糖尿病治疗新策略

Researchers are trying new approaches to treat Type 2 diabetes amid widespread uncertainty about the most effective therapies and concerns that current strategies might be doing some patients more harm than good.

在人们普遍对何种糖尿病疗法最有效感到不确定、并且担忧当前的治疗策略对某些患者可能弊大于利的情况下，研究人员正在尝试治疗II型糖尿病的新方法。

New guidelines for treating the disease, which many experts consider a public-health crisis among millions of mostly overweight individuals, suggest doctors vary treatments depending on a patient's age, general health and even personal preferences. The recently updated guidelines recommend that doctors back away from pushing patients to get their blood sugar down to a standard targeted level. Aiming for a very low blood-sugar level might be appropriate for a younger person, for example, while older patients might do better with a less aggressive approach, according to the guidelines, published in June in the journal Diabetes Care.

糖尿病被许多专家视为是一个公共健康危机，患病人数达数以百万计，其中大多数为体重超重的人。6月份发表在《糖尿病护理》(Diabetes Care)杂志上的糖尿病治疗最新指引建议医生要根据患者的年龄、总体健康状况甚至是个人偏好来改变治疗方案。该指引建议，医生要避免强迫患者将血糖降至标准的目标水平。例如，该指引提出，制定一个非常低的血糖水平目标或许适用于年轻患者，但是采取更温和的治疗方法对年纪较大的患者效果或许会更好。

'We need to be less dogmatic about what matters and be open to different approaches and give patients a voice' in treatment decisions, says Victor Montori, a diabetes specialist at Mayo Clinic, in Rochester, Minn., who wasn't involved with writing the guidelines but supports the new direction.

美国明尼苏达州罗切斯特市梅奥诊所(Mayo Clinic)的糖尿病专家维克多·蒙托里(Victor Montori)说，“关于什么是重要因素，我们应该要不那么固守成规，要愿意接受不同的方法，并让患者（在决定治疗方案上）拥有话语权。蒙托里并未参与撰写这份新指引，但他对这个新方向持支持态度。

Another approach gaining wider acceptance for some patients is the use of bariatric surgery, which results in dramatic weight loss. Though it comes with risk of serious complications, the operation has been shown in recent studies to lead to a rapid lowering of blood sugar, often enabling patients to go off most or all of their diabetes medicines.

对于某些患者而言，另外一个获得较广泛认可的治疗方法是施行可大幅降低体重的减肥手术。虽然严重并发症风险会随之产生，但近期一些研究显示该手术能使血糖水平迅速降低，常常可使患者停用大部分或全部在服的糖尿病药物。

Some experts also are questioning the benefits of gradually stepping up the intensity of drug therapy, a widely accepted approach that was reaffirmed in the latest guidelines. The aim is to maintain a patient's blood-sugar level while keeping up with the progressive nature of the disease. But researchers at UT Southwestern Medical Center in Dallas, for instance, argue in a recent small study that hitting the disease early and hard is better.

有些专家也对逐渐增强药物疗法强度的益处提出质疑，这一获得广泛认可的方法在最新的指引中也再次得到肯定。该疗法的目的是要维持患者的血糖水平，同时也要跟上糖尿病会不断加重的这种特性。其中，位于达拉斯的德克萨斯大学西南医学中心(UT Southwestern Medical Center)的研究人员在最近一次小规模研究中提出，早早采用高强度疗法治疗糖尿病会更好。

More than 24 million Americans have Type 2 diabetes, the version of the disease usually associated with being overweight and living a sedentary lifestyle. By some estimates the number could double by 2025.

美国目前有2400多万II型糖尿病患者，该类型糖尿病通常与体重超重或是久坐不运动的生活方式存在关联。据估计，II型糖尿病的患病人数到2025年可能会翻番。

In diabetes, the body isn't able to effectively use insulin or to make enough of it to metabolize glucose in the food we eat, resulting in higher than normal levels of blood sugar. Heart attacks and strokes, kidney failure, nerve damage, blindness and vascular problems leading to amputation are among the long-term complications when the disease isn't well controlled. That makes diabetes a precursor to many of medicine's most debilitating conditions. Annual costs for treatment and loss of productivity associated with the disease are about $174 billion, according to the American Diabetes Association, an education and research association that devised the new treatment guidelines in collaboration with its counterpart the European Association for the Study of Diabetes.

