Severe Glycemic Events Linked to Development of Dementia in Older Patients with Type 1 Diabetes

Rachel Whitmer, PhD

New research from UC Davis School of Medicine indicates a single hospitalization for hypoglycemia or hyperglycemia was linked to increased risk for developing dementia among older patients with type 1 diabetes.

A longitudinal cohort study spanning nearly 2 decades, results suggest hospitalization for either severe hypoglycemia or hyperglycemia was associated with significant increase in risk for developing dementia while patients who experienced both had a more than 6-fold greater risk of developing dementia.

“People with type 1 diabetes are living longer than before, which may place them at risk of conditions such as dementia. If we can potentially decrease their risk of dementia by controlling their blood sugar levels, that could have beneficial effects for individuals and public health overall,” said study author Rachel A. Whitmer, PhD, of the University of California Davis School of Medicine in Sacramento, in a statement.

With advances in diabetes management extending the life expectancies of patients with type 1 diabetes, identification of events of factors increasing risk of dementia among these patients could improve quality of life and alleviate potential burden on healthcare systems.

Spurred by this and previous data linking severe glycemic events to increased dementia risk in patients with type 2 diabetes, Whitmer and a team of colleagues sought to determine whether such an association exists among older patients with type 1 diabetes. To fill this apparent knowledge gap, investigators designed the current study as a longitudinal study of patients within the Kaiser Permanente Northern California (KPNC) Diabetes Registry.

For the purpose of analysis, investigators identified patients within the registry from 1996-2013 aged 50 years and older who had type 1 diabetes, filled insulin prescriptions during the study period, and did not fill prescriptions for any other hypoglycemic agents. Once considered eligible for inclusion, exposure and covariate status were ascertained from start of the study period for up to 365 days after the date of eligibility. After this period, patients were entered into the cohort and follow-up began.

Patients were followed for up to 18 years or until a dementia diagnosis, death, lapse in KPNC membership for more than 90 days, or the end of the study period, which was September 30, 2015. Severe glycemic events were identified through use of ICD codes and dementia risk was calculated using Cox proportional hazard models adjusted for age, sex, race/ethnicity, HbA1c, depression, stroke, and presence of nephropathy.

A total of 2821 patients meeting eligibility criteria were included in the study. The mean follow-up time for the study population was 6.9 (SD, 5.0) years, the mean age at cohort entry was 56.5 (SD, 7.8) years, 48% were female, and 81% were White.

At cohort entry, 398 (14.1%), 355 (11.9%), and 87 (3.1%) patients experienced a severe hypoglycemic event, a severe hyperglycemic event, and both, respectively. Overall, 153 (5.4%) of patients received a diagnosis of dementia during the study period.

Compared to those without a severe hypoglycemic event, those experiencing hypoglycemic events were at a 66% increased risk of developing dementia (HR, 1.66; 95% CI, 1.09-2.53). Compared to those without a severe hyperglycemic event, those experiencing hyperglycemic events were at a more than 2-fold increased risk of developing dementia (HR, 2.11; 95% CI, 1.24-3.59). Among the subgroup of patients experiencing both severe hypoglycemic and severe hyperglycemic events, the risk of developing dementia was more than 6 times greater than those who experienced neither (HR, 6.20; 95% CI, 3.02-12.70).

“Our findings suggest that exposure to severe glycemic events may have long-term consequences on brain health and should be considered additional motivation for people with diabetes to avoid severe glycemic events throughout their lifetime,” Whitmer said.

This study, “Association of Type 1 Diabetes and Hypoglycemic and Hyperglycemic Events and Risk of Dementia,” was published in Neurology.