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Audiological profile in diabetes mellitus in correlation with inflammatory markers.

INTRODUCTION: Diabetes mellitus is a common medical disorder world-wide. Diabetes is derived from the Greek WORD "siphon" and implies that lot of urine is made. The second term "mellitus" comes from the Latin word Mel which means honey, and was used because the urine was sweet. World-wide around 150 million people suffer from diabetes mellitus and without preventive measures it is expected to reach 300 million by the year 2025.

Diabetes mellitus is a medical disease characterized by high blood sugar levels that result from defective insulin secretion, or action, or both. Normally blood glucose levels are tightly controlled by insulin, a hormone produced by the beta cells in the islets of Langerhans in the pancreas. Insulin lowers the blood glucose levels. When the blood glucose elevates, insulin is released from the pancreas to normalize the glucose levels. In patients with diabetes, the absence or insufficient production of insulin causes hyperglycemia.

Diabetes mellitus is of two types-types 1 and Type 2. In type 1 diabetes mellitus the beta cells degenerate and so the body cannot make enough insulin of its own. In type 2 diabetes mellitus beta cells produce insulin but there is resistance in cells to insulin. Diabetes is a chronic medical condition, meaning that although it can be controlled, it lasts a life time. Over time, diabetes can lead to retinopathy, nephropathy and neuropathy.

This type of damage is the result of injury to smaller vessels, referred to as Micro vascular Disease. Diabetes is also an important factor in accelerating the hardening and narrowing of arteries-Atherosclerosis leading to strokes, coronary artery disease, and other large blood vessel disorder, referred to as Macro-Vascular disease. The Cochlea and Auditory nerve can also be affected by raised blood sugar levels, possibly a micro vascular complication of diabetes. Sensorineural hearing loss accounts for about 90% of all hearing loss.

This is sometime also called Nerve Deafness although the term is not entirely accurate, leaving out disorders of the hair cells of the cochlea. The relationship between diabetes mellitus and hearing loss has been debated for many years. Jordao in 1857 reported a case of diabetic patient with hearing loss (1, 2, 3) and Edgar in 1915 (4) was the first to report a high frequency hearing loss in a diabetic patient.

MATERIALS AND METHODS: A 2 year prospective study of audio-logical profile in diabetic patients and its correlation with inflammatory markers was done in 35 diabetic patients attending the Diabetic and ENT OPD at RMMCH between 2012-2014. Patients with diabetes mellitus on oral hypoglycaemic agents were subjected to: Pure Tone Audiometry using Arphi Audiometer-Model 700 MK4 and Inflammatory markers study.

INCLUSION CRITERIA: All patients with type 2 diabetes mellitus on insulin or oral hypoglycaemic drugs between the ages of 15-50 years.

EXCLUSION CRITERIA: Previous history of ear discharge, noise trauma and recurrent upper respiratory tract infection and conductive hearing loss. Patients were followed up serially after the diagnosis at 1st, 2nd, 3rd, and 4th and 6 months for control of diabetic status and their audio-logical profile. The same was correlated with the inflammatory markers. The results were statistically analyzed. The audiograms were also analyzed by an outside audio-metrician not involved in the study to overcome bias in results. Inflammatory marker study was done by ELISA method.

ELISA Test: ELISA is the abbreviation for Enzyme Linked Immuno Sorbent Assay. The ELISA technique are widely used not only for hormone measurements but also for detecting growth factors, tumor markers, bacterial or viral antigens and antibodies against microbes and other antigens or antibodies in biological fluids. Antigen Detection by ELISA: Specific antibody is fixed to the wall of micro titer plate. The patient's serum is added to the well, and incubated for 30minutes at 37 [degrees]C.

By the time, if the serum contains antigen, it is fixed on the antibody. Excess antigen and other unwanted proteins are washed out. Then specific antigen tagged with horse- radish peroxidase is added. If the antigen is already fixed, the antibody. HRP conjugate will be fixed in the well. Then the colour reagent containing hydrogen peroxidase ([H.sub.2][O.sub.2]) and diaminobenzidine (DAB) are added.

