【作者】 苏冠明；

【导师】 张力辉；

【作者基本信息】 河北医科大学 ， 内科学， 2010， 硕士

【摘要】 目的：糖尿病周围神经病变(diabetic peripheral neuropathy, DPN)是2型糖尿病常见并发症之一,是导致足部溃疡,感染及坏疽的主要危险因素。早期发现并强化血糖控制及加强足部护理可显著降低足部溃疡和截肢的发生率,提高患者的生活质量。已有研究表明糖尿病周围神经病变与高血糖、年龄、病程、吸烟、维生素缺乏及遗传素质等因素密切相关。严格控制高血糖,尤其是控制波动性高血糖,可以降低或延缓糖尿病周围神经病变的发生与发展。糖化血清蛋白(GSP)能有效地反映患者过去2-3周内平均血糖水平,是反映糖代谢紊乱的指标之一。24小时血糖谱(7时点或8时点法)能比较全面的了解患者全天血糖控制情况,并且在一定程度上反映血糖的波动情况。为了解糖代谢紊乱与糖尿病周围神经病变之间的关系,我们对初诊的伴有或不伴有周围神经病变的2型糖尿病患者的糖化血清蛋白及8时点血糖进行了测定,并探讨两指标之间的相关性,以及与2型糖尿病周围神经病变的关系,为早期诊断、早期防治提供理论依据。方法：选择河北医科大学第二医院住院的新确诊且未接受过任何糖尿病的干预治疗(饮食、运动及药物等)的2型糖尿病患者60例(其中男性37例,女性23例,平均年龄53.90±12.86岁)。所有入选人员均符合1999年世界卫生组织(WHO)提出的糖尿病诊断标准,并且均排除感染、吸烟、急性代谢紊乱、肝肾疾病、心功能不全、恶性肿瘤、免疫风湿性疾病、脑血管疾病、糖尿病周围血管病变(彩色多普勒超声探查双侧颈动脉及双侧下肢动脉)、脑血管病、应用激素等。所有受试者入院次日行肌电图检查,包括右侧正中神经、尺神经及双侧腓总神经的运动功能和双侧正中神经、尺神经、腓总神经、腓肠神经的感觉功能,主要对其运动传导速度(MCV)、感觉传导速度(SCV)、潜伏期、波幅和F波作分析。糖尿病周围神经病变的诊断标准：1.符合以下5条标准：有确定的糖尿病,即符合2型糖尿病的诊断标准；四肢或双下肢有持续疼痛和(或)感觉障碍；一侧或双侧拇趾振动觉减退；双侧踝反射消失；主侧(即利手侧)腓神经传导速度低于同年龄组正常值的1个标准差；2.或者符合2型糖尿病诊断标准且2个或2个以上神经传导速度(NCV)检查异常(排除其他原因所致的周围神经病变)。进行病变程度评定：无肌电图指标异常者为正常；<5个肌电图指标有异常者为轻度；5-10个肌电图指标有异常者为中度；>10个肌电图指标有异常者为重度。根据糖尿病周围神经病变程度的不同,将受试者分为3组：1.无周围神经病变组(A组,20例)2.轻度周围神经病变组(B组,20例)3.中重度周围神经病变组(C组,20例)。所有入组患者均晨起采空腹肘静脉血分别测定空腹血糖(FPG)、糖化血红蛋白(HbAlc)、肝肾功能、血脂、纤维蛋白原(FIB)、β2-微球蛋白(β2-MG)等。并记录收缩压(SBP)、舒张压(DBP)、年龄、性别、身高、体重等各项指标。所有受试者均给予正规糖尿病饮食,同时要求受试者在整个研究过程中保持原有的睡眠和运动习惯。入院后均给予强化胰岛素治疗(门冬胰岛素和精蛋白生物合成人胰岛素或甘精胰岛素)。进餐时间：早餐7：00,午餐11：00,晚餐17：00。测指尖血糖时间：6：00,午、晚餐前20分钟(注射胰岛素前),三餐后2小时,22：00及次日凌晨3：00。受试者于入院次日开始测8时点血糖,此后每隔1天测1次,共7次,第7次8时点血糖检测后3天内查糖化血清蛋白(GSP)。监测日每天测8个点,每例受试者共计56个数据。在监测日如果已经开始监测而出现了无法预料的不适或较不规范的饮食或运动行为,则可选择生活规律性较好的另一日顺延监测。如果受试者不慎遗忘了个别监测点,可在生活规律相似的另一天补测遗漏的监测点。记录观察并计算出以下数据：1.7个监测日所有的血糖数值2.采用受试者入院次日的8时点血糖计算出以下各项指标,包括如下：(1)全天8个点的血糖平均值(MBG8)及标准差(SD)(2)三餐后血糖漂移幅度(PPGE):餐后2小时血糖与相应餐前血糖的差值(3)全天8个点平均血糖波动幅度(MAGE8) (4)全天8个点最大血糖波动幅度(LAGE8) 3.将受试者7个监测日的8时点血糖汇总得出以下各项指标,包括如下：空腹血糖(FPG)、三餐后2小时血糖(PBG)、午晚饭前血糖、22：00血糖、3：00血糖、全天8个点的血糖平均值(MBG8)、三餐后血糖漂移幅度(PPGE)。所有数据均采用SPSS13.0统计软件包处理。数据用均数±标准差表示,统计分析多组之间比较采用完全随机设计的方差分析,两组之间比较采用两样本均数t检验。以有无周围神经病变(无=0,有=1)为变量,对病变的危险因素作Logistic回归分析。相关性采用Pearson相关分析,P<0.05有统计学意义。结果：1 C组的年龄、纤维蛋白原、β2-MG均显著大于A、B两组(P<0.05),A、B两组之间比较无显著性差异(P>0.05)。B、C两组合并后与A组比较,两组间年龄有显著性差异(P<0.05)。A、B、C三组之间比较性别、体重指数、收缩压、舒张压、空腹血糖、糖化血红蛋白、血脂均无显著性差异(P>0.05)。2以有无周围神经病变(无=0,有=1)为因变量,对年龄、体重指数、收缩压、舒张压、糖化血红蛋白、纤维蛋白原、GSP等因素作Logistic回归分析,仅有年龄(OR=2.06,P<0.05)进入回归方程,是2型糖尿病周围神经病变的危险因素,其他变量均无统计学意义。3伴有周围神经病变与无周围神经病变组相比较,入院次日的各项血糖指标中SD、MAGE8、LAGE8、早PPGE、晚PPGE均明显增高(P<0.05),午PPGE、MBG8均无显著性差异(P>0.05)。4 GSP与7个监测日汇总的各项指标中的FPG、早PBG、午PBG、晚PBG及MBG8均显著正相关(OR值分别为0.407,0.374,0.403,0.446,0.543,P<0.05)。与午饭、晚饭前血糖、22：00和3：00血糖、早PPGE、午PPGE、晚PPGE均不相关(P>0.05)。5C组的GSP均显著大于A、B两组(P<0.05)。A、B两组之间比较无显著性差异(P>0.05)。将B、C两组合并后与A组比较,两组之间GSP有显著性差异(P<0.05)。结论：1新诊断的2型糖尿病患者中,与无周围神经病变相比,伴有周围神经病变的患者血糖波动幅度更大,具体表现为入院次日的各项血糖指标中的SD、MAGE8、LAGE8、早PPGE、晚PPGE均明显增高。提示波动性高血糖在2型糖尿病周围神经病变发生发展中发挥了重要作用,我们在以后的临床工作中应该平稳降糖,尽量减轻患者的血糖波动。2中重度糖尿病周围神经病变组的年龄、纤维蛋白原、β2-微球蛋白均显著高于无周围神经病变组和轻度周围神经病变组,尤其是年龄进入Logistic回归方程,是2型糖尿病周围神经病变发生的危险因素。提示年龄增长、高凝状态、内皮损伤均促进了2型糖尿病周围神经病变的发生发展。3 GSP与空腹血糖、三餐后2小时血糖及全天8个点的平均血糖均密切相关,能比较全面的反映全天血糖水平,提示GSP是反映近期血糖控制的良好指标,具有临床使用价值。4伴有周围神经病变组的GSP比不伴有周围神经病变组更高,提示GSP可能与糖尿病周围神经病变的发生发展有关。更多还原

【Abstract】 Objective:Diabetic peripheral neuropathy is one of the common complications of type 2 diabetes. It is the major risk factors for leading to foot ulcers, infections and gangrene. Early detection and to strengthen the control of blood glucose and foot care can significantly reduce the incidence of foot ulcers and amputation, and improve the patient’s quality of life. Researchs has shown that peripheral neuropathy is closely related to hyperglycemia, age, course of disease, smoking, vitamin deficiency, and genetic predisposition etc. To strictly control high blood sugar,in particular the control of fluctuations in blood glucose, can reduce or delay the occurrence and development of diabetic peripheral neuropathy.Glycosylated serum protein(GSP) can effectively reflect the patients’ average blood glucose level in the past 2-3 weeks. It is one of the indicators of glucose metabolism disorders.24-hour blood glucose spectrum (7 point or 8 point method) is able to understand the blood glucose control situation of the day a little comprehensivly, and to a certain extent reflect the fluctuations in blood glucose. In order to understand the relationship between glucose metabolism disorders and diabetic peripheral neuropathy, we measured glycosylated serum protein and 8-point blood glucose in newly diagnosed type 2 diabetic patients with peripheral neuropathy, to explore the correlation between the two indicators and the relationship with peripheral neuropathy. This can provide a theoretical basis for early diagnosis, early prevention and treatment.Methods:Select 60 cases was hospitalized in Hebei Medical University Second Hospital patients with type 2 diabetes, they are all newly diagnosed and did not receive any intervention in diabetes treatment (diet, exercise and drugs, etc, of which 37 cases of male, female 23 cases, with an average age(53.90±12.86) years. All elected cases are in line with the 1999 WHO diagnostic criteria of diabetes, and have ruled out infection, smoking, acute metabolic disorders, liver and kidney disease, heart failure, cancer, rheumatoid autoimmune diseases, diabetic peripheral vascular disease(using color Doppler to detect carotid artery and lower extremity arteries), cerebral vascular disease, use hormones etc. All patients underwent electromyography, including the motor function of the right of the median nerve, ulnar nerve, the both sides of common peroneal nerve, and the sensory function of the both sides of the bilateral median nerve, ulnar nerve, common peroneal nerve and sural nerve. Analysis of its sensory nerve conduction velocity (SCV) and motor conduction velocity (MCV) and latency, amplitude, F-wave. The diagnostic criteria for diabetic peripheral neuropathy:1. meet the following five criteria: have a definite diabetes, or meet the diagnostic criteria for type 2 diabetes mellitus; Limbs or both lower extremities persistent pain and (or) sensory disturbance; One or both toe vibration perception diminished; Pairs of ankle reflex disappear; The peroneal nerve conduction velocity of the primary side (right-handed side) is a standard deviation lower than the normal value of the same age group.2. Or meet the diagnostic criteria for type 2 diabetes mellitus and two or more of the NCV examination is abnormal (excluding other causes of peripheral neuropathy). Assessment of disease extent:No lesions was normal;<5 abnormal EMG indicators were mild; 5-10 abnormal EMG indicators were moderate lesions;>10 abnormal EMG indicators were severe. According to the degree of diabetic peripheral neuropathy will be divided into three groups, non-peripheral neuropathy group(A group,20 cases), mild peripheral neuropathy group (B group,20 cases), moderate and severe peripheral neuropathy group (C group,20cases). All enrolled patients were taken early morning fasting venous blood of elbow and measured fasting plasma glucose(FPG), glycosylated hemoglobin(HbAlc), liver and kidney function, blood lipids, fibrinogen (FIB),β2-microglobulin (P2-MG) et al. And record the systolic blood pressure(SBP), diastolic blood pressure(DBP), age, sex, height, weight and other indicators.All subjects were given regular diabetic diet, and required patients to maintain the original sleep and exercise habits throughout the course of the study. All subjects were treated with intensive insulin therapy after they were admitted to hospital (insulin aspart and protamine bio-synthetic human insulin or insulin glargine). Meal time:Breakfast 7:00, lunch 11:00, supper 17:00. Fingertip blood glucose test time:6:00,20 minutes before lunch and supper (Before inject insulin),2h postprandial blood glucose,22:00, and 3:00 of the next day. One day after the subjects was hospitalized we start to test 8-point blood glucose, Measured every other day, a total of 7 times, After 7 times, we detect glycosylated serum protein (GSP) within 3 days. We have measured 8 point in the monitoring of day, each subjects to monitor a total of 56 data. If you have already started to monitor in the monitoring day, but there is a irregular discomfort or rarely eating or exercise behavior, you can choose another regularly day to monitor. If the participants accidentally forgotten individual monitoring points, we can test omissive monitoring points additionally in one day that similar patterns of life.Record and calculate the following data:1. all the blood glucose values of the monitoring day 2. the blood sugar targets of the next day when the subjects was hospitalized, Include the following:(1) MBG8:the mean blood glucose and standard deviation (SD) of the 8 point (2) drift range of postprandial blood glucose (PPGE):2h postprandial blood glucose minus the corresponding blood glucose before meals (3) the mean amplitude of glycemic excursions of the 8 point (MAGE8) (4) the largest amplitude of glycemic excursions of the 8 point (LAGE8) 3. the summary various indicators of the monitoring day, including the following:Fasting plasma glucose (FPG), blood glucose 2 hours after meals (PBG), the blood glucose of prelunch and predinner, the blood glucose of 22:00,3:00, MBG8, PPGE.All the data were deal with statistical software packages SPSS 13.0. Data expressed using average addition and subtraction standard deviation. Comparative analysis between the many groups using completely randomized design analysis of variance. Between the two groups were compared using two-sample t test. Whether or not has peripheral neuropathy (no=0, with=1) for the variables, disease risk factors for Logistic regression analysis. Correlation using Pearson correlation to analysis, P<0.05 has statistically significant.Result:1 The age, fibrinogen,β2-MG of C were significantly higher than A, B (P<0.05), between A and B showed no significant difference (P>0.05). B and C combined to one group, compared with A, between the two groups of age was significantly different (P<0.05). A, B, C comparison with the three groups of sex, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, glycated hemoglobin, lipids was non-significant (P>0.05).2 Whether or not has peripheral neuropathy disease(no=0, has=1) as the dependent variables, age, body mass index, systolic blood pressure, diastolic blood pressure, glycosylated hemoglobin, fibrinogen, GSP and other factors were analysis using Logistic regression. Only age (OR= 2.06, P<0.05) entered the regression equation, was risk factors of diabetic peripheral neuropathy. Other variables had no statistical significance.3 With or without peripheral neuropathy lesions compared, the SD, MAGE8, LAGE8, vary range in blood glucose after breakfast and supper of the next day when the subjects was hospitalized were significantly higher (P<0.05). Vary range in blood glucose after lunch,MBG8 had no significant differences.4 GSP was significantly correlated with FPG,2h postprandial and MBG8 of the summary various indicators of the monitoring day (OR values were 0.407, 0.374,0.403,0.446,0.543 P<0.05). GSP had no correlated with prelunch, presupper, blood glucose of 22:00 and 3:00, drift range of postprandial blood glucose, the average blood glucose of fasting blood glucose and 2h postlunch and the average blood glucose of fasting blood glucose and 2h postsupper (P >0.05).5 The GSP of C was significantly higher than A, B (P<0.05). A, B showed no significant difference (P>0.05). B and C combined to one group compared with A, between two groups of GSP were significantly different(P<0.05).Conclusion:1 Compared with patients without peripheral neuropathy there was a there is a more severe fluctuations in blood glucose levels in patients with peripheral neuropathy of type 2 diabetes who are newly diagnosed. The specific performance of it was the SD, MAGE8, LAGE8, vary range in blood glucose after breakfast and supper of the next day when the subjects was hospitalized were significantly higher, prompted that the fluctuations in blood glucose played an important role in the occurrence and development of type 2 diabetes peripheral neuropathy. In the subsequent clinical work, we should reduce the blood glucose smoothly to minimize fluctuations in blood glucose in patients.2 The age, fibrinogen,β2-MG of moderate and severe peripheral neuropathy group were significantly higher than non-peripheral neuropathy group and mild peripheral neuropathy group. In particular, age entered the Logistic regression equations and it’s a risk factor of type 2 diabetes peripheral neuropathy. It showed that age, hypercoagulability, endothelial injury promoted the occurrence and development of peripheral neuropathy of type 2 diabetes.3 GSP is closely related to fasting blood glucose, the 2h postprandial and MBG8 can comprehensive reflect the blood glucose levels of the day, It showed that GSP is a good indicator to reflect the glycemic control recently, it has a clinical value.4 GSP of patients with peripheral neuropathy is higher than the patients without peripheral neuropathy. It showed that,GSP may be related to the occurrence and development of diabetic peripheral neuropathy.更多还原