Dave Smith found out he had Type 2 diabetes by accident, after a urine test.
“Whoa, look at the sugar in here,” his doctor told him. Mr. Smith’s blood sugar level was sky high and glucose was spilling into his urine.
That was about nine years ago, and from then on Mr. Smith, like so many with diabetes, became fixated on his blood sugar. His doctor warned him to control it or the consequences could be dire — he could end up blind or lose a leg. His kidneys could fail.
Mr. Smith, a 43-year-old pastor in Fairmont, Minn., tried hard. When dieting did not work, he began counting carbohydrates, taking pills to lower his blood sugar and pricking his finger several times a day to measure his sugar levels. They remained high, so he agreed to add insulin to his already complicated regimen. Blood sugar was always on his mind.
But in focusing entirely on blood sugar, Mr. Smith ended up neglecting the most important treatment for saving lives — lowering the cholesterol level. That protects against heart disease, which eventually kills nearly everyone with diabetes.
He also was missing a second treatment that protects diabetes patients from heart attacks — controlling blood pressure. Mr. Smith assumed everything would be taken care of if he could just lower his blood sugar level.
Blood sugar control is important in diabetes, specialists say. It can help prevent dreaded complications like blindness, amputations and kidney failure. But controlling blood sugar is not enough.
Nearly 73,000 Americans die from diabetes annually, more than from any disease except heart disease, cancer, stroke and pulmonary disease.
Yet, largely because of a misunderstanding of the proper treatment, most patients are not doing even close to what they should to protect themselves. In fact, according to the federal Centers for Disease Control and Prevention, just 7 percent are getting all the treatments they need.
“That, to me, is mind-boggling,” said Dr. Michael Brownlee, director of the JDRF International Center for Diabetic Complications Research at the Albert Einstein College of Medicine in New York. “It makes me ask, What is going on? I can only conclude that people are not aware of their risks and what could be done about them.”
In part, the fault for the missed opportunities to prevent complications and deaths lies with the medical system. Most people who have diabetes are treated by primary care doctors who had just a few hours of instruction on diabetes, while they were in medical school. Then the doctors typically spend just 10 minutes with diabetes patients, far too little for such a complex disease, specialists say.
In part it is the fault of proliferating advertisements for diabetes drugs that emphasize blood sugar control, which is difficult and expensive and has not been proven to save lives.
And in part it is the fault of public health campaigns that give the impression that diabetes is a matter of an out-of-control diet and sedentary lifestyle and the most important way to deal with it is to lose weight.
Most diabetes patients try hard but are unable to control their disease in this way, and most of the time it progresses as years go by, no matter what patients do.
Mr. Smith, like 90 percent of diabetes patients, has Type 2 diabetes, the form that usually arises in adulthood when the insulin-secreting cells of the pancreas cannot keep up with the body’s demand for the hormone. The other form of diabetes, Type 1, is far less common and usually arises in childhood or adolescence when insulin-secreting pancreas cells die.
And, like many diabetes patients, Mr. Smith ended up paying the price for his misconceptions about diabetes. Last year, he had a life-threatening heart attack.
The Heart Disease
Just after returning from church last October, Mr. Smith had a discomforting sensation. Deciding to focus on something else, he went to a local newspaper office where he was weekend editor. But the strange feeling persisted and intensified.
“I felt a pain in my chest,” Mr. Smith recalled. “It wasn’t sharp — it was more of a kind of pressure, a feeling like something is contracting.”
The pain spread, to his neck, along his shoulder, down to his biceps. Mr. Smith, alone and frightened, looked up heart attack symptoms on the American Heart Association’s Web site. They were exactly what he was experiencing.
An hour later, Mr. Smith was at the Mayo Clinic in Rochester, Minn., in the throes of a major heart attack, transported by helicopter while his wife and two young sons frantically drove two and a half hours to be with him. A main artery to his heart was 90 percent blocked. If he had waited to seek help or if his local hospital and doctor had not acted quickly and sent him to the Mayo Clinic, he probably would have died.
