Insulin Shock! Diabetics die from too LITTLE sugar
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 U.S. 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.
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 alone, 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 amputation. 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."
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 had spent years and made enormous efforts, 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," Hirsch said. "Telling these patients to get their blood sugar up will be very difficult."
He added that organizations like the American Diabetes Association and the American Association of Clinical Endocrinologists would be in a quandary. Their 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 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.
The study tested three types of treatments simultaneously - intense or less intense blood-sugar control; intense or less intense cholesterol control; and intense or less intense blood-pressure control. The cholesterol and-blood pressure parts of the study are continuing.
The researchers asked whether there were any drugs or drug combinations that might have been to blame for the higher death rate. They found none, said Dr. Denise 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, 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 Nissen, chairman of the department of cardiovascular medicine at the Cleveland Clinic.
Or it may be that participants reduced their blood sugar too fast, 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.
Created 60 years ago as a cornerstone of the welfare state, the National Health Service is devoted to the principle of free medical care for everyone in Britain. But recently it has been wrestling with a problem its founders never anticipated: how to handle patients with complex illnesses who want to pay for parts of their treatment while receiving the rest free from the health service.
Although the government is reluctant to discuss it, hopscotching back and forth between private and public care has long been standard here for those who can afford it. But a few recent cases have exposed fundamental contradictions between policy and practice in the system, and tested its founding philosophy to its very limits.
One such case was Debbie Hirst's. Her breast cancer had metastasized, and the health service would not provide her with Avastin, a drug that is widely used in the United States and Europe to keep such cancers at bay. So, with her oncologist's support, she decided last year to try to pay the roughly £60,000, or $116,000, cost herself, while continuing with the rest of her publicly financed treatment.
By December, she had raised £10,000 and was preparing to sell her house to raise more. But then the government, which had tacitly allowed such arrangements before, put its foot down. Hirst heard the news from her doctor.
"He looked at me and said, 'I'm so sorry, Debbie. I've had my wrists slapped from the people upstairs, and I can no longer offer you that service,' " Hirst said.
"I said, 'Where does that leave me?' He said, 'If you pay for Avastin, you'll have to pay for everything' " - in other words, for all her cancer treatment, far more than she could afford.
Officials said that allowing Hirst and others like her to pay for extra drugs to supplement government care would violate the philosophy of the health service by giving richer patients an unfair advantage over poorer ones.
Patients "cannot, in one episode of treatment, be treated on the NHS and then allowed, as part of the same episode and the same treatment, to pay money for more drugs," Health Secretary Alan Johnson told Parliament. "That way lies the end of the founding principles of the NHS."
But Hirst, who is 57 and was first diagnosed with cancer in 1999, went to the news media, and so did other patients in similar situations. And it became clear that theirs were not isolated cases.
In fact, it is widely acknowledged by patients, doctors and officials across the health care system that patients suffering from every imaginable complaint regularly pay for some parts of their treatment while receiving the rest free.
"Of course it's going on in the NHS all the time, but a lot of it is hidden - it's not explicit," said Dr. Paul Charlson, a general practitioner in Yorkshire and a member of Doctors for Reform, a group that is highly critical of the health service. Last year, he was the co-author of a paper laying out examples of how patients with the initiative and the money dip in and out of the system, in effect buying upgrades to their basic free medical care.
"People swap from public to private sector all the time, and they're topping up for virtually everything," he said.
For instance, he said, a patient put on a five-month waiting list to see an orthopedic surgeon might pay £120 for a private consultation, and then switch back to the health service for the actual surgery from the same doctor.
"Or they'll buy an MRI scan because the wait is so long, and then take the results back to the NHS," Charlson said.
In his paper, he also wrote about a 46-year-old woman with breast cancer who paid £250 for a second opinion when the health service refused to provide her with one; an elderly man who spent thousands of pounds on a new hearing aid instead of enduring a year-long wait on the health service; and a 29-year-old woman who - with her doctor's blessing - bought a three-month supply of Tarceva, a drug to treat pancreatic cancer, for more than £3,150 on the Internet because she could not get it through the NHS.
Asked why these were different from cases like Hirst's, a spokeswoman for the health service said that no officials were available to comment.
In any case, the rules about private co-payments, as they are called, in cancer care are contradictory and hard to understand, said Nigel Edwards, the policy director of the NHS Confederation, which represents hospitals and other health-care providers. "I've had conflicting advice from different lawyers," he said, "but it does seem like a violation of natural justice to say that either you don't get the drug you want, or you have to pay for all your treatment."
Karol Sikora, a professor of cancer medicine at the Imperial College School of Medicine and one of Charlson's co-authors, said that co-payments were particularly prevalent in cancer care. Armed with information from the Internet and patients' networks, cancer patients are increasingly likely to demand, and pay for, cutting-edge drugs that the health service considers too expensive to be cost-effective.
"You have a population that is informed and consumerist about how it behaves about health care information, and an NHS that can no longer afford to pay for everything for everybody," he said.
As wrenching as it can be to administer more sophisticated drugs to some patients than to others, he said, "if you're a doctor working in the system, you should let your patients have the treatment they want, if they can afford to pay for it."
In any case, he said, the health service is riddled with inequities. Some drugs are available in some parts of the country and not in others. Waiting lists for treatment vary wildly from place to place. Some regions spend £140 per capita on cancer care, Sikora said, while others spend just £45.
In Hirst's case, the confusion was compounded by the fact that three other patients at her hospital were already doing what she had been forbidden to do - buying extra drugs to supplement their cancer care. The arrangements had "evolved without anyone questioning whether it was right or wrong," said Laura Mason, a hospital spokeswoman. Because their treatment began before the Health Department explicitly condemned the practice, they have been allowed to continue.
The rules are confusing.
"It's quite a fine line," Mason said. "You can't have a course of NHS and private treatment at the same time on the same appointment - for instance, if a particular drug has to be administered alongside another drug which is NHS-funded."
But, she said, the health service rules seem to allow patients to receive the drugs during separate hospital visits - the NHS drugs during an NHS appointment, the extra drugs during a private appointment.
One of Hirst's troubles came, it seems, because the Avastin she proposed to pay for would have had to be administered at the same time as the drug Taxol, which she was receiving free on the health service. Because of that, she could not schedule separate appointments.
But in a final irony, Hirst was told early this month that her cancer had spread and her condition had deteriorated so much that she could have the Avastin after all - paid for by the health service. In other words, a system that forbade her to buy the medicine earlier was now saying that she was so sick she could have it at public expense.
Hirst is pleased, but only to a point. Avastin is not a cure, but a way to extend her life, perhaps only by several months, and she has missed valuable time. "It may be too bloody late," she said.