Metformin与降低神经退化性疾病风险有关


  【24drs.com】新研究认为,Metformin对于阿兹海默氏症与巴金森氏症等神经退化性疾病可能有长期的保护效果。
  
  这篇回溯性纵向研究的资料来自Veterans' Affairs的电子病历,路易西安那州纽奥良杜兰大学博士候选人Qian Shi在6月11日于美国糖尿病协会(ADA)2016年科学研讨会发表研究结果。
  
  Shi小姐表示,对于使用metformin超过2年者,我们发现神经退化性疾病显著减少;Metformin可能有神经保护性。
  
  研究者校正肾功能、慢性肾脏病与其它糖尿病药物之后,研究结果依旧成立。她指出,机转还不清楚,但是,已知metformin可以通过血脑障蔽。
  
  会议主持人、格鲁吉亚州亚特兰大Emory大学医学院医学教授Lawrence S Phillips医师受邀发表评论时表示,Metformin有多效性,基于多种原因而令人有极大兴趣。
  
  他指出,在日前的ADA会议中,有一整个座谈会探讨有关metformin的新研究结果,包括它在癌症与心脏病的可能预防作用。
  
  但是,Phillips医师同时也提出提醒,虽然研究者控制了肾功能与其它可能的干扰因素,所有流行病学分析中最难回答的问题,是根据适应症排除干扰因素。不论患者没有使用或者一直使用metformin,可能在分析所用的估计肾丝球过滤速率(eGFR)之外的其它检测方式是更严重的,我认为这在管理资料库的流行病学分析是难以分辨的。
  
  尽管如此,他表示,这绝对值得进一步研究。
  
  Shi小姐表示,之前有关metformin和退化性疾病的资料互有矛盾,有两篇人口研究显示,长期使用metformin治疗可以降低认知衰退风险,其它资料指出,服用metformin之患者的认知表现可能恶化,可能是因为缺乏维他命B12。另一篇试验中,长期使用该药与阿兹海默氏症的风险略为增加有关。
  
  目前这篇研究纳入Veterans' Affairs电子病历的50岁以上、接受胰岛素治疗之第二型糖尿病患者的资料,从诊断当时追踪到死亡或研究结束。
  
  符合条件的150,435人中,41,696因为神经病变、缺乏维他命B12、之前的神经退化性疾病、认知缺损、脑血管疾病的后续影响、癌症、末期肾病等干扰因素而排除;使用胰岛素的时间小于三分之二研究期间的患者也被排除。
  
  最后的研究样本共有6,046名患者(90%以上是男性),平均年龄63岁,追踪期中位数为5.25年。
  
  除了肾功能与其它糖尿病药物,Shi小姐等人也控制了年龄、性别、种族、抽菸、肥胖、其它并发症病史、研究开始时的共病症。
  
  在追踪期间,有334例诊断为失智症,其中100例为巴金森氏症、71例为阿兹海默氏症、19例为认知缺损。
  
  发生一种或一种以上神经退化性疾病的校正发生率为,未曾使用metformin者为2.08/100人-年,使用metformin不到1年者为2.47/100人-年,不到2年者为1.61/100人-年,2-4年者为1.30/100人-年,4年以上者为0.49 /100人-年。
  
  Metformin和神经退化性疾病之间的保护效果,只有在2年后才有统计上的显著意义。
  
  相较于未曾使用metformin者,使用metformin 2-4年者之所有神经退化性疾病的风险比为0.623,使用4年以上者为0.216。
  
  失智症的结果也很显著(2-4年为0.567,4年以上为0.252),巴金森氏症和阿兹海默氏症只有4年以上者有显著意义(分别是0.038和0.229)。
  
  Shi小姐解释,在失智症和巴金森氏症有类似的风险降低结果,但是其它亚型急病则无,可能是因为案例数有限。
  
  她结论指出,需要大型前瞻世代研究来确认,使用metformin和神经退化性疾病风险之间的这个关系与因果。
  
  资料来源:http://www.24drs.com/
  
  Native link:Metformin Linked to Lower Neurodegenerative Disease Risk

Metformin Linked to Lower Neurodegenerative Disease Risk

By Miriam E Tucker
Medscape Medical News

NEW ORLEANS — Metformin may exert a long-term protective effect against neurodegenerative diseases including Alzheimer's and Parkinson's, new research suggests.