患糖尿病后，人体会无法有效地利用胰岛素或是无法分泌足量的胰岛素来使我们从食物中摄取的葡萄糖发生代谢，从而导致血糖水平高于正常水平。糖尿病若没有控制好会引发一些慢性并发症，包括心脏并中风、肾衰竭、神经损伤、失明和会导致截肢的血管问题等。这使糖尿病成为药物所引发的最易使体质变差的诸多症状的前兆。美国糖尿病协会(American Diabetes Association，简称“ADA)的数据显示，美国用于治疗糖尿病的费用以及与该疾病相关的生产力的损失每年达到1740亿美元左右。ADA为一家教学和研究机构，其与欧洲糖尿病研究协会(European Association for the Study of Diabetes)合作制订了这份糖尿病治疗新指引。

There have been conflicting findings over the benefits for patients of keeping blood sugar strictly controlled, helping to fuel uncertainty about how best to treat the disease. Some popular diabetes drugs come with side effects─including weight gain, bone loss and even a small risk of certain cancers. And some data have shown that aggressive efforts to achieve tight glucose control, until recently considered a desirable goal, can lead to troubling episodes of low blood sugar called hypoglycemia or to increased risk for serious heart-related problems.

关于严格控制血糖水平的益处一直存在一些相互抵触的研究结果，这也加大了何种糖尿病疗法最有效这一问题的不确定性。一些常见的糖尿病药物具有副作用，例如体重增加、骨质疏松，甚至还有引发某些癌症的小风险。此外，一些数据也显示，采取激进疗法来严格控制住葡萄糖含量（直到最近还被认为是一个理想的目标）可能会造成患者有些时候血糖低的麻烦问题（即低血糖症），也可能会加大出现严重心脏问题的风险。

Although available drugs all improve blood-sugar levels, there is a lack of data to show whether they actually prevent or delay development of diabetes' long-term consequences.

尽管现有的药物都能改善血糖水平，但仍然缺乏有关它们是否真能阻止或延迟糖尿病的慢性并发症进一步加重的数据。

'The goal for treatment and the choice of individual drug must be personalized depending on the patient,' says Vivian Fonseca, the ADA's president for science and medicine and chief of endocrinology at Tulane University Health Sciences Center, in New Orleans.

ADA科学与医学事务主席、新奥尔良杜兰大学医学中心(Tulan University Health Sciences Center)内分泌学主任薇薇安·冯塞卡(Vivian Fonseca)认为，必须根据病人的情况制定专门的治疗目标和选择药物。

For most patients newly diagnosed with Type 2 diabetes, the first line of therapy is to improve diet and exercise habits to reduce blood-sugar levels. Usually metformin, a basic diabetes medication, is also prescribed. But patients with only mildly elevated blood-sugar levels may try to improve their health habits for up to six months to see if they can control the disease before beginning medication.

对于大多数新近被诊断患有II型糖尿病的患者，首先展开的系列疗法就是改善饮食和锻炼习惯以降低血糖水平，同时医生常常还会给他们开一种名为二甲双胍的治疗糖尿病的基本药物。不过，如果患者的血糖水平只是温和上升，他们可能要先试着改善自己的生活习惯六个月时间，以看看是否能在用药之前控制住糖尿玻

Blood sugar is typically defined as being under control for diabetic patients when it is below 7%, using a measure known as hemoglobin A1c, or HbA1c, according to the ADA. Under the new guidelines, that level is still desirable. But younger, newly diagnosed and well-motivated patients with a long life expectancy may want to aim for even lower levels, closer to 6%, according to the recommendations. Such aggressive therapy is expected to better keep the disease from progressing.

ADA称，糖化血红蛋白(HbA1c)水平低于7%的糖尿病患者通常会被认定血糖受到控制。新发布的指引也认为这一水平比较理想。但是，指引中还提到，年纪较轻、新近被诊断患并强烈希望自身长寿的患者可能要把血糖控制在接近6%的更低水平。这一比较激进的治疗方案可能会更好地防止糖尿病加重。

For older patients vulnerable to severe hypoglycemia or who may already have advanced cardiovascular disease, less stringent targets of up to 8% or even a little higher would be sufficient, the guidelines say. This also could reduce the burden of side effects from medications.

新指引称，对于易患严重低血糖症的老年患者或是可能已经患有心血管疾病的患者，目标可以放松一些，8%甚至是略高一些的血糖水平就足够了。这可能会减轻药物副作用带来的负担。

If patients fail to maintain control of their blood sugar with metformin plus diet and exercise, treatment guidelines call for them to add a second diabetes drug. This could include Januvia, made by Merck & Co.; Takeda Pharmaceuticals Co.'s Actos; NovoNordisk's Victoza and Sanofi's insulin drug Lantus.

如果患者服用二甲双胍、外加改善饮食和运动都不能控制住血糖水平，指引建议他们要另外再服用一种糖尿病药物，可以是默克公司(Merck & Co.)生产的西他列廷武田制药(Takeda Pharmaceuticals Co.)的艾可拓、诺和诺德(NovoNordisk)出产的利拉鲁口或赛诺菲 (Sanofi)的胰岛素药物来得时。

With hardly any trials comparing these drugs against each other on long-term benefits, the new diabetes guidelines urge doctors and patients to discuss the pros and cons of each drug. The Mayo Clinic, for instance, has developed an online tool for patients that takes account of such factors as weight change, cost, low blood-sugar risk, blood-testing requirements and side effects. Patients for whom weight gain is a concern─and that's the leading worry among diabetics, according to Mayo's Dr. Montori─may steer clear of drugs where that is an important side effect.

由于几乎没有什么试验将这些药物的长期药效进行比较，新指引建议医生和病人要讨论各种药物的利与弊。比如说，梅奥诊所开发了一个可让患者记录体重变化、费用、低血糖风险、验血要求以及副作用等因素的在线工具。该医院的蒙托里医生称，担心体重增加问题的患者（这也是糖尿病患者最大的担忧）可能要远离主要副作用就是增加体重的药物。

Typically, many diabetics progress through three or four treatment tiers, ultimately adding insulin injections to help control their blood sugar. Researchers at UT Southwestern Medical Center argue that such a graduated treatment strategy does little to change the disease process and means that patients' own insulin-producing beta cells remain continuously exposed to high blood sugar.

通常说来，许多糖尿病患者会依次经历三级或四级治疗方案，最终会加上胰岛素注射来控制他们的血糖。德克萨斯大学西南医学中心的研究人员认为，这种逐渐增强的治疗策略对于改变糖尿病的发展进程几乎没有什么作用，而且它还意味着患者自己分泌胰岛素的β细胞会持续暴露于高血糖风险之下。

In a study presented last month at the annual meeting of the ADA, UT Southwestern researcher Ildiko Lingvay said two types of more aggressive treatments using insulin and drugs started when patients were initially diagnosed effectively preserved the function of beta cells in a study of 58 patients followed for three years. The regimen included three months of insulin injections combined with metformin for all patients. Then patients were randomly assigned to either the same treatment or a combination of three oral drugs, which continued for more than three years. The study had important limitations, including the small number of patients and the lack of a control group that was followed with standard therapy to compare benefits and side effects.

德克萨斯大学西南医学中心的研究员伊尔迪科·林格维(Ildiko Lingvay)上个月在ADA年度会议上公布了一项研究结果。他说，当患者一开始得到有效诊断并且保留了β细胞的机能时，两类使用了胰岛素和药物的更加激进的治疗方案就可以启动。这项研究涉及58名患者，持续了三年时间。在该治疗方案中，研究人员会对所有患者进行三个月的胰岛素注射和二甲双胍治疗，随后会随机为患者实施同样的治疗方案或是实施由三种口服药组成的组合治疗方案，治疗时间持续了三年多。这项研究存在一些重大的不足之处，包括患者人数少、缺乏后续接受了标准治疗的控制组来比较二者之间的优点和副作用。

'At our institution we treat patients intensively from the time of diagnosis,' Dr. Lingvay says. 'We have no question this pays off in the long term.'

林格维称，“在我们中心我们从诊断之初就对患者实施高强度治疗，我们不怀疑从长远来看它能够产生效果。

Other research efforts to treat patients early with insulin have had mixed results at best. In the UT Southwestern, patients on both regimens gained weight.

其他一些在早期就利用胰岛素治疗患者的研究项目，其效果最多只能说好坏兼有。在德克萨斯大学西南医学中心的那项研究中，两种治疗方案中的患者体重均有所增加。

Gordon Weir, a researcher at Harvard-affiliated Joslin Diabetes Center, Boston, believes a strategy using short-term insulin treatment─a couple of weeks or months─to drive blood sugar back to safer levels, may eventually prove effective and become a treatment strategy.

位于波士顿的哈佛大学附属乔斯林糖尿病中心(Harvard-affiliated Joslin Diabetes Center)的研究员戈登·威尔(Gordon Weir)认为，利用短期（几周或几个月时间）胰岛素治疗方法促使血糖回降至安全水平可能最终会被证明是有效的方案并成为一种治疗策略。

But overall, diabetes, driven so intensely by overweight and obesity, 'is a terribly difficult problem,' Dr. Weir says. 'If we had a great treatment for obesity, that would make a huge impact.'

尽管如此，总体而言，威尔博士称受到超重和肥胖问题强烈影响的糖尿病是一个极难解决的问题。他说，“如果我们能有一种治疗肥胖的绝佳方法，那将会产生巨大影响。