IN THE PIPELINE: Researchers Nearing Artificial Pancreas
Angela Ente's pancreas stopped working properly 25 years ago, but she has a new one of sorts.
Last year, Ente became one of just six diabetics in the U.S. and 24 worldwide to receive an experimental device mimicking the human pancreas manufactured by Medtronic MiniMed, a division of Medtronic Inc. (MDT). It's made a big difference in the life of the 30-year-old recently married California nursing student.
"I feel so free," Ente said. "I'm so normal now."
The medical industry, led by companies like Medtronic and TheraSense Inc. (THER), is on the verge of several technological breakthroughs for diabetics. A true artificial pancreas, the Holy Grail of diabetes research, remains years away. But studies like the one Ente is in make it clear that such a device is indeed on the horizon - perhaps four years off, Medtronic says.
But long before an artificial pancreas becomes available, insulin-dependent diabetics will have easier and more accurate ways to monitor and manage the illness than they do now. Devices that continuously monitor glucose levels and deliver instant readings to the patient could be 18 to 30 months away.
"I think it will be very exciting," said Dr. Eugene Barrett , president of the American Diabetes Association. "A lot of people will be helped a great deal by a device that can monitor continuously or near continuously. People have tried long and hard to get that, and there's been outstanding progress the last few years in that direction."
Patients with Type 1 diabetes no longer produce insulin, a hormone made by the pancreas that enables the body to use glucose found in foods for energy. People with Type 1 diabetes, who account for about 5% to 10% of the 17 million diabetics in the U.S., must take daily insulin injections to survive, and need to test their blood as often as 10 to 12 times daily to make sure glucose levels remain in the right range.
When glucose levels are too high for too long, a condition known as hyperglycemia, diabetics can suffer heart attacks, strokes, blindness, kidney failure, blood vessel disease that requires an amputation, nerve damage and impotence in men. Low glucose levels, or hypoglycemia, can lead to fainting and even death.
Ente got her diabetes diagnosis at the age of five. She remembers being teased by her brothers because glucose monitoring back then required urine tests.
In her twenties, Ente received an external pump for insulin injections. Though the pump helped keep the disease under control for the first time in her life, it also stuck out from under her clothes, making her feel awkward.
"I always looked different because I had this thing attached to me," Ente said.
The device she got last year as part of a Medtronic MiniMed clinical trial is called the Long Term Sensor System. It consists of an implantable pump and implantable sensor. The sensor - which measures glucose using an enzyme-based electrochemical technology - was inserted into Ente's bloodstream near the right atrium of the heart. An abdominal lead connects the sensor to the three-inch pump placed just under the skin of the lower abdomen, which can be programmed to deliver insulin using a hand-held remote programmer.
At weekly intervals during the study, glucose readings taken by the implantable sensor are compared with Ente's own tests of blood from her fingertips. The idea is to see how accurate the sensor is, with the goal of one day having it communicate with the pump and automatically regulate insulin delivery - a so-called "closed loop." That would amount to having a true artificial pancreas.
Lori Hahn, 41, a mother of three who's been insulin-dependent for 12 years and is part of the same trial, said the system has made her "a whole person."
"With the implantable pump, I can actually forget I'm a diabetic," Hahn said. "I honestly don't know how much better it can get."
Medtronic MiniMed has had several successful "closed loop" trials, each of which took place over a two-day period. In the brief trials, the subjects' glucose levels stayed in the proper range.
To close the loop, mathematical algorithms must be developed, said Dr. Alan Moses, chief medical officer at Joslin Diabetes Center and a professor of medicine at Harvard Medical School. A closed-loop device must determine the proper level of insulin based on recent ups or downs in the diabetic's glucose levels, not depend simply on "point in time" readings.
TheraSense is working with Deltec Inc., a maker of drug delivery products, on an artificial pancreas.
"We'll approach closed loop with a series of incremental steps and use the human brain to override," said Tim Goodnow, vice president of research and development at TheraSense. Any failure of the device to properly communicate between sensor and pump, he noted, could have catastrophic results for the patient. That's why experts believe even when an artificial pancreas is common, patients will still have to monitor the device themselves.
Progress On Monitoring Devices
Long before an artificial pancreas comes to market, diabetics should have better ways to monitor the disease.
The problem with current blood glucose monitoring systems is they only give a smattering of readings over time, making it hard for patients to find patterns. It's like trying to make a weather forecast without a satellite photo.
Also, they require regular finger or forearm pricking, which some patients find painful and avoid.
Medtronic recently introduced a device called CGMS System Gold, in which a sensor is slipped under the skin for up to 72 hours. Information is transmitted to a monitor, and a physician can download readings on a computer to get a sense of a patient's glucose patterns.
"It's a very important first step," Moses said.
TheraSense hopes to introduce a system called the Freestyle Navigator by late 2004 or early 2005 depending on FDA approval that will give patients real-time glucose readings with far fewer finger sticks.
The device consists of a very small sensor, the size of a hair, that goes about five millimeters under the skin of the abdomen and gives continuous glucose readings on a small pager-like device. A patient using the device would have to test his or her blood about once a day by pricking the skin just to verify consistency, or 10% of the pricks required with current products.
One challenge of such a system is biological, Barrett of the ADA said. The body tends to break down enzymes like the ones in the sensors.
"Developing something to put under the skin or in the bloodstream and stay there a long time is no mean trick," Barrett said.
"We're attempting to place the system on the market at a cost equivalent to what a person testing themselves four times a day pays now," said Mark Lortz, CEO of TheraSense, in an interview.
Moses is very keen on the TheraSense device.
"It literally measures every minute and displays the value to the patient," he said. "You'll have a true glucose value constantly being updated, allowing the patient to make an injection to maintain steady glucose."
