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When Sugar Kills

People with type 1 diabetes may now have another reason to maintain tight control over their blood sugar levels — a reduced risk of heart disease.

One of three types of diabetes, type 1, formerly called juvenile diabetes, is a disease that requires lifelong injections of insulin. While researchers have extensively studied heart disease risk in people with type 2 diabetes, which occurs in adults, much less is known about the factors that contribute to heart disease risk in people with type 1 diabetes.

A recent study, however, has found that intensive diabetes therapy appears to reduce the thickening of the blood vessels, a process that increases risk of heart attack and stroke.

The study, co-chaired by Dr. David Nathan, professor of medicine at Harvard Medical School and director of the Diabetes Center at the Massachusetts General Hospital, was part of the Epidemiology of Diabetes Interventions and Complications study.

This study followed patients from the Diabetes Control and Complications Trial, or DCCT, which began enrolling patients in 1983. The DDCT population is the largest group of people with type 1 diabetes to have been studied for such a long period of time.

Over the years, researchers have collected information on participants' heart disease risk factors, such as their cholesterol levels and smoking status, as well as their blood sugar levels. By examining these risk factors, Nathan explains, researchers have been able to discern that high blood sugar seems to be related to the development of the blood vessel narrowing process called atherosclerosis.

Below, Nathan discusses how this information can help people with type 1 diabetes and how close control may reduce their heart disease risk.

Why did you decide to look at heart disease risk factors in patients with type 1 diabetes?
Heart disease remains a major cause of mortality in type 1 diabetes as it is in type 2 diabetes. And we know really very little about it. This is a disease that has its major onset during youth and adolescence. If you consider that most people of that age are not having very much heart disease, any increase in heart disease in the type 1 diabetic population will be considerable.

How is the thickness of the carotid artery wall a measure of heart disease?
The carotid artery is the major artery that takes blood to your brain. The process of atherosclerosis, which is really the thickening of vessel walls that ultimately leads to blockage of those vessels, is the underlying process of stroke as well as heart disease. It's very difficult to measure the blood vessels in the heart directly, and in most relatively healthy populations, that's not a method you can use.

Instead, we turn to this other vessel, the carotid artery, and we are able to measure the thickness of the wall with ultrasound. This is same kind of device that is used, for example, in pregnant women to look at the fetus as it's growing in the womb. The thicker the wall appears on the ultrasound, the more likely it is that there is atherosclerosis there.

Why did you think that high blood sugar might be a risk factor for heart disease?
Looking at high blood sugar levels seems to be a pretty natural target. It is the major factor that differentiates diabetes from non-diabetes. We have known for some time now, based on the Diabetes Control and Complications Trial, that high blood sugar is one of the major risk factors for developing the eye disease, kidney disease and nerve disease that occurs in type 1 diabetes. So naturally, we felt that maybe high blood sugar was also related to heart disease.

How is intensive therapy different than conventional therapy?
What we used to call intensive therapy is now accepted as the standard of care. It involves trying to match insulin levels, or the insulin that is given by the patient, to the insulin requirement. This requires that patients with type 1 diabetes test their blood sugar, usually at least three times a day, using a finger stick device. With that information in hand, they can choose an insulin dose before each meal, for example, that will match what they need in order to keep the blood sugar in good control. What we're aiming for is to keep their average blood sugar as close to non-diabetic range as we can.

The Diabetes Control and Complications Trial demonstrated that if patients maintained this kind of glucose control, we could decrease the occurrence of eye disease, kidney disease and nerve disease that leads to amputations by about 75 percent. So we've known now since 1993, when the DCCT ended, that intensive therapy was really the way to go.

What are drawbacks of intensive therapy?
Intensive therapy really places an enormous burden on the patients. It involves lots of finger-stick blood testing and usually people take at least three injections a day or treat themselves with an insulin pump. They have to be conscientious about their diet and their activity levels, and they have to be taught to choose the right doses for a given meal.

In addition, there is a risk with intensive therapy. Because it is not a perfect system of treatment, sometimes the blood sugar can drop too low, and people can experience "hypoglycemia," or a low blood sugar reaction. These reactions can sometimes make people feel sweaty and weak. Sometimes they can get so severe that they can cause loss of consciousness or a seizure.

On balance, we think that the reduction of eye, kidney and nerve disease and now, maybe heart disease as well, makes intensive therapy worthwhile for most patients with type 1 diabetes.

Did the standard heart disease risk factors increase risk in the diabetic patients?
In studying the other risk factors that we usually consider in non-diabetics for heart disease, such as smoking, high blood pressure and high cholesterol, we found that our diabetes population suffered from the same kinds of risks. Those who smoked, for example, were at greater risk for developing this atherosclerosis.

The difference for the diabetic population is that, on top of all of those risk factors, high blood sugar or higher blood sugar was a risk factor compared to lower blood sugar.

Why did atherosclerosis progress even in the people on intensive therapy?
In our population, even in the intensive treatment group, the vessel walls tended to get thicker over time. That's mostly due to the normal process of aging. If you look at non-diabetic patients, their vessel walls also get thicker as they get older.

Are people with diabetes who develop heart disease treated the same as nondiabetics with heart disease? Because diabetic patients have a higher level of heart disease, the current recommendations are to treat them even more intensively with regard to things like blood pressure and cholesterol. So, for example, in the nondiabetic population, we might be satisfied with an DL cholesterol, the bad form of cholesterol, of 130. In the diabetic population, we want them to have a level less than 100.

This stricter recommendation includes not only lifestyle changes, but also the earlier and more aggressive use of medication.

What sort of research remains to be done?
This research raises lots of questions. For example, we have demonstrated that we can slow down the rate of thickening of the vessel wall, but that isn't absolutely the same as showing that we can decrease heart attacks. We continue to need to follow our population to see whether there are differences in the rate of heart disease, compared to what we would have predicted.

We also need to better understand how elevated blood sugars damage the vessel wall. If we can understand that better, we may be able to find even better ways of preventing heart disease.

It's extremely important that all patients with type 1 diabetes not only look after their sugar levels, but also manage their blood pressure and cholesterol levels as best they can. These are known to be risk factors, and the more risk factors patients control, the more likely they are to live long, healthy lives without heart disease. xml_type1diabeties

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