Two new studies, one adding to previous research and the other upending prior assumptions, appear in the June 5 issue of the New England Journal of Medicine.
Some 17 million people in the United States suffer from diabetes. Most of these people have type 2 diabetes, in which the body's ability to produce insulin is hampered but not completely destroyed. In the case of type 1 diabetes, which comprises about 10 percent of all cases, the body's immune system attacks the insulin-producing cells so the body can't produce the essential hormone at all. Either type of diabetes can cause blindness, kidney failure, amputations, heart disease and stroke.
Both of the new studies look specifically at type 1 diabetes but, as an accompanying editorial points out, results of type 1 diabetes trials can, with certain limitations, be extended to type 2 diabetes.
About a decade ago, the landmark Diabetes Control and Complications Trial (DCCT) found people with type 1 diabetes who tightly controlled their blood glucose levels reduced the risk of eye, nerve and kidney complications by 35 percent to 76 percent. The study participants were too young, however, to assess the affect on atherosclerosis, or hardening of the arteries due to plaque buildup.
The new trial, the Epidemiology of Diabetes Interventions and Complications (EDIC) study, presents the good news that intensive diabetes management can also reduce the risk of atherosclerosis in people with type 1 diabetes.
The EDIC trial involved 1,229 patients with type 1 diabetes who had also been in the earlier DCCT trial. They were divided into two groups: 611 who received conventional treatment and 618 who received intensive management. The researchers used ultrasound to measure the thickness of the wall of the participant's carotid arteries at the beginning of the trial and, again, after five years. The carotid arteries, located in the neck, carry blood from the heart to the brain.
"We're measuring the innermost layer and then the next layer in. Those are the layers that are characteristically affected by athersclerosis, and it presages the development of vascular disease," explains study author Dr. David M. Nathan.
After five years, the thickness was significantly less in the diabetics who had followed an aggressive glucose-management campaign during the earlier trial.
"The group that was treated intensively had a slower rate of progression," says Nathan, director of the Diabetes Center at Massachusetts General Hospital and a professor of medicine at Harvard Medical School. "It appears that the advantage of therapy aimed at keeping blood glucose levels as close to the nondiabetic range as possible benefits not only diabetes-specific complications, but also cardiovascular diseases."
Nathan was quick to add that, so far, the regimen didn't decrease heart attacks or strokes. But the atherosclerosis measurement is "a well-recognized surrogate marker" of disease, and "we were able to make a difference. . . You need to apply this therapy as early as possible, and continue to apply it."
The second study looked at microalbuminuria, or the presence of protein in the urine, which is the earliest sign of kidney disease.
Until now, conventional wisdom held that kidney disease was inevitable in people who had microalbuminuria. The best you could do was slow the progression of a disease that would eventually lead, in one-third of patients, to end-stage renal disease and dialysis or a transplant.
This study has found that diabetics can do better than just slow down the disease. "In the early stages, it looks like the disease process can be reversed if patients do the optimal things," says study author Dr. Bruce Perkins, a fellow in endocrinology at the Joslin Diabetes Center in Boston. "The important finding was that it does look like there is a mechanism where the kidney can heal itself and, in fact, it seems to do it quite often."
The researchers authors looked at 386 patients with type 1 diabetes and with microalbuminuria that had been present for two years. The subjects were followed for an additional six years. At the end of that time, 58 percent of the participants no longer had any protein leakage.
"People who do reverse tend to have the lowest blood sugars, lowest blood pressure and, most importantly, the lowest cholesterol levels," Perkins says. "It seems likely that aggressive treatment is necessary to reverse microalbuminuria."
The first message, then, is that screening is critical. "Someone with diabetes shouldn't allow years to go by without being screened for microalbuminuria because if it's identified early, if we do the right things, it can be reversed," Perkins says.
Physicians and patients alike should perhaps also pay more attention to cholesterol levels, including the possibility of taking cholesterol-lowering drugs, although this should first be studied in a clinical trial.
That's the good immediate news.
In the longer term, the findings may help identify targets for new drugs. A priority is to figure out how the kidney manages to repair itself even after early initial damage. Perkins and his colleagues believe a different part of the kidney's filtering structure, the tubules, may be more central than originally thought.
"This is a fundamentally important thing because it changes the way we think about understanding kidney disease and also finding treatments for it," Perkins says.
The Joslin Diabetes Center has a page on complications. For general information about the disease, try the National Institute of Diabetes and Digestive and Kidney Diseases.