Cognition Is Not Impaired by Intensive Glycemic Control

WASHINGTON – Tight glycemic control early in the course of type 1 diabetes does not result in later cognitive decline, according to new findings from two studies with an average of 18 years of follow-up data.

“Because of the length of follow-up and extent of cognitive testing, this study strongly supports the safety of intensive diabetes therapy,” Dr. Alan M. Jacobson said at the annual scientific sessions of the American Diabetes Association.

The results should allay the serious concerns that have been raised about whether tight glycemic control might lead to more severe hypoglycemic episodes and subsequent decreased cognitive ability, said Dr. Jacobson, head of the behavioral and mental health research section at the Joslin Diabetes Center, Boston.

But the recurrent, severe hypoglycemic events that are more likely to occur with tight glycemic control could still possibly have a negative cognitive effect on older adults, very young children, or those with a longer disease duration, he added.

The results from the multicenter, randomized Diabetes Control and Complications Trial (DCCT) and its continuation in the long-term observational Epidemiology of Diabetes Interventions and Complications (EDIC) study showed that patients who received intensive glycemic control during the DCCT did not have any differences in cognition, compared with conventional treatment, as measured by an extensive test battery involving eight cognitive domains (problem solving, learning, immediate memory, delayed recall, spatial information, attention, psychomotor efficiency, and motor speed), Dr. Jacobson reported.

The 18 years of combined follow-up make the DCCT and the EDIC the largest, longest-term prospective study that has implemented a cognitive assessment of patients with any clinical condition, he said.

Among patients in either group, there were no differences in cognitive functioning in those who had no hypoglycemic episodes, one to five episodes, or more than five episodes.

Control of HbA_1c (glycosylated hemoglobin) values to less than 7.9% similarly showed no significant effects, except in sparing patients from small reductions in psychomotor efficiency and in improving motor speed. The “very modest” declines in psychomotor efficiency and motor speed that were associated with higher HbA_1c values (7.9% or greater) were “consistent with emerging literature on the effects of persistent hyperglycemia on mental and motor slowing,” Dr. Jacobson said.

The results did not change when the investigators removed 28 patients with potentially confounding illnesses–strokes, decreased vision, renal insufficiency–from the analysis, except that patients who had prior tight glycemic control in the DCCT had a significantly lower decline in psychomotor efficiency than did patients who received conventional treatment.

All of the analyses were adjusted to account for the confounding variables of baseline age, gender, years of education, length of follow-up, and the number of cognitive tests taken. (Patients took different numbers of tests because they entered the DCCT at different times.)

The initial results at the end of the DCCT showed that maintenance of near normal glycemic control reduced the risk of developing–or the progression of–microvascular complications.

After 10 years of additional follow-up in the EDIC study, the patients who had prior intensive treatment still had reduced progression of retinopathy, nephropathy, neuropathy, and cardiovascular events.

As patients in the intensive treatment arm of the DCCT finished the trial and entered the EDIC study, they did not maintain the same level of glycemic control during the ensuing years, whereas individuals who were in the conventional treatment arm of the DCCT received training on how to maintain tight glycemic control and soon began doing so on their own. Both groups had a mean HbA_1c value of 7.8% at the end of 12 years of follow-up in the EDIC study, which includes more than 90% of the original DCCT patients.

At the end of those 12 years, a significantly greater percentage of the 583 patients who were in the intensive treatment arm of the DCCT had one or more severe hypoglycemic events leading to coma or seizures than did the 553 patients who received conventional treatment (44%, or 258 patients with 880 events, vs. 34%, or 187 patients with 452 events).

Most (97%) of the participants were white and were 27 years old on average when they entered the DCCT, where they received a mean of 6.5 years of intervention; they were 45 years old on average after 12 years of follow-up in the EDIC trial. At the last follow-up, all of the participants were adults and about 50% were employed as professionals.

The patients in the study were “unusually healthy and subject to careful follow-up, which may suggest that those in worse control may show worse cognitive outcomes,” he said.

WASHINGTON – Tight glycemic control early in the course of type 1 diabetes does not result in later cognitive decline, according to new findings from two studies with an average of 18 years of follow-up data.

“Because of the length of follow-up and extent of cognitive testing, this study strongly supports the safety of intensive diabetes therapy,” Dr. Alan M. Jacobson said at the annual scientific sessions of the American Diabetes Association.

The results should allay the serious concerns that have been raised about whether tight glycemic control might lead to more severe hypoglycemic episodes and subsequent decreased cognitive ability, said Dr. Jacobson, head of the behavioral and mental health research section at the Joslin Diabetes Center, Boston.

But the recurrent, severe hypoglycemic events that are more likely to occur with tight glycemic control could still possibly have a negative cognitive effect on older adults, very young children, or those with a longer disease duration, he added.

The results from the multicenter, randomized Diabetes Control and Complications Trial (DCCT) and its continuation in the long-term observational Epidemiology of Diabetes Interventions and Complications (EDIC) study showed that patients who received intensive glycemic control during the DCCT did not have any differences in cognition, compared with conventional treatment, as measured by an extensive test battery involving eight cognitive domains (problem solving, learning, immediate memory, delayed recall, spatial information, attention, psychomotor efficiency, and motor speed), Dr. Jacobson reported.

The 18 years of combined follow-up make the DCCT and the EDIC the largest, longest-term prospective study that has implemented a cognitive assessment of patients with any clinical condition, he said.

Among patients in either group, there were no differences in cognitive functioning in those who had no hypoglycemic episodes, one to five episodes, or more than five episodes.

Control of HbA_1c (glycosylated hemoglobin) values to less than 7.9% similarly showed no significant effects, except in sparing patients from small reductions in psychomotor efficiency and in improving motor speed. The “very modest” declines in psychomotor efficiency and motor speed that were associated with higher HbA_1c values (7.9% or greater) were “consistent with emerging literature on the effects of persistent hyperglycemia on mental and motor slowing,” Dr. Jacobson said.

The results did not change when the investigators removed 28 patients with potentially confounding illnesses–strokes, decreased vision, renal insufficiency–from the analysis, except that patients who had prior tight glycemic control in the DCCT had a significantly lower decline in psychomotor efficiency than did patients who received conventional treatment.

All of the analyses were adjusted to account for the confounding variables of baseline age, gender, years of education, length of follow-up, and the number of cognitive tests taken. (Patients took different numbers of tests because they entered the DCCT at different times.)

The initial results at the end of the DCCT showed that maintenance of near normal glycemic control reduced the risk of developing–or the progression of–microvascular complications.

After 10 years of additional follow-up in the EDIC study, the patients who had prior intensive treatment still had reduced progression of retinopathy, nephropathy, neuropathy, and cardiovascular events.

As patients in the intensive treatment arm of the DCCT finished the trial and entered the EDIC study, they did not maintain the same level of glycemic control during the ensuing years, whereas individuals who were in the conventional treatment arm of the DCCT received training on how to maintain tight glycemic control and soon began doing so on their own. Both groups had a mean HbA_1c value of 7.8% at the end of 12 years of follow-up in the EDIC study, which includes more than 90% of the original DCCT patients.

At the end of those 12 years, a significantly greater percentage of the 583 patients who were in the intensive treatment arm of the DCCT had one or more severe hypoglycemic events leading to coma or seizures than did the 553 patients who received conventional treatment (44%, or 258 patients with 880 events, vs. 34%, or 187 patients with 452 events).

Most (97%) of the participants were white and were 27 years old on average when they entered the DCCT, where they received a mean of 6.5 years of intervention; they were 45 years old on average after 12 years of follow-up in the EDIC trial. At the last follow-up, all of the participants were adults and about 50% were employed as professionals.

The patients in the study were “unusually healthy and subject to careful follow-up, which may suggest that those in worse control may show worse cognitive outcomes,” he said.

WASHINGTON – Tight glycemic control early in the course of type 1 diabetes does not result in later cognitive decline, according to new findings from two studies with an average of 18 years of follow-up data.

“Because of the length of follow-up and extent of cognitive testing, this study strongly supports the safety of intensive diabetes therapy,” Dr. Alan M. Jacobson said at the annual scientific sessions of the American Diabetes Association.

The results should allay the serious concerns that have been raised about whether tight glycemic control might lead to more severe hypoglycemic episodes and subsequent decreased cognitive ability, said Dr. Jacobson, head of the behavioral and mental health research section at the Joslin Diabetes Center, Boston.

But the recurrent, severe hypoglycemic events that are more likely to occur with tight glycemic control could still possibly have a negative cognitive effect on older adults, very young children, or those with a longer disease duration, he added.

The results from the multicenter, randomized Diabetes Control and Complications Trial (DCCT) and its continuation in the long-term observational Epidemiology of Diabetes Interventions and Complications (EDIC) study showed that patients who received intensive glycemic control during the DCCT did not have any differences in cognition, compared with conventional treatment, as measured by an extensive test battery involving eight cognitive domains (problem solving, learning, immediate memory, delayed recall, spatial information, attention, psychomotor efficiency, and motor speed), Dr. Jacobson reported.

The 18 years of combined follow-up make the DCCT and the EDIC the largest, longest-term prospective study that has implemented a cognitive assessment of patients with any clinical condition, he said.

Among patients in either group, there were no differences in cognitive functioning in those who had no hypoglycemic episodes, one to five episodes, or more than five episodes.

Control of HbA_1c (glycosylated hemoglobin) values to less than 7.9% similarly showed no significant effects, except in sparing patients from small reductions in psychomotor efficiency and in improving motor speed. The “very modest” declines in psychomotor efficiency and motor speed that were associated with higher HbA_1c values (7.9% or greater) were “consistent with emerging literature on the effects of persistent hyperglycemia on mental and motor slowing,” Dr. Jacobson said.

The results did not change when the investigators removed 28 patients with potentially confounding illnesses–strokes, decreased vision, renal insufficiency–from the analysis, except that patients who had prior tight glycemic control in the DCCT had a significantly lower decline in psychomotor efficiency than did patients who received conventional treatment.

All of the analyses were adjusted to account for the confounding variables of baseline age, gender, years of education, length of follow-up, and the number of cognitive tests taken. (Patients took different numbers of tests because they entered the DCCT at different times.)

The initial results at the end of the DCCT showed that maintenance of near normal glycemic control reduced the risk of developing–or the progression of–microvascular complications.

After 10 years of additional follow-up in the EDIC study, the patients who had prior intensive treatment still had reduced progression of retinopathy, nephropathy, neuropathy, and cardiovascular events.

As patients in the intensive treatment arm of the DCCT finished the trial and entered the EDIC study, they did not maintain the same level of glycemic control during the ensuing years, whereas individuals who were in the conventional treatment arm of the DCCT received training on how to maintain tight glycemic control and soon began doing so on their own. Both groups had a mean HbA_1c value of 7.8% at the end of 12 years of follow-up in the EDIC study, which includes more than 90% of the original DCCT patients.

At the end of those 12 years, a significantly greater percentage of the 583 patients who were in the intensive treatment arm of the DCCT had one or more severe hypoglycemic events leading to coma or seizures than did the 553 patients who received conventional treatment (44%, or 258 patients with 880 events, vs. 34%, or 187 patients with 452 events).

Most (97%) of the participants were white and were 27 years old on average when they entered the DCCT, where they received a mean of 6.5 years of intervention; they were 45 years old on average after 12 years of follow-up in the EDIC trial. At the last follow-up, all of the participants were adults and about 50% were employed as professionals.

The patients in the study were “unusually healthy and subject to careful follow-up, which may suggest that those in worse control may show worse cognitive outcomes,” he said.