Tight diabetes control does not impact cognitive ability in type 1 diabetes

A study led by researchers at Joslin Diabetes Center provides good news for patients with type 1 diabetes who want to maintain tight blood glucose control and thus significantly reduce their risk of developing the devastating complications of the disease, heart disease, kidney failure, eye disease and blindness and nerve damage.

The study, which is part of the Epidemiology of Diabetes Interventions and Complications study (EDIC) funded by the National Institutes of Health (NIH), will be published in the May 3, 2007, issue of the New England Journal of Medicine.

The EDIC is a follow-up study of the Diabetes Control and Complication Trial (DCCT), a large NIH-funded study that compared intensive management of blood glucose to conventional control in people with type 1 diabetes. The study's findings established the effectiveness of tight blood glucose control in dramatically slowing the onset and progression of diabetes complications. However, intensive control increased episodes of severe hypoglycemia , abnormally low blood glucose levels that can cause confusion, irrational behavior, convulsions and unconsciousness , that is associated with tight control. After following participants for 12 more years, the researchers have shown that multiple episodes of severe hypoglycemia do not lead to long-term loss of cognitive ability. They cautioned, however, that further study is needed to determine whether hypoglycemic episodes in young children have any lasting cognitive effects, since the youngest DCCT participants were 13 years old at the beginning of the study.

"The EDIC study provides further support for the safety of intensive diabetes therapy and the benefits of maintaining good glycemic control," says the study's principal investigator, Alan M. Jacobson, M.D., head of Joslin's Behavioral and Mental Health Research Section and Professor of Psychiatry at Harvard Medical School. Preliminary findings from the EDIC study were presented at the June 2006 Scientific Sessions of the American Diabetes Association. "While acute episodes of hypoglycemia can impair thinking and can even be life-threatening, type 1 diabetes patients do not have to worry that such episodes will impair their long-term abilities to perceive, reason and remember."

"Hypoglycemia is a serious, frightening experience," said Catherine Cowie, Ph.D., who oversees EDIC for the NIH. "However, given the importance of intensive blood glucose control in preventing the complications of diabetes, it is tremendously heartening to know that such episodes have no long-term cognitive effects in the age groups studied in the DCCT/EDIC."

The DCCT findings confirmed Dr. Elliott P. Joslin's theory on the benefits of tight diabetes control in reducing diabetes complications. The DCCT investigators examined 1,441 subjects, ages 13 to 39, with type 1 diabetes. About half of the group received intensive therapy with either an insulin pump or three or more daily insulin injections. The remaining subjects received conventional therapy of one to two insulin injections daily. During the study, the patients' A1C readings, which reflect average blood glucose levels over several months, differed between the two groups by about 2 percentage points (7.1 percent for the intensive therapy group vs. 9.0 percent for the conventional). At the study's conclusion in 1993, researchers reported that the group receiving intensive therapy experienced 76 percent less eye disease, 50 percent less kidney disease, and 60 percent less nerve disease. As a result of their findings, intensive therapy was recommended for all subjects taking part in the trial.

But the DCCT also showed that tight control comes at a cost: patients who received intensive therapy were three times as likely to experience hypoglycemic episodes severe enough to require the assistance of another person than patients who were on conventional therapy. This finding raised the fear that, although tight control may lower the risk of developing serious diabetes complications, it might also lead to a long-term loss of cognitive ability.

At the start of the DCCT, in order to evaluate the potential impact of diabetes treatment and recurrent hypoglycemic episodes on cognitive ability, all patients were given a comprehensive battery of cognitive tests. These tools analyzed abilities in eight domains: problem solving, learning, immediate memory, delayed recall, spatial information, attention, psychomotor efficiency and motor speed. When these tests were repeated during the DCCT on an average of 6.5 years after its start, no adverse effects were observed that were associated with either treatment type or with the number of severe hypoglycemic episodes experienced.

Although these findings were encouraging, the researchers recognized the need for longer-term follow-up to determine if the increase in hypoglycemic episodes would affect cognitive ability over time. Furthermore, a longer-term study would allow them to examine whether the added effect of increasing age and duration of the disease might also contribute to a decline in cognitive ability.

To answer these questions, Dr. Jacobson and his colleagues at 28 other medical centers around the country examined 1,144 participants from the original DCCT trial: 588 patients who had received intensive therapy, and 556 patients who received conventional therapy. Tracking for hypoglycemic comas or seizures over the 12-year period following the DCCT, 889 patients reported no such events; 246 reported from one to five events; and nine patients reported more than five.

"While it is most gratifying to find little evidence of a direct effect of moderately severe hypoglycemia on intelligence, diabetic patients still need to avoid hypoglycemia because very low blood sugar levels can trigger a temporary reduction in their ability to pay attention and react quickly, which may, in turn, lead to serious injuries," said Christopher Ryan, Ph.D., Professor of Psychiatry, Psychology, and Health & Community Systems at the University of Pittsburgh School of Medicine.

The researchers evaluated all of the patients using the same neuropsychological tests administered during the DCCT trial. Adjusting for age, sex, years of education, length of follow-up, and the number of cognitive tests taken, the researchers found no change in any of the eight areas examined. Higher A1C readings among patients , which indicate less, not tighter, control , were associated with a modest decline in motor speed and psychomotor efficiency, but no other cognitive domain was affected.

"The DCCT/EDIC is a study of the complications of type 1 diabetes that is entering its 23rd year and will continue through 2016. The study has been heralded for the high rate of ascertainment and the quality of the data," said Patricia A. Cleary, M.S., who is the director of the data coordinating center for DCCT/EDIC at the Biostatistics Center of The George Washington University.

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