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Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
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For most patients, experiencing several weeks of polyuria, polydipsia, fatigue, and significant weight loss may indicate the presence of diabetes. Furthermore, adults displaying the phenotypic appearance of type 2 diabetes (particularly those who are obese and not initially insulin-requiring), may have islet cell autoantibodies, suggesting autoimmune-mediated β cell destruction and a diagnosis of latent autoimmune diabetes of adults (LADA). The categorization of glucose homeostasis is...
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Is Our Understanding of Hyperosmolar Hyperglycemic State Accurate?

Boris Shvarts1, Evgeny Golbets1, Iftach Sagy2

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The Journal of Emergency Medicine
|November 13, 2025
PubMed
Summary

Hyperosmolar hyperglycemic state (HHS) and diabetic ketoacidosis (DKA) are serious diabetes emergencies. While HHS has higher mortality, comorbidities and age, not just metabolic issues, significantly impact outcomes.

Keywords:
clinical outcomesdiabetes complicationsdiabetic ketoacidosishyperosmolar hyperglycemic statemetabolic emergencies

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Area of Science:

  • Endocrinology
  • Internal Medicine
  • Critical Care Medicine

Background:

  • Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are distinct hyperglycemