be a risk factor for SSNHL [
Therefore, we conducted a retrospective review to evaluate the clinical factors associated with prognosis and compare the efficacy of simultaneous and sequential systemic steroid and ITD treatment in diabetic patients with SSNHL. Also, we evaluated the clinical features of SSNHL in diabetic patients including the laboratory data which are known to be related to systemic inflammation and glycemic control.
We retrospectively reviewed the medical records of all diabetic patients who admitted to Dankook University Hospital for SSNHL between January 2014 and July 2018. All patients in the present study exhibited unilateral SSNHL of at least 30 dB across at least three frequencies and occurring within 3 days of hearing loss. All patients received systemic high dose steroid therapy within one month after onset and had more than one month of follow-up audiogram. DM was defined as previously diagnosed type 2 DM and the use of antidiabetic medications, such as oral antihyperglycemic agents or insulin. Exclusion criteria for the study included 1) a history of previous SSNHL; 2) bilateral SSNHL; 3) any recognized cause of SSNHL such as Meniere’s disease, active viral infection, vestibular schwannoma, or congenital anomalies; 4) a history of chronic otitis media or otologic surgery; and 5) more than one month of the onset of the disease.
The basic characteristics of the patients, initial and followup audiograms, laboratory data, and methods of steroid treatment were collected. The basic characteristics included age, sex, side of affected ear, onset of symptoms, the presence of dizziness, and comorbid disease such as hypertension (HTN), cerebrovascular accident (CVA), and cardiovascular disease (CVD). Laboratory data, which included random plasma glucose, total cholesterol, glycosylated hemoglobin (HbA1c), and complete blood cell counts, were obtained before steroid treatment. The neutrophil-to-lymphocyte ratio (NLR), platelet-tolymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) were calculated as the ratio of neutrophil count to lymphocyte count, as the ratio of platelet count to lymphocyte count, and as the ratio of count lymphocyte to monocyte count, respectively. After steroid was administered, glucose stick test was daily performed to measure fasting glucose. Fasting glucose level in the morning (7 am) was collected to evaluate the glucose control during the high dose steroid treatment.
All patients received antiviral agent and systemic high dose steroid therapy (48 mg in the morning, 12 mg in the evening, total 60 mg of methylprednisolone for 7 days, followed by a taper for 7 days) within one month after onset. ITD injection was administered as a combination therapy along with the systemic high dose steroid or a salvage therapy for patients who did not exhibit recovery after an initial one week of systemic high dose steroid treatment. IT injections were performed 3-5 times with dexamethasone (4 mg/mL) within 2 weeks of diagnosis. The combination group defined as patients who received ITD injection along with the systemic high dose steroid. The non-combination group defined as patients who received only high dose steroid therapy or who received ITD injection as a salvage therapy after high dose steroid therapy. No additional treatment, including prostaglandin, vitamins, or hyperbaric oxygen therapy were used as second line treatments.
The initial audiogram was performed before receiving steroid treatment. Mean pure-tone thresholds were calculated at 0.5, 1, 2, and 4 kHz for air conduction thresholds. The degree of hearing loss was calculated as the difference of mean pure-tone thresholds between affected ear and unaffected ear for low frequencies (0.25 and 0.5 kHz), middle frequencies (1 and 2 kHz), and high frequencies (4 and 8 kHz). Hearing recovery was evaluated based on the result of the latest audiogram performed at least one month after treatment. The hearing gain was calculated as the difference between initial and final audiograms. Hearing improvement was assessed by modifying Siegel’s criteria [
The association of clinical or laboratory parameters with the hearing impairment were evaluated using Pearson’s correlation, Spearman’s correlation, independent t-test, and MannWhitney test. The differences between two different treatment groups were analyzed using independent t-test, chi-square test, and Mann-Whitney test. To investigate the clinical factors related to hearing recovery, independent t-test, Mann-Whitney test, and chi-square test were used. Multivariate logistic regression model was performed to assess the independent association of treatment method and hearing recovery. Clinical factors found to have possible association in univariate analysis (
This retrospective study protocol was approved by the Dankook University Hospital Institutional Review Board (IRB No. 2019-12-008), and it was performed in accordance with relevant guidelines and regulations. All data were fully anonymized before analyzing and the Institutional Review Board waived the requirement for informed consent.
