目的

全球范围内，听力损失（Hearing Loss, HL）患病人数超过15亿人，其负面影响超越健康问题的范畴。糖尿病和高血压与HL之间的关系已研究数十年，但相关结论仍存争议。针对糖尿病和高血压的聚集模式、病程和发病年龄与HL的研究证据有限，且相关危险因素的贡献程度尚未得到充分研究。本研究旨在1）探讨这些主题对低/中、语频及高频HL的影响；2）估算糖尿病和高血压相关危险因素的人群归因分值（Population attributable fraction，PAF）及顺位；3）探究不同特征亚人群中关联强度和归因风险。

方法

本研究是基于中国国民健康调查2023年开展的横断面研究，共有6291名年龄在20至88岁之间的人群纳入本次研究。通过临床诊断的气导纯音听力计测量听力。低/中频（0.5、1和2 kHz）、语频（0.5、1、2和4 kHz）及高频（4、6和8 kHz）HL定义为好耳纯音听阈平均值>20 dB。

（1）糖尿病和高血压与听力损失的关联研究

本研究排除373名曾患有耳部疾病（如中耳炎、传导性HL和耳部手术）的人群，5918例用于分析。 满足以下条件之一则定义为糖尿病：1）自报糖尿病史；2）抗糖尿病药物服用史；3）空腹血糖≥7.0mmol/L。满足以下条件之一则定义为高血压：1）自报高血压史；2）降压药服用史；3）平均收缩压≥140mmHg或舒张压≥90mmHg。糖尿病和高血压的病程通过调查日期－确诊日期计算获得。糖尿病和高血压的发病年龄通过确诊日期－出生日期计算获得。我们采用logistic回归分析估计HL风险的比值比（odds ratio, OR）及95%置信区间（Confidence interval，CI）。

（2）糖尿病和高血压相关危险因素与听力损失的人群归因风险研究

糖尿病和高血压相关危险因素包括社会经济因素（城乡、收入水平、教育程度）、和心血管代谢性危险因素（吸烟、饮酒、糖尿病、高血压、异常体质指数和血脂异常）。基于多因素logistic回归模型通过平均归因分值法估算PAF及95% CI。

结果

（1）糖尿病和高血压与听力损失的关联研究

与非糖尿病/非高血压相比，糖尿病/高血压与低/中频、语频和高频HL均具有显著关联，与高频HL的关联强度最大，其OR值及95%CI分别为1.65 (1.32, 2.07)和1.69 (1.46, 1.95)。与无高血压和糖尿病组相比，仅患高血压组、仅患糖尿病组及糖尿病和高血压共患组与HL间存在显著关联，尤其是高频。糖尿病和高血压共患组风险大于仅患单一疾病组，其与高频HL的OR (95%CI) 为2.29 (1.70, 3.09）。

多因素调整后，高血压长病程和糖尿病长病程与HL风险增加相关，尤其是高频HL。与非糖尿病组相比，对于高频HL，糖尿病病程为0至<5年、5至10年以及超过10年组，其OR和95% CI分别为1.32 (1.00, 1.74) (P=0.0495)、2.06 (1.32, 3.21)和2.85 (1.57, 5.19)。与非高血压组相比，高血压病程为0至<5年、5至10年及10年以上组，对于高频HL，其OR (95%CI) 分别为1.55 (1.31, 1.82）、1.81 (1.38,  2.38) 和2.59 (1.88, 3.57)。

早发糖尿病和早发高血压与HL间无显著性关联。在排除存在血脂异常和高血压者后，我们观察到早发糖尿病（与晚发糖尿病相比）与HL风险增加的显著性关联。如，对于高频HL，其OR和95% CI为10.25 (1.76, 59.74)。

此外，以上关联强度总体上在年轻人、无血脂异常者和女性中更强。

（2）糖尿病和高血压相关危险因素与听力损失的人群归因风险研究

整体来看，17.51%（95%CI [13.63%, 21.39%]）的低/中频HL、17.88%（14.16%, 21.59%）的语频HL及12.93%（9.89%, 15.77%）的高频HL归因于心血管代谢性危险因素。高血压是首要的归因危险因素，其PAF为低/中频5.61%（3.34%, 7.87%）、语频5.23%（3.09%, 7.37%）、高频5.50%（4.19%, 6.80%）。

