Diabetes Study Partially Halted After Deaths

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自由時報摘要

糖尿病降血糖更危險？
降低血糖 反而提高死亡機率
〔編譯羅彥傑／紐約時報七日報導〕數十年來，科學家相信，如果糖尿病患者將血糖降至一般水準，就不再會是心臟病猝死的高危險群。但美國聯邦政府所屬的國家心、肺暨血液研究院針對逾一萬名中年以上、患有第二型糖尿病的民眾所做的一項大型研究，卻發現降低血糖事實上反而提高死亡機率。研究人員因此宣佈，決定緊急暫停部份的研究，因為此一令人震驚的結果挑戰了糖尿病的治療方式。

這項結果不代表降血糖毫無意義。降血糖能避免罹患腎臟病、失明與截肢，但新的研究發現卻使得過去認定血糖愈低愈好及降血糖至正常水準能提高存活機率等金科玉律受到質疑。醫學專家都大感震驚。進行這項研究的研究人員強調，糖尿病患者仍應先向自己的醫師諮商，然後才考慮改變其用藥方式。

研究結果 顛覆傳統治療方式
主張低血糖的學理根深柢固，大多數人都認定血糖愈低愈好，但從來沒人嚴格驗證此一說法。所以這項研究要問的是，如果第二型糖尿病患（占全部病患的九十五％）的血糖量很低，是否能免於得心臟病與增加活命機會。

參與這項研究的患者，是以隨機方式指定降低血壓至接近正常水準，結果密集降血糖組與未嚴格控制血糖水準的對照組相比，多出五十四件死亡案例。研究人員立刻中止密集降血糖的療法，改以較溫和的治療方式。這些患者加入研究的時間，迄今平均為四年。
執行這項計畫的賽門斯莫頓博士說，他們本來懷疑是否是任何藥物或合併用藥造成患者死亡率提高，但後來發現不是；就連被懷疑會增加糖尿病患心臟病死亡機率的藥物Avandia，在研究中也沒有造成這種效果。

醫師主張 仍應努力控制血糖
威斯康辛大學糖尿病專家赫許博士說，這項結果很難說服那些花了好幾年且透過飲食與服藥來降血糖的患者，「他們不會想就此鬆懈」，「要這些患者提高血糖將難如登天」。
〔記者田瑞華／台北報導〕耕莘醫院新陳代謝科主治醫師裴馰表示，國內的糖尿病患普遍血糖控制仍不夠良好，很難達到正常血糖值，因此不可以看到這項研究發現就鬆懈控制血糖。而且，在這項研究結果獲得進一步討論和更多研究證實之前，糖尿病患仍應該遵照醫師指示，努力控制血糖比較好。



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【聯合報╱編譯王麗娟／報導】
2008.02.08 08:02 am

數十年來，研究人員始終認為，糖尿病患降低血糖，同時可降低死於心臟病的機率。但美國官方衛生機構一項大規模研究發現，嚴格控制血糖反而提高死亡率。由於結果出人意外，這項以上萬名中老年第二型糖尿病患為對象的研究，已緊急喊停。

儘管如此，研究人員建議，任何病患想換藥使用，均需徵求醫生的意見。目前，研究人員仍不清楚嚴格控制血糖反而提高死亡率的原因。

紐約時報報導，這項六日公布的研究發現，將血糖降到正常濃度的一組，死亡人數較血糖控制較不嚴格的一組多出五十四人。這些接受實驗的病患平均參與四年。

上述結果並不代表控制血糖毫無意義。降血糖可減少糖尿病患發生腎臟病、眼盲和截肢等併發症，但新發現顯示，傳統認為把血糖降得越低越好，或血糖應盡量降到正常值的信條，不見得是定律。

醫學專家對上述結果頗感驚訝。「美國心臟病學院」院長杜夫說：「新發現令人不安與困擾。五十年來，我們一直強調降血糖。」華盛頓大學的糖尿病研究人員赫許表示很難向病患解釋上述研究結果，許多病患嚴格執行飲食控制與用藥多年，很難說服他們放寬對自己的要求。
預期「美國糖尿病協會」也會陷入兩難之境，該組織的指導原則至今仍是患者血糖越接近正常越好。

糖尿病分為先天性的第一型糖尿病和成年後罹患的第二型糖尿病，後者占所有糖尿病的九成五。由於降低血糖理論根深柢固，因此一九九○年美國國家衛生研究院「國家心肺及血液研究中心」與「國家糖尿病、消化、腎臟疾病研究中心」建議作這項糖尿病研究時，完全沒料到會出現這樣的結果。

參加研究的對象平均六十二歲，糖尿病史十年，除了高血糖，這些病患可能還有心臟病、高血壓、高膽固醇等毛病。

研究共分成血糖、膽固醇、高血壓三組。血糖的實驗已停止，其他兩組仍繼續進行。血糖組分成兩個對照組，嚴格執行血糖控制的一組，一天可能施打四到五次胰島素，或一天檢查血糖七到八次，有時還配合藥物使用，將血糖降到儘可能正常，沒想到死亡率還高於血糖控制較不嚴格的對照組。

研究人員原本懷疑某種藥物或藥物間的交互作用造成這種現象，但經仔細研究分析，已排除這種可能。兩組患者的死亡病例也大多是因為心臟病，而非其他不尋常的死因。這項顛覆性的發現究竟原因為何，有待進一步研究。


Diabetes Study Partially Halted After Deaths

By GINA KOLATA
Published: February 7, 2008

For decades, researchers believed that if people with diabetes lowered their blood sugar to normal levels, they would no longer be at high risk of dying from heart disease. But a major federal study of more than 10,000 middle-aged and older people with Type 2 diabetes has found that lowering blood sugar actually increased their risk of death, researchers reported Wednesday.

Related
Times Health Guide: Diabetes »

The researchers announced that they were abruptly halting that part of the study, whose surprising results call into question how the disease, which affects 21 million Americans, should be managed.

The study’s investigators emphasized that patients should still consult with their doctors before considering changing their medications.

Among the study participants who were randomly assigned to get their blood sugar levels to nearly normal, there were 54 more deaths than in the group whose levels were less rigidly controlled. The patients were in the study for an average of four years when investigators called a halt to the intensive blood sugar lowering and put all of them on the less intense regimen.

The results do not mean blood sugar is meaningless. Lowered blood sugar can protect against kidney disease, blindness and amputations, but the findings inject an element of uncertainty into what has been dogma — that the lower the blood sugar the better and that lowering blood sugar levels to normal saves lives.

Medical experts were stunned.

“It’s confusing and disturbing that this happened,” said Dr. James Dove, president of the American College of Cardiology. “For 50 years, we’ve talked about getting blood sugar very low. Everything in the literature would suggest this is the right thing to do,” he added.

Dr. Irl Hirsch, a diabetes researcher at the University of Washington, said the study’s results would be hard to explain to some patients who have spent years and made an enormous effort, through diet and medication, getting and keeping their blood sugar down. They will not want to relax their vigilance, he said.

“It will be similar to what many women felt when they heard the news about estrogen,” Dr. Hirsch said. “Telling these patients to get their blood sugar up will be very difficult.”
Dr. Hirsch added that organizations like the American Diabetes Association would be in a quandary. Its guidelines call for blood sugar targets as close to normal as possible.
And some insurance companies pay doctors extra if their diabetic patients get their levels very low.

The low-blood sugar hypothesis was so entrenched that when the National Heart, Lung and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases proposed the study in the 1990s, they explained that it would be ethical. Even though most people assumed that lower blood sugar was better, no one had rigorously tested the idea. So the study would ask if very low blood sugar levels in people with Type 2 diabetes — the form that affects 95 percent of people with the disease — would protect against heart disease and save lives.

Some said that the study, even if ethical, would be impossible. They doubted that participants — whose average age was 62, who had had diabetes for about 10 years, who had higher than average blood sugar levels, and who also had heart disease or had other conditions, like high blood pressure and high cholesterol, that placed them at additional risk of heart disease — would ever achieve such low blood sugar levels.

Study patients were randomly assigned to one of three types of treatments: one comparing intensity of blood sugar control; another comparing intensity of cholesterol control; and the third comparing intensity of blood pressure control. The cholesterol and blood pressure parts of the study are continuing.

Dr. John Buse, the vice-chairman of the study’s steering committee and the president of medicine and science at the American Diabetes Association, described what was required to get blood sugar levels low, as measured by a protein, hemoglobin A1C, which was supposed to be at 6 percent or less.

“Many were taking four or five shots of insulin a day,” he said. “Some were using insulin pumps. Some were monitoring their blood sugar seven or eight times a day.”

They also took pills to lower their blood sugar, in addition to the pills they took for other medical conditions and to lower their blood pressure and cholesterol. They also came to a medical clinic every two months and had frequent telephone conversations with clinic staff.

Those assigned to the less stringent blood sugar control, an A1C level of 7.0 to 7.9 percent, had an easier time of it. They measured their blood sugar once or twice a day, went to the clinic every four months and took fewer drugs or lower doses.

So it was quite a surprise when the patients who had worked so hard to get their blood sugar low had a significantly higher death rate, the study investigators said.

The researchers asked whether there were any drugs or drug combinations that might have been to blame. They found none, said Dr. Denise G. Simons-Morton, a project officer for the study at the National Heart, Lung and Blood Institute. Even the drug Avandia, suspected of increasing the risk of heart attacks in diabetes, did not appear to contribute to the increased death rate.

Nor was there an unusual cause of death in the intensively treated group, Dr. Simons-Morton said. Most of the deaths in both groups were from heart attacks, she added.
For now, the reasons for the higher death rate are up for speculation. Clearly, people without diabetes are different from people who have diabetes and get their blood sugar low.

It might be that patients suffered unintended consequences from taking so many drugs, which might interact in unexpected ways, said Dr. Steven E. Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic.

Or it may be that participants reduced their blood sugar too fast, Dr. Hirsch said. Years ago, researchers discovered that lowering blood sugar very quickly in diabetes could actually worsen blood vessel disease in the eyes, he said. But reducing levels more slowly protected those blood vessels.

And there are troubling questions about what the study means for people who are younger and who do not have cardiovascular disease. Should they forgo the low blood sugar targets?
No one knows.

Other medical experts say that they will be discussing and debating the results for some time.

“It is a great study and very well run,” Dr. Dove said. “And it certainly had the right principles behind it.”

But maybe, he said, “there may be some scientific principles that don’t hold water in a diabetic population.”