Of 77 patients with unilateral SSNHL and DM, 47 patients were followed more than one month. Finally, 47 patients (25 male and 22 female) with a mean age of 58±14 (range 31-82) years were included in this study. Clinical characteristics are shown in
Fifteen (31.9%) patients had unilateral SSNHL in the right ears, whereas 32 (68.1%) patients had left ear involvement. On the initial audiogram of affected ear, the mean pure tone threshold was 85.3±20.3 dB HL and the mean word recognition score (WRS) was 12.4±25.8%. Fifteen patients (31.9%) presented with associated dizziness. All patients received high dose steroid treatment on average 4.8±6.3 days after onset. Among them, 25 patients (53.2%) received ITD injections as a combination therapy, 6 patients (12.8%) received ITD injections as a salvage therapy, and 16 patients (34%) received no ITD injections. During the systemic steroid, mean fasting glucose level in the morning was 216±92 mg/dL. The mean follow-up period was 54±38 days.
Twenty-five patients who received ITD injections as a combination therapy belonged to the combination group, and 22 patients who received no ITD injection or ITD injections as a salvage therapy belonged to the non-combination group. Two groups showed no statistically significant differences in age, sex, side of the lesion, onset of symptoms, presence of dizziness, comorbid disease, and duration of follow-up (
Among 47 patients, 25 patients were hearing non-improved group, and 22 patients were improved group.
DM is one of the most common metabolic disorders, which is associated with hearing impairment [
Our data clearly revealed hearing deficits of unaffected ear with increasing age in all frequencies (
Previous study reported that a high postprandial plasma glucose level had a significant negative correlation with the degree of hearing and a positive correlation with the baseline hearing thresholds loss in middle frequencies [
Systemic steroids are widely used for SSNHL, but its effectiveness may be decreased by their limited permeability through the blood-perilymphatic barrier [
The factors responsible which influence the hearing recovery in diabetics were evaluated. In univariate analysis, age, the presence of dizziness, initial pure tone thresholds of affected ear were significantly associated with hearing recovery (
There are several limitations in our study. The first, since this was a retrospective study, some diabetic patients were dropped out during follow-up periods. Second, the sample size was small to generalize. Third, the results may have been influenced by cotreatment with ginko biloba. We prescribed a ginko biloba inconsistently depending on the history of taking anticoagulant or antiplatelet drugs. Forth, chronic complications of diabetes such as nephropathy, retinopathy, and neuropathy were not recorded in detail. In our data, all diabetic patients with comorbid dizziness had HTN. Thus, comorbid disease could not reflect the severity of diabetic complications.
In summary, diabetic patients with SSNHL tended to have increased NLR, LMR, and PLR, which are reported to be associated with microvascular angiopathy. Baseline hearing thresholds were worse in older diabetics or diabetics with dizziness and hypertension. However, there was no clinical factor or laboratory parameter associated with the degree of hearing loss. After steroid treatment, less than half patients (47%) showed hearing recovery. Simultaneous ITD injections with systemic steroid did not confer an additional hearing gain or an earlier recovery rate. Initial hearing thresholds and timing of steroid treatment were significantly associated with hearing prognosis in diabetic patients with SSNHL.
None.
The authors have no financial conflicts of interest.
Conceptualization: Ji Eun Choi. Data curation: Yeo Rim Ju. Formal analysis: Ji Eun Choi. Methodology: Yeo Rim Ju and Ji Eun Choi. Project administration: Min Young Lee and Jae Yun Jung. Resources: Ji Eun Choi, Min Young Lee, and Jae Yun Jung. Software: Yeo Rim Ju and Ji Eun Choi. Supervision: Ji Eun Choi and Jae Yun Jung. Validation: Min Youn Lee and Ji Eun Choi. Visualization: Ji Eun Choi. Writing—original drift: Yeo Rim Ju and Ji Eun Choi. Writing—review & editing: Yeo Rim Ju and Ji Eun Choi. Approval of final manuscript: all authors.