[ILLUSTRATION OMITTED]

This is known as "SANDWICH ELISA". Development of a brown colour indicates that the antigen is originally present in patient's serum. Therefore intensity of the colour may be measured, from which the concentration of antigen is calculated.

STATISTICAL METHODS: P-value was found out by ANOVA method to find out the significance of auditory thresholds between various categories of parameters.

RESULTS:
Table 1: Distribution of age

RESULTS:

Age Number of Patients Percentage

21 to 30 Years 2 5.71
31 to 40 Years 6 17.14
41 to 49 Years 27 77.14

TOTAL 35 100.0


In this study the maximum number of patients with hearing loss was in the age group between 41-49 accounting for 77.14%.

[GRAPHIC OMITTED]

Females were more affected by hearing loss in our study accounting for 77.14%.

[GRAPHIC OMITTED]

In our study the hearing loss in diabetes mellitus was predominantly bilateral, symmetrical, sensor neural type hearing loss affecting the higher frequencies.

In 77.14% of our patients the duration of diabetes mellitus from diagnosis was less than 5 years.

NS-Not Significant P>0.05 S-Significant P <0.05. The duration of diabetes mellitus is compared with the hearing loss in db in all frequencies and is not statistically significant (P>0.05 not significant by ANOVA method)

NS- Not Significant P >0.05 S-Significant (P<0.05)

In the first month auditory thresholds at all frequencies had no correlation with severity of diabetes in both fasting and post prandial blood sugar levels(P>0.05 not significant by ANOVA method).

NS- Not Significant P>0.05 S-Significant. After 6 months of treatment the auditory threshold improved at higher frequencies (4000,6000,8000 Hz) in both fasting and postprandial blood sugar levels (P<0.05 significant by ANOVA method)

S-Significant NS-Non Significant.

P value<0.05 P value 0.05.

The fasting and post prandial blood sugars of 1st and 6th Month. In our study the control of diabetes leading to improvement in hearing thresholds was significant only in high frequencies P value <0.05 by ANOVA method.

CORRELATION ANALYSIS:
Table 11: Correlation between hearing loss and inflammatory markers

 TNF [alpha] IL-6 CRP FREE RADICALS/T BARS

Hearing loss in 0.033 0.095 0.135 0.019
all frequencies


The hearing loss in all frequencies were correlated with the inflammatory markers (TNF[alpha],IL 6,CRP and Free radicals) and a positive relation was found.

Highly Significant P<0.01

The hearing loss in all frequencies is compared with the inflammatory markers and is found to be statistically significant <0.01) by ANOVA method.

DISCUSSION: There are various studies that have been done which shows high frequency sensorineural hearing loss and elevated inflammatory markers (TNF[alpha], IL-6, CRP) to be associated with patients who are having diabetes mellitus. In the present study the maximum number of patients with hearing loss was in the age group between 41-49 years (77.14%) followed by the age group 3140(17.14) and was comparable with other studies. Females were more affected in the ratio 3.3:1.

The type of hearing loss was predominantly bilateral, symmetrical, and sensori-neural type affecting the higher frequencies in diabetes mellitus. In 77.14% of our patients the duration of diabetes mellitus was less than 5 years. The duration of diabetes mellitus had no significant correlation with hearing loss (P>0.05-NS). In the present study, control of diabetes mellitus evidenced by reduced FBS and PPBS levels lead to improvement in hearing thresholds and was significant only in high frequencies (4000, 6000, 8000Hz) (P<0.05).

In our study of 35 patients, we found that there is significant increase in inflammatory markers in all cases (p>0.01) and a positive correlation was found between inflammatory markers and hearing loss. Free radicals are not so significantly increased when compared to inflammatory markers in cases of diabetes associated with deafness.

SUMMARY AND CONCLUSION: Sensori-neural hearing loss in diabetes mellitus more commonly affected patients in the age group between 41-49 years accounting for 77.14%.Females were more affected in our study in the ratio of 3.3:1. Hearing loss was predominantly bilaterally symmetrical and of sensori-neural type affecting mainly the higher frequencies. In 77.1% of our patients the duration of diabetes mellitus was less than 5 years. However there was no correlation between duration of diabetes mellitus and hearing loss.