Mr. Smith thought his biggest risk from diabetes was blindness or amputations. He never thought about heart disease and had no idea how important it was to control cholesterol levels and blood pressure. He said his doctor had not advised him to take a cholesterol-lowering or blood pressure drug and he did not think he needed them.
Most people with diabetes are equally unaware of the danger that heart disease poses for them.
A recent survey by the American Diabetes Association conducted by RoperASW found that only 18 percent of people with diabetes believed that they were at increased risk for cardiovascular disease.
Yet, said Dr. David Nathan, director of the Diabetes Center at Massachusetts General Hospital, “when you think about it, it’s not the diabetes that kills you, it’s the diabetes causing cardiovascular disease that kills you.”
Dr. Brownlee said he was stunned by the results of the diabetes association poll. “If you are one of those 82 percent who don’t think you are at increased risk,” he said, “finding out that you are and that you can decrease that risk substantially could literally change your life.”
The science is clear on the huge benefits for people with diabetes of lowering cholesterol and controlling blood pressure. After multiple studies, costing hundreds of millions of dollars and involving tens of thousands of subjects, national guidelines were rewritten to reflect the new data, and professional organizations issued recommendations for diabetes care.
With cholesterol, the guidelines say that levels of LDL cholesterol, the form that increases heart disease risk, should be below 100 milligrams per deciliter and, if possible, 70 to 80. Yet, Dr. Brownlee said, diabetes patients with LDL cholesterol levels of 100 to 139 often are told that their levels — ideal for a healthy person without diabetes — are terrific.
“Many practicing doctors just don’t know that an LDL cholesterol number that is normal for someone without diabetes is not normal for someone with diabetes,” he said.
Mr. Smith found all that out too late. The heart attack, he said, “really blindsided me.”
He also did not know the other measures proven to prevent complications in diabetes. He was correct that high blood sugar is dangerous. It can damage the small blood vessels in the eyes, leading to blindness; the nerves in the feet, leading to amputations; and the kidneys, leading to kidney failure.
But no matter how carefully patients try to control their blood sugar, they can never get it perfect — no drugs can substitute for the body’s normal sugar regulation. So while controlling blood sugar can be important, other measures also are needed to prevent blindness, amputations, kidney failure and stroke. Mr. Smith was doing none of them.
He also made the common assumption that Type 2 diabetes is simply a consequence of being fat. And that losing weight will help cure it.
Obesity does increase the risk of developing diabetes, but the disease involves more than being obese. Only 5 percent to 10 percent of obese people have diabetes, and many with diabetes are not obese. To a large extent, Type 2 diabetes is genetically determined — if one identical twin has it, the other has an 80 percent chance of having it too. In many cases, weight loss can help, but, as Mr. Smith has learned, most who lose weight are not cured of the disease. He lost 40 pounds but still has diabetes.
“Everybody in the act of losing weight will have a pretty dramatic improvement pretty quickly,” said Dr. C. Ronald Kahn, a diabetes researcher and professor of medicine at Harvard Medical School. Blood sugar levels drop precipitously and the disease seems to be under control. But that is because the metabolic process of weight loss lessens diabetes. Once weight is lost, he added, and people stabilize at a lower weight, their diabetes may remain.
When it comes to weight loss, Dr. Kahn said, “there is a range of susceptibilities in how people react.”
Complex Regimens
Before he left the hospital, Mr. Smith’s doctors told him about his new diabetes regimen: a statin to drive his cholesterol level very low, two drugs to lower his blood pressure, an aspirin, insulin and two drugs to reduce his blood sugar levels. That new list of drugs was what he should have been taking all along.
Mr. Smith is taking them now, terrified that his heart disease will progress.
“I’ll never be out of the woods,” he said. “I’ve got to face that.”
Diabetes researchers say stories like Mr. Smith’s are all too familiar.
The statistics are grim: A quarter to a third of all heart attack patients have diabetes, even though diabetes patients constitute just 9.3 percent of the population. Another 25 percent of heart attack patients are verging on diabetes with abnormally high blood sugar levels.