Hearing outcome in combination and non-combination groups. Fig. 1 shows the results of PTA and WRS in combination group (A and B) and non-combination group (C and D). Pure tone thresholds and WRSs were presented at three different time points (baseline, one week after treatment, and last follow-up). *post hoc analysis between baseline and last follow-up. PTA: pure-tone average, WRS: word recognition score.
Hearing improvement between combination and non-combination groups. Fig. 2 shows a comparison of hearing improvement in pure tone thresholds and WRSs between combination group and noncombination group. The non-combination group showed a slight better hearing improvement in pure tone thresholds and WRSs, but which was not statistically significant. Avg: average, WRS: word recognition score.
Clinical characteristics of the study population (n=47)
Variables | |
---|---|
Age (years) | 58±14 |
Sex (male:female) | 25:22 |
Side (right:left) | 15:32 |
Onset of symptoms (days) | 4.8±6.3 |
Dizziness (no:yes) | 32:15 |
Comorbid disease (no:yes) | 16:31 |
Audiogram of affected ear | |
Initial PTA (4 FA, dB HL) | 85.3±20.3 |
Initial word recognition scores (%) | 12.4±25.8 |
Laboratory data | |
Random plasma glucose (mg/dL) | 217±92 |
Glycosylated hemoglobin (%) | 8.2±1.6 |
Total cholesterol (mg/dL) | 172±32 |
Neutrophil-to-lymphocyte ratio | 4.49±3.25 |
Platelet-to-lymphocyte ratio | 158.7±83.5 |
Lymphocyte-to-monocyte ratio | 10.34±17.16 |
Fasting glucose level during steroid treatment (mg/dL) | 216±92 |
Steroid treatment | |
Systemic steroid only | 16 |
Systemic steroid+IT injections (sequential) | 6 |
Systemic steroid+IT injections (simultaneous) | 25 |
Duration of follow-up (days) | 82±35 |
Continuous variables are presented with mean±standard deviation or n. Comorbid disease included hypertension, cerebrovascular accident, and cardiovascular disease. Mean PTA was calculated for 4 FA. PTA: pure-tone average, 4 FA: four frequencies (0.5, 1, 2, and 4 kHz), IT: intratympanic
Associations of clinical and laboratory parameters with the hearing impairment
Variables | Unaffected ear |
Affected ear |
Degree of hearing loss |
||||||
---|---|---|---|---|---|---|---|---|---|
LT | MT | HT | LT | MT | HT | LT | MT | HT | |
Pure tone thresholds (dB HL) | 18±12 | 20±13 | 38±21 | 79±21 | 86±22 | 83±17 | 62±21 | 66±23 | 46±26 |
Age | |||||||||
r | 0.502 | 0.642 | 0.599 | 0.193 | 0.054 | 0.079 | -0.105 | -0.300 | -0.429 |
|
<0.001 |
<0.001 |
<0.001 |
0.194 |
0.720 |
0.599 |
0.484 |
0.041 |
0.003 |
Sex | |||||||||
Male | 17±10 | 19±11 | 44±20 | 76±24 | 84±23 | 84±15 | 59±22 | 65±22 | 40±23 |
Female | 19±15 | 21±14 | 31±20 | 83±16 | 89±21 | 83±19 | 65±18 | 68±24 | 52±27 |
|
0.923 |
0.772 |
0.023 |
0.416 |
0.471 |
0.845 |
0.411 |
0.597 |
0.087 |
Dizziness | |||||||||
No | 16±10 | 16±10 | 37±20 | 75±22 | 83±22 | 81±19 | 59±21 | 67±23 | 45±26 |
Yes | 21±16 | 27±15 | 41±22 | 88±16 | 81±19 | 88±12 | 67±19 | 66±23 | 47±26 |
|
0.218 |
0.011 |
0.516 |
0.039 |
0.168 |
0.296 |
0.250 |
0.938 |
0.747 |
