Study participants
NHS I and NHS II are prospective cohort studies where participants have been followed with biennial questionnaires, eliciting information on diet, lifestyle and various health outcomes, with a follow-up of >90% of the eligible person-time.
We limited the analysis to those women who provided information on their hearing on the 2012 (NHS I), 2009 and/or 2013 (both NHS II) questionnaires. We excluded women who reported a hearing problem that started before baseline in the NHS I (1984) and NHS II (1995) and women who reported a history of cancer other than non-melanoma skin cancer.
The NHS I/II were approved by the Institutional Review Board. The Institutional Review Board allows for the return of questionnaires as implied consent.
Ascertainment of type 2 diabetes
Women who reported a physician-diagnosis of diabetes on baseline or biennial questionnaires were sent supplementary questionnaires to categorise reported causes: type 1 diabetes, type 2 diabetes (possible, probable, definite/confirmed), gestational diabetes, impaired glucose tolerance and secondary diabetes. The confirmation of diabetes in NHS I and NHS II has been described in detail [4, 5]. We included only women who had a confirmed or probable diagnosis of type 2 diabetes.
A confirmed diagnosis of type 2 diabetes was defined as: (1) an elevated fasting plasma glucose (FPG) concentration and at least one classic symptom related to diabetes; (2) at least two elevated plasma glucose measurements on different 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 with one of the following: (1) elevated plasma glucose measured on one occasion but no symptoms or drug therapy; or (2) classic symptoms and glycosuria. In both cohorts, information on type 2 diabetes was updated every 2 years.
Ascertainment of diabetes duration
In NHS I and NHS II, we excluded individuals with prevalent diabetes before 1976 (n = 288) and before 1989 (n = 499), respectively. We included women with incident type 2 diabetes diagnosed between 1976 and 1984 in NHS I.
Ascertainment of hearing loss
The primary outcome was self-reported moderate or worse hearing loss. In NHS I, information was obtained from the 2012 long-form questionnaire in which participants were asked, ‘Do you have a hearing problem?’ (response options: none, mild, moderate, severe), and if so, at what age a change in hearing was first noticed. In NHS II, information was obtained from the 2009 and 2013 questionnaires. In the 2009 long-form questionnaire, participants were asked, ‘Do you have a hearing problem?’ (response options: no, mild, moderate, severe), and ‘At what age did you first notice a change in your hearing?’ In the 2013 main questionnaire, participants were asked, ‘Which best describes your hearing?’ (response options: excellent, good, a little hearing trouble, moderate hearing trouble, deaf), and ‘Have you noticed a change in your hearing?’ If the response to the latter was ‘Yes’, participants were asked, ‘At what age did you first notice a change in your hearing?’
A priori, we chose to examine the incidence of self-reported moderate or worse hearing loss to minimise misclassification. In a validation study of self-reported hearing loss, compared with audiometrically measured hearing loss, the sensitivity of a single question to detect moderate or worse hearing loss (classified by audiometry as better ear-pure tone average [(PTA)0.5,1,2,4 kHz] >40 dB) among women aged less than 70 years was 95%, and the specificity was 65% [6]. As a secondary outcome, we also assessed the incidence of mild hearing loss.
Ascertainment of covariates
Covariate data were obtained and updated from biennial questionnaires. In this analysis, we considered the following covariates: age; race; tinnitus; BMI; waist circumference; alcohol consumption (g/day); physical activity (quintiles of metabolic equivalents of task [METs]/week); smoking (never, past, current smoker); hypertension; frequent use of non-steroidal anti-inflammatory drug (NSAIDs), aspirin and paracetamol (also known as acetaminophen); and alternate Mediterranean diet (AMED) scores (a healthy dietary pattern inversely associated with hearing loss) [7].
Statistical analysis
Analyses were performed prospectively, with person-time allocated according to exposure status (type 2 diabetes) at the start of each follow-up period. Participants were censored at the reported onset of hearing loss or new cancer diagnosis.
We used Cox proportional hazards regression analysis to estimate the HR of moderate or worse hearing loss. Women who reported a history of impaired FPG, gestational diabetes or secondary diabetes contributed follow-up time as non-diabetic participants and re-entered the analysis if they subsequently developed confirmed or probable type 2 diabetes. Women who reported mild hearing loss on the 2009 NHS II questionnaire were excluded but re-entered the analysis if they subsequently reported moderate or worse hearing loss in the 2013 questionnaire. We investigated the risk of moderate or worse hearing loss and mild hearing loss in each cohort, and then pooled the multivariable-adjusted HRs. We then examined the association between hearing loss and duration of type 2 diabetes.
We used backward selection, with type 2 diabetes and covariates as time-dependent variables, and a p value threshold of <0.10 for retaining covariates. For consistency, we retained the following covariates in all models: age, AMED score, waist circumference, BMI, physical activity, hypertension, tinnitus, paracetamol use, ibuprofen use and race. We tested for collinearity between age and duration of type 2 diabetes in each cohort; Spearman’s correlation coefficients were < 0.2 when tested at multiple time points. SAS software, version 9.4 (Cary, NC, USA) was used for all analyses.