If the company is indeed able to sell the device for the price its CEO predicts, "it will turn the field upside down," Moses said. "They'll have a huge advantage over others."
Moses is on TheraSense's medical advisory board but doesn't receive any compensation from the company.
人造胰腺即将研制成功
今年30岁的安杰拉．恩蒂(Angela Ente)的胰腺功能失常已经25年了，不过，她又有了一个新的"胰腺"。
去年，恩蒂移植了一种模仿人类胰腺机能的装置。这种尚处于试验阶段的装置是由Medtronic Inc. (MDT)下属的Medtronic MiniMed子公司制造的。在美国，接受这种装置移植的糖尿病患者只有6个，在全世界也只有24个。这种装置给这位刚刚结婚的护理专业学生的生活带来了翻天覆地的变化。
恩蒂表示，她现在感到非常自由，像个正常人了！
以Medtronic和TheraSense Inc. (THER)等为首的制药公司在糖尿病治疗方面的技术性突破指日可待。虽然真正的人造胰腺还需数年时间才能研制成功，但Medtronic指出，恩蒂携带的这种装置表明，人造胰腺已经浮出水面，4年之内或许就能研制成功。
不过在真正的人造胰腺出现前的这段时间，依赖胰岛素生活的糖尿病患者可望拥有比现在更为简便也更为精确的方式监控病情。持续监督血糖水平，并向患者立即显示血糖读值的装置有望在18至30个月之内研制成功。
美国糖尿病学会(American Diabetes Association)主席尤金．巴雷特(Eugene Barrett)认为，这将非常激动人心。一种能够持续或近乎持续监督患者血糖水平的装置能够令许多人大大受益。长期以来，人们一直在努力寻求这种
装置，近几年终于获得突出进展。
由于I型糖尿病患者体内无法分泌胰岛素，患者必须每日注射胰岛素，而且每天需要进行多达10至12次血糖测量，以确保其血糖处于正常水平。I型糖尿病人大约占美国1,700万糖尿病人总数的5%-10%。
一旦血糖长时间偏高，糖尿病患者有可能发生心脏病、中风、失明、肾衰、血管疾病、神经坏损，男性有可能发生阳萎。而低血糖症则有可能导致昏迷甚至死亡。
恩蒂是在5岁时被确诊患有糖尿病的，当时监控血糖还需要验尿。
恩蒂20多岁时开始携带胰岛素注射泵。在这种注射泵的帮助之下，她有生以来第一次控制住了病情，不过，这个显露在衣服下面的装置也使她备感尴尬。
她说，这个玩意使她总是显得与众不同。
她去年安装的新装置名为长期感应系统(Long Term Sensor System)，这是Medtronic MiniMed对治疗糖尿病装置临床研究的组成部分。该设备包括一个可植入注射泵及感应器。该感应器利用基于酵素的电化技术测量血糖值，安装在恩蒂右心房附近的血管中。感应器与植入小腹部的3英寸长的注射泵相连，患者可以使用一个手持遥控装置控制胰岛素的注射。
罗利．韩(Lori Hahn)今年41岁，已经是三个孩子的母亲。十二年来一直依赖胰岛素的她参加了同样的临床试验。她说，这种装置使她变成了一个没有残疾的健全人。
韩说，有了这种装置，她几乎忘记了自己是个糖尿病患者。它实在是好得不能再好了。
Medtronic MiniMed已经进行过几次成功的试验。在为期两天的短暂试验中，受试者的血糖水平都维持正常。
血糖监控装置的发展
人造胰腺面世尚需假以时日，而在此之前糖尿病患者应当有更好的方式监控病情。
当前用于监控血糖水平的设备的问题，在于他们测试血糖需要时间，而且测出的数字也不准确，因此患者很难从中发现规律。这种做法，有点像是没有卫星云图但却偏偏还要进行天气预报。
此外，这种装置还需要频繁验血，一些患者感到痛苦因而设法避免。
Medtronic近来还推出了一种名为CGMS System Gold的装置。传感器可以植入皮下多达72小时。信息传输给监控器，而医生能够通过电脑下载其读值，以便对患者血糖的规律形成一个概念。
Joslin Diabetes Center的医疗部门负责人、哈佛医学院教授阿伦．摩斯(Alan Moses)说，这第一步非常重要。
TheraSense希望在2004年底或2005年初以前推出Freestyle Navigator系统，这种装置将使患者能够随时测试血糖水平而无需频繁验血。不过，具体上市时间将取决于美国食品和药物管理局(FDA)的批准时间。
这种装置由一个微小的传感器组成。它只有头发粗细，深入腹部皮肤大约5毫米处，然后通过一个类似传呼器的小型装置显示血糖水平。利用这种装置，患者一天只需验血一次以保证测试的持续性，验血次数只有当前产品的10%。
美国糖尿病学会的巴雷特说，此类装置面临的挑战之一来自生物本能反应，人体可能会分解感应器中的酵素。
开发一种置于皮下或血管内并需长期植入的装置可不是简单把戏。
TheraSense首席执行长马克．洛茨(Mark Lortz)在接受采访时表示，公司将设法以目前一天验血四次的产品价格将这种新装置推向市场。
摩斯对TheraSense设备很感兴趣。
他说，该装置能在每一分钟都向患者显示出血糖读值。真正实现血糖读值的时时更新，以便使患者及时注入胰岛素以维持血糖稳定。
摩斯说，如果公司确实能以其首席执行长预测的价格出售这种设备，竞争的格局将完全改观。他们将拥有巨大的优势。
摩斯是TheraSense医疗顾问委员会成员之一，但他不从公司收取任何报酬。
