| Title: | Prediabetic HbA1c and Cortical Atrophy: Underlying Neurobiology |
| Journal: | Diabetes Care |
| Published: | 12 Oct 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37824790/ |
| DOI: | https://doi.org/10.2337/dc23-1105 |
| URL: | https://diabetesjournals.org/care/article-pdf/46/12/2267/739465/dc231105.pdf |
Publication 9393
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Abstract
OBJECTIVE: To investigate the relationship between blood glycated hemoglobin (HbA1c) and cerebral cortical thickness (CT) and identify potential cellular mechanisms involved.</p>
RESEARCH DESIGN AND METHODS: A cohort of 30,579 adults age 45 to 81 (mean ± SD: 64 ± 7.5) years with available data on brain MRI and blood HbA1c levels was analyzed. The relationship between HbA1c and CT was probed using independent spatial profiles of cell-specific gene expression. Lastly, a genome-wide association study was conducted on the shared variance between HbA1c and CT.</p>
RESULTS: The HbA1c-CT association was noncontinuous, emerging negatively within the prediabetic range (39.6 mmol/mol). This association was strongest in brain regions with higher expression of genes specific to excitatory neurons and lower expression of genes specific to astrocytes and microglia. A significant locus implicated mitochondrial maintenance and ATP generation.</p>
CONCLUSIONS: Effective glycemia control at prediabetic levels is warranted to preserve brain health and prevent prediabetes-related neurobiologic perturbations.</p>
5 Authors
- Jean Shin
- Yash Patel
- Nadine Parker
- Tomas Paus
- Zdenka Pausova
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