Association between severe hypoglycaemia and risk of dementia in patients with type 2 diabetes mellitus: A systematic review and meta‐analysis

Abstract

The aim of this systematic review was to analyse whether there is an association between severe hypoglycaemia and the incidence of dementia in patients with type 2 diabetes mellitus. We systematically searched the MEDLINE, Scopus, and Cochrane databases from their inception until September 2022 for observational studies on the association between hypoglycaemia and the risk of dementia. The DerSimonian and Laird method was used to compute a pooled estimate of the risk for such association. Risk ratio (RR) and its respective 95% confidence interval (95% CI). Two analyses were performed to estimate the risk of dementia: (i) any hypoglycaemia versus no hypoglycaemia and (ii) a dose-response analysis for one, two, or more than three hypoglycemic events versus no hypoglycaemia. PROS-PERO registration number CRD42020219200. Seven studies were included. The pooled RR for the association of severe hypoglycaemia and risk of dementia was 1.47 (95% CI: 1.24-1.74). When the dose-response trend was analysed, the pooled RR for the risk of dementia was increased according to the hypoglycaemia events as follows: 1.29 (95% CI: 1.15-1.44) for one hypoglycemic event; 1.68 (95% CI:1.38-2.04) for two hypoglycemic events; and 1.99 (95% CI: 1.48-2.68) for three or more hypoglycemic events. Our study demonstrates a 54% higher risk of dementia among people who suffer a hypoglycaemia event compared to nonhypoglycaemia. Considering our results and the prevalence of people suffering from diabetes mellitus, health education for both newly diagnosed and already diagnosed people could be a useful tool for glycaemic control, thus avoiding hypoglycaemic events.

Diabetes, antidiabetic medications and risk of dementia: A systematic umbrella review and meta‐analysis

“…5‐6). Of the 100 included reviews, 32 related diabetes to cognitive function in mixed diabetic populations, 2,6,8,26–54 seven examined the effect of type 1 diabetes, 3,55–60 19 focused on type 2 diabetes, 5,7,61–77 14 observed brain structure in diabetes, 1,4,78–89 two examined genetic and other biomarkers of dementia 90,91 and 26 focused on cognitive effects of antidiabetic treatment 14,15,20–22,92–112 . Of the 27 studies included in the meta‐analyses, 15 related metformin use to risk of dementia, 113–127 10 were used in the thiazolidinedione meta‐analysis, 113,122–130 four for pioglitazone, 126,129–131 seven for DPP‐4is, 123,125–127,132–134 five for α‐glucosidase inhibitors, 123,126,127,129,135 two for meglitinides, 126,129 seven for insulin, 122,123,125,127,129,136,137 11 for sulphonylureas,…”

The relationship between diabetes and the dementia risk: a meta-analysis

“…Additionally, a systematic review has quantified this relationship, noting that severe hypoglycemic events raise the risk of dementia [RR: 1.47, 95%CI (1.24–1.74)]. The risk escalates with the frequency of episodes: one event increases the risk by 29% [RR: 1.29, 95%CI (1.15–1.44)], two episodes by 68% [RR: 1.68, 95%CI (1.38–2.04)], and three or more episodes double the risk [RR: 1.99, 95%CI (1.48–2.68)] [ 51 ]. These findings highlight the significant role of hypoglycemic events as a factor in the development of dementia in diabetic patients.…”

Management of Outpatients With Diabetes at High Risk of Hypoglycemia

“…Level 1 hypoglycemia is defined as blood glucose of 54 to 70 mg/dL; level 2 is less than 54 mg/dL; and severe hypoglycemia (level 3) occurs when low blood glucose levels cause neurologic or physical symptoms that require help from others. Furthermore, recurrent severe hypoglycemia increases risk of future dementia . Hypoglycemia occurs more often in people with lower education, lower income, and food insecurity .…”