Perspective from Vinni Makin, MD, FACE
Disclosures: The authors report no relevant financial disclosures.
October 12, 2020
4 min read

Improving glucose control, not weight, associated with better cognition in type 2 diabetes

Perspective from Vinni Makin, MD, FACE
Disclosures: The authors report no relevant financial disclosures.
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Adults with type 2 diabetes who improved blood glucose during an intensive lifestyle intervention saw improvements in cognitive test scores after a decade of follow-up, according to a study.

However, associations between weight loss and brain health were mixed, the researchers wrote in The Journal of Clinical Endocrinology and Metabolism.

Owen T. Carmichael, PhD, professor and director of biomedical imaging at Pennington Biomedical Research Center in Baton Rouge, Louisiana.

“It is very well known that a clinical diagnosis of diabetes is associated with an increased risk for dementia later on in life,” Owen T. Carmichael, PhD, professor and director of biomedical imaging at Pennington Biomedical Research Center in Baton Rouge, Louisiana, told Healio. “Diabetes is a very treatable disease with many therapeutic options. Many people are able to change their lifestyle, receive medical treatment and get their blood glucose under control. So the question is, if someone gets the diagnosis and essentially ‘dials back’ the diabetes, does that reduce risk for dementia back to normal levels? The overarching question is whether something inside the brain becomes permanently broken when you get to the diabetes disease state, or, is the brain fixable?”

Look AHEAD data

Carmichael and colleagues analyzed data from adults aged 45 to 76 years with type 2 diabetes and overweight or obesity participating in Look AHEAD, a randomized controlled trial comparing an intensive lifestyle intervention with standard care with long-term follow-up. Recruitment began in 2001 and interventions ended in September 2012 (mean length of intervention, 9.9 years).

Researchers conducted two to three cognitive assessments with 1,089 adults participating in one of three ancillary studies: the Look AHEAD Movement and Memory Study, the Look AHEAD Brain MRI study and the Look AHEAD Continuation study; the first and last cognitive tests occurred a mean 8.6 and 11.5 years after enrollment in the main Look AHEAD study. Verbal learning and memory were evaluated with the Rey Auditory Verbal Learning Test. Speed of processing and working memory were evaluated with the Digit Symbol Coding test. Executive function was evaluated with the Modified Stroop Color and Word Test and the Trail Making Test-Part B. Global cognitive functioning was evaluated with the Modified Mini-Mental Status Exam.

Researchers found that greater improvements in fasting blood glucose levels were associated with better cognitive scores on the Rey Auditory Verbal Learning Test (P = .0148) and the Digit Symbol Coding test (P = .036), and they observed an association between HbA1c improvement and Digit Symbol Coding (P = .0477).

Weight loss, cognition questions

The researchers also found weight loss had mixed associations with cognitive scores. A greater BMI reduction during follow-up in Look AHEAD was associated with poorer mean score during follow-up on the Rey Auditory Verbal Learning Test (P = .0053). Additionally, researchers observed that a greater BMI reduction was associated with better Digit Symbol Coding scores among participants with overweight, but not obesity at baseline (P = .01).

The researchers noted that associations were strongest among those who had overweight vs. obesity at baseline, as well as among those with a history of cardiovascular disease at baseline.

“I assumed doing all of the ‘right’ things — increasing physical activity, losing weight, controlling blood glucose — would be associated with better cognition. It turns out, that was not entirely true,” Carmichael said in an interview. “We found that intuitive message in glucose control. The more you lowered your blood glucose, the better cognitive function was. Weight loss was a mixed bag. People who lost more weight had better scores on some tests and worse scores on the others.”

Carmichael said the obesity results could suggest that some interventions may be “too little, too late,” given that participants saw little cognitive benefit if they had obesity at baseline.

“The main message is that the implications of developing diabetes go far beyond just blood glucose and far beyond the current moment in life,” Carmichael said. “A person should not assume that if they have prediabetes or early type 2 diabetes, they can wait and treat with drugs later. If you do that, it can have long-lasting implications for your brain health.”

For more information:

Owen T. Carmichael, PhD, can be reached at Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808; email: