Diabetes-related hearing loss may be sensorineural, whereby a cochlear or neural lesion impedes the transmission of auditory signals to the brain. We hypothesized a biological model in which diabetes contributes to hearing impairment through a vascular or neuropathic mechanism, with either related to hyperglycemia. We tested this hypothesis by evaluating the extent to which controlling for A1C and markers of vascular, neurologic, and inflammatory pathology explained the greater prevalence of hearing impairment among subjects with diabetes (1
Diabetic neuropathy is a heterogeneous disorder that affects sensory and motor nerves and those responsible for autonomic functions (16
). Using monofilament testing on the sole of the foot, a common screening test for diabetic peripheral neuropathy, we found some evidence that peripheral neuropathy is mediating the association with low/mid- but not high-frequency hearing impairment. Using one or more insensate sites to classify insensate foot yields moderately high sensitivity and specificity (~80%) (17
), but the degree of false-positivity may differ by diabetes status. The full effect of a possible mediator (or confounder) may not be detected if a variable is subject to misclassification. Alternatively, our measure may be a poor proxy for neuropathy of the cochlea.
Histopathological evidence of the inner ear suggests that angiopathic mechanisms plays a role in diabetes-related hearing impairment (5
). We used albuminuria as a proxy for cochlear vasculopathy because there is increasing recognition of pathological mechanisms that may be shared by the renal and otological systems (18
). We found a modest effect of controlling for albuminuria, which reduced the association of diabetes with high-frequency hearing impairment (odds ratio 1.67–1.54) but did not affect the association for low/mid-frequency impairment. Previous epidemiological evidence of an association between nephropathy (defined as renal transplant, dialysis, gross proteinuria [≥100 mg/dl], or creatinine ≥1.6 mg/dl) and hearing impairment among subjects with diabetes suggests that the relationship may only be observable with more severe kidney dysfunction (2
We found no evidence that any vascular component to diabetes-related hearing loss is mediated through or confounded by high cholesterol, low HDL, hypertension, or history of cardiovascular events. These results are consistent with studies by Helzner et al. (19
) and Torre et al. (20
), although Torre et al. and Gates et al. (8
) identified an association of cardiovascular disease with cochlear impairment among women, a result we did not replicate. Comparisons should be made cautiously, however, because methodological differences of the previous studies include sampling older individuals, excluding mild cases of hearing impairment, assessing preclinical hearing impairment, and not adjusting for diabetes. The low overall prevalence of peripheral vascular disease and arterial stiffness (3 and 1.5%, respectively) in our relatively young sample may have limited our ability to detect any effect of these macrovascular conditions. Of all cardiovascular disease risk factors that we examined, only BMI attenuated the preliminary associations. Our fully adjusted models do not include BMI, so obesity may be a marker for an inflammatory process that promotes atherosclerosis or neuropathy (6
Our results showing CRP may mediate the association of diabetes with high-frequency hearing impairment suggest the role of an inflammatory mechanism. Inflammatory diseases resulting in sensorineural hearing loss have been described in clinical studies (22
), but to our knowledge, this inflammatory marker has not been correlated with diabetes-related hearing impairment in population-based studies. CRP correlates with cardiovascular risk factors such as obesity, HDL, hypertension, and smoking, which might implicate an atherosclerotic mechanism, so it is unclear why our results do not suggest a role of other vascular measures (24
Glycemia may be a factor in diabetes-related hearing impairment. In our analysis, controlling for A1C diminished the odds ratio for diabetes with low/mid-frequency hearing impairment slightly from 2.03 to 1.90 but attenuated the association with high-frequency hearing impairment to a nonsignificant level. Because most of the variance in A1C is explained by diabetes, interpreting the role of A1C as a mediator may be overstating the case. Glycated hemoglobin has not been associated with hearing impairment, both in a general population and among people with diabetes (2
). However, we previously demonstrated a gradient in hearing impairment prevalence by glycemic status (comparing persons with diabetes, impaired fasting glucose, and normal glucose metabolism), implicating hyperglycemia as a possible mediator of diabetes-related hearing impairment (1
These cross-sectional data limit our ability to distinguish between factors acting as mediators and those operating as confounders, because statistical adjustment for either will diminish the preliminary association. When we derived models adjusting for all independently associated potential mediators or confounders, there remained a 98% increased odds of low/mid-frequency hearing impairment and a 50% increased odds of high-frequency hearing impairment associated with diabetes that was left unexplained. This evidence may indicate that the measures available in these survey data do not adequately represent the neuropathic and microvascular mechanisms we hypothesized and highlights the difficulty in studying the pathology of the inner ear using noninvasive measures. Alternatively, there may exist unexplored biological mechanisms including glucose sensitivity, insulin resistance, temporal bone pathology, more frequent ear infections, or genetic factors that predispose to hearing loss and cosegregate with other genetic factors that predispose to diabetes.
In summary, we find that factors related to neuropathy, microangiopathy, inflammation, and glycemia explain part of the association between diabetes and hearing impairment. Additional studies are necessary to delineate temporal relationships among diabetes, potential mediators, and hearing impairment.