{"title":"2型糖尿病,抗糖尿病和肌萎缩侧索硬化的风险。","authors":"Tian-Shin Yeh, Ran S Rotem, Marc G Weisskopf","doi":"10.1080/21678421.2025.2515913","DOIUrl":null,"url":null,"abstract":"<p><p><i>Background:</i> Research on the link between Type 2 Diabetes mellitus (T2DM) and amyotrophic lateral sclerosis (ALS) has produced mixed results. The potential role of antidiabetic medications in ALS etiology is also unclear. To contribute to these discussions, we aimed to examine the connections between T2DM, antidiabetic medications, and ALS using data from a large Israeli health fund. <i>Methods:</i> A total of 504 ALS cases diagnosed in 2002-2018 and 42,873 matched controls were considered in this population-based nested case-control study. T2DM was ascertained using diagnosis codes, laboratory test results, and medication use history, employing a 3-year lag from initial ALS diagnosis date to minimize chances for reverse causation. Multivariable-adjusted odds ratios (OR) were estimated for the association between T2DM, antidiabetic medications, and ALS. <i>Results:</i> T2DM overall was not linked with ALS (multivariable-adjusted odds ratio (OR) = 0.94, 95% confidence interval (CI): 0.72-1.23). However, T2DM with a history of insulin use showed a protective association with ALS (OR = 0.29; 95% CI = 0.09-0.92) compared to the non-T2DM group. A similar trend of protective associations with ALS was observed for T2DM with history of use of other antidiabetic medications, but none were statistically significant, and all associations were further attenuated after adjusting for insulin use. <i>Conclusions:</i> We observe a potential protective effect of T2DM-linked insulin use on risk of ALS. Although caution is necessary due to the limited number of ALS cases with insulin exposure, the observed protective association may suggest a biological pathway worth exploring for future therapeutic development.</p>","PeriodicalId":72184,"journal":{"name":"Amyotrophic lateral sclerosis & frontotemporal degeneration","volume":" ","pages":"1-9"},"PeriodicalIF":0.0000,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Type 2 diabetes mellitus, antidiabetics, and the risk of amyotrophic lateral sclerosis.\",\"authors\":\"Tian-Shin Yeh, Ran S Rotem, Marc G Weisskopf\",\"doi\":\"10.1080/21678421.2025.2515913\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><i>Background:</i> Research on the link between Type 2 Diabetes mellitus (T2DM) and amyotrophic lateral sclerosis (ALS) has produced mixed results. The potential role of antidiabetic medications in ALS etiology is also unclear. To contribute to these discussions, we aimed to examine the connections between T2DM, antidiabetic medications, and ALS using data from a large Israeli health fund. <i>Methods:</i> A total of 504 ALS cases diagnosed in 2002-2018 and 42,873 matched controls were considered in this population-based nested case-control study. T2DM was ascertained using diagnosis codes, laboratory test results, and medication use history, employing a 3-year lag from initial ALS diagnosis date to minimize chances for reverse causation. Multivariable-adjusted odds ratios (OR) were estimated for the association between T2DM, antidiabetic medications, and ALS. <i>Results:</i> T2DM overall was not linked with ALS (multivariable-adjusted odds ratio (OR) = 0.94, 95% confidence interval (CI): 0.72-1.23). However, T2DM with a history of insulin use showed a protective association with ALS (OR = 0.29; 95% CI = 0.09-0.92) compared to the non-T2DM group. A similar trend of protective associations with ALS was observed for T2DM with history of use of other antidiabetic medications, but none were statistically significant, and all associations were further attenuated after adjusting for insulin use. <i>Conclusions:</i> We observe a potential protective effect of T2DM-linked insulin use on risk of ALS. 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引用次数: 0
摘要
背景:关于2型糖尿病(T2DM)和肌萎缩侧索硬化症(ALS)之间关系的研究产生了不同的结果。抗糖尿病药物在ALS病因学中的潜在作用也不清楚。为了促进这些讨论,我们的目的是研究2型糖尿病、抗糖尿病药物和ALS之间的联系,使用来自以色列一个大型卫生基金的数据。方法:在这项基于人群的巢式病例对照研究中,共考虑了2002-2018年诊断的504例ALS病例和42,873例匹配的对照。T2DM是通过诊断代码、实验室检查结果和用药史来确定的,从最初的ALS诊断日期起,使用3年的滞后时间来减少反向因果关系的机会。估计T2DM、抗糖尿病药物和ALS之间的多变量校正优势比(OR)。结果:T2DM总体上与ALS无关(多变量校正优势比(OR) = 0.94, 95%可信区间(CI): 0.72-1.23)。然而,有胰岛素使用史的2型糖尿病患者与ALS有保护关系(OR = 0.29;95% CI = 0.09-0.92)与非t2dm组比较。在使用其他降糖药物的T2DM患者中,也观察到类似的与ALS的保护性关联趋势,但没有统计学意义,并且在调整胰岛素使用后,所有关联都进一步减弱。结论:我们观察到t2dm相关胰岛素使用对ALS风险的潜在保护作用。尽管由于胰岛素暴露的ALS病例数量有限,因此谨慎是必要的,但观察到的保护性关联可能为未来的治疗开发提供了一个值得探索的生物学途径。
Type 2 diabetes mellitus, antidiabetics, and the risk of amyotrophic lateral sclerosis.
Background: Research on the link between Type 2 Diabetes mellitus (T2DM) and amyotrophic lateral sclerosis (ALS) has produced mixed results. The potential role of antidiabetic medications in ALS etiology is also unclear. To contribute to these discussions, we aimed to examine the connections between T2DM, antidiabetic medications, and ALS using data from a large Israeli health fund. Methods: A total of 504 ALS cases diagnosed in 2002-2018 and 42,873 matched controls were considered in this population-based nested case-control study. T2DM was ascertained using diagnosis codes, laboratory test results, and medication use history, employing a 3-year lag from initial ALS diagnosis date to minimize chances for reverse causation. Multivariable-adjusted odds ratios (OR) were estimated for the association between T2DM, antidiabetic medications, and ALS. Results: T2DM overall was not linked with ALS (multivariable-adjusted odds ratio (OR) = 0.94, 95% confidence interval (CI): 0.72-1.23). However, T2DM with a history of insulin use showed a protective association with ALS (OR = 0.29; 95% CI = 0.09-0.92) compared to the non-T2DM group. A similar trend of protective associations with ALS was observed for T2DM with history of use of other antidiabetic medications, but none were statistically significant, and all associations were further attenuated after adjusting for insulin use. Conclusions: We observe a potential protective effect of T2DM-linked insulin use on risk of ALS. Although caution is necessary due to the limited number of ALS cases with insulin exposure, the observed protective association may suggest a biological pathway worth exploring for future therapeutic development.