Sex-specific associations between diabetes and dementia: the role of age at onset of disease, insulin use and complications

Abstract

Background Whether the association of type 2 diabetes (T2DM) with dementia was differed by sex remains unclear, and the roles of age at onset of disease, insulin use and diabetes’ complications in their association are unknown. Methods This study analyzed data of 447 931 participants from the UK Biobank. We used Cox proportional hazards models to estimate sex-specific hazard ratios (HRs) and 95% confidence intervals (CI), and women-to-men ratio of HRs (RHR) for the association between T2DM and incident dementia [all-cause dementia, Alzheimer's disease (AD), and vascular dementia (VD)]. The roles of age at onset of disease, insulin use and diabetes’ complications in their association were also analyzed. Results Compared to people with no diabetes at all, people with T2DM had increased risk of all-cause dementia (HR 2.85, 95% CI 2.56–3.17). The HRs between T2DM and AD were higher in women than men, with an RHR (95%CI) of 1.56 (1.20, 2.02). There was a trend that people who experienced T2DM before age 55 had higher risk of VD than those who had T2DM after age 55. In addition, there was a trend that T2DM had higher effect on VD that occurred before age 75 years than events that occurred after age 75. Patients with T2DM using insulin had higher risk of all-cause dementia than those without insulin, with an RHR (95%CI) of 1.54 (1.00–2.37). People with complications had doubled risk of all-cause dementia, AD and VD. Conclusions Adopting a sex-sensitive strategy to address the risk of dementia in patients with T2DM is instrumental for a precision medicine approach. Meanwhile, it is warranted to consider patients' age at onset of T2DM, insulin use status and complications conditions.

A case for seeking sex-specific treatments in Alzheimer’s disease

“…Type 2 diabetes confers a significant risk of developing AD and a recent study that analyzed data from 450,000 individuals determined that females with type 2 diabetes had a higher risk of developing AD than men with type 2 diabetes ( Zhou et al, 2023 ). Significantly, the evidence suggests that type 2 diabetes is more prevalent in women than men ( Ashraf et al, 2021 ).…”

Effect of glycemic control on cognitive function in patients with type 1 diabetes mellitus: a systematic review and meta-analysis

“…It is suggested by some clinical studies hyperglycemia is a potential risk factor for mild cognitive impairment (MCI) or Alzheimer’s disease, and MCI patients are more likely to develop dementia than the general population [ 8 ]. Moreover, reports have confirmed that people with diabetes have twice the risk of developing dementia as people without diabetes [ 9 ]. This may be related to the fact that the hyperglycemia can increase the accumulation of β-amyloid in brain lesions, aggravating oxidative stress, neuroinflammation and mitochondrial dysfunction, and damage neuronal integrity [ 10 ].…”

Healthy lifestyle and all‐cause and cause‐specific dementia in individuals with type 2 diabetes and the roles of diabetes duration and insulin use in UK Biobank cohort

“…22 Limited evidence suggested that a longer duration of diabetes might lead to a higher risk of dementia. 23,24 In addition, insulin use has been associated with the increased risk of dementia, 25 which may be related to hypoglycaemia caused by insulin. 26 Therefore, diabetes duration and insulin use status may affect the association of healthy lifestyle with risk of dementia in people with T2DM.…”