Disclosures: Barzilay no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
November 19, 2021
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Diabetic peripheral neuropathy linked to cognitive decline in type 2 diabetes

Disclosures: Barzilay no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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Diabetic peripheral neuropathy is associated with a decline in cognition for people with type 2 diabetes, according to study findings published in the Journal of Diabetes and its Complications.

In findings from the Glycemia Reduction Approaches in Diabetes Study (GRADE), diabetic peripheral neuropathy was associated with worse results in cognitive tests, but no association was found with cardiovascular autonomic neuropathy and cognition.

Barzilay is an an endocrinologist at Kaiser Permanente of Georgia and adjunct professor of medicine in the division of endocrinology at Emory University School of Medicine.

“It would appear that cognitive function and peripheral nervous system function share common antecedents and arise, in part, together,” Joshua I. Barzilay, MD, an endocrinologist at Kaiser Permanente of Georgia and adjunct professor of medicine in the division of endocrinology at Emory University School of Medicine, told Healio. “If indeed subclinical peripheral neuropathy arises together with subclinical cognitive dysfunction in people with diabetes, it suggests that people with peripheral neuropathy may be at risk later on for more serious clinical cognitive dysfunction.”

Barzilay and colleagues analyzed data from 4,559 participants in GRADE. Participants were aged 20 years or older if they were American Indian or Alaskan native or aged 30 years or older for all other participants, and had type 2 diabetes duration of less than 10 years, a baseline HbA1c between 6.8% and 8.5%, and an estimated glomerular filtration rate of 30 ml/min/1.73 m2 or higher. The Michigan Neuropathy Screening Instrument was used to assess diabetic peripheral neuropathy, and indices of heart rate variability were used to assess cardiovascular autonomic neuropathy. Participants completed the Spanish English Verbal Learning Test to measure verbal learning and immediate and delayed recall. The Digit Symbol Substitution Test and animal and letter fluency tests were conducted to assess frontal-executive abilities. Fasting glucose and HbA1c were measured at baseline, and 1,543 participants had highly sensitive C-reactive protein measured as part of a substudy.

Of the study cohort, 27.5% had definite diabetic peripheral neuropathy and 9.8% had definite cardiovascular autonomic neuropathy. After adjusting for covariates, the presence of diabetic peripheral neuropathy was associated with lower scores on the Digit Symbol Substitution Test, though only 1.2% of the test score variation was explained by diabetic peripheral neuropathy alone.

After adjusting for covariates, no significant associations were observed between definite cardiovascular autonomic neuropathy and any cognitive markers. Barzilay said he was not surprised no link was found between cardiovascular autonomic neuropathy and cognition.

In fully adjusted models, highly sensitive C-reactive protein, HbA1c, systolic blood pressure and alcohol intake were not associated with diabetic peripheral neuropathy. LDL cholesterol was associated with definite diabetic peripheral neuropathy, but not continuous diabetic peripheral neuropathy. Waist circumference and urine albumin creatinine ratio were the strongest covariates in the association between diabetic peripheral neuropathy and cognitive impairment.

Barzilay said more studies are needed to investigate the possible mechanisms behind the association between diabetic peripheral neuropathy and cognitive decline.

“Recently there was a scientific study demonstrating that peripheral nerve stimulation leads to MRI changes in the parts of the brain associated with cognition,” Barzilay said. “Such scientific studies can help explain how and why such associations exist.”

For more information:

Joshua I. Barzilay, MD, can be reached at joshua.barzilay@kp.org.