diabetes and hearing loss - catholic health · type 1 diabetic patients 60 years old or younger may...

Diabetes and Hearing Loss

Mohammed Al‐SofianiInternal Medicine Department

University at Buffalo‐Catholic Health System


Background: We have clear evidence that diabetes has pathologic effects on many

systems in the body (micro‐ and macrovascular complications) The association between diabetes and the auditory system is still

controversial. It seems logical that micro‐ vascular complications would have an impact

on the extensive vascularity of the cochlea.

Copyright A.K. Vats


Animal studies: Changes consistent with diabetic micro‐vascular complications were found

in cochlear capillaries of rats in which diabetes was induced by streptozotocin injections.

Loss of the outer hair cells was found in 5‐month‐ old genetically diabetic rats and increased loss was noted at 10.5 months of age, suggesting increasing damage with increased duration of diabetes.

*Smith TL, et al. Insulin‐dependent diabetic microangiopathy in the inner ear. Laryngoscope 1995. *Rust KR, Prazma J, Triana RJ, et al. Inner ear damage secondary to diabetes mellitus: II. Changes in aging SHR/N‐cp rats. Arch Otolaryngol Head Neck Surg 1992;118:397–400.

Figure: Interaction between Advanced Glycation End‐products (AGEs) and Receptors for AGE (RAGEs) contributes to the micro‐ and macrovascular complications of DM.


Molecular studies:

Manigrasso, et al. Unlocking the biology of RAGE in diabetic microvascular complications. January 2014.

Figure: Cleavage of sRAGE from the cell surface by ADAM10 and by expression of a splice variant of sRAGE.


Molecular studies:

Ramasamy, et al. RAGE: therapeutic target and biomarker of the inflammatory response‐the evidence mounts. Journal of Leukocyte Biology. September 2009.

Human studies: There is insufficient evidence of a significant relationship between

diabetes and hearing impairment in human.

NHANES showed that over two thirds of diabetics (self‐reported DM) are affected by some degree of hearing impairment (about twofold higher than that of the non‐diabetic population)

Bainbridge KE, Hoffman HJ, Cowie CC. Diabetes and hearing impairment in the United States: audiometric evidence from the National Health and Nutrition Exam‐ ination Survey, 1999 to 2004. Ann Intern Med 2008;149:1–10


HHIE‐S Score<10: No self‐perceived handicap≥10: Self‐perceived handicap

The Hearing Handicap Inventory for the Elderly Screening Version (HHIE‐S)

Proportion of patients with self‐perceived hearing handicap using the HHIE‐S questionnaire.

No handicap

Self‐perceived handicap

f

No HearingHandicap

Hearing Handicap

P value

Age (years) 56.32± 12.23 58.67± 14.68 0.45

Gender

Male 47 45.8 1Duration of DM (years)

5.73± 6.21 12.18± 10.44 0.001

Diabetic complications (%)

Retinopathy 9.1 8.3 1

Nephropathy 13.6 25 0.21

Neuropathy 12.1 20.8 0.32

CAD 6.1 12.5 0.4

Stroke/TIA 1.5 8.3 0.17

A1c (%) 7.2± 1.72 8± 2.31 0.08

HTN (%) 81.8 83.3 1

On insulin (%) 22.7 50 0.02

Demographic and health characteristics of diabetic patients stratified by hearing handicap.

Percentage of patients with and without hearing handicap stratified by duration of DM

P= 0.001

Type 1 Diabetes Mellitus (T1DM) and Hearing Loss: Audiometric Assessment

Hypothesis:Hearing loss is more prevalent in type 1 diabetics with a longer durationof diabetes compared to those with a shorter duration of DM.

Type 1 DM and hearing loss

Primary endpoints: To evaluate the hearing function in type 1 diabetic subjects. To evaluate the impact of duration of DM on hearing function in

T1DM. Secondary endpoints:

To evaluate the correlation between hearing loss and the developmentof other micro‐ and macrovascular complications of T1DM.

To evaluate the correlation of metabolic control with hearingimpairment in T1DM.

To evaluate the correlation between serum levels of CRP, VEGF, andsRAGE and hearing function in T1DM.

To evaluate the correlation between urinary levels of oxidative stressmarkers (isoprostane) and hearing function in T1DM

Methods: Approved by UB‐IRB.

A written informed consent was obtained from all study subjects prior to their enrolment in the study.

Patients were interviewed at the time of their regular visits to the endocrinology office at R&B Medical Group.

Levels of CRP, VEGF, sRAGE and isoprostane were measured by ELISA.


Inclusion criteria: Adults (aged 20‐60 years old) at start of screening. Type 1 DM.

Exclusion criteria: History of recurrent otitis media. History of Meniere's disease Noise exposure (Occupational, recreational, or military) Use of toxic drugs:

High dose aspirin (6‐8 g/day)Recurrent exposure to aminoglycoside, erythromycin, tetracycline.CisplatinLoop diuretic5‐FluorouracilBleomycin

Cocaine abuse. Congenital diseases associated with hearing

impairment such as Arnold Chiari malformation.


