2型糖尿病患者肾损伤程度与听力损害的关系研究
发布时间：2018-08-16 07:51
【摘要】：研究目的:糖尿病是一组以高血糖为特征的代谢性疾病,表现为慢性高血糖、蛋白质及脂肪代谢紊乱,可引起多器官损害和功能障碍,导致一系列的临床并发症,包括心脑血管的大血管病变和微血管病变。其中由糖尿病引起的肾损伤是糖尿病病人最重要的并发症之一,研究发现早期糖尿病患者即可出现尿微量白蛋白。同时,糖尿病患者听力下降的现像近年来受到了越来越多的关注,相关研究逐渐增多。但是有关糖尿病患者肾损伤与听力下降的关系研究甚少,本研究旨在探讨2型糖尿病(T2DM)患者合并不同程度白蛋白尿时听力功能的改变,并讨论T2DM患者基本临床指标变化与听力损害的关系,包括尿微量白蛋白(U-MA)、糖化血红蛋白AlC(HbAlC)、尿素氮(BUN)、血肌酐(Cr)、甘油三酯(TG)、胆固醇(Chol)、低/高密度脂蛋白(LDL-C/HDL-C)、同型半胱氨酸(Hcy)、胱抑素C(Cys-C)及尿酸(UA)等,为糖尿病肾损伤与听力损害的关系提供理论依据。研究方法:收集2型糖尿病合并尿微量白蛋白(T2DM早期肾病期组)、糖尿病合并临床白蛋白尿患者(T2DM临床肾病期组)各30例及健康正常人20例分别进行性别、年龄、体重指数(BMI)、腰臀比、尿微量白蛋白(U-MA)、尿蛋白、糖化血红蛋白A1C(HbAlC)、尿素氮(BUN)、血肌酐(Cr)、胆固醇(Chol)、甘油三酯(TG)、低/高密度脂蛋白(LDL-C/HDL-C)、同型半胱氨酸(Hcy)、胱抑素C(Cys-C)、尿酸(UA)、眼底及神经传导检查测定等基本临床指标的检测和记录。对T2DM早期肾病期组、T2DM临床肾病期组及健康对照组患者分别进行纯音测听、听觉脑干反应、耳声发射及耳蜗电图检测,研究两组不同程度肾脏损害糖尿病患者听力功能状况及听力损害定位。依据纯音测听、听觉脑干反应、耳声发射及耳蜗电图检测结果探讨T2DM早期肾病期组、T2DM临床肾病期组各临床指标与听觉系统各部分损害的关系。研究结果:1.临床基本指标观察结果对照组、T2DM早期肾病组和T2DM临床肾病组之间BMI、U-MA、HbAlC、BUN、Cr、Hcy、Cys-C及UA等指标均有统计学差异(*P0.05),而TG、CHOL、LDL-C和HDL-C等指标未见显著性统计学差异(P0.05);与对照组比较,T2DM早期肾病组和临床肾病组的BMI、U-MA、HbAlC、Cr、Hcy等指标均显著升高,T2DM临床肾病组的BUN、Cys-C及UA显著高于对照组(*P0.05),而T2DM早期肾病组的BUN、Cys-C及UA较对照组虽然有所上升但是未见统计学差异(P0.05)。另外,与T2DM早期肾病组相比较,T2DM临床肾病组中BUN、Cr、Hcy、Cys-C和UA显著升高(#P0.05)。2.视网膜病变和周围神经病变结果分析视网膜病变检测结果发现健康对照组视网膜正常者占19/20,仅1例双眼见病变(1/20),未见单眼病变(0/20);T2DM早期肾病组视网膜正常者占15/30,3例单眼见病变(3/30),12例双眼见病变(12/30);T2DM临床肾病组视网膜正常者占11/30,1例单眼见病变(1/30),18例双眼见病变(18/30)。周围神经病变结果发现各组神经传导减慢者所占比例分别为健康对照组15%,T2DM早期肾病组40%,而T2DM临床肾病组70%,包括左右正中神经传导减慢、左右胫减慢、双侧减慢等情况。3.纯音测听结果与对照组相比较,低频条件下(250 Hz和500 Hz),T2DM早期肾病组和T2DM临床肾病组左耳和右耳的测听结果均未见显著改变;但是从1000 Hz开始,T2DM早期肾病组和T2DM临床肾病组左耳和右耳的听阈结果均显著升高(*P0.05),提示糖尿病患者中高频有听力损失。至8000Hz时,对照组、T2DM早期肾病组和T2DM临床肾病组左耳的听阈分别为(15.25±3.34)dB、(32.33±8.57)dB和(46.33±6.79)dB,右耳的听阈分别为(11.8±2.93)dB、(29.5±7.34)dB和(47.17±6.15)dB。同时,从1000Hz开始,T2DM临床肾病组患者左耳和右耳的听阈值均显著高于T2DM早期肾病组(#P0.05),提示肾损伤程度重的患者高频听力损害加重。4.ABR检测结果T2DM组左耳和右耳Ⅰ波、Ⅲ波、Ⅴ波及潜伏间期Ⅰ—Ⅲ、Ⅲ—Ⅴ、Ⅰ—Ⅴ相较于对照组均明显延迟,差异具有统计学意义(*P0.05)。进一步对比T2DM早期肾病组及T2DM临床肾病组患者左耳和右耳的ABR测试结果,发现T2DM临床肾病组患者左耳在潜伏间期Ⅰ-Ⅲ、Ⅲ-Ⅴ、Ⅰ-Ⅴ较T2DM早期肾病组左耳显著延迟(#P0.05),右耳在潜伏期III波、V波及潜伏间期Ⅰ-Ⅲ、Ⅰ-Ⅴ较T2DM早期肾病组右耳显著延迟(#P0.05)。T2DM临床肾病组患者左耳和右耳在V波潜伏期延迟,其中左耳V波潜伏期为(6.2±0.42)ms,右耳V波潜伏期为(6.24±0.40)ms。5.DPOAE检测结果对照组、T2DM早期肾病组、T2DM临床肾病组三组在各个频率下(0.5,0.75,1.0,1.4,2.0,3.0,4.0,6.0,8.0kHz)左耳和右耳听力异常者所占的百分比大小依次是T2DM临床肾病组T2DM早期肾病组对照组;尤其在中高频时(1.0-4.0 kHz),各组间的差值最大;提示糖尿病患者中高频时(1.0-4.0kHz)的外毛细胞功能损伤最严重,且随着肾脏损伤程度的加重,外毛细胞功能损伤逐渐加重,以中高频时(1.0-4.0kHz)加重最明显。6.耳蜗电图(ECochG)结果分析以SP/AP0.4为结果正常,SP/AP≥0.4为结果异常比较健康对照组、T2DM早期肾病组、T2DM临床肾病组患者左耳和右耳听力情况。结果显示,左耳听力异常比例为健康对照15%、T2DM早期肾病组53.33%、T2DM临床肾病组86.67%;右耳听力异常比例为健康对照20%、T2DM早期肾病组50%、T2DM临床肾病组86.67%。提示随着糖尿病患者肾脏损伤程度的加重,耳蜗电图检测结果正常的左右耳比例明显下降,异常比例值明显升高。研究结论:1、T2DM 伴肾损伤患者 BMI、U-MA、HbAlC、Cr、Hcy、BUN、Cys-C 及 UA等指标均显著升高,尤其是BUN、Cys-C及UA升高最显著,且视网膜病变和周围神经病变明显加重,提示更严重的肾损伤。2、T2DM伴肾损伤患者听力损失主要表现为中高频的听阈升高,且在高频条件下(4000-8000 Hz)听力损失的程度随着肾脏损伤程度的加重而加重。3、T2DM伴肾损伤患者中高频时(1000-4000 kHz)外毛细胞功能损伤较严重,且外毛细胞功能损伤程度随着肾脏损伤程度的加重而加重。4、T2DM伴肾损伤患者高频条件下(4000-8000Hz)多伴有耳蜗内积水,这可能是高频条件下T2DM伴肾损伤患者听力损失加重的原因之一。5、年龄、BMI、HbAlC、Cr、UA、Hcy/TG、CHOL 和 LDL-C 等指标是 T2DM伴肾损伤患者听力损害的风险预测因素。
[Abstract]:Objective: Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia, characterized by chronic hyperglycemia, disorders of protein and fat metabolism, which can cause multiple organ damage and dysfunction, leading to a series of clinical complications, including cardiovascular and cerebrovascular disease and microvascular disease. Among them, diabetic renal injury is caused by glucose. Microalbuminuria is one of the most important complications in patients with diabetes mellitus. At the same time, the phenomenon of hearing loss in diabetic patients has attracted more and more attention in recent years. To investigate the changes of hearing function in patients with type 2 diabetes mellitus (T2DM) complicated with different degrees of albuminuria, and to discuss the relationship between the changes of basic clinical indicators and hearing impairment, including urinary microalbumin (U-MA), glycosylated hemoglobin AlC (HbAlC), urea nitrogen (BUN), serum creatinine (Cr), triglyceride (TG), cholesterol (Chol), low/high density lipid eggs. White (LDL-C/HDL-C), homocysteine (Hcy), cystatin C (Cys-C) and uric acid (UA) provide theoretical basis for the relationship between diabetic nephropathy and hearing impairment. Methods: 30 patients with type 2 diabetes mellitus complicated with urinary microalbumin (early nephropathy group of T2DM), 30 patients with diabetes mellitus complicated with clinical albuminuria (clinical nephropathy group of T2DM) and 30 patients with healthy. 20 healthy people were divided into sex, age, body mass index (BMI), waist-hip ratio, urinary microalbumin (U-MA), urinary protein, glycosylated hemoglobin A1C (HbAlC), urea nitrogen (BUN), serum creatinine (Cr), cholesterol (Chol), triglyceride (TG), low/high density lipoprotein (LDL-C/HDL-C), homocysteine (Hcy), cystatin C (Cys-C), uric acid (UA), fundus and spirit. The patients in early stage of T2DM nephropathy, clinical stage of T2DM nephropathy and healthy control group were examined by pure tone audiometry, auditory brainstem response, otoacoustic emission and cochlear electrogram respectively. Objective:To investigate the relationship between the clinical parameters and the impairment of auditory system in early stage of T2DM nephropathy and clinical stage of T2DM nephropathy according to the results of pure tone audiometry, auditory brainstem response, otoacoustic emission and electrocochlear electrogram. BMI, U-MA, HbAlC, Cr, Hcy, Cys-C and UA in early stage of T2DM nephropathy group and clinical nephropathy group were significantly higher than those in control group (P 0.05). * P 0.05), while BUN, Cys-C and UA in the early stage of T2DM nephropathy group were higher than those in the control group, but there was no significant difference (P 0.05). In addition, BUN, Cr, Hcy, Cys-C and UA in the early stage of T2DM nephropathy group were significantly higher than those in the early stage of T2DM nephropathy group (#P 0.05). 2. Retinopathy and peripheral neuropathy results analysis of retinopathy detection showed that In healthy control group, 19/20 had normal retina, only 1 case had binocular lesion (1/20), and no single eye lesion (0/20); 15/30 had normal retina in early stage of T2DM, 3 had monocular lesion (3/30), 12 had binocular lesion (12/30); 11/30 had normal retina in clinical stage of T2DM, 1 had monocular lesion (1/30) and 18 had binocular lesion (18/30). The results of peripheral neuropathy showed that 15% of the patients in the healthy control group, 40% in the early stage of T2DM nephropathy group, and 70% in the T2DM clinical nephropathy group, including the slow conduction of left and right median nerves, the slow tibia, bilateral slowdown and so on. There was no significant change in left and right ear audiometry in early renal disease group and T2DM clinical nephropathy group, but from 1000 Hz, the left and right ear audiometry in early renal disease group and T2DM clinical nephropathy group increased significantly (*P 0.05), suggesting that high-frequency hearing loss occurred in patients with diabetes mellitus. The auditory thresholds of the left ear were (15.25+3.34) dB, (32.33+8.57) dB, and (46.33+6.79) dB in the 2DM clinical nephropathy group, respectively. The auditory thresholds of the right ear were (11.8+2.93) dB, (29.5+7.34) dB and (47.17+6.15) dB in the T2DM clinical nephropathy group were significantly higher than those in the T2DM early nephropathy group (#P 0.05), suggesting that the auditory thresholds of the left ear and right ear were significantly higher than those in the T2DM early nephropathy group (#P High-frequency hearing impairment was aggravated in severe patients. 4. ABR test results showed that the left and right ear I, III, V wave and latency I-III, III-V, I-V of T2DM group were significantly delayed compared with the control group, the difference was statistically significant (*P 0.05). Further compared with T2DM early nephropathy group and T2DM clinical nephropathy group, ABR of left and right ear were significantly delayed. The results showed that the latency of left ear in T2DM group was significantly delayed (#P 0.05) and that of right ear was significantly delayed (#P 0.05) in the latency phase III wave, V wave and latency phase I-III, I-V wave compared with the right ear in T2DM group (#P 0.05). The latency of left ear and right ear in T2DM group was significantly delayed (#P 0.05). The latency of V wave in left ear was (6.2.42) ms, and that in right ear was (6.24.40) Ms. The difference between the two groups was the greatest, especially in the middle and high frequency (1.0-4.0 kHz), suggesting that the function damage of outer hair cells was the most serious in the middle and high frequency (1.0-4.0 kHz) of diabetes mellitus patients, and with the aggravation of kidney injury, the function damage of outer hair cells was gradually aggravated, especially in the middle and high frequency (1.0-4.0 kHz). The results of electrocochleogram (ECochG) analysis showed that SP/AP 0.4 was normal, SP/AP (>0.4) was abnormal in healthy control group, T2DM early nephropathy group, T2DM clinical nephropathy group, left and right ear hearing. The results showed that the proportion of abnormal left ear hearing was 15% in healthy control group, 53.33% in T2DM early nephropathy group, 86.67% in T2DM clinical nephropathy group. The abnormal ratio was 20% in the healthy control group, 50% in the early stage of T2DM nephropathy group and 86.67% in the T2DM clinical nephropathy group. UA and other indicators were significantly increased, especially BUN, Cys-C and UA, and retinopathy and peripheral neuropathy were significantly aggravated, suggesting more serious kidney injury. 2, T2DM patients with kidney injury hearing loss is mainly manifested in high-frequency hearing threshold increased, and in high-frequency conditions (4000-8000Hz) hearing loss with the extent of kidney damage. External hair cell function damage was more serious in T2DM patients with kidney injury at high frequency (1000-4000 kHz), and the degree of external hair cell function damage was aggravated with the aggravation of kidney injury. 4. In T2DM patients with kidney injury at high frequency (4000-8000 Hz), cochlear hydrocele was more common, which may be T2DM patients with kidney injury at high frequency. Age, BMI, HbAlC, Cr, UA, Hcy/TG, CHOL and LDL-C are risk factors for hearing loss in T2DM patients with kidney injury.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.2
[Abstract]:Objective: Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia, characterized by chronic hyperglycemia, disorders of protein and fat metabolism, which can cause multiple organ damage and dysfunction, leading to a series of clinical complications, including cardiovascular and cerebrovascular disease and microvascular disease. Among them, diabetic renal injury is caused by glucose. Microalbuminuria is one of the most important complications in patients with diabetes mellitus. At the same time, the phenomenon of hearing loss in diabetic patients has attracted more and more attention in recent years. To investigate the changes of hearing function in patients with type 2 diabetes mellitus (T2DM) complicated with different degrees of albuminuria, and to discuss the relationship between the changes of basic clinical indicators and hearing impairment, including urinary microalbumin (U-MA), glycosylated hemoglobin AlC (HbAlC), urea nitrogen (BUN), serum creatinine (Cr), triglyceride (TG), cholesterol (Chol), low/high density lipid eggs. White (LDL-C/HDL-C), homocysteine (Hcy), cystatin C (Cys-C) and uric acid (UA) provide theoretical basis for the relationship between diabetic nephropathy and hearing impairment. Methods: 30 patients with type 2 diabetes mellitus complicated with urinary microalbumin (early nephropathy group of T2DM), 30 patients with diabetes mellitus complicated with clinical albuminuria (clinical nephropathy group of T2DM) and 30 patients with healthy. 20 healthy people were divided into sex, age, body mass index (BMI), waist-hip ratio, urinary microalbumin (U-MA), urinary protein, glycosylated hemoglobin A1C (HbAlC), urea nitrogen (BUN), serum creatinine (Cr), cholesterol (Chol), triglyceride (TG), low/high density lipoprotein (LDL-C/HDL-C), homocysteine (Hcy), cystatin C (Cys-C), uric acid (UA), fundus and spirit. The patients in early stage of T2DM nephropathy, clinical stage of T2DM nephropathy and healthy control group were examined by pure tone audiometry, auditory brainstem response, otoacoustic emission and cochlear electrogram respectively. Objective:To investigate the relationship between the clinical parameters and the impairment of auditory system in early stage of T2DM nephropathy and clinical stage of T2DM nephropathy according to the results of pure tone audiometry, auditory brainstem response, otoacoustic emission and electrocochlear electrogram. BMI, U-MA, HbAlC, Cr, Hcy, Cys-C and UA in early stage of T2DM nephropathy group and clinical nephropathy group were significantly higher than those in control group (P 0.05). * P 0.05), while BUN, Cys-C and UA in the early stage of T2DM nephropathy group were higher than those in the control group, but there was no significant difference (P 0.05). In addition, BUN, Cr, Hcy, Cys-C and UA in the early stage of T2DM nephropathy group were significantly higher than those in the early stage of T2DM nephropathy group (#P 0.05). 2. Retinopathy and peripheral neuropathy results analysis of retinopathy detection showed that In healthy control group, 19/20 had normal retina, only 1 case had binocular lesion (1/20), and no single eye lesion (0/20); 15/30 had normal retina in early stage of T2DM, 3 had monocular lesion (3/30), 12 had binocular lesion (12/30); 11/30 had normal retina in clinical stage of T2DM, 1 had monocular lesion (1/30) and 18 had binocular lesion (18/30). The results of peripheral neuropathy showed that 15% of the patients in the healthy control group, 40% in the early stage of T2DM nephropathy group, and 70% in the T2DM clinical nephropathy group, including the slow conduction of left and right median nerves, the slow tibia, bilateral slowdown and so on. There was no significant change in left and right ear audiometry in early renal disease group and T2DM clinical nephropathy group, but from 1000 Hz, the left and right ear audiometry in early renal disease group and T2DM clinical nephropathy group increased significantly (*P 0.05), suggesting that high-frequency hearing loss occurred in patients with diabetes mellitus. The auditory thresholds of the left ear were (15.25+3.34) dB, (32.33+8.57) dB, and (46.33+6.79) dB in the 2DM clinical nephropathy group, respectively. The auditory thresholds of the right ear were (11.8+2.93) dB, (29.5+7.34) dB and (47.17+6.15) dB in the T2DM clinical nephropathy group were significantly higher than those in the T2DM early nephropathy group (#P 0.05), suggesting that the auditory thresholds of the left ear and right ear were significantly higher than those in the T2DM early nephropathy group (#P High-frequency hearing impairment was aggravated in severe patients. 4. ABR test results showed that the left and right ear I, III, V wave and latency I-III, III-V, I-V of T2DM group were significantly delayed compared with the control group, the difference was statistically significant (*P 0.05). Further compared with T2DM early nephropathy group and T2DM clinical nephropathy group, ABR of left and right ear were significantly delayed. The results showed that the latency of left ear in T2DM group was significantly delayed (#P 0.05) and that of right ear was significantly delayed (#P 0.05) in the latency phase III wave, V wave and latency phase I-III, I-V wave compared with the right ear in T2DM group (#P 0.05). The latency of left ear and right ear in T2DM group was significantly delayed (#P 0.05). The latency of V wave in left ear was (6.2.42) ms, and that in right ear was (6.24.40) Ms. The difference between the two groups was the greatest, especially in the middle and high frequency (1.0-4.0 kHz), suggesting that the function damage of outer hair cells was the most serious in the middle and high frequency (1.0-4.0 kHz) of diabetes mellitus patients, and with the aggravation of kidney injury, the function damage of outer hair cells was gradually aggravated, especially in the middle and high frequency (1.0-4.0 kHz). The results of electrocochleogram (ECochG) analysis showed that SP/AP 0.4 was normal, SP/AP (>0.4) was abnormal in healthy control group, T2DM early nephropathy group, T2DM clinical nephropathy group, left and right ear hearing. The results showed that the proportion of abnormal left ear hearing was 15% in healthy control group, 53.33% in T2DM early nephropathy group, 86.67% in T2DM clinical nephropathy group. The abnormal ratio was 20% in the healthy control group, 50% in the early stage of T2DM nephropathy group and 86.67% in the T2DM clinical nephropathy group. UA and other indicators were significantly increased, especially BUN, Cys-C and UA, and retinopathy and peripheral neuropathy were significantly aggravated, suggesting more serious kidney injury. 2, T2DM patients with kidney injury hearing loss is mainly manifested in high-frequency hearing threshold increased, and in high-frequency conditions (4000-8000Hz) hearing loss with the extent of kidney damage. External hair cell function damage was more serious in T2DM patients with kidney injury at high frequency (1000-4000 kHz), and the degree of external hair cell function damage was aggravated with the aggravation of kidney injury. 4. In T2DM patients with kidney injury at high frequency (4000-8000 Hz), cochlear hydrocele was more common, which may be T2DM patients with kidney injury at high frequency. Age, BMI, HbAlC, Cr, UA, Hcy/TG, CHOL and LDL-C are risk factors for hearing loss in T2DM patients with kidney injury.
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.2
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