Hypoglycemic Events in Individuals With Type 2 Diabetes Mellitus Linked to Increased Dementia Risk

Individuals with type 2 diabetes mellitus (T2DM) who experience severe hypoglycemic events are at a higher risk for dementia, according to results published in the journal Diabetes/Metabolism Research Reviews. 

Researchers conducted a systematic review and meta-analysis of the current literature concerning the association between hypoglycemia and dementia risk. The researchers searched publication databases, including MEDLINE, Scopus, and Cochrane, from their inception until September 2022. Studies were included if the participants had T2DM, if the study was determining an association between severe hypoglycemia and cognitive decline, if studies provided data for the association between hypoglycemia and dementia risk, and if observational studies provided risk ratio (RR) values of dementia risk. Studies were excluded if they were non-English, did not have a longitudinal design, were duplicate reports, or included participants with gestational diabetes. 

In total, 995 studies were initially selected, of which 7 met the criteria for inclusion. The researchers utilized the DerSimonian and Laird method to estimate RR and performed two separate analyses to evaluate dementia risk. They first analyzed the RR of dementia in individuals with hypoglycemia vs no hypoglycemia. They also performed a dose-response analysis comparing the risk for dementia after 1, 2, or 3 or more hypoglycemic episodes versus no episodes. I²  values were used to measure and stratify heterogeneity. 

In the first analysis, the RR for the association of dementia risk and severe hypoglycemia was 1.54 (95% CI, 1.36-1.74) with significant heterogeneity (I² = 60.8%, P =.001). In the second analysis, the researchers found that the risk for dementia increased with each subsequent hypoglycemic event. For 1 hypoglycemic event, the RR was 1.29 (95% CI, 1.15-1.44); for 2 events, the RR was 1.68 (95% CI, 1.38-2.04); for 3 or more events, the RR was 1.99 (95% CI, 1.48-2.68).

In the final analysis, the researchers determined that there is a 54% higher risk for dementia among individuals with T2DM who suffer a hypoglycemic episode compared with individuals who have not experienced severe hypoglycemia. The authors also reported that each additional hypoglycemic event increases the risk for dementia by 30%. 

Limitations include that a majority of the studies evaluated by the researchers demonstrated a moderate risk of bias and significant heterogeneity; additionally, the studies used only evaluated episodes of severe hypoglycemia (not mild or moderate), which may limit the generalizability of the results. 

The authors concluded, “In summary, our study demonstrates a 54% higher risk of dementia among people who suffer a hypoglycaemia event compared to nonhypoglycaemia. Furthermore, each increase in the number of hypoglycemic episodes increases the risk of dementia by approximately 30%.”