Association Between Trajectory of Severe Hypoglycemia and Dementia in Patients With Type 2 Diabetes: A Population-based Study

Background: We aimed to investigate associations between exposure to various trajectories of severe hypoglycemic events and risk of dementia in patients with type 2 diabetes. Methods: In 2002-2003, 677,618 patients in Taiwan were newly diagnosed as having type 2 diabetes. Among them, 35,720 (5.3%) experienced severe hypoglycemic events during the 3-year baseline period following diagnosis. All patients were followed from the first day after baseline period to the date of dementia diagnosis, death, or the end of 2011. A group-based trajectory model was used to classify individuals with severe hypoglycemic events during the baseline period. Cox proportional hazard models with the competing risk method were used to relate dementia risk to various severe hypoglycemia trajectories. Results: After a median follow-up 6.70 and 6.10 years for patients with and without severe hypoglycemia at baseline, respectively, 1,952 (5.5%) individuals with severe hypoglycemia and 23,492 (3.7%) without developed dementia during follow-up, for incidence rates of 109.80 and 61.88 per 10,000 person-years, respectively. Four groups of severe hypoglycemia trajectory were identified with a proportion of 18.06%, 33.19%, 43.25%, and 5.50%, respectively, for Groups 1 to 4. Groups 3 (early manifestation but with later decrease) and 4 (early and sustained manifestation) were associated with a significantly increased risk of dementia diagnosis, with a covariate-adjusted subdistribution hazard ratio of 1.22 (95% confidence interval, 1.14-1.31) and 1.25 (95% confidence interval, 1.02-1.54), respectively. Conclusion: Our analysis highlighted that early manifestation of severe hypoglycemic events may contribute more than does late manifestation to the risk of dementia among individuals newly diagnosed as having type 2 diabetes.