Hypoglycemia and Dementia Risk in Older Patients with Type 2 Diabetes Mellitus: A Propensity-Score Matched Analysis of a Population-Based Cohort Study

Abstract

Background: Type 2 diabetes mellitus (T2DM) is associated with an increased risk for dementia. The effects of hypoglycemia on dementia are controversial. Thus, we evaluated whether hypoglycemia increases the risk for dementia in senior patients with T2DM. Methods: We used the Korean National Health Insurance Service Senior cohort, which includes >10% of the entire senior population of South Korea. In total, 5,966 patients who had ever experienced at least one episode of hypoglycemia were matched with those who had not, using propensity score matching. The risk of dementia was assessed through a survival analysis of matched pairs. Results: Patients with underlying hypoglycemic events had an increased risk for all-cause dementia, Alzheimer's dementia (AD), and vascular dementia (VaD) compared with those who had not experienced a hypoglycemic event (hazard ratio [HR], 1.254; 95% confidence interval [CI], 1.166 to 1.349; P<0.001 for all-cause dementia; HR, 1.264; 95% CI, 1.162 to 1.375; P<0.001 for AD; HR, 1.286; 95% CI, 1.110 to 1.490; P<0.001 for VaD). According to number of hypoglycemic episodes, the HRs of dementia were 1.170, 1.201, and 1.358 in patients with one hypoglycemic episode, two or three episodes, and more than three episodes, respectively. In the subgroup analysis, hypoglycemia was associated with an increased risk for dementia in both sexes with or without T2DM microvascular or macrovascular complications. Conclusion: Our findings suggest that patients with a history of hypoglycemia have a higher risk for dementia. This trend was similar for AD and VaD, the two most important subtypes of dementia.

Severe hypoglycaemia and absolute risk of cause-specific mortality in individuals with type 2 diabetes: a UK primary care observational study

“…20%). As these two estimates are unadjusted and the epidemiological evidence in this area is contrasting [32][33][34][35], further studies should be conducted, ideally with a detailed phenotypical assessment of dementia to minimise coding misspecification.…”

Low‐glucose‐sensitive TRPC6 dysfunction drives hypoglycemia‐induced cognitive impairment in diabetes

“…As a major detrimental factor in hypoglycemic therapy for both T1DM and T2DM, recurrent moderate hypoglycemia (RH) is difficult to avoid in clinical practice. Despite RH has been reported to prevent age‐related decline in hippocampally cognitive function in nondiabetic rats, 44 it exerts significant detrimental effects on cognition under diabetic condition and the mechanism remains unclear 13,45–48 . Here, we provide experimental and clinical evidence to identify TRPC6 as a potential intervention target for RH‐induced cognitive impairment in diabetic patients.…”

“…Treatment with hyperforin represses cognitive impairment in diabetic mice undergoing recurrent hypoglycemia by activating TRPC6 nondiabetic rats, 44 it exerts significant detrimental effects on cognition under diabetic condition and the mechanism remains unclear. 13,[45][46][47][48] Here, we provide experimental and clinical evidence to identify TRPC6 as a potential intervention target for RH-induced cognitive impairment in diabetic patients. We found that the repressed TRPC6 is related to the cognitive impairment caused by RH, and the absence of TRPC6 directly led to cognitive dysfunction in STZ-induced type 1 diabetic mice.…”

Meta-Analysis: Association Between Hypoglycemia and Serious Adverse Events in Older Patients Treated With Glucose-Lowering Agents

“…Association between hypoglycemia and dementia 9 studies confirmed a significant association between hypoglycemia and dementia (8,9,15,24,27,33,41,42) with a pooled odds ratio of 1.50 (95% CI 1.29-1.74). There was substantial heterogeneity with I 2 = 85% ( Figure 6).…”

“…The included studies took account of potential confounding through the use of multivariate logistic regression models. Five studies used propensity score matching (18,24,34,43,47).…”