Findings from a retrospective longitudinal study of data from Veterans' Affairs electronic medical records were presented June 11 here at the annual American Diabetes Association (ADA) 2016 Scientific Sessions by Qian Shi, a PhD candidate at Tulane University, New Orleans, Louisiana.

"For metformin exposure longer than 2 years, we found a significant reduction in neurodegenerative disease.…Metformin may be neuroprotective," Ms Shi told Medscape Medical News.

The results were consistent even after researchers controlled for kidney function, chronic renal disease, and other diabetes medications.

The mechanism is unclear, but metformin is known to cross the blood-brain barrier, she noted.

Asked to comment, session moderator Lawrence S Phillips, MD, professor of medicine at Emory University School of Medicine, Atlanta, Georgia, said: "Metformin has pleiotropic effects, and it is of great interest for a variety of reasons."

He added that there was an entire symposium here yesterday at the ADA meeting devoted to emerging findings regarding metformin, including its possible preventive roles in cancer and heart disease.

But at the same time, Dr Phillips cautioned that even though the investigators controlled for renal function and other potential confounders, "the hard question in all of these epidemiologic analyses is ruling out confounding by indication.…You wonder if the patients who didn't get metformin or stay on it were somehow sicker in ways other than what [estimated glomerular filtration rate] eGFR might have been picked up in the analysis. I think that's very hard to tell in an epidemiologic analysis of an administrative database."

Nonetheless, he told Medscape Medical News, "It absolutely deserves further study."

Effect Seen After 2 Years

Ms Shi said that prior data on metformin and neurodegenerative diseases have been conflicting. While two previous population studies have shown that long-term treatment with metformin may reduce the risk of cognitive decline, other data indicated that cognitive performance was worse among patients taking metformin, possibly due to vitamin B12 deficiency. And long-term use of the drug was associated with a slightly increased risk for Alzheimer's disease in another trial.

The current study population consisted of patients with type 2 diabetes older than 50 years from the Veterans Affairs electronic medical records database who were receiving insulin treatment. They were followed from the time of diagnosis until death or outcome.

Out of 150,435 who met those criteria, 41,696 were excluded for a variety of confounders, including neuropathy, vitamin B12 deficiency, prior neurodegenerative diseases, cognitive impairment, or late effects of cerebrovascular disease, cancer, or end-stage renal disease. Patients who took insulin for less than two-thirds of the study period were also excluded.

The final study sample was 6046 patients (over 90% male) with a mean age of 63 years. They were followed for a median of 5.25 years.

In addition to renal function and other diabetes medications, Ms Shi and colleagues also controlled for age, gender, race, tobacco use, obesity, and history of other complications and comorbidities at baseline.

During follow-up, 334 cases of dementia were diagnosed, as were 100 of Parkinson's, 71 Alzheimer's disease cases, and 19 with cognitive impairment.

The adjusted incidence of developing one or more neurodegenerative diseases per 100 person-years was 2.08 for those who never used metformin, 2.47 for those using metformin less than 1 year, 1.61 for less than 2 years, 1.30 for 2 to 4 years, and 0.49 for 4 or more years.

The protective relationship between metformin and neurodegenerative disease was statistically significant only after 2 years.

Compared with no metformin, the hazard ratios for 2 to 4 years of metformin therapy for all neurodegenerative diseases combined was 0.623 and for 4 or more years 0.216.

The findings were also significant for dementia specifically (0.567 at 2–4 years and 0.252 for 4+ years) and for Parkinson's and Alzheimer's diseases only beyond 4 years (0.038 and 0.229, respectively).

"Similar risk reductions occurred in dementia and Parkinson's but were not duplicated to other subtype diseases, most likely due to the limited numbers of events," Ms. Shi explained.

"A large-scale prospective cohort study may be needed to confirm the relationship and the causality between metformin exposure and the risk for neurodegenerative disease," she concluded.

Dr Shi has no relevant financial relationships. Dr Phillips has served on scientific advisory boards for Boehringer Ingelheim and Janssen and has or had research support from Merck, Amylin, Eli Lilly, Novo Nordisk, Sanofi, PhaseBio, Roche, Abbvie, Vascular Pharmaceuticals, and the Cystic Fibrosis Foundation.

For more diabetes and endocrinology news, follow us on Twitter and on Facebook.

American Diabetes Association 2016 Scientific Sessions; June 11, 2016; New Orleans, Louisiana.

    
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