Comorbid disease | |||||||||
No | 12±5 | 13±8 | 33±22 | 78±19 | 86±19 | 86±14 | 66±18 | 73±23 | 53±27 |
Yes | 21±14 | 23±13 | 41±20 | 80±22 | 86±24 | 82±19 | 59±22 | 63±23 | 42±25 |
|
0.011 |
0.005 |
0.516 |
0.597 |
0.168 |
0.715 |
0.250 |
0.938 |
0.747 |
Glucose (mg/dL) | |||||||||
r | 0.181 | 0.191 | -0.020 | -0.135 | -0.077 | -0.149 | -0.247 | -0.179 | -0.083 |
|
0.223 |
0.198 |
0.893 |
0.366 |
0.605 |
0.317 |
0.094 |
0.229 |
0.579 |
Glycosylated hemoglobin (%) | |||||||||
r | -0.171 | 0.063 | -0.177 | -0.236 | -0.252 | -0.321 | -0.104 | -0.140 | 0.005 |
|
0.286 |
0.698 |
0.267 |
0.137 |
0.112 |
0.041 |
0.517 |
0.381 |
0.973 |
Total cholesterol (mg/dL) | |||||||||
r | -0.217 | -0.254 | -0.324 | 0.028 | -0.092 | -0.072 | 0.159 | 0.053 | 0.218 |
|
0.167 |
0.105 |
0.037 |
0.860 |
0.563 |
0.649 |
0.314 |
0.738 |
0.166 |
Neutrophil-to-lymphocyte ratio | |||||||||
r | -0.116 | -0.049 | 0.114 | -0.188 | -0.265 | -0.224 | -0.264 | -0.151 | -0.286 |
|
0.436 |
0.743 |
0.444 |
0.206 |
0.072 |
0.130 |
0.073 |
0.312 |
0.052 |
Platelet-to-lymphocyte ratio | |||||||||
r | -0.192 | -0.173 | -0.061 | -0.109 | -0.086 | -0.133 | 0.003 | 0.013 | -0.040 |
|
0.197 |
0.244 |
0.685 |
0.464 |
0.566 |
0.373 |
0.983 |
0.934 |
0.791 |
Lymphocyte-to-monocyte ratio | |||||||||
r | -0.025 | 0.143 | 0.006 | -0.220 | -0.155 | -0.141 | -0.013 | -0.034 | -0.006 |
|
0.867 |
0.338 |
0.968 |
0.137 |
0.300 |
0.344 |
0.929 |
0.821 |
0.968 |
Continuous variables are presented with mean±standard deviation.
pearson’s correlation analysis,
spearman correlation analysis,
independent t-test,
Mann-Whitney test.
LT: low tone (0.25 and 0.5 kHz), MT: middle tone (1 and 2 kHz), HT: high tone (4 and 8 kHz).
Comparison of demographic and clinical parameters according to method of steroid treatment
Variables | Combination group | Non-combination group | |
---|---|---|---|
Number of patients | 25 | 22 | |
Age (years) | 59.8 (31-82) | 58.0 (31-76) | 0.620 |
Sex (male:female) | 14:11 | 11:11 | 0.681 |
Side lesion (right:left) | 10:15 | 5:17 | 0.205 |
Onset of symptoms (days) | 4.81±5.48 | 4.60±6.17 | 0.879 |
Dizziness (no:yes) | 15:10 | 17:5 | 0.205 |
Comorbid disease (no:yes) | 7:18 | 9:13 | 0.351 |
Audiogram | |||
Initial pure-tone average (4 FA, dB HL) | 82.3±20.2 | 85.1±20.4 | 0.758 |
Initial word recognition scores (%) | 13.2±25.9 | 12.6±26.0 | 0.268 |
Degree of hearing loss (4 FA, dB HL) | 58.5±19.4 | 62.8±21.4 | 0.547 |
Laboratory data | |||
Random plasma glucose (mg/dL) | 209.2±96.8 | 224.8±87.4 | 0.567 |
Hemoglobin A1c (%) | 8.04±1.35 | 8.19±1.64 | 0.234 |
Total cholesterol (mg/dL) | 172.2±31.3 | 172.3±32.3 | 0.602 |
Neutrophil-to-lymphocyte ratio | 4.77±3.32 | 4.46±3.28 | 0.587 |
Platelet-to-lymphocyte ratio | 156.7±73.2 | 157.9±84.2 | 0.908 |
Lymphocyte-to-monocyte ratio | 9.8±16.1 | 10.4±17.3 | 0.394 |
Fasting glucose level during steroid treatment (mg/dL) | 179.3±48.7 | 188.0±50.9 | 0.382 |
Duration of follow-up (days) | 72±32 | 94±35 | 0.432 |
Continuous variables are presented with mean±standard deviation or n.
