1218例肌萎缩侧索硬化患者糖尿病患病率 的临床研究

研究背景：肌萎缩侧索硬化(Amyotrophic lateral sclerosis，ALS)是累及上、下运动神经元的神经退行性疾病。代谢性疾病特别是糖尿病与ALS有多种关系。既往研究提示与一般人群相比，ALS患者的糖尿病患病率较低。多数研究认为糖尿病与ALS患者生存率无关，但发病时间延迟。北京协和医院是国内较大的ALS诊治中心之一。本研究拟通过对北京协和医院ALS队列进行分析，并与既往研究数据对比，探索我国合并糖尿病的ALS患者的特点。 研究方法：纳入2013年3月至2021年1月期间在北京协和医院就诊的、符合2000年修订版E1Escorial诊断标准ALS患者，除外临床资料及随访结果中未记录糖尿病信息的患者。根据WHO糖尿病诊断标准，将患者分为ALS．DM组和ALS．无DM组。首先，比较两组患者在性别、起病年龄、居住地、民族、起病前BMI、诊断延迟时间、病程、起病部位、临床类型、诊断级别等临床特征上有无显著差异。对于ALS．DM组患者记录糖尿病类型、治疗方式。计算ALS患者总糖尿病患病率和各年龄段糖尿病患病率，与中国一般人群同年龄段糖尿病患病率及不同国家ALS队列的糖尿病患病率相比较。对于发病前诊断2型糖尿病的患者，比较其与发病前无2型糖尿病患者的起病年龄差异，寻找影响起病年龄的因素，将p<0．05的变量纳入多重线性回归分析。此外，对ALS．DM患者中突变基因检测中的阳性结果总结其特点。 研究结果：本研究共入组1218名ALS患者，其中合并糖尿病的ALS患者152例(12．5％)。ALS．DM患者的特点为男性比例显著偏高(65．8％VS 50．9％，p；0．001)，起病年龄推迟5．4岁(57．24-9．0岁VS 51．7±10．9岁，p=0．007)，起病前BMI较ALS．无DM显著增高1．27kg／m2(25．44-4．4kg／m2VS24．1±3．7kg／m2，p=0．022)，起病前肥胖的患者占比更多(19．4％VS．1 1．3％，p=O．002)。对于能获得随访资料的6l例ALS．DM患者，大多数患者采用口服降糖药治疗(53．3％)。ALS人群总糖尿病患病率高于一般中国人群的总糖尿病患病率(12．4％VS．11．2％)，高于其他国家地区ALS队列的糖尿病患病率。分析124例在ALS发病前即患有2型糖尿病的患者，其起病年龄延迟6．4岁(58．24-8．7岁VS．51．8±10．9岁，p=0．003)。多重线性回归模型显示起病前是否合并T2DM、是否球部起病这两项与起病年龄具有统计学意义的关联。调整后，起病前合并T2DM患者的ALS起病时间比不合并T2DM患者延迟6．3年。ALS．DM患者阳性基因检测结果中，已知的致病突变包括SODl突变4例，TARDBP突变1例。 研究结论；北京协和医院ALS队列中合并糖尿病的ALS患者占12．5％。其特点为男性比例高、起病年龄推迟5．4岁、起病前BMI较高、起病前肥胖的患者较多。ALS人群总糖尿病患病率高于一般中国人群的总糖尿病患病率，且高于其他国家地区ALS队列的糖尿病患病率。ALS发病前即患有2型糖尿病的患者占10．2％，起病年龄延迟6．3岁。ALS．DM患者阳性基因检测结果中，己知的致病突变包括SOD1和TARDBP突变。Research Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease that affects both upper and lower motor neurons. Metabolic diseases, particularly diabetes mellitus (DM), have multiple associations with ALS. Previous studies have suggested that the prevalence of diabetes is lower in ALS patients compared with the general population. Most studies hold that diabetes has no correlation with the survival rate of ALS patients, but delays the onset time of ALS. Peking Union Medical College Hospital is one of the largest ALS diagnosis and treatment centers in China. This study aims to analyze the ALS cohort from Peking Union Medical College Hospital and compare it with previous research data, so as to explore the characteristics of ALS patients with diabetes in China. Research Methods: We enrolled ALS patients who visited Peking Union Medical College Hospital from March 2013 to January 2021 and met the 2000 revised El Escorial diagnostic criteria for ALS, excluding those without documented diabetes information in their clinical data and follow-up results. According to the WHO diagnostic criteria for diabetes mellitus, the patients were divided into ALS-DM group and ALS-non-DM group. First, we compared the significant differences in clinical characteristics between the two groups, including gender, age at onset, place of residence, ethnicity, pre-onset BMI, diagnostic delay, disease duration, onset site, clinical type, and diagnostic level. For patients in the ALS-DM group, we recorded the type of diabetes and treatment methods. We calculated the overall prevalence of diabetes and age-specific prevalence of diabetes among ALS patients, and compared them with the age-specific prevalence of diabetes in the general Chinese population and the prevalence of diabetes in ALS cohorts from different countries. For patients diagnosed with type 2 diabetes mellitus before ALS onset, we compared the difference in age at onset between them and those without type 2 diabetes mellitus before ALS onset, identified factors affecting age at onset, and included variables with p<0.05 in the multiple linear regression analysis. In addition, we summarized the characteristics of positive results from gene mutation testing in ALS-DM patients. Research Results: A total of 1218 ALS patients were enrolled in this study, including 152 cases (12.5%) of ALS patients with comorbid diabetes. The characteristics of ALS-DM patients were as follows: a significantly higher proportion of males (65.8% vs 50.9%, p=0.001), a delayed age at onset by 5.4 years (57.2±9.0 years vs 51.7±10.9 years, p=0.007), a significantly higher pre-onset BMI by 1.27 kg/m² (25.4±4.4 kg/m² vs 24.1±3.7 kg/m², p=0.022), and a higher proportion of pre-onset obese patients (19.4% vs 11.3%, p=0.002). Among the 61 ALS-DM patients with available follow-up data, most were treated with oral hypoglycemic agents (53.3%). The overall prevalence of diabetes in the ALS population was higher than that in the general Chinese population (12.4% vs 11.2%), and also higher than that in ALS cohorts from other countries and regions. Analysis of 124 patients who had type 2 diabetes mellitus before ALS onset showed that their age at onset was delayed by 6.4 years (58.2±8.7 years vs 51.8±10.9 years, p=0.003). The multiple linear regression model revealed that two variables, namely pre-onset comorbidity of T2DM and bulbar onset, were statistically significantly associated with age at onset. After adjustment, ALS patients with pre-onset T2DM had an onset time delayed by 6.3 years compared with those without pre-onset T2DM. Among the positive gene mutation test results of ALS-DM patients, the known pathogenic mutations included 4 cases of SOD1 mutations and 1 case of TARDBP mutations. Research Conclusions: Among the ALS cohort from Peking Union Medical College Hospital, 12.5% of ALS patients had comorbid diabetes. These patients were characterized by a higher proportion of males, a delayed age at onset by 5.4 years, a higher pre-onset BMI, and a higher proportion of pre-onset obese patients. The overall prevalence of diabetes in the ALS population was higher than that in the general Chinese population, as well as that in ALS cohorts from other countries and regions. Patients with type 2 diabetes mellitus before ALS onset accounted for 10.2% of all ALS patients, with their age at onset delayed by 6.3 years. Among the positive gene mutation test results of ALS-DM patients, the known pathogenic mutations included SOD1 and TARDBP mutations.