1型糖尿病胰岛移植的新方法

来自美国、加拿大、瑞典以及挪威等11个国家的医学中心的学者们开始测试一种针对1型难治性糖尿病的胰岛群移植方法。这个项目主要由美国卫生研究所赞助，目的是：确定对胰岛移植方法的改进是否能够更加持久有效地控制血糖，并且不会因此增加副作用。

在胰岛移植过程中，医生需要从一个胰腺捐赠者的体内提取胰岛群然后注入到接受者的肝脏中。如果移植成功的话，胰岛将会被植入到肝脏中并开始分泌胰岛素。

“这个项目的主要目的是探索一种治疗糖尿病的新方法，凭借这种方法那些被自身免疫所破坏的胰岛素分泌细胞可以被替换更新，”国家卫生研究所所长Elias A. Zerhouni说，“这些研究是建立在免疫学和医学移植研究的进展之上的，或许能为比较严重的1型糖尿病患者提供一个能被广泛采用的胰岛移植方法。”

在21，000，000的糖尿病人群中，大约有5%到10%是1型糖尿病，以前被称为青少年型或胰岛素依赖型糖尿病。在这种糖尿病中，病人的免疫细胞会攻击自身的β细胞，而这些β细胞的主要作用是产生生存所需的胰岛素，并和其他类型的细胞一起调节机体的血糖水平。尽管每天使用胰岛素泵接受3次或3次以上的胰岛素注射可以使患者的血糖保持一个稳定水平，但1型糖尿病人最后还是会出现心血管、眼、神经以及肾脏方面等的并发症。而且尽管糖尿病管理也有稳步的发展，但由于心脏病及中风的发作的原因，1型糖尿病患者的寿命还是会缩短15年。

在2000年，一个由加拿大埃德蒙顿的阿尔伯塔大学的James Shapiro博士所领导的研究小组报告称，有7个患者从2到4个胰岛捐献者那里获得胰岛移植后可以长期不用注射胰岛素生活（考虑到可能会对胰岛产生毒性作用，研究人员并没有使用糖皮质激素进行免疫抑制治疗）。在此后的几年中，其他研究人员便开始陆续使用这个“埃德蒙顿方案“，而且大部分的医学中心也开始采用这种胰岛移植方法。

治疗结果显示对于严重的1型糖尿病患者这种方案获得了很好的效果，但它通常需要植入两个或两个以上的胰岛，而且随着时间的推移，这些胰岛往往会失去分泌功能。一般来讲，以下人员可接受这种胰岛移植的治疗方法（研究）：有严重的低血糖（血糖水平过低，有一定危险性）的人，因肾脏衰竭（糖尿病并发症的一种）而接受肾移植的1型糖尿病患者。

现在，研究人员正在进行第一和二个阶段—小规模的实验制剂研究以及第三阶段，即对埃德蒙顿方案改进方面的研究。如果在第三阶段可以成功的控制血糖水平的话，那么研究人员就可以要求食品和药物管理局通过这个可以为难治性1型糖尿病患者带来福音的治疗方案了。

随着埃德蒙顿方案的发展，科学家们正在致力于延长受体胰岛的寿命以及减少可以防止机体对捐赠者胰岛进行破坏的药物的副作用，如：贫血、神经、肾脏疾患以及易感染性等方面的研究。在这些研究中，研究人员们会在移植之前对胰岛进行培养以增加他们的生存能力。他们还将会对特定的抗排斥药物进行比较，以期在最大限度内增加胰岛的寿命并减少药物的毒性。当治疗过程变得更加安全并且有新的β细胞来源的时候，将会有更多的患者可以从中受益。

“如果这些方法可以成功的延长胰岛分泌的时间并可以减少药物的毒性作用的话，那么难治性的1型糖尿病患者就又有了一个控制疾病的新方法了。“迈阿米大学研究主席Camillo Ricordi博士说。

参加这项研究的患者主要有经过强效的药物治疗之后仍然不能控制血糖的1型糖尿病患者，严重的发作性的低血糖患者（血糖水平严重低下），具有严重的低血糖以及低血糖昏迷的患者（这些患者不能感知血糖的下降而且可以在没有预兆的情况下丧失意识）以及一些已经移植了一个肾脏并开始使用免疫抑制类药物的一类糖尿病患者。