Control in the severity of diabetes mellitus lead to improvement in hearing thresholds which was spastically significant at higher frequencies. There was positive correlation between inflammatory markers and hearing loss in diabetes mellitus however inclusion of elevated inflammatory markers as a prognostic index to assess the degree of deafness and its relation to microangiopathy needs further studies and its role in prevention of diabetes mellitus needs further evaluation.

DOI: 10.14260/jemds/2014/3676

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V. U. Shanmugam [1], Ruta Shanmugam [2], R. G. Mariappan [3], Balaji Swaminathan [4], Srikanth Nandipati [5], Praveen John [6]

AUTHORS:

[1.] V. U. Shanmugam

[2.] Ruta Shanmugam

[3.] R. G. Mariappan

[4.] Balaji Swaminathan

[5.] Srikanth Nandipati

[6.] Praveen John

PARTICULARS OF CONTRIBUTORS:

[1.] Professor, Department of ENT, Rajah Muthiah Medical College.

[2.] Professor & HOD, Department of ENT, Rajah Muthiah Medical College.

[3.] Professor, Department of ENT, Rajah Muthiah Medical College.

[4.] Reader, Department of ENT, Rajah Muthiah Medical College.

[5.] Lecturer, Department of ENT, Rajah Muthiah Medical College.

[6.] Post Graduate, Department of ENT, Rajah Muthiah Medical College.

NAME ADDRESS EMAIL ID OF THE

CORRESPONDING AUTHOR:

Dr. Praveen John,

# 324, Priya Illam,

1st Cross Left, Muthiah Nagar,

Chidambaram-608001,

Tamil Nadu.

Email: prvnjhn@yahoo.co.in

Date of Submission: 04/10/2014.

Date of Peer Review: 05/10/2014.

Date of Acceptance: 20/10/2014.

Date of Publishing: 22/10/2014.
Table 2: Distribution of gender

Gender Number of patients Percentage

Male 8 22.86
Female 27 77.14

TOTAL 35 100

Table 3: Type of hearing loss

Type of hearing Number of low Number Of Mid Number Of High
loss frequency loss frequency loss frequency loss

Sensorineural 5 30 35
hearing loss B/L

Mixed hearing 30 5 --
loss B/L

TOTAL 35 35 35

Table 4: Distribution of duration of diabetes mellitus

Duration of diabetes Number of patients Percentage
mellitus

0-5 Years 27 77.1
6-10 Years 7 20
11-15 Years 0 0
Above 15 Years 1 2.9

TOTAL 35 100

Table 5: Duration of diabetes mellitus with hearing loss

 Duration of diabetes mellitus with
 hearing loss in decibels

Frequency 0-5 Years 6-10 Years 11-15 Years
in Hertz (n=27) (n=7) (n=0)

500 54.21 [+ or -] 11.46 53.44 [+ or -] 15.64 --
1000 59.42 [+ or -] 14.62 59.12 [+ or -] 13.63 --
2000 62.64 [+ or -] 13.54 61.59 [+ or -] 11.48 --
3000 56.34 [+ or -] 12.37 55.36 [+ or -] 12.56 --
4000 60.00 [+ or -] 13.81 60.64 [+ or -] 13.81 --
6000 62.96 [+ or -] 15.29 62.50 [+ or -] 15.86 --
8000 64.72 [+ or -] 16.18 64.46 [+ or -] 17.59 --

 Duration of diabetes mellitus
 with hearing loss in decibels

Frequency Above 15 Years P value
in Hertz (n=1) (ANOVA)

500 53.64 [+ or -] 0.00 0.264(NS)
1000 58.94 [+ or -] 0.00 0.642(NS)
2000 62.16 [+ or -] 0.00 0.112(NS)
3000 67.50 [+ or -] 0.00 0.658(NS)
4000 70.00 [+ or -] 0.00 0.269(NS)
6000 85.00 [+ or -] 0.00 1.006(NS)
8000 82.50 [+ or -] 0.00 0.571(NS)

Table 6: Auditory thresholds in Decibels at various levels
of FBS-1ST Month

 Severity of diabetes mellitus with hearing
 loss in db (Mean [+ or -] SD)