Most worrisome are diabetes patients who already have symptoms of heart disease, like chest pains or a previous heart attack. “That is a terrible situation,” said Dr. James Cleeman, coordinator of the National Cholesterol Education Program at the National Institutes of Health. Those patients, Dr. Cleeman said, are set up for a fatal heart attack and should be stringently controlling their cholesterol and blood pressure.
And it is not just that many diabetes patients are overweight, as people with Type 1 diabetes, who often are thin, also have a high risk of heart disease. There is something about diabetes itself, researchers say, that leads to high levels of LDL cholesterol and a form of LDL cholesterol particles that is particularly dangerous. Diabetes also leads to increased levels of triglycerides, which are fats in the blood that increase heart disease risk, and in diabetes is linked to high blood pressure.
Being obese or overweight, in contrast, are “weak contributors to heart attack risk,” Dr. Nathan said.
Type 2 diabetes “does not exist in isolation,” Dr. Nathan said. “Underlying diabetes are all these cardiovascular risk factors.”
Somehow, though, it has taken quite a while for the alarm bells to go off.
One reason might be that it was heart disease researchers, not diabetes researchers, who conducted the seminal studies.
The key to saving lives is to reduce levels of LDL cholesterol to below 100 and also control other risk factors like blood pressure and smoking. The cholesterol reduction alone can reduce the very high risk of heart attacks and death from cardiovascular disease in people with diabetes by 30 percent to 40 percent, Dr. Cleeman said. And clinical trials have found that LDL levels of 70 to 80 are even better for people with diabetes who already have overt heart disease.
Studies of blood sugar control have been more problematic than those of cholesterol lowering.
In Type 2 diabetes, the most ambitious effort was a huge study in Britain. It found that rigorous blood sugar control could lower the risk of complications that involved damage to small blood vessels, a list that includes blindness, nerve damage and kidney damage. But there was no effect on the overall death rate. There was a small decrease in the number of heart attacks but it was not statistically significant, meaning it could have occurred by chance.
The National Institutes of Health is trying again, with a larger study of blood sugar control that includes enough patients to detect more subtle effects on the heart attack rate if they exist. For now, though, the answer simply is not known.
In Type 1 diabetes, a large federal study did find evidence that rigorous blood sugar control could reduce heart disease risk. But the effect emerged 12 years after the study ended and most of the patients, in those years, had not been able to sustain the blood sugar control that they had had during the study. Did the short period of rigorous control exert a delayed effect on heart disease or was the effect caused by some other factor during the study or afterward, some asked? While most think it was caused by blood sugar control, it is impossible to know for sure.
The result, notes Dr. John Buse, president-elect for science and medicine at the American Diabetes Association, is that for people with Type 1 and, especially, for those with Type 2 diabetes, there are still questions about whether and to what extent blood sugar control protects against heart disease and saves lives.
That leaves cholesterol lowering, for patients with Type 1 and Type 2 diabetes, as the most effective and easiest way by far to reduce the risk of heart disease and the only treatment proven to save lives. But doctors say achieving the recommended cholesterol levels usually means taking a statin. Some patients resist, wary of intense drug company marketing to patients and afraid of side effects like muscle or liver damage which, although extremely rare, have frightened many away from the drugs, Dr. Brownlee and other diabetes specialists said. (Dr. Brownlee said he had no financial ties to statin makers.)
Others point to drug company advertising itself.
Statin advertising, said Dr. Irl B. Hirsch, a professor of medicine and director of the diabetes clinic at the University of Washington, is all about heart disease, and the advertisements do not mention diabetes. The diabetes advertisements are all about blood sugar. Dr. Hirsch has seen few that put the two together.
Yet lowering cholesterol with statins, Dr. Hirsch and others said, is much simpler than anything else diabetes patients are asked to do. And, he added, the drugs are among the best studied and the safest on the market. (Dr. Hirsch said he had no financial ties to statin makers.)
Dr. Hirsch has a message for diabetes patients: If he had to rate the different regimens for a typical middle-age person with Type 2 diabetes, the first priority would be to take a statin and lower the LDL cholesterol level.
Dr. Brownlee agreed, but added that the two other measures to protect against heart disease, blood pressure control and taking an aspirin to prevent blood clots, should not be neglected.
