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https://doi.org/10.1007/s00125-018-4766-0
SHORT COMMUNICATION
Abstract
Aims/hypothesis Type 2 diabetes mellitus has been implicated as a risk factor for hearing loss, with possible mechanisms including
microvascular disease, acoustic neuropathy or oxidative stress. A few small studies have examined the longitudinal association
between type 2 diabetes and hearing loss, but larger studies are needed. Our objective was to examine whether type 2 diabetes
(including diabetes duration) is associated with incident hearing loss in two prospective cohorts: Nurses’ Health Studies (NHS) I and II.
Methods We conducted a longitudinal study of 139,909 women to examine the relationship between type 2 diabetes and the risk
of self-reported incident hearing loss. A physician-diagnosis of diabetes was ascertained from biennial questionnaires. The
primary outcome was hearing loss reported as moderate or worse in severity (categorised as a ‘moderate or severe’ hearing
problem, or ‘moderate hearing trouble or deaf’) on questionnaires administered in 2012 in NHS I and 2009 or 2013 in NHS II.
Cox proportional hazards regression was used to adjust for potential confounders.
Results During >2.4 million person-years of follow-up, 664 cases of moderate or worse hearing loss were reported among those
with type 2 diabetes and 10,022 cases among those without type 2 diabetes. Compared with women who did not have type 2
diabetes, those with type 2 diabetes were at higher risk for incident moderate or worse hearing loss (pooled multivariable-adjusted
HR 1.16 [95% CI 1.07, 1.27]). Participants who had type 2 diabetes for ≥8 years had a higher risk of moderate or worse hearing
loss compared with those without type 2 diabetes (pooled multivariable-adjusted HR 1.24 [95% CI 1.10, 1.40]).
Conclusions/interpretation In this large longitudinal study, type 2 diabetes was associated with a modestly higher risk of
moderate or worse hearing loss. Furthermore, longer duration diabetes was associated with a higher risk of moderate or worse
hearing loss.
Abbreviations
AMED Alternate Mediterranean diet
Sharon G. Curhan and Gary C. Curhan are joint senior authors. FPG Fasting plasma glucose
Electronic supplementary material The online version of this article NHS Nurses’ Health Study
(https://doi.org/10.1007/s00125-018-4766-0) contains peer-reviewed but
unedited supplementary material, which is available to authorised users.
Because prospective data are limited, we examined the re- A confirmed diagnosis of type 2 diabetes was defined as:
lationship between type 2 diabetes and incident hearing loss in (1) an elevated fasting plasma glucose (FPG) concentration
the Nurses’ Health Studies (NHS) I and II (n = 139,909). We and at least one classic symptom related to diabetes; (2) at
also assessed whether longer duration of disease was associ- least two elevated plasma glucose measurements on different
ated with a higher risk of hearing loss. occasions, in the absence of symptoms; or (3) treatment with
blood glucose-lowering medications. A probable diagnosis of
type 2 diabetes was defined as self-reported diabetes, along
Methods with one of the following: (1) elevated plasma glucose mea-
sured on one occasion but no symptoms or drug therapy; or
Study participants NHS I and NHS II are prospective cohort (2) classic symptoms and glycosuria. In both cohorts, infor-
studies where participants have been followed with biennial mation on type 2 diabetes was updated every 2 years.
questionnaires, eliciting information on diet, lifestyle and var-
ious health outcomes, with a follow-up of >90% of the eligible Ascertainment of diabetes duration In NHS I and NHS II, we
person-time. excluded individuals with prevalent diabetes before 1976 (n =
We limited the analysis to those women who provided 288) and before 1989 (n = 499), respectively. We included
information on their hearing on the 2012 (NHS I), 2009 and/ women with incident type 2 diabetes diagnosed between
or 2013 (both NHS II) questionnaires. We excluded women 1976 and 1984 in NHS I.
who reported a hearing problem that started before baseline in
the NHS I (1984) and NHS II (1995) and women who report- Ascertainment of hearing loss The primary outcome was self-
ed a history of cancer other than non-melanoma skin cancer. reported moderate or worse hearing loss. In NHS I, informa-
The NHS I/II were approved by the Institutional Review tion was obtained from the 2012 long-form questionnaire in
Board. The Institutional Review Board allows for the return of which participants were asked, ‘Do you have a hearing prob-
questionnaires as implied consent. lem?’ (response options: none, mild, moderate, severe), and if
so, at what age a change in hearing was first noticed. In NHS
Ascertainment of type 2 diabetes Women who reported a II, information was obtained from the 2009 and 2013 ques-
physician-diagnosis of diabetes on baseline or biennial ques- tionnaires. In the 2009 long-form questionnaire, participants
tionnaires were sent supplementary questionnaires to catego- were asked, ‘Do you have a hearing problem?’ (response op-
rise reported causes: type 1 diabetes, type 2 diabetes (possible, tions: no, mild, moderate, severe), and ‘At what age did you
probable, definite/confirmed), gestational diabetes, impaired first notice a change in your hearing?’ In the 2013 main ques-
glucose tolerance and secondary diabetes. The confirmation tionnaire, participants were asked, ‘Which best describes your
of diabetes in NHS I and NHS II has been described in detail hearing?’ (response options: excellent, good, a little hearing
[4, 5]. We included only women who had a confirmed or trouble, moderate hearing trouble, deaf), and ‘Have you no-
probable diagnosis of type 2 diabetes. ticed a change in your hearing?’ If the response to the latter
Diabetologia
was ‘Yes’, participants were asked, ‘At what age did you first worse hearing loss and mild hearing loss in each cohort, and
notice a change in your hearing?’ then pooled the multivariable-adjusted HRs. We then exam-
A priori, we chose to examine the incidence of self- ined the association between hearing loss and duration of type
reported moderate or worse hearing loss to minimise misclas- 2 diabetes.
sification. In a validation study of self-reported hearing loss, We used backward selection, with type 2 diabetes and co-
compared with audiometrically measured hearing loss, the variates as time-dependent variables, and a p value threshold
sensitivity of a single question to detect moderate or worse of <0.10 for retaining covariates. For consistency, we retained
hearing loss (classified by audiometry as better ear-pure tone the following covariates in all models: age, AMED score,
average [(PTA)0.5,1,2,4 kHz] >40 dB) among women aged less waist circumference, BMI, physical activity, hypertension, tin-
than 70 years was 95%, and the specificity was 65% [6]. As a nitus, paracetamol use, ibuprofen use and race. We tested for
secondary outcome, we also assessed the incidence of mild collinearity between age and duration of type 2 diabetes in
hearing loss. each cohort; Spearman’s correlation coefficients were < 0.2
when tested at multiple time points. SAS software, version
Ascertainment of covariates Covariate data were obtained and 9.4 (Cary, NC, USA) was used for all analyses.
updated from biennial questionnaires. In this analysis, we con-
sidered the following covariates: age; race; tinnitus; BMI;
waist circumference; alcohol consumption (g/day); physical Results
activity (quintiles of metabolic equivalents of task [METs]/
week); smoking (never, past, current smoker); hypertension; There were 936 participants with type 2 diabetes at baseline
frequent use of non-steroidal anti-inflammatory drug and 7009 women who developed type 2 diabetes during fol-
(NSAIDs), aspirin and paracetamol (also known as acetamin- low-up. During 2,418,720 person-years of follow-up, 664 in-
ophen); and alternate Mediterranean diet (AMED) scores (a cident cases of moderate or worse hearing loss developed
healthy dietary pattern inversely associated with hearing loss) among women with type 2 diabetes and 10,022 cases in those
[7]. without type 2 diabetes (Table 1). The pooled multivariable-
adjusted HR for moderate or worse hearing loss in those with
Statistical analysis Analyses were performed prospectively, type 2 diabetes was 1.16 (95% CI 1.07, 1.27) compared with
with person-time allocated according to exposure status (type individuals without diabetes.
2 diabetes) at the start of each follow-up period. Participants There was a higher risk of moderate or worse hearing loss
were censored at the reported onset of hearing loss or new in those participants who had type 2 diabetes for 8 or more
cancer diagnosis. years compared with those without type 2 diabetes (pooled
We used Cox proportional hazards regression analysis to multivariable-adjusted HR 1.24 [95% CI 1.10, 1.40; Table 2).
estimate the HR of moderate or worse hearing loss. Women There was no statistically significant interaction with age or
who reported a history of impaired FPG, gestational diabetes BMI (data not shown).
or secondary diabetes contributed follow-up time as non- Baseline characteristics of participants are shown in ESM
diabetic participants and re-entered the analysis if they subse- Table 1. In a secondary analysis, type 2 diabetes was associ-
quently developed confirmed or probable type 2 diabetes. ated with a slightly higher risk of mild hearing loss (multivar-
Women who reported mild hearing loss on the 2009 NHS II iable-adjusted HR 1.08 [95% CI 1.01, 1.14]) compared with
questionnaire were excluded but re-entered the analysis if they no type 2 diabetes (ESM Table 2). The cohort-specific results
subsequently reported moderate or worse hearing loss in the for the relationship between duration of diabetes and the risk
2013 questionnaire. We investigated the risk of moderate or of moderate or worse hearing loss are shown in ESM Table 3.
Table 1 Age-adjusted and multivariable-adjusted HRs for moderate or worse hearing loss among women in NHS I/II with type 2 diabetes
No type 2 diabetes Type 2 diabetes No type 2 diabetes Type 2 diabetes No type 2 diabetes Type 2 diabetes
Table 2 Pooled age-adjusted and multivariable-adjusted HRs for risk of moderate or worse hearing loss based on duration of type 2 diabetes among
women in the NHS I/II
Variable No type 2 diabetes 0 to <4 years duration 4 to <8 years duration ≥8 years duration
Exposure: duration of type 2 diabetes in years; outcome: moderate or worse hearing loss
a
Covariates: AMED score, waist circumference, BMI, physical activity, hypertension, tinnitus, paracetamol use, ibuprofen use and race
Contribution statement All authors contributed to this work. All authors 8. Curhan SG, Eavey RD, Wang M, Stampfer MJ, Curhan GC (2013)
made substantial contributions to the conception and design, acquisition Body mass index, waist circumference, physical activity, and risk of
of data, or analysis and interpretation of data. All authors participated in hearing loss in women. Am J Med 126(12):1142.e1-8. https://doi.
drafting the article and revising it critically for important intellectual con- org/10.1016/j.amjmed.2013.04.026
tent. All authors give their final approval for this version of the manuscript 9. Loffredo L, Martino F, Carnevale R et al (2012) Obesity and hy-
to be published. GC is responsible for the integrity of the work as a whole. percholesterolemia are associated with NOX2 generated oxidative
stress and arterial dysfunction. J Pediatr 161(6):1004–1009. https://
doi.org/10.1016/j.jpeds.2012.05.042
10. Aladag I, Eyibilen A, Güven M, Atis O, Erkorkmaz U (2009) Role
of oxidative stress in hearing impairment in patients with type two
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