Association of Hypoglycemia with Subsequent Dementia in Older Patients with Type 2 Diabetes Mellitus

Abstract

Background: Studies have found conflicting evidence regarding the association of hypoglycemia with dementia. We evaluated an association of hypoglycemia with subsequent dementia in patients with type 2 diabetes. Methods: This retrospective longitudinal cohort study used the Clinical Practice Research Datalink, an electronic medical records data from the United Kingdom, from 2003 to 2012. We included patients aged >65 years diagnosed with type 2 diabetes, with no prior diagnosis of dementia. Dementia was defined using diagnosis codes from medical records. All patients were followed from the date of initial diabetes diagnosis. To account for competing risk of death, we used Fine and Gray's competing risk model to determine the association of hypoglycemia with dementia while adjusting for potential confounders. Hypoglycemia was modeled as a time-dependent covariate. Results: Of 53,055 patients, 5.7% (n = 3,018) had at least one hypoglycemia episodes. The overall incidence rate of dementia was 12.7 per 1,000 person-years. In the fully adjusted model that controlled for all confounders, the occurrence of at least one hypoglycemia episode was associated with 27% higher odds of subsequent dementia (hazard ratio = 1.27; 95% confidence interval = 1.06-1.51). The risk increased with the number of hypoglycemia episodes: one episode (hazard ratio = 1.26; 95% confidence interval = 1.03-1.54); two or more episodes (hazard ratio = 1.50; 95% confidence interval = 1.09-2.08). Conclusions: Hypoglycemia is associated with a higher risk of dementia and may be responsible in part for the higher risk of dementia in patients with diabetes. Alternatively, hypoglycemia may be a marker for undiagnosed cognitive impairment, and we cannot rule out the possibility of reverse causation between hypoglycemia and dementia.