How low to push blood sugar, and how to do it?

How low to push blood sugar, and how to do it?

How low to push blood sugar, and how to do it?

Heart disease is the leading cause of death for people with type 2 diabetes. Surely, then, the way to dodge this bullet is to treat the disease and lower blood sugar. Well, maybe. Growing evidence suggests that the method by which blood sugar is lowered may make a big difference in heart risk. That has raised a medical dilemma affecting tens of millions of people with type 2 diabetes — and for the doctors who treat them.

Some diabetes drugs lower blood sugar, yet somehow can increase the chances of heart attacks and strokes. Other medications have no effect on heart risk, while still others lower the odds of heart disease but may have other drawbacks, like high cost or side effects.

It’s becoming clear, researchers say, that there’s far too little evidence on how diabetes drugs affect the heart to make rational evidence-based judgments. “If you think the landscape is confusing, it really is,” said Dr Leigh Simmons, an internist in Boston.

“Daunting” is how Dr JoAnn Manson, chief of preventive medicine at Brigham and Women’s Hospital, describes the situation for patients and their doctors.

There are 12 classes of drugs on the market and two or three different agents in each class. The drugs range in price from about $4 a month for older drugs to $700 a month for newer ones, and they have varying side effects. Many patients take more than one drug.

The older, cheaper and more popular diabetes drugs were never tested for their effects on the heart — they were approved before any links were noticed.

A particular drug’s effect on blood sugar does not predict its effects on the heart. Even understanding the chemistry at work — the drugs act in very different ways to lower blood sugar — does not predict whether a particular medication will increase heart risk in a particular patient, researchers say.

“We can’t predict what happens to people just based on the mechanisms of these drugs,” said Dr Kasia J Lipska, a diabetes expert at Yale University who wrote a recent paper on the issue. “We have to study large groups of patients and examine what drugs reduce complications of diabetes such as heart attacks, and in which patients.”

But that has rarely been done. These drugs are already approved; there is little incentive to do such expensive studies now. “It’s a disgrace” that so little is known, said Dr Victor M Montori, a diabetes expert at the Mayo Clinic.

No one disputes the importance of lowering blood sugar when levels are very high. Doing so may help prevent complications like kidney disease, nerve damage and damage to the eyes, and may alleviate symptoms like fatigue and frequent urination. The starting point for lowering blood sugar is diet and exercise. But for many patients, that is not sufficient. Then doctors and patients are faced with two questions: How low should blood sugar go? And what drugs should be used to lower it?

Doctors track blood sugar by testing for levels of a protein, hemoglobin A1C, which reveals average levels over the previous three months. The higher a patient’s A1C, the greater the risk of complications of diabetes.

While this measurement is a good predictor of risk, “the question is, who benefits from intensive blood sugar lowering and which drugs are best for whom?” said Dr Harlan Krumholz, a cardiologist at Yale.

The target level varies among patients, though many do not realise it. They and their doctors often aim, at times obsessively, for an A1C level of seven. Yet that level is actually appropriate only for young, newly diagnosed people who have no other medical problems, Manson and others said.

Older patients with other chronic conditions, like atherosclerosis, should not aim for such a low level, the researchers added. Studies find no obvious benefit to them — no real reduction in the rate of complications like kidney, nerve or eye disease.

Perhaps more distressing, while higher levels of A1C are linked to an increased risk of heart disease, “what is not clear is whether a drug that reduces A1C will also improve cardiovascular risk,” said Montori. That was made abundantly clear in recent years when, at the insistence of the Food and Drug Administration, companies making some of the newer diabetes drugs began testing them to be certain they were not actually raising the chances of heart disease even as they lowered A1C in patients.

The results were a surprise. At identical A1C levels, some drugs lowered risk, some did not change it — and some actually increased the chances of heart disease. Older and much cheaper diabetes medications, like metformin, have not been subjected to such tests, although they do have long and well established safety records. But whether they actually prevent heart problems is unknown, Montori noted.

Greater risk

None of that has stopped doctors from urging patients to lower blood sugar at all costs. But many of their patients, particularly older ones, often take other medications, too. The more drugs they take to get to an A1C level of seven, the greater the risk of ensuing complications. And they run the risk that blood sugar levels will dip too low.

Vito Ciaccia, 64, of Old Saybrook, Connecticut, learned he had diabetes 30 years ago. He spent years chasing an A1C of seven, spurred on by doctors who focused single-mindedly on that number. “They were always upping the dosage of drugs, wanting to get to seven” he said. “One doctor was very adamant and very demanding. He told me if I didn’t do what he said, I would not be here much longer.” “I felt the treatment was just to pound drugs in and hope they work,” Ciaccia added.

But he rarely hit that A1C target, and the drugs caused uncomfortable side effects. While he was taking them, his blood sugar dipped up and down, often going so low that he experienced sweating, confusion and dizziness. Had his doctors realised how tenuous was the connection between lowering A1C and heart disease, the biggest threat to these patients, they might have been less insistent. And he might have been less worried.

“I have patients who flip out if their A1C level is above seven,” said Dr John Buse, an endocrinologist at the University of North Carolina at Chapel Hill. “Some are desperate to get it to six. I try to talk them down, but sometimes I fail.” “I don’t think there is evidence for such zealotry,” he added.

Ciaccia is now being cared for by Lipska. She tells him he’ll do fine with an A1C level higher than seven, and can avoid the low blood sugar episodes that were so distressing.

And it was OK to take one drug — insulin — which he preferred over a pile of diabetes drugs. Her approach, Lipska said, is to be straightforward with patients about the choices of treatment. “I tell them, this is what we know and this is what we don’t know,'” she said.