Severe Hypoglycemia Requiring Hospitalization Increases Premature Death Risk in People With T1D

Among individuals with type 1 diabetes (T1D), the strongest predictor for time to death was having 2 or more episodes of severe hypoglycemia that required hospitalization, according to a study published in Diabetes, Obesity and Metabolism.

To come to this finding, researchers conducted a national retrospective observational cohort study among individuals with T1D who received a diagnosis between 2000 and 2018. They assessed various clinical, comorbidity, and demographic factors to determine their influence on mortality among patients with zero, 1, 2, and 3 or more severe hypoglycemic episodes requiring hospitalization. Time to death from the timepoint of the last severe episode was modelled using a parametric survival model.

The study included 8224 individuals with T1D in Wales, with a median (IQR) age of 28 (16.9-45.1) years. Of this group, 3655 (44.2%) were female, the median hemoglobin A_1C (HbA_1C) was 70.5 (58.0-74.5) mmol/mol, and 1702 (20.7%) individuals lived in areas defined as most deprived. The median follow-up time from hypoglycemia episode to endpoint was 4.70 (1.75-9.32) years and from diagnosis to endpoint, 9.77 (4.64-14.75) years.

Per 1000 person-years, among patients with no occurrence of severe hypoglycemia requiring hospitalization, the crude mortality rate was 6.9 (6.1-7.8) deaths and the age-adjusted mortality rate was 15.31 (13.3-17.63) deaths.

For 1 episode, the crude and age-adjusted mortality rates were 24.9 (21.0-29.6) and 53.8 (44.6-64.7) deaths per 1000 person-years, respectively; for 2 episodes, 28.0 (23.1-34.0) and 72.8 (59.2-89.5) deaths; and for 3 or more episodes, 33.5 (30.0-37.3) and 86.3 (71.7-103.9) deaths.

A parametric survival model revealed that having 2 episodes of severe hypoglycemia requiring hospitalization was the most influential factor in predicting the time until death, indicated by the accelerated failure time coefficient of 0.073 (95% CI, 0.009-0.565). The second strongest predictor was having 1 episode, with an accelerated failure time coefficient of 0.126 (95% CI, 0.036-0.438). These were followed by age at the most recent episode of severe hypoglycemia requiring hospitalization, with a coefficient of 0.917 (95% CI, 0.885-0.951), indicating its moderate impact on the time until death.

“Having 3 or more episodes of severe hypoglycaemia requiring hospitalization did not meet our chosen statistical significance threshold, but the trend observed for 1 and 2 episodes suggests this was because there were insufficient data to reject the null hypothesis that 3 or more episodes of severe hypoglycaemia requiring hospitalization was not associated with an increase in mortality,” the authors said.

They also noted that patients who died had a higher body mass index compared with patients who remained alive, but these patients also had a higher number of severe episodes. Additionally, despite having the same number of severe episodes requiring hospitalization, the patients with T1D who were older were more likely to die vs their younger counterparts.

Patients who died had a median age of 62.4 (48.8-74.4) years at the occurrence of the last severe episode, while the general life expectancy in Wales is 79.4 years for men and 83.1 years for women. Of note, those with at least 3 severe episodes who died had a median age of 55.1 (41.9-75.6) years, suggesting that, after a closer look, age may have had only a moderate impact on mortality.

Reference

Moser O, Rafferty J, Eckstein ML, et al. Impact of severe hypoglycaemia requiring hospitalization on mortality in people with type 1 diabetes: a national retrospective observational cohort study. Diabetes Obes Metab. Published online May 4, 2023. doi:10.1111/dom.15102