Insulin therapy increases heart disease risk
Intensive therapy safe for 75% of patients
Researchers are confronting a new dilemma in their efforts to improve outcomes for Type I diabetics: Intensive insulin therapy can minimize complications of the disease, but for those who gain more than 30 pounds, the trade-off is a dramatically increased risk of heart disease. This new information is likely to change the current approach to treating the disease, at least for some patients, says one expert.
The study by a team of researchers led by Jonathan Q. Purnell, MD, acting instructor at University of Washington School of Medicine in the division of metabolism, endocrinology, and nutrition in Seattle, published in the July 8 Journal of the American Medical Association, is an outgrowth of the 6.5-year Diabetes Control and Complications Trial (DCCT).
Purnell's team focused on the rising lipid levels and blood pressure among DCCT subjects who gained weight under intensive therapy.
Purnell is quick to defend the benefits of intensive insulin therapy for most Type I diabetics. "The second and third quartiles (who gained from 0 to 20 pounds) did gain a modest amount of weight, but their cholesterol levels still demonstrated they had benefits from intensive therapy, so literally three-fourths of the group did great.
"It's [in] the fourth quartile that we're worried [whether] the benefit is worth the extra risk they're getting of heart disease since that's the thing that's going to kill them," he writes.
Since coronary artery disease is the leading cause of death among patients with Type I diabetes, Purnell's study is raising red flags among medical professionals.
John McDonald, RN, MS, CPAQ, vice president of clinical services for the Network Quality Council in Nashville, TN, and a member of the editorial advisory board of Diabetes Management, says the current school of thought is likely to be changed by Purnell's findings. Since the DCCT, good glycemic control, has been thought to significantly decrease a patient's risk of heart disease. "I always thought if you control the blood sugars, you are going to benefit the patient; you are going to improve the quality of life," McDonald says. "That's not necessarily so for those people who have this [central obesity] syndrome."
McDonald says Purnell's work is causing him to consider stepping up his efforts in the Network Quality Council's diabetes disease management program to monitor lipid control especially for Type I diabetics who begin gaining weight.
The intensive insulin therapy described in Purnell's study involved efforts to bring the patients' glucose as close to the normal range of 80-120 mg/dl through a variety of methods, including the following:
4 blood sugar checks three to four times a day;
4 multiple insulin dosing either through injection or with a pump;
4 four physician visits a year;
4 one to four visits a year with a nutritionist;
4 increased access to health care professionals who are part of the treatment team, usually nurse-practitioners.
By contrast, conventional treatment for Type I diabetics has no specific goal for glycemic control other than to keep a patient from going too high (over 200 mg/dl) and/or becoming symptomatic. Patients generally test their blood sugar levels infrequently (weekly or even less often), take one or two insulin shots per day, and have one to three physician visits a year.
Of the 586 patients in Purnell's intensive treatment study, approximately 25% (the fourth quartile) began to show a tendency for rapid weight gain within the first two years of the six-year treatment plan. Those most affected were those who displayed the characteristic tendency toward central obesity or carrying their weight around their midsections.
Interestingly, Purnell notes, this is the same profile that increases the risk of heart disease two- to threefold for non-diabetics with central obesity. In other words, bringing these patients into the normal glycemic range causes them to present the same disease patterns as the general population.
There's more bad news for Type I diabetics who tend toward central obesity under intensive therapy: It's very difficult to reverse the weight gain.
"They were given more intensive nutritional intervention. They were identified earlier. The nutritionist worked harder to get them to restrict their fat intake, and they were actually told to try to limit their caloric intake to either maintain weight or to try to achieve their ideal body weight. And still they zoomed up," Purnell says
He says the patients in his study showed their weight gain within the first year or two of intensive therapy.
Weight gain/hypoglycemic connection?
Purnell says he has a theory that those who gain the most weight may also be the ones who become hypoglycemic most frequently, causing them to be "hungry all the time."
A 10-year follow-up on the DCCT is expected to answer some questions and perhaps raise a few more. Purnell says, "We're doing the ten-year follow-up on this to find if the balance between improving glucose control and the accompanying changes we're finding in blood pressure is worth it. Now that may be all sort of a moot point if clinicians who are taking care of these subjects begin to treat everybody with cholesterol-lowering drugs."
That is what happened when Purnell's team began to look at kidney problems. ACE inhibitors started to dramatically lower the incidence of proteinuria or protein in the patients' urine, benefiting patients but making the study more complicated. "We may see that same phenomenon as people start to get treated with cholesterol-lowering drugs that will benefit them but may delay our ability to actually pick up the difference for many years," Purnell says.
The mortality rate during the DCCT trial was only about 25 of 1,168 participants, Purnell says.
"A small number of people died during the study, and the numbers are too few; it's way too premature to say what that means in terms of outcomes. That's why they are doing the 10-year follow-up study now. During this 10-year time period is when the number of deaths would be expected to rise."
Purnell notes that, despite the increased risk of heart disease, the intensive-therapy group he studied had a lower rate of other complications than expected. "There was a marked reduction in the kidney problems, nerve problems, and eye problems. There were actually very few people who ended up getting complications. It was something like 200 or 300. It was statistically insignificant."
Some experts think some of the same findings for Type I diabetics may apply to Type II (adult onset) diabetics, but no one is certain. Studies currently under way in Britain and Japan may shed more light on the subject, McDonald says, but both groups are composed of a few hundred people and are much smaller than the DCCT.
Despite the increased risk of heart disease for those patients who gained excessive amounts of weight, Purnell is an enthusiastic supporter of intensive insulin therapy and aggressive glucose control. He says a program can be implemented fairly simply, but it must be done through a team approach including a physician, a nutritionist, and nurse-practitioners who can help with the callbacks.
"Most times, it's a diabetologist who heads up the team, but certainly there are internists and family practitioners who are doing this as well," Purnell says. "The thing that can't be done is just to have someone do it solo. It has to be a team approach. But as long as there's a team approach, it can be done by almost anybody."
McDonald says the study has already caused some changes in his approach to Type I patients. "It's not something that's going to cause me to change the way we aggressively manage blood glucose other than for those who tend to be obese. [We'll work] to manage their lipids as well. This is good proof that you need to do that. Better proof than we had before."
For more information, contact:
Jonathan Purnell, MD, Acting Instructor, University of Washington School of Medicine, Division of Metabolism, Endocrinology, and Nutrition, Seattle. Telephone: (206) 543-3470. E-mail: [email protected].
John McDonald, RN, MS, CPHQ, Vice President for Clinical Services, Network Quality Council, Nashville, TN. Telephone: (615) 463-1177.
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