independent t-test,
Mann-Whitney test,
chi-square test.
4 FA: four frequencies (0.5, 1, 2, and 4 kHz)
Clinical factors related to hearing recovery
Variables | Non-improved (n=25) | Improved (n=22) | Univariate |
Multivariate |
||||
---|---|---|---|---|---|---|---|---|
B | SE | OR | 95% CI | |||||
Age (years) | 62±13 | 53±13 | 0.021 |
|||||
Sex (male:female) | 11:14 | 14:08 | 0.178 |
|||||
Side lesion (right:left) | 7:18 | 8:14 | 0.539 |
|||||
Onset of symptoms (days) | 4.8±6.3 | 4.6±6.3 | 0.116 |
-0.328 | 0.159 | 0.720 | 0.527-0.984 | 0.039 |
Dizziness (no:yes) | 13:12 | 19:3 | 0.012 |
-1.689 | 0.866 | 0.185 | 0.034-1.007 | 0.051 |
Comorbid disease (no:yes) | 8:17 | 8:14 | 0.753 |
|||||
Initial PTA (4 FA, dB HL) | ||||||||
Unaffected ear | 24.3±12.6 | 20.1±12.1 | 0.232 |
|||||
Affected ear | 92.0±18.8 | 77.8±19.6 | 0.015 |
-0.064 | 0.025 | 0.938 | 0.893-0.985 | 0.010 |
Initial WRS (%) | ||||||||
Unaffected ear | 95.0±12.9 | 96.7±6.1 | 0.540 |
|||||
Affected ear | 5.6±17.3 | 20.1±31.7 | 0.049 |
|||||
Laboratory data | ||||||||
Random plasma glucose (mg/dL) | 206±86 | 228±99 | 0.431 |
|||||
Glycosylated hemoglobin (%) | 8.03±1.68 | 8.33±1.61 | 0.548 |
|||||
Total cholesterol (mg/dL) | 169±32 | 175±32 | 0.535 |
|||||
Neutrophil-to-lymphocyte ratio | 4.33±2.65 | 4.67±3.88 | 0.639 |
|||||
Platelet-to-lymphocyte ratio | 149±56 | 169±107 | 0.435 |
|||||
Lymphocyte-to-monocyte ratio | 10.5±18.7 | 10.2±15.7 | 0.701 |
|||||
Fasting glucose during steroid treatment (mg/dL) | 182±50 | 194±51 | 0.413 |
|||||
Duration of follow-up (days) | 63±44 | 44±28 | 0.071 |
|||||
Steroid treatment (combination:non-combination) | 14:11 | 11:11 | 0.681 |
Continuous variables are presented with mean±standard deviation or n. Variables (age, sex, onset of symptom, dizziness, initial PTA, initial WRS, and duration of follow-up) found to have possible association in univariate analysis (
independent t-test,
Mann-Whitney test,
chi-square test,
logistic regression test.
4 FA: four frequencies (0.5, 1, 2, and 4 kHz), PTA: pure-tone average, WRS: word recognition score, SE: standard error, OR: odds ratio, CI: confidence interval