Excluded (n=12)• Had one or more of the

exclusion criteria (n=10)• Refused to participate

(n=2)

Audiometric test Collection of blood and

urine samples

Eligible patients(n=30)

42 Type 1 diabetics (20‐60 Y.O)(n=42)

Screen

ing

Phase

Data collection

History (comorbidities, medication list, etc.) Physical exam (including MNSI*) Results of most recent labs (A1c, BMP, urinalysis for

proteinuria)

*MNSI: Michigan Neuropathy Screening Instrument

Storage of samples (‐80⁰c) until the time of lab analysis.D

ata an

alysis


Normal

MILD

MODERATE

SEVERE

PROFOUND

Normal Hearing

The World Health Organization (WHO) classification of hearing loss (HL)

The Welch Allyn AM282 Audiometer

Mild Hearing Loss

Moderate Hearing Loss

Severe Hearing Loss

Profound Hearing Loss

n Mean/Percentage

Age (mean +- SD) 30 43.8 ±11.4Race (%)

White

African American

Others

27 90%0 0%3 10%

Gender (%)Male 15 50%

Duration of DM (mean +- SD) 30 27.2 ±10.8

BMI (mean +- SD) 30 28.2 ±4.5

A1c (mean +- SD) 29 7.6 ±1.4

Retinopathy (%) 10 33.3%Nephropathy (%) 3 10%Neuropathy (%) 4 13.3%CAD (%) 2 6.7%Stroke/TIA (%) 0 0%PAD (%) 1 3.3%History of HTN (%) 3 10%

Type 1 DM and hearing loss:

63.33%

36.67%

Figure 1: Proportion of patients with high frequency hearing loss.

Table 1: Baseline characteristics of the study subjects.

High Frequencies

P valueNo Hearing Impairment (n=11)

Hearing Impaired(n=19)

Age (years) 36.2 ±10.8 48.16 ±9.5 0.004

Gender

Male 63.6% 42.1% 0.45

Race 0.54

White

African American

Others

81.8% 94.7%

0 0

18.2% 5.3%

Duration of DM (years) 21.2 ±8.9 30.7 ±10.5 0.02

BMI 27.28±3 28.4 ±5.2 0.74

Most recent A1c (%) 7.6 ±1.1 7.6 ±1.6 0.88

Average A1c (%) 7.8 ±1.1 7.6 ±1.4 0.63


Table 2: Demographic and health characteristics of diabetic patients stratified by hearing function at high frequency sounds.

High Frequencies

No Hearing Impairment (n=11)

Hearing Impaired(n=19)

P value

Retinopathy 36.4% 31.6% 1

Nephropathy 0% 15.8% 0.28

CAD 0 10.5% 0.52

Stroke/TIA 0 0 NA

PAD 0 5.3% 1

Abnormal MNSI* 9.1% 57.9% 0.02

History of HTN 0 15.8% 0.28

Insulin Pump 90.9% 78.9% 0.63

ASA 18.2% 42.1% 0.25


Cont. Table 2: Demographic and health characteristics of diabetic patients stratified by hearing function at high frequency sounds. * MNSI: Michigan Neuropathy Screening Instrument.

Figure 2: Average pure‐tone thresholds in both ears among type 1 diabetic subjects by duration of diabetes.

Mild Hearing Loss


Severe Hearing Loss


Duration of Diabetes (years)


Figure 3: Average pure‐tone thresholds in the right ear among type 1 diabetic subjects by duration of diabetes.



Mild Hearing Loss


Severe Hearing Loss


Figure 4: Average pure‐tone thresholds in the left ear among type 1 diabetic subjects by duration of diabetes.


Mild Hearing Loss


Severe Hearing Loss



Figure 5: Average pure‐tone thresholds in both ears among type 1 diabetics stratified by presence of diabetic neuropathy.

Mild Hearing Loss


Severe Hearing Loss



Figure 6: Average pure‐tone thresholds in both ears among type 1 diabetics (diabetes for ≥35 years) and non‐diabetic subjects (40‐59 years old).

Mild Hearing Loss


Severe Hearing Loss



P value= 0.41


Figure 7: Serum levels of VEGF in diabetic patients with hearing loss compared to diabetic patients with normal hearing at high frequency sounds.

P value= 0.68


Figure 8: Serum levels of CRP in diabetic patients with hearing loss compared to diabetic patients with normal hearing at high frequency sounds.

Figure 9: Urine levels of isoprostane in diabetic patients with hearing loss compared to diabetic patients with normal hearing at high frequency sounds.

P value= 0.82

*P value= 0.03

Figure 10: Serum levels of sRAGE in diabetic patients with hearing loss compared to diabetic patients with normal hearing at high frequency sounds.


Conclusion: Type 1 diabetic patients 60 years old or youngermay show early high‐

frequency hearing loss similar to early presbycusis.

High‐frequency hearing loss is significantly and positively associated with age, duration of DM, and presence of peripheral neuropathy.

Diabetic patients between 40 and 60 years old with duration of DM ≥35 years have significantly higher hearing thresholds at 6000 and 8000 Hz compared to age matched non‐diabetic control subjects.


Conclusion: sRAGE blood levels are significantly lower in type 1 diabetic patients who

have hearing loss compared with diabetic patients with normal hearing.

This may support the hypothesis that sRAGE, by limiting the interaction of AGE with cell membrane RAGE, can provide protection against AGE toxicity.


R&B Medical Group

Howard Lippes, MD, FACPJohn Hall, MD, FACPKara Brenton, RNHannan Imam, PA

Acknowledgment

Sisters of Charity HospitalHenry Woodman, MD, FACPJames Stephen, MDSara MacLeod, MD

Clinical and Translational Research Center (CTRC)Husam Ghanim, Ph.D

Department of Communicative Disorders and Sciences/ UBNancy A. Stecker, Ph.D

diabetes and hearing loss - catholic health · type 1 diabetic patients 60 years old or younger may...

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