Cosmos Study

High and Low HbA1c Values Associated with Increased Risk of Alzheimer’s Disease in Diabetic Patients

August 20, 2024

Team A:Sam Butler, MDJoe Deckert, PhD

Team B:Kersten Bartelt, RNEric Barkley

Key Findings

Diabetic patients diagnosed with Alzheimer’s disease are more likely to have average HbA1c values less than 6.5% or more than 8% in the five years prior to their Alzheimer’s diagnoses than diabetic patients not diagnosed with Alzheimer’s.

Some studies have suggested that insulin resistance might be correlated with neurodegeneration leading to Alzheimer’s disease.^1,2 To better understand how diabetic control might be linked to Alzheimer’s disease, we studied 173,270 diabetic patients aged 65–75 with at least three HbA1c readings. HbA1c measures blood glucose over time. We compared the average HbA1c values over a five-year period for patients who were diagnosed with Alzheimer’s disease to those not diagnosed.

We adjusted for patient sex, Social Vulnerability Index (SVI), race and ethnicity, comorbid conditions, and whether the patient was prescribed insulin. We found that patients with average HbA1c values less than 6.5% or greater than 8% were at an increased risk of developing Alzheimer’s disease. Patients with average HbA1c values greater than 10% were 47% more likely to have Alzheimer’s disease, while patients with values less than 5.7% were 43% more likely.

Figure 1

Likelihood of Alzheimer’s Disease in Diabetic Patients

Figure 1. The likelihood of diabetic patients to be diagnosed with Alzheimer’s disease stratified by average HbA1c.

Additionally, we found that patients who required insulin to help manage their diabetes were 45% more likely to be diagnosed with Alzheimer’s disease. Diabetic males were 23% less likely than diabetic females to be diagnosed with Alzheimer’s disease. We found no difference in likelihood of Alzheimer’s disease between patients in any of the social vulnerability index quartiles.

These data come from Cosmos, a dataset created in collaboration with a community of Epic health systems representing more than 270 million patient records from 1,568 hospitals and more than 35,000 clinics from all 50 states, Lebanon, and Saudi Arabia. This study was completed by two teams that worked independently, each composed of a clinician and research scientists. The two teams came to similar conclusions. Graphics by Brian Olson.

References

Nguyen T.T., Ta Q.T.H., Nguyen T.T.D., Le T.T., Vo V.G. Role of Insulin Resistance in the Alzheimer’s Disease Progression. Neurochem. Res. 2020 doi: 10.1007/s11064-020-03031-0. 
Caberlotto L., Nguyen T.P., Lauria M., Priami C., Rimondini R., Maioli S., Cedazo-Minguez A., Sita G., Morroni F., Corsi M., et al. Cross-disease analysis of Alzheimer’s disease and type-2 Diabetes highlights the role of autophagy in the pathophysiology of two highly comorbid diseases. Sci. Rep. 2019;9:3965. doi: 10.1038/s41598-019-39828-5.