在年轻人中，糖尿病和高血压相关危险因素对HL的PAF大约是老年人的两倍，如高频：33.72%（29.10%, 38.34%）vs. 12.69%（4.73%, 20.64%）。男性的PAF也高于女性，如高频：29.74%（24.00%, 35.49%）vs. 15.48%（11.24%, 19.72%）。此外，对于女性来说，异常BMI是低/中频和语频HL首要心血管代谢归因危险因素。

结论

在中国江苏和吉林两省人群中，（1）糖尿病和高血压与HL风险存在显著性关联，尤其是与高频HL的关联强度最大。糖尿病和高血压病程较长者患HL的风险更高，且随着病程延长而增加。此外，糖尿病与高血压对HL存在联合作用。高血压是HL的首要归因危险因素。（2）在亚人群中，关联强度和PAF具有异质性。非血脂异常人群中，糖尿病及高血压与HL的关联强度更大，年轻人群中PAF大于老年人群、女性人群中异常BMI是首要的归因危险因素。（3）因为HL是可预防的，对血压、血糖、体重进行控制，将降低糖尿病、高血压、肥胖及HL的风险，考虑到危险因素随时间的累积作用，还需尽早干预，从而达到提高百姓健康水平和生活质量的目的。干预的侧重点可根据人群特点而定，以进一步达到精准预防的目的。

Objective

Hearing loss (HL) is a preventable common disease with over 1.5 billion patients globally, affecting beyond health conditions. The associations of diabetes and hypertension with HL have been studied for decades, but remain controversial. There was limited evidence on co-occurrence, long duration, and early onset of diabetes and hypertension; the contribution of its risk factors has been incompletely studied. We aimed 1) to examine the effect of these issues on speech-, low/mid-, and high-frequency HL; 2) to estimate the attributions of certain preventable cardiometabolic causes and identify the leading attributable risk factors for HL; 3) to explore the strength of association and attributable risk in subgroups with different characteristics.

Methods

We did a cross-sectional study using data from the China National Health Survey. We included 6291 participants aged 20-88 years who completed the audiometric examination and structured questionnaire. The hearing was measured using clinical diagnostic air-conduction pure-tone audiometry. Low/mid-frequency (pure-tone average [PTA] threshold at 0.5, 1, and 2 kHz) speech-frequency (PTA threshold at 0.5, 1, 2, and 4 kHz), and high-frequency (PTA threshold at 4, 6, and 8 kHz) HL were defined as PTA >20 dB hearing loss in the better ear.

The associations of diabetes and hypertension with hearing loss

373 participants with previous ear diseases like otitis media, conductive HL, and ear surgeries were additionally excluded, and the remaining 5918 were used for our analysis. Diabetes was defined based on self-reported physician diagnosis, self-reported treatments for diabetes, or fasting blood glucose ≥7.0 mmol/L. Hypertension was defined based on self-reported physician diagnosis, use of hypertension medications, or an average systolic blood pressure ≥140 mm Hg or an average diastolic blood pressure ≥90 mm Hg. The duration of diabetes and hypertension was calculated by subtracting the date of diagnosis from the date of investigation. The onset age of diabetes and hypertension was calculated by subtracting the date of diagnosis from the date of birth. We did logistic regression analysis to obtain odds ratios (OR) and 95% confidence intervals (CI) for the risk of HL.

The population attributable fraction of diabetes-hypertension related risk factors for hearing loss

The diabetes-hypertension related risk factors include socioeconomic (location, income level, and education level) and cardiometabolic (diabetes, hypertension, dyslipidemia, abnormal BMI, smoking, and drinking) risk factors. We estimated the population attributable fractions (PAF) and 95% confidence interval (CI) using sequential and average method based on multivariable logistic models.

Results

The associations of diabetes and hypertension with hearing loss

Compared to non-diabetic/non-hypertensive individuals, diabetes/hypertension showed significant associations with HL, particularly high-frequency HL, with adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of 1.65 (1.32, 2.07) and 1.69 (1.46, 1.95), respectively. Compared with neither hypertension nor diabetes individuals, the hypertension only, diabetes only, and co-occurrence with both diabetes and hypertension showed significant associations with HL, particularly at high frequency. Co-occurrence of diabetes and hypertension has the strongest association than the single disease group compared with no diabetes and no hypertension, after full adjustment for baseline risks, particularly at high frequency, the ORs and 95% CIs for high-frequency HL was 2.29 (1.70, 3.09).

After full adjustment for related covariates, longer durations of both hypertension and diabetes were associated with increased HL risk, particularly high-frequency HL. Compared with non-diabetic individuals, for high-frequency HL, the ORs and 95% CIs for diabetes duration groups of 0 to <5 years, 5-10 years, and >10 years were 1.32 (1.00, 1.74) (P=0.0495), 2.06 (1.32, 3.21), and 2.85 (1.57, 5.19), respectively. Compared with non-hypertensive individuals, for high-frequency HL, the ORs (95% CI) for hypertension duration groups of 0 to <5 years, 5-10 years, and >10 years were 1.55 (1.31, 1.82), 1.81 (1.38, 2.38), and 2.59 (1.88, 3.57), respectively.

There were no significant associations of early-onset diabetes and hypertension with HL. However, after excluding individuals with dyslipidemia and hypertension, we observed a significant association between early-onset diabetes (compared with late-onset diabetes) and an increased risk of HL (OR and 95% CI of 10.25 [1.76, 59.74] for high-frequency HL).

Moreover, the above-mentioned association strength was generally stronger in younger individuals, those without dyslipidemia, and females.

The population attributable fraction of diabetes-hypertension related risk factors for hearing loss

Overall, 17.51% (95% CI [13.63%, 21.39%]) of low/mid-frequency HL events, 17.88% (95% CI [14.16%, 21.59%]) of speech-frequency HL events, and 12.93% (95% CI [9.89%, 15.77%]) of high-frequency HL events, respectively, were attributable to cardiometabolic risk factors. Hypertension was the leading attributable risk factor among cardiometabolic risk factors, with a PAF of 5.61% (95% CI [3.34%, 7.87%]), 5.23% (95% CI [3.09%, 7.37%]), and 5.50% (95% CI [4.19%, 6.80%]) for low/mid-, speech-, and high-frequency HL, respectively.

The PAFs of selected risk factors for HL were about twice as high in younger than older adults (e.g., 33.72% [29.10%, 38.34%] versus 12.69% [4.73%, 20.64%] at high frequency) and in the male than the female (e.g., 29.74% [24.00%, 35.49%] versus 15.48% [11.24%, 19.72%] at high frequency). In the females, abnormal BMI was the strongest cardiometabolic population attributable risk factor among the females for low/mid- and speech-frequency HL.

Conclusions

Overall, in Chinese population, 1) diabetes and hypertension are significantly associated with the risk of HL, particularly at high frequency. The risk of HL is higher in individuals with a longer duration of diabetes and hypertension, and it increases with the length of the condition. Additionally, there is a joint effect of diabetes and hypertension on HL. Hypertension is the leading attributable risk factor for HL. 2) The strength of the association and PAFs were heterogeneous across subgroups. In the population without dyslipidemia, the association of diabetes and hypertension with HL was stronger. The PAF in the young population was higher than that in the elderly population, and abnormal BMI in female was the main attributable risk factor. 3) Since HL is preventable, controlling blood pressure, blood sugar, and weight can reduce the burden of diabetes, hypertension, obesity, and HL. Considering the cumulative effect of risk factors over time, it is necessary to intervene as early as possible to achieve the purpose of improving the health level and quality of life of the people. The focus of intervention can be determined according to the characteristics of the population to further achieve the purpose of precise prevention.