Frequency 50-100mg/ 101-150mg/ 151-200mg/
in Hertz dl (n=5) dl (n=18) dl (n=5)

500 -- 54.21 [+ or -] 11.64 54.62 [+ or -] 12.45
1000 -- 55.64 [+ or -] 10.21 55.16 [+ or -] 11.64
2000 -- 56.94 [+ or -] 13.54 56.26 [+ or -] 12.11
3000 -- 57.50 [+ or -] 12.59 59.75 [+ or -] 12.61
4000 -- 61.18 [+ or -] 15.49 59.75 [+ or -] 12.61
6000 -- 65.29 [+ or -] 16.88 68.75 [+ or -] 16.13
8000 -- 67.65 [+ or -] 15.99 68.00 [+ or -] 17.39

 Severity of diabetes
 mellitus with hearing
 loss in db
 (Mean [+ or -] SD)

Frequency Above200mg/ P value
in Hertz dl (n=7) by ANOVA

500 54.55 [+ or -] 12.65 0.612(NS)
1000 55.62 [+ or -] 11.22 0.882(NS)
2000 56.33 [+ or -] 12.64 0.112(NS)
3000 58.13 [+ or -] 9.23 0.894(NS)
4000 58.13 [+ or -] 9.23 0.910(NS)
6000 63.44 [+ or -] 14.45 0.773(NS)
8000 65.94 [+ or -] 17.83 0.962(NS)

Table 7: Auditory thresholds in decibels at various levels
of PPBS 1st Month

 Severity of diabetes mellitus
 with hearing loss in decibels

Frequency 100-150mg/ 151-200mg/
 dl(n=6) dl(n=1)

500 55.31 [+ or -] 9.11 55.64 [+ or -] 10.32
1000 56.64 [+ or -] 10.34 56.21 [+ or -] 11.12
2000 57.24 [+ or -] 9.64 57.64 [+ or -] 9.66
3000 56.25 [+ or -] 9.97 52.73 [+ or -] 9.65
4000 60.00 [+ or -] 10.95 55.23 [+ or -] 10.98
6000 62.92 [+ or -] 9.54 60.23 [+ or -] 12.77
8000 65.42 [+ or -] 10.54 62.05 [+ or -] 10.17

 Severity of diabetes mellitus
 with hearing loss in decibels

Frequency 201-250mg/ Above250mg/ P value
 dl(n=2) dl (n=9) by ANOVA

500 55.21 [+ or -] 11.62 55.11 [+ or -] 10.22 0.321(NS)
1000 56.11 [+ or -] 11.26 56.64 [+ or -] 10.11 0.642(NS)
2000 57.99 [+ or -] 10.42 57.99 [+ or -] 10.64 0.112(NS)
3000 61.94 [+ or -] 14.57 62.78 [+ or -] 10.03 0.177(NS)
4000 64.72 [+ or -] 18.22 64.72 [+ or -] 16.02 0.395(NS)
6000 71.39 [+ or -] 19.41 69.17 [+ or -] 18.11 0.390(NS)
8000 72.22 [+ or -] 20.67 70.28 [+ or -] 20.71 0.524(NS)

Table 8: Auditory thresholds in decibels at various
levels of FBS 6th month

 Severity of diabetes mellitus with
 hearing loss in decibels

Frequency 50-100mg/ 101-150mg/
in Hertz dl(n=5) dl(n=18)

500 61.61 [+ or -] 10.34 61.22 [+ or -] 9.97
1000 59.98 [+ or -] 9.98 59.79 [+ or -] 9.78
2000 60.64 [+ or -] 10.64 61.14 [+ or -] 10.11
3000 59.50 [+ or -] 11.24 62.36 [+ or -] 14.69
4000 61.50 [+ or -] 13.18 63.47 [+ or -] 13.62
6000 52.00 [+ or -] 12.55 54.72 [+ or -] 11.08
8000 55.00 [+ or -] 13.69 56.53 [+ or -] 12.55

 Severity of diabetes mellitus with
 hearing loss in decibels

Frequency 151-200mg/ Above 200mg/ P value
in Hertz dl(n=7) dl(n=7) by ANOVA

500 61.49 [+ or -] 10.99 62.64 [+ or -] 11.14 0.64(NS)
1000 59.97 [+ or -] 10.64 59.12 [+ or -] 10.11 0.421(NS)
2000 62.34 [+ or -] 9.64 60.21 [+ or -] 9.12 0.342(NS)
3000 70.00 [+ or -] 18.37 76.43 [+ or -] 16.76 0.159(NS)
4000 69.50 [+ or -] 18.91 80.00 [+ or -] 19.15 0.010(S)
6000 65.00 [+ or -] 8.48 67.14 [+ or -] 8.09 0.013(S)
8000 67.00 [+ or -] 14.40 72.14 [+ or -] 13.18 0.041(S)

Table 9: Auditory thresholds in decibels at various levels
of PPBS-6th Month

 Severity of diabetes mellitus with
 hearing loss in db(Mean [+ or -] SD)

Frequency 100-150mg/ 151-200mg/
in Hertz dl(n=6) dl(n=11)

500 54.34 [+ or -] 11.21 55.21 [+ or -] 10.42
1000 55.36 [+ or -] 9.64 55.14 [+ or -] 9.24
2000 56.33 [+ or -] 11.64 55.31 [+ or -] 10.22
3000 57.00 [+ or -] 10.59 58.75 [+ or -] 11.26
4000 62.50 [+ or -] 11.84 59.69 [+ or -] 14.54
6000 65.75 [+ or -] 10.93 64.06 [+ or -] 16.03
8000 64.50 [+ or -] 12.36 67.19 [+ or -] 16.00

 Severity of diabetes mellitus with
 hearing loss in db(Mean [+ or -] SD)

Frequency 201-250mg/ Above250mg/ P value
in Hertz dl(n=9) dl(n=9) by ANOVA

500 55.64 [+ or -] 9.64 55.21 [+ or -] 10.36 0.242(NS)
1000 56.64 [+ or -] 10.31 56.11 [+ or -] 11.45 0.452(NS)
2000 55.11 [+ or -] 9.64 55.64 [+ or -] 10.42 0.642(NS)
3000 55.91 [+ or -] 14.46 64.17 [+ or -] 8.01 0.565(NS)
4000 58.64 [+ or -] 17.80 64.17 [+ or -] 12.81 0.014(S)
6000 64.55 [+ or -] 19.13 70.83 [+ or -] 18.82 0.012(S)
8000 66.27 [+ or -] 20.01 67.50 [+ or -] 19.43 0.044(S)

Table 10: Control of diabetes mellitus and hearing

 Number Diabetes Mean Mean Hearing loss
 [+ or -] SD in decibels

 1st Month

FBS 1st 35 158.14 [+ or -] Low 55.31 [+ or -]
Month 67.55 16.34

PPBS 1st 35 225.14 [+ or -] Mid 59.41 [+ or -]
Month 93.34 15.64

FBS 6th 35 159.23 [+ or -] High 64.52 [+ or -]
Month 42.96 18.84

PPBS 6th 35 200.66 [+ or -]
Month 61.6

 Mean Hearing loss F-Value P Value
 in decibels

 6th Month

FBS 1st 55.64 [+ or -] 1.642 0.642(NS)
Month 14.64

PPBS 1st 58.64 [+ or -] 1.483 0.242(NS)
Month 15.21

FBS 6th 61.46 [+ or -] 61.925 0.001(S)
Month 25.6

PPBS 6th
Month

Table 12: ANOVA TABLE

 N Mean SD F-VALUE P-VALUE

Hearing loss in 35 63.07 24.20 45.711 0.001(S)
all frequencies

TNF [alpha] 35 12.51 23.31

IL-6 35 40.04 36.84

CRP 35 6.90 8.84

Free radicals/ 35 2.17 1.04
T bars

TOTAL 175 24.94 32.26
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Title Annotation:ORIGINAL ARTICLE
Author:Shanmugam, V.U.; Shanmugam, Ruta; Mariappan, R.G.; Swaminathan, Balaji; Nandipati, Srikanth; John, P
Publication:Journal of Evolution of Medical and Dental Sciences
Article Type:Clinical report
Date:Oct 23, 2014
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