New Approaches To Islet Transplantation In Type 1 Diabetes

Researchers from 11 medical centers in the United States, Canada, Sweden, and Norway have begun testing new approaches to transplanting clusters of insulin-producing islets in adults with difficult-to-control type 1 diabetes. The clinical studies, funded by the National Institutes of Health (NIH), will determine whether changes to current methods of islet transplantation lead to improved, long-lasting control of blood glucose with fewer side effects.

In islet transplantation, clusters of islets are extracted from a donor pancreas and infused into the recipient's liver. In a successful transplant, the islets become embedded in the liver and begin producing insulin.

"A major goal of the NIH research program in type 1 diabetes is to develop therapies that replace the insulin-producing cells destroyed by the autoimmune process," said NIH Director Elias A. Zerhouni, M.D. "These studies, which build on advances in immunology and transplantation research, may open the door to more widespread use of islet transplantation for patients with severe type 1 diabetes."

About 5 percent to 10 percent of the nearly 21 million people with diabetes have type 1, formerly known as juvenile onset diabetes or insulin-dependent diabetes. In type 1 diabetes, a person's own immune cells attack and destroy pancreatic beta cells, which produce the hormone insulin needed for survival. Beta cells, along with several other types of cells that work together to balance blood glucose, reside in islets, also known as islets of Langerhans, in the pancreas. Three or more insulin injections a day or treatment with an insulin pump are often needed to maintain blood glucose control, but most people with type 1 diabetes still develop complications, including damage to the heart and blood vessels, eyes, nerves, and kidneys. Despite steady improvements in managing the disease, type 1 diabetes cuts lives short by about 15 years, with early deaths due mainly to heart attacks and strokes.

In 2000, a research team led by Dr. James Shapiro at the University of Alberta in Edmonton, Canada, reported sustained insulin independence in seven patients transplanted with islets from two to four donor pancreases and treated with an immunosuppressive regimen that omitted glucocorticoids, thought to be toxic to islets. In the next few years, other researchers replicated the "Edmonton protocol," and most centers adopted this approach to islet transplantation.

The protocol greatly benefits some patients with severe type 1 diabetes, but two or more infusions of islets are usually needed, and the islets tend to lose their insulin-producing function over time. Participating in an islet transplant study is appropriate for people with severe hypoglycemia (dangerously low levels of blood sugar) and for those with type 1 diabetes who have had a kidney transplant to treat kidney failure, a complication of diabetes.

Since the Edmonton advance, scientists have been working to lengthen the survival of donor islets and reduce the side effects--such as anemia, nerve and kidney damage, and vulnerability to infection--of drugs that prevent the body's destruction of donor islets. In the new studies, the researchers will culture islets before transplantation to enhance their viability. They will also compare specific anti-rejection drugs for the ability to maximize islet survival while reducing toxicity. As the procedure becomes safer and new sources of beta cells become available, more people are likely to benefit.

The researchers are conducting pilot, or phase 1/2, studies of experimental agents as well as phase 3 studies that modify the Edmonton protocol. If the phase 3 studies succeed in safely controlling blood glucose levels, the investigators may ask the Food and Drug Administration to approve the procedure for people with poorly controlled type 1 diabetes.

"If these approaches are successful in prolonging islet function with less drug toxicity, type 1 diabetes patients with severe problems controlling their blood glucose may have another treatment option for controlling their diabetes," said study chair Dr. Camillo Ricordi of the University of Miami.

The studies are enrolling individuals with type 1 diabetes who have serious difficulty controlling their blood glucose despite intensive medical therapy and who suffer from episodes of severe hypoglycemia (dangerously low levels of blood glucose). Also eligible are patients with severe hypoglycemia and hypoglycemia unawareness, who cannot sense a drop in blood glucose and may lose consciousness without warning. In addition, researchers are accepting type 1 diabetes patients who have had a kidney transplant and are already taking immunosuppressive drugs.