“Right now, without waiting for lots of exciting things that are almost in the pipeline or in the pipeline, starting tomorrow, if everyone did these things — taking a statin, taking a blood pressure medication, and maybe taking an aspirin — you would reduce the heart attack rate by half.”
The Burnout
Even when patients do take the right steps to control diabetes, the grueling process can simply wear them down.
Virgil Umbarger learned that he had Type 2 diabetes when he was 39 and had a medical exam for a life insurance policy.
That was 25 years ago, and the start of a journey that diabetes specialists say ends up fundamentally changing a person’s world. Unlike Mr. Smith, who has just awakened to the danger he is in, Mr. Umbarger, a funeral director in Yakima, Wash., has lived with diabetes and its increasingly complex regimen for decades. And, as happens with most diabetes patients eventually, he feels he is reaching a point where he just cannot continue to do all that he should to protect his health.
In a sense, Mr. Umbarger said, he was not completely surprised when he learned he had diabetes, because it runs in his family. But he never thought it would happen to him. At 6 feet tall and 195 pounds, he was not heavy.
Still, Mr. Umbarger’s first thought was to lose weight. “I starved myself,” he said, and lost 15 pounds. But he still had diabetes and the pounds crept back on.
Dr. Buse said his patients knew how important it was to diet and exercise, but most could not do it enough to make a difference, and some were also thwarted by medications to control blood sugar that make patients gain weight.
In the end, Mr. Umbarger decided to seek care from a diabetes specialist. He chose Dr. Hirsch, even though it meant driving nearly three hours each way for an office visit. There was no one nearby with that kind of expertise, Mr. Umbarger said.
On his first visit, Dr. Hirsch gave him a fistful of prescriptions, including a statin, blood pressure medications and one for the drug Mr. Umbarger dreaded — insulin. He also told Mr. Umbarger to have regular checks for eye, nerve and kidney damage. And he has to watch what he eats and count carbohydrates.
Dr. Hirsch and other diabetes specialists say they are well aware of how daunting the program can be.
“Many come here once or twice and walk away saying, ‘I don’t want to do this,’ ” Dr. Hirsch said.
Not Mr. Umbarger. For years, he tried to do all that was required. He can cope with the medications and the long drives to see Dr. Hirsch. The problem for him, as for most diabetes patients eventually, is the blood sugar monitoring. He is supposed to prick his finger six or more times a day to measure his glucose levels and adjust his insulin dose accordingly.
Every time he checks his blood sugar is like getting a report card — was he eating too many carbohydrates? Did he get the insulin dose right?
“I don’t want to look,” he said.
“Pricking your finger, seeing that number day after day, it wears on you,” Mr. Umbarger said. “It’s like a ball and chain.” He confesses that he has only been checking his blood sugar once or twice a day, guessing at many of his insulin doses. His blood sugar levels have been rising and guilt hangs over him.
Meanwhile, no matter what they do, most people with Type 2 diabetes get worse as the years go by. Patients make less and less insulin and their cells become less and less able to use the insulin they do produce.
“That is why it is not uncommon to start initially with diet therapy, then after a few years we need to add a drug that improves insulin sensitivity,” Dr. Kahn said. “Then when that drug isn’t enough, we add a second drug that improves insulin sensitivity by a different mechanism. Then we add a drug that stimulates that pancreas to make more insulin.”
Then, he added, patients with Type 2 diabetes may need insulin itself, but when that happens they have to take even more than a person with Type 1 diabetes — two or even three times as much — because their cells no longer respond adequately to the hormone.
While it is not easy to re-energize burned-out patients, Dr. Hirsch said, at the very least, doctors and patients should know what is important.
“We already have the miracle pills” — statins and blood pressure medications, he said. And they are available for pennies a day, as generics.
“We need patient education and physician training that this stuff is out there and this is what we should be focusing on to make a difference in lives.”
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香港大學林大慶教授訪談 
） 【医】予後; 予測.
prog・nos・ti・cate
prog・nos・ti・ca・tion ━━ n. （前兆による）予知, 予言, 予測; 前兆.
The team's novel discovery opens up opportunities for the design of new drugs to combat high blood pressure 
