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Causal Link Found Between T2D and Dementia

Researchers published the study covered in this summary on MedRxiv as a preprint that has not yet been peer reviewed.

Key Takeaways

  • A study of more than 334,000 mostly male veterans in the United States found evidence for a significant, causal association between type 2 diabetes and dementia.

Why This Matters

  • The prevalence of diabetes and dementia are projected to increase in the US, so it is critical to understand the relationship between these two diseases.

  • In observational studies, people with diabetes had a 1.4- to 2.2-fold greater rate of developing dementia compared with people without diabetes. Two-sample Mendelian randomization studies did not find any increased risk, but this analytic approach has limitations and hence the current study used a one-sample Mendelian randomization strategy.

  • Establishing a causal relationship between diabetes and dementia, as in the current study, is a step toward understanding how the increasing prevalence of diabetes may affect the increasing incidence of dementia and determining whether diabetes prevention, treatment, or both might mitigate this risk.

Study Design

  • The researchers identified 334,672 participants in the Million Veteran Program who were at least age 65 years and met other study criteria, including 82,980 with a diagnosis of type 2 diabetes and 251,692 without diabetes.

  • They performed a two-stage, least-squared Mendelian randomization analysis to estimate the causal association between type 2 diabetes and dementia.

Key Results

  • Compared with patients without type 2 diabetes, those with type 2 diabetes were more likely to have all-cause dementia. The prevalence was 8.7% in those with diabetes compared with 6.7% in those without.

  • The prevalence of vascular dementia was 2% in those with diabetes and 1% in those without diabetes. The prevalence of Alzheimer’s disease was roughly similar in the two subgroups, with a 1.4% rate in those with diabetes and a 1.3% in those without diabetes.

  • For each standard deviation increase in genetically predicted diabetes, White individuals had a significant 7% higher risk for all-cause dementia, a significant 11% higher risk for vascular dementia, and a significant 6% higher risk for Alzheimer’s disease.

  • For the same metric, African American individuals had a significant 6% increased risk for all-cause dementia, a significant 11% risk higher risk for vascular dementia, and a significantly 12% increased risk for Alzheimer’s disease.

  • Individuals who self-identified as Hispanic and had type 2 diabetes did not have a significantly increased risk for any of these dementia outcomes.


  • The study participants were almost all male, so the findings cannot be generalized to women.

  • Diagnoses were based on physicians’ diagnoses, which may have been imprecise.

  • The calculations were built on previous work by the researchers involving people of European ancestry, and thus may not be as applicable to African American and Hispanic populations.


  • The study received no commercial funding.

  • Co-authors Lawrence S. Phillips and Sridharan Raghavan disclosed financial relationships with commercial entities that are listed in the preprint.

This is a summary of a preprint research study , “Mendelian randomization study of diabetes and dementia in the Million Veteran Program,” written by researchers affiliated with the US VA Healthcare system as well as other US institutions, published on medRxiv and provided to you by Medscape. This preprint has not yet been peer reviewed. The full text of the preprint can be found on medRxiv.org.

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  • Posted on March 21, 2023