Is Our Understanding of Hyperosmolar Hyperglycemic State Accurate?

Background Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are two distinct hyperglycemic emergencies with different pathophysiological and clinical profiles. While DKA is more common, HHS carries higher mortality rates. Although low-dose insulin protocols used for DKA are often applied, no optimal, evidence-based strategies specific to HHS have been established. Objectives To examine clinical characteristics and the outcomes of HHS and DKA syndromes, and to characterize the factors contributing to a higher mortality rate in HHS. To contribute to the development of effective treatment strategies, with the goal of reducing HHS mortality in future research. Methods A retrospective analysis of admissions for HHS and DKA in adult patients between 2015 and 2021 in a large tertiary center. Clinical characteristics and outcomes of patients with HHS vs. DKA were compared. The primary outcome was in-hospital mortality. Results Total 608 patients were included in the study, 223 (37%) patients in the HHS group and 385 (63%) in the DKA group. Patients in the HHS group were older (77.4 vs. 43.6 years, p < 0.001), had more infection as a trigger (41.7% vs. 20.5%, p < 0.001) and more co-morbidities. In-hospital mortality rate was higher in the HHS group (41.2% vs. 4.7%, p < 0.001), however, matched multivariate analysis showed no significant differences for in-hospital mortality (OR 0.43, 95% CI 0.18–1.02). Conclusion Metabolic abnormalities alone do not appear to explain the worse outcomes observed in HHS compared to DKA. Our findings indicate that baseline comorbidities, age and infection trigger have more significant impact on outcomes than the patients' metabolic status.