Researchers who compared intensive glucose-lowering treatment with standard glucose control in older patients with type 2 diabetes found that contrary to expectations, super-tight control of blood sugar did not slow the mental decline of diabetes-related dementia, and in the case of their study participants, it was actually linked to a higher rate of death.

Lead author Lenore J Launer, from the Laboratory of Epidemiology, Demography and Biometry at the US National Institute on Aging, and colleagues report their results from the MIND substudy of the ACCORD trial in the 28 September issue of The Lancet Neurology.

Older people with type 2 diabetes are at higher risk of mental or cognitive impairment than counterparts without diabetes, and also at higher risk of brain atrophy, say researchers.

Intensive glucose-lowering treatment aims to keep blood sugar at below 6% (measured by the hemoglobin A1c test). The current standard treatment aims to keep it between 7 and 7.5%.

Studies have shown that intensive control appears to reduce the risk of developing kidney, eye and cardiovascular problems, so it seemed reasonable to assume that it might also slow the rate of diabetes-related cognitive impairment: that was the motive for the study.

For the study, where they compared the effect of intensive versus standard glycaemic control on cognitive function and brain volume, Launer and colleagues worked with the Memory in Diabetes (MIND) subgroup of North American patients who took part in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial.

They enrolled 2,977 patients between 55 and 80 years old with type 2 diabetes and at high risk for heart disease who had been randomly assigned to receive either intensive blood-sugar lowering (1,378 patients) or current treatment (1,416) in the ACCORD trial.

614 of the patients had also undergone a brain MRI scan to measure brain volume and tests of cognitive function at the start and end of the study, so the researchers included 230 assigned to receive intensive treatment and 273 assigned to receive standard treatment in their primary MRI analysis.

The results showed that after 40 months, although the patients in the intensive treatment group had a significantly larger mean total brain volume (TBV) than the standard treatment group, there was no difference between the two groups on the cognitive function test (they used the Digit Symbol Substitution Test, DSST).

The difference in TBV was 4.62, with 95% confidence interval CI ranging from 2.0 to 7.3 and a statistically significant p=0.0007.

The difference in the mean DSST score was 0.32, with 95% CI from 0.28 to 0.1 and p=0·2997, so not statistically significant.

The arm of the main ACCORD trial where patients underwent the intensive glucose control was actually stopped before the planned endpoint because it appeared there was an increased risk of death in this group, no benefit to the heart and problems developed linked to weight gain and low blood sugar.

Launer and colleagues concluded that:

“Although significant differences in TBV [brain volume] favoured the intensive treatment, cognitive outcomes were not different. Combined with the non-significant effects on other ACCORD outcomes, and increased mortality in participants in the intensive treatment group, our findings do not support the use of intensive therapy to reduce the adverse effects of diabetes on the brain in patients with similar characteristics to those of our participants.”

An expert writing a commentary in the same issue of the journal, who was not involved in the study, questioned whether the measure of cognitive function the researchers used was a sufficient measure of dementia.

Neurologist Dr. Geert Jan Biessels, who is with the Rudolf Magnus Institute of Neuroscience at the University Medical Center in Utrecht, the Netherlands, wrote that although on average cognitive function did not improve in the intensive glucose control group:

“… the absence of an effect of treatment on mean cognitive functioning cannot yet be regarded as proof that the treatment may not delay dementia.”

However, “at present the results do not support specific treatments to prevent cognitive decline in diabetes,” he added.

Funds from the US National Institute on Aging and US National Heart, Lung, and Blood Institute paid for the study.

Written by Catharine Paddock