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Effect of Strict Diabetes Control on Heart Still Unclear
Date:6/9/2009

Reviews show it wasn't to blame for excess deaths in one trial, but when therapy starts could be key

TUESDAY, June 9 (HealthDay News) -- Reviews of two large diabetes trials show that the relationship between tight blood sugar control and the risk of heart trouble is still far from certain.

The first analysis found that a troubling number of deaths seen in a large diabetes trials appears not to have been caused by low blood glucose levels, as originally thought.

It's still not completely clear, however, what factors might explain the 451 deaths that occurred in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, which was shut down early after researchers found a 20 percent increased risk of death among those in the more intensive blood sugar control group.

Meanwhile, analyses of another trial, the VA Diabetes (VADT) trial, found that intensive blood sugar control that's begun many years after diagnosis may actually do more harm than good when it comes to cardiovascular problems.

Both sets of analyses, which were presented Tuesday during a teleconference at the American Diabetes Association (ADA) annual meeting in New Orleans, suggest that diabetes treatment needs to be tailored to the particular needs and characteristics of each patient.

"Treatment should be individualized," Dr. William C. Duckworth, VADT co-chair and director of diabetes research at the Carl T. Hayden VA Medical Center in Phoenix, said during the Tuesday teleconference. "Type 2 diabetes is an extremely heterogenous disease, so if you treat different populations or different groups within the population you're studying you may get different results."

"We are withholding specific recommendations, but there may be potentially different glucose-control targets for different groups of people," added Dr. Matthew C. Riddle, member of the ACCORD Glycemia Management Group and professor of medicine at Oregon Health Science University. "If we can objectively identify which individuals fall into which groups, that would be a big step forward."

Type 2 diabetes, which affects some 24 million Americans, can result in devastating complications such as kidney disease, amputation, blindness and heart disease. A common test for measuring blood sugar levels looks at hemoglobin A1C values spread over two to three months.

"The central role of glucose control in preventing microvascular eye, kidney and nerve disease is fairly well-established," said Dr. Rick Bergenstahl, executive director of the International Diabetes Center in Minneapolis and ADA's president-elect of medicine and science. "Data related to macrovascular effects on the heart are less well understood or less conclusive."

Research presented last year on the ACCORD trial found that intensive lowering of blood sugar in people with poorly controlled type 2 diabetes did not have a significant effect on reducing cardiovascular events, such as heart attack and stroke. In fact, it appeared to raise the risk of death.

At the time, scientists speculated that the increased mortality risk was due to low blood sugar, but this turned out not to be the case.

Instead, "people who achieved a rapid and sustained reduction of A1C from higher levels at the beginning had the lower risk, and the ones who were unable to rapidly reduce glucose from the beginning had the higher risk," Riddle explained. In other words, those who struggled to get their glucose under control seem to be at higher risk for heart trouble.

Meanwhile, analyses from the VADT trial indicates that intensive diabetes treatment begun earlier after a diagnosis is more likely to do good, while intensive treatment started 15 years after diagnosis is more likely to do harm.

Starting rigorous control of blood sugar two decades or more after a diagnosis of diabetes actually upped the risk of cardiovascular problems, at least in this population of mostly older males.

Similar to the ACCORD trial, the authors reported no beneficial effect of intensive glucose control on cardiovascular events and, ever since, have been trying to figure out why.

One message, however, is that tight blood sugar control is not bad overall, which is in line with previous thinking.

"The closer to normal range the better, and that is what we've been recommending all along," said Dr. Helena W. Rodbard, past president of both the American Association of Clinical Endocrinologists and the American College of Endocrinology. "We have to aim for good control, but good control early on."

More information

Visit the American Diabetes Association for more on type 2 diabetes.



SOURCES: Helena W. Rodbard, M.D., medical director, Endocrine and Metabolic Consultants, Rockville, Md., past-president, American Association of Clinical Endocrinologists and past president, American College of Endocrinology; June 9, 2009, teleconference with Richard M. Bergenstahl, M.D., executive director, International Diabetes Center, Minneapolis; Matthew C. Riddle, M.D., professor, medicine, Oregon Health Science University, and member, ACCORD Glycemia Management Group; and William C. Duckworth, M.D., director, diabetes research, Carl T. Hayden VA Medical Center, Phoenix, and professor, clinical medicine, University of Arizona, and co-chair, VA Diabetes Trial


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