Type 2 diabetes may have causal association with dementia

"Using a one-sample Mendelian randomization (M.R.) analysis, with access to individual data, we found evidence of causality between diabetes and dementia," Elizabeth M Litkowski, VA Eastern Colorado Healthcare System, Aurora, CO, USA, and colleagues wrote in their study. The researchers overcome the limitations of prior studies utilizing two-sample M.R. techniques.

Dementia and diabetes are diseases that carry a high healthcare burden worldwide. Patients with diabetes have a 1.4 to 2.2 times higher risk of dementia.

"Establishing a causal relationship between dementia and diabetes, as in the current study, is a step toward understanding how the rising prevalence of diabetes may impact the increasing dementia incidence and determining whether diabetes prevention, treatment, or both might reduce this risk", the authors pointed out.

The study was conducted to evaluate evidence of causality between these two common diseases (diabetes and dementia).

For this purpose, the researchers conducted a one-sample Mendelian randomization analysis in the U.S. Department of Veterans Affairs Million Veteran program. The study comprised 334,672 participants ≥65 years of age with dementia and type 2 diabetes case-control status and genotype data.

The study led to the following findings:

• Patients with type 2 diabetes were likelier to have all-cause dementia than those without type 2 diabetes. The prevalence was 8.7% in patients with diabetes versus 6.7% in those without.
• In diabetes patients, the prevalence of vascular dementia was 2% and 1% in those without the disease.
• Alzheimer's disease prevalence was roughly the same in the two subgroups, with a 1.4% rate in people with diabetes and 1.3% in those without.
• White people had a remarkably 7% higher risk for all-cause dementia, a 6% higher risk for Alzheimer's disease, and a significantly 11% higher risk for vascular dementia for each standard deviation increase in genetically predicted diabetes.
• For the same metric, African Americans had a significantly 11% higher vascular dementia risk, a significantly 12% increased Alzheimer's disease risk, and a significant 6% increased all-cause dementia risk.
• People who self-identified as Hispanic and had type 2 diabetes did not have a remarkably increased risk for dementia outcomes.

The investigators found evidence of causality between diabetes and dementia using a one-sample M.R. study, with access to individual-level data, overcoming limitations of prior studies that used two-sample M.R. techniques.

Reference:

Mendelian randomization study of diabetes and dementia in the Million Veteran Program. Elizabeth M Litkowski, Mark W Logue, Rui Zhang, Brian R Charest, Ethan M Lange, John E Hokanson, Julie A Lynch, Marijana Vujkovic, Lawrence S Phillips, Richard L Hauger, Leslie A Lange, Sridharan Raghavan. medRxiv 2023.03.07.23286526; doi: https://doi.org/10.1101/2023.03.07.23286526