Severe Hypoglycemia Increases Dementia Risk and Related Mortality: A Nationwide, Population-based Cohort Study

Context: There are few studies focused on the relationship between hypoglycemia and new-onset dementia in patients with type 2 diabetes and no study regarding mortality of dementia after hypoglycemia. Objective: We investigated the effect of severe hypoglycemia on dementia subtypes and its relation to overall mortality in patients with type 2 diabetes. Methods: We evaluated incident dementia, including Alzheimer disease and vascular dementia, among health checkup participants aged 40 years or older in the National Health Insurance System in Korea from January 2009 to December 2015. Episodes of severe hypoglycemia were examined for 3 years before the date of the health checkup. Results: Among 2032689 participants (1172271 men, 860418 women), 14443 (0.7%) experienced severe hypoglycemia, during a mean follow-up period of 6.9±1.7 years. Individuals in the severe hypoglycemia group were more likely to be diagnosed with dementia compared to individuals without severe hypoglycemia (23.3% vs 7.3%; P<.001) and the overall incidence of Alzheimer disease was higher than vascular dementia. Dementia risk rose with increasing number of severe hypoglycemic episodes (1 episode [hazard ratio (HR)=1.54; 95% CI, 1.48-1.60], 2 or more episodes [HR=1.80; 95% CI, 1.66-1.94]). Overall mortality was higher in participants with dementia, but without severe hypoglycemia (HR=2.03; 95% CI, 1.96-2.10) and severe hypoglycemia, but without dementia (HR=4.24; 95% CI, 4.29-4.40), and risk of death was highest in those with both severe hypoglycemia and dementia (HR=5.08; 95% CI, 4.83-5.35). Conclusion: Severe hypoglycemia is associated with dementia, especially Alzheimer disease and mortality; together, they have an additive effect on overall mortality.