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Randomized Controlled Trial

Long-term Effect of Diabetes and Its Treatment on Cognitive Function

Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study Research Group et al. N Engl J Med.

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  • N Engl J Med. 2009 Nov 5;361(19):1914


Background: Long-standing concern about the effects of type 1 diabetes on cognitive ability has increased with the use of therapies designed to bring glucose levels close to the nondiabetic range and the attendant increased risk of severe hypoglycemia.

Methods: A total of 1144 patients with type 1 diabetes enrolled in the Diabetes Control and Complications Trial (DCCT) and its follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study were examined on entry to the DCCT (at mean age 27 years) and a mean of 18 years later with the same comprehensive battery of cognitive tests. Glycated hemoglobin levels were measured and the frequency of severe hypoglycemic events leading to coma or seizures was recorded during the follow-up period. We assessed the effects of original DCCT treatment-group assignment, mean glycated hemoglobin values, and frequency of hypoglycemic events on measures of cognitive ability, with adjustment for age at baseline, sex, years of education, length of follow-up, visual acuity, self-reported sensory loss due to peripheral neuropathy, and (to control for the effects of practice) the number of cognitive tests taken in the interval since the start of the DCCT.

Results: Forty percent of the cohort reported having had at least one hypoglycemic coma or seizure. Neither frequency of severe hypoglycemia nor previous treatment-group assignment was associated with decline in any cognitive domain. Higher glycated hemoglobin values were associated with moderate declines in motor speed (P=0.001) and psychomotor efficiency (P<0.001), but no other cognitive domain was affected.

Conclusions: No evidence of substantial long-term declines in cognitive function was found in a large group of patients with type 1 diabetes who were carefully followed for an average of 18 years, despite relatively high rates of recurrent severe hypoglycemia. ( number, NCT00360893.)


Figure 1
Figure 1. Effects of DCCT Treatment Group, Severe Hypoglycemia, and Glycated Hemoglobin on Changes in Cognition, from Entry into DCCT to Year 12 in the EDIC Study
The bars show the changes within cognitive domains between cognitive testing at baseline in DCCT and follow-up testing (a mean of 18 years after baseline) expressed as changes in z scores for intensive versus conventional treatment (Panel A), frequency of episodes of severe hypoglycemia (coma or seizure) (Panel B), and mean glycated hemoglobin values (Panel C). Across the three groups, higher levels of glycated hemoglobin were associated with moderate declines in psychomotor efficiency (P<0.001) and motor speed (P=0.001), but no other cognitive domain was affected significantly. Cognitive domains are numbered as follows: 1, problem solving; 2, learning; 3, immediate memory; 4, delayed recall; 5, spatial information; 6, attention; 7, psychomotor efficiency; and 8, motor speed.

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