Do neuropathy and hypertension associated with increased risk of hearing loss among
type 2 diabetic patients?
The aim of this study was to investigate the relation between neuropathy and hearing loss among type 2 diabetes mellitus (T2DM)
Cross sectional study carried on subjects aged between 20 and 60 years who visited the Ear Nose Throat (ENT), diabetic
metabolic syndrome, and Endocrinology outpatient clinics registry of the Medipol International School of Medicine, Medipol Hospital
during the study period from February 2015 to May 2017. Of the total 850 diabetic patients approached, 610 (71.9%), gave their consent.
During the study period, prevalence, hearing, audiological test, family history and medical problems associated with hearing impairment
in middle aged patients were recorded. Two audiometers Grason Stadler GSI 61 and Interacoustics AC40 Clinical audiometer were used to evaluate the hearing loss.
The mean age (± SD, in years) for neuropathy with hearing loss versus normal subjects was 47.7 ±10.2 vs.48.5±9.1. The associated
risk factors were significantly higher in T2DM with hearing loss, hypertension, (32.6% vs 15.7%), tinnitus (40.0% vs 18.0%),
vertigo (59.7% vs 26.8%) and headache (54.9% vs 45.3%), than in normal hearing diabetes. There were statistically significant differences
between hearing impairment versus normal hearing for vitamin D [18.09±7.65 ng/ml vs 22.85±9.00 ng/ml; p<0.001], calcium
(p<0.001), magnesium (p<0.001), phosphorous (p<0.001), ceatinine (p=0.007), cholesterol [(p<0.001), HDL (p<0.001), LDL (p<0.001),
albumin (p=0.010), systolic blood pressure [129.75±10.60 Hg vs 126.73±12.39 Hg; p=0.017] and, diastolic blood pressure [81.09±9.2
mm Hg vs 79.29±7.95 mm Hg; p=0.012] and microalbuminuria (p=0.001). Multivariable logistic regression analysis revealed that
variables for predictors of hearing loss with neuropathy among diabetic patients were vertigo (p<0.001), numbness (p<0.001), hypertension
(p<0.001), duration of DM (p<0.001), head ache (p<0.001), Vitamin D deficiency (p<0.001), sleeping disturbance (p=0.012),
BMI (p=0.033), and cigarette smokers considered at higher risk as a predictors of neuropathy with hearing loss among diabetic patients.
The current study results suggests a strong positive association between neuropathy and hearing impairment among
T2DM. The study confirms that the Hypertensive and diabetic patients have moderately increased risk of future hearing loss.
Premature; Newborn with Asphyxia; Neonatal Hypoxia; Perinatal Anoxia; (fetal distress), Absence of Oxygen at Birth.
Type 2 diabetes mellitus (T2DM), one of the main threats to ageing
population health in the 21st century, is described as a worldwide
epidemic as it affects the health and economy of almost all countries
regardless of socioeconomic status or geographic location .
It is based on high blood glucose, insulin resistance and relative
insulin deficiency. T2DM leads to an increase in the risk of future
cardiovascular disease [2-4] and is the primary reason of mortality
and morbidity in most high-income and developing countries [3-5].
Lifestyle factors, sleep duration, physical activity, regular exercise
and healthy-balanced diet are essential components in prevention
of pre-diabetes [4-5].
Hearing loss and its complications reveal commonly in type 2 diabetes
mellitus (T2DM) [6-8]. A number of studies have attempted to
identify the source of hearing loss in those with DM [9-14]. Several
studies investigated that T2DM leads to side effects of hyperglycemia
which may be retinopathy, neuropathy, nephropathy, vascular
diseases. The several studies reported that hearing impairments
can affect even the simplest tasks of daily life [4,9,17]. The relation
between hearing loss and T2DM among middle aged population
and patients are documented and reported in detailed [11-17]. The aim
of this study was to investigate the relation between neuropathy
and hearing loss among type 2 diabetes mellitus (T2DM) patients.
Subjects and Methods
Cross sectional study carried on subjects aged between 20 and
60 years who visited the Ear Nose Throat (ENT), diabetic metabolic
syndrome, and Endocrinology outpatient clinics registry of
the Medipol International School of Medicine, Medipol Hospital
during the study period from February 2015 to May 2017. IRB
ethical approval for this study was obtained from the Medipol International
School of Medicine, Istanbul Medipol University, and
informed written consent was obtained from patients before the
start of the study.
The current sample size was determined by considering prevalence
rate of 10%-12% impaired hearing loss among diabetes patients in
Istanbul [1,7] assuming 99% confidence interval and 2% bound on
the error of estimation. The minimum sample size detected as 850
subjects. Finally, of the 850 registered with diagnosed diabetes and
showed indications, only 610 (71.7%). agreed to participate this
study at the Medipol International School of Medicine, Istanbul
The patients were considered to have DM if they have a history
of DM and are currently taking oral medications for diabetes.
The World Health Organization (WHO)  and International Diabetes
Federation (IDF)  Bener et al. [4-5] defined DM when fasting
venous blood glucose concentration is equal or higher than
7.0 mmol/L and/or for a 2 hour post-glucose tolerance test (GTT)
venous blood glucose concentration is higher than 11.1 mmol/L. A
glucose meter used to measure fasting blood glucose of all patients.
Oral glucose tolerance test (OGTT) was carried out only if blood
sugar was less than 7 mmol/l. The inclusion criteria comprised of
diagnosis of T2DM in conformity with international standards by
WHO and IDF [2-3], fasting plasma glucose (FPG) higher than 7.0
mmol/L and/or 2 hours postprandial plasma glucose (PPG) or random
plasma glucose higher than 11.1 mmol/L (5). Furthermore,
having regular anti-diabetic drug treatment for at least 3 year, aged
between 20 and 60 years, residence in a city of Istanbul for more
than 3 years-period.
The questionnaire, included socio-demographic, age, gender, nationality,
education level, lifestyle habits, BMI, co-morbid symptoms,
diabetic complications , systolic and diastolic blood pressures,
Clinical biochemistry serum triglyceride, total cholesterol,
high-density lipoprotein (HDL) cholesterol, low density lipoprotein
(LDL) cholesterol, Hemoglobin A1c (HbA1c) and fasting glucose
levels (FPG) were collected.
Physical examination and measurements
BMI was calculated as; weight in kilogram divided by the square
of height in meters. According to WHO criteria , if it is greater
than 25 kg/m2, the subjects were assumed as overweight and
greater than to 30 kg/m2, the subjects were considered as obese
[4-5]. WHO  International Society of Hypertension Writing
Group defined standardized criteria of hypertension when Systolic
Blood Pressure (SBP) ≥ 140 mmHg or Diastolic Blood Pressure
(DBP) ≥90 mmHg or using anti-hypertensive medication.. Patients
who walking or cycling for more than 30 minutes/day were classified
as physically active.
Hearing assessment method:
Pure-tone audiometry is a behavioral test used to measure hearing
sensitivity. This measure involves the peripheral and central
auditory systems [5, 16]. Two clinical digital audiometers (Garson
Stadler GSI 61 and Interacoustics AC40 Clinical audiometer) are
used to be a device for diagnosing hearing loss that are regularly
calibrated to international standards were perform by pre-trained
technicians to test patients’ hearing level. Hearing loss evaluation
described as follows [5,16]: normal (≤ 26 dB) and 26 dB above, hearing
Nerve conduction studies
Motor nerve conduction, F response, and sensory nerve conduction
studies are important methods of documentation and follow
up of nerve functions in Diabetic neuropathy (DN) . Motor
nerve conduction studies are affected in a small subset of DN
(large fibre neuropathies). Even in large diameter fibre neuropathy
nerve conduction velocity (NCV) is insensitive for many pathological
changes known to be associated with DN. The nerve conduction
changes are non specific and key to the diagnosis lies in
excluding other causes or those superimposed on DN. Entrapment
neuropathies are common in diabetic patients and result in unilateral
NCV changes, especially across the entrapped segment of
the nerve. The commonest abnormality in diabetes is reduction
in the amplitude of motor or sensory action potentials because of
axonopathy. Pronounced slowing of NCV suggests demyelinating
neuropathy, which is rarely associated with diabetes; therefore
pronounced slowing of NCV in a diabetic patients should prompt
investigations for an alternative diagnosis. However, the likelihood
of chronic inflammatory demyelinating neuropathy (CIDP)
occurring in diabetic patients is 11 times higher than the normal
population . The NCV is gradually diminished in DN, with estimates of a loss of about 0.5 m/s/y .
The statistical analysis was performed by using the Statistical
Package for Social Sciences [SPSS]. Student’s t test was used
to ascertain the significance of differences between mean values
of two continuous variables and non-parametric Mann-Whitney
tests were used to determine if the results differed, indicating lack of normal distribution of the variable. Chi-square test Fisher’s exact test (two-tailed) were performed to test for differences in proportions of categorical variables between two or more groups.
A multivariate logistic regression model was performed to evaluate
the relation between selected lifestyle factors, neuropathy, and
presence of hearing loss. Confounders were assessed statistically
through change in beta coefficient (crude β-adjusted β), and if the
change was more than 10%, the variable was considered as a confounder
and retained in the final model. Model fit was assessed
through the Hosmer-Lemeshow goodness of fit test. An insignificant
p value for Hosmer-Lemshow indicated that model was good
fit. The cut-off value for significance was chosen as 0.05.
Table 1 shows the socio-demographic characteristics of subjects
with hearing impairment and subjects with normal hearing. Majority
of the hearing loss observed at the age above 45 years old.
Over 90% of the studied patients were frequent users of mobile
phones and approximately 88% of subjects with hearing loss were
watching TV. The mean duration of diabetes was 9.54±5.31 years,
duration of sleep was 5.88±1.25Hours, 27.8% had positive family
history of diabetes Subjects with hearing impairment had worst
risk factor profile than T2DM patients with normal hearing: hypertension,
(32.6% vs 15.7%), tinnitus (40.0% vs 18.0%), vertigo
(59.7% vs 26.8%) and headache (54.9% vs 45.3%), than in normal
hearing diabetes. There was a statistically significant differences
between hearing impairment and normal hearing among T2DM regarding
smoking (p=0.047) and sleeping disturbances (p<0.001).
Comparison of socio-demographic and clinical characteristics between diabetic neuropathy patients with and without hearing loss (N=610)
Table 2 shows baseline chemistry biomarker values among the
two groups. There were statistically significant differences between
hearing impairment versus normal hearing for vitamin
D [18.91±7.65 ng/ml vs 22.85±9.00 ng/ml; p<0.001], calcium
[2.19±0.38 ng/ml vs 1.96±0.14 mmol/L; p<0.001], magnesium
[0.81±0.08 mmol/L vs 0.87±0.14 mmol/L ; p<0.001], phosphorous
[1.42±0.30 mmol /L vs 1.56±0.26 mmol/L; p<0.001], ceatinine
[69.61±14.43 mmol/L vs 75.1±18.72 mmol/L; p=0.007],
cholesterol [3.36±0.67 mmol/L vs 3.07±0.84 mmol/L ; p<0.001],
HDL(1.43±0.90 mmol /L vs 1.21±0.30 mmol/L; p=0.001], LDL
[1.97±0.91 mmol /L vs 1.72±0.70 mmol/L; p=0.001], albumin
[40.0±4.34 mmol/L vs 38.31±3.96 mmol/L; p=0.010], systolic
blood pressure [129.75±10.60 Hg vs 126.73±12.39 Hg; p=0.017]
and, diastolic blood pressure [81.09±9.2 mm Hg vs 79.29±7.95
mm Hg; p=0.012] and microalbuminuria [14.75±2.51 mmol /L vs
7.29±0.96 mmol /L p=0.001].
Clinical biochemistry baseline value among neuropathy hearing loss and normal hearing subject among T2DM patients
Table 3 presents multivariable logistic regression analysis of variables
for predictors of hearing loss with neuropathy among diabetic
patients. Vertigo (OR 10.90 95% CI (8.77-12.81); p<0.001),
numbness (OR 4.60 95%CI (2.48-8.50); p<0.001), hypertension
(OR 2.57 95%CI (1.58-4.29); p<0.001), duration of DM (OR 2.83
95%CI 1.75-4.98; p<0.001), head ache (OR 2.26 95%CI 1.60-
3.12; p<0.001), Vitamin D deficiency (OR 2.05; 95%CI 1.89-
2.23, p<0.001), sleeping disturbance (OR 2.64; 95%CI 2.46-2.84,
p=0.012), BMI (OR 3.10 95%CI 2.50-4.10; p=0.033), and cigarette
smokers (OR 1.90; 95%CI 1.31-273, p=0.042) were considered
at higher risk as a predictors of neuropathy with hearing loss
among diabetic patients.
Multivariate stepwise logistic regression analysis for predictors of hearing loss for neuropathic among T2DM patients (N=638)
The present study has revealed hearing loss as an important consequence
of diabetes associated with the metabolic syndrome and
can be used as a tool for diagnosing patients presenting hearing
loss. Diabetes mellitus is an incurable disease and its management
should be focused on preventing chronic complications associated
with diabetes. Although, hearing loss is usually recognized complication
of diabetes . Therefore, effective control of diabetes is
essential to reduce the incidence of hearing loss in the middle age
group and may affect the quality life.
More recently, Bener et al. [5,6] studied 1,633 diabetic patients and
reported an overall prevalence of peripheral neuropathy was 9.5 %
among them. The analysis showed that the condition was significantly
associated age, being male, consanguinity, family history of
DM and having high blood pressure were significant predictors of
diabetic neuropathy. Similarly, more recently Unmar et al  determined
the prevalence of diabetic peripheral neuropathy (DPN)
and subclinical DPN (sDPN) in 240 patients with T2DM using
nerve conduction study (NCS) as a diagnostic tool. The results
showed that 50.8% of the participants had DPN, and among them,
17.1% had sDPN. sDPN showed significant independent associations
with age, height, HbA1c, presence of atherosclerosis and
The current study results are in concordance t with previous reported
T2DM is related to high-frequency sensorineural hearing
loss  and impaired auditory brainstem responses [9,13]. These results
are in support of the fact that diabetes mellitus may have very
complex repercussion on the auditory pathways.
Usually, the chronic hyperglycemia of diabetes may affect its metabolic
balance and function leading to hearing impairment and
several reported studies have indicated that hearing impairment is
associated with DM (3,9,12). Also, angiopathy and neuropathy of
diabetes have been considered as reasons for hearing impairment
as well . Furthermore, Kang et al  reported that HbA1c level
was associated with hearing impairment in the non-diabetic participants
of current study and the high HbA1c levels might be closely
monitored for hearing loss. A recent meta-analysis concluded that
mild hearing loss is more prevalent in participants with DM  .
The correlation between hearing loss and hypertension can be considered
as an important risk factors. There a number of studies
have indicated the strong association between hypertension-related
hearing loss [6,11,14,19-20]. Most previous studies reported that
hypertension was associated with high-frequency hearing impairment,
and likewise, in this study, we found a positive association
between these variables [6,18-23].
The current study revealed strong association between high prevalence
of hearing impairment, vertigo and tinnitus in T2DM patients
(5-6,20-22). The results of the present study indicate that
neuropathy, hypertension and hearing impairment are commoner
in T2DM patients.
The current study results supports a strong positive association
between neuropathy and hearing impairment among T2DM. The
study confirms that the Hypertensive and diabetic patients have
moderately increased risk of future hearing loss. Meanwhile, hyperglycemia
could be considered as a modifiable risk factor for
diabetic neuropathy, the regularly glycemic control may be the
most effective and important therapy for reducing the incidence
or slowing the progression of neuropathy and improving quality of
life in T2DM patients.
AB designed and supervised the study and was involved in data
collection, statistical analysis the writing of the paper. MÖ, LH, MG and HC were involved in data collection, interpretation of
data and writing manuscript. RAD and MAG reviewed and revised
the manuscript. All authors approved the final version.
Acknowledgment: This work was supported by the Istanbul Medipol
University, International School of Medicine . The authors
would like to thank the Istanbul Medipol University for their support
and ethical approval (Research Protool and IRB# 10840098-
Competing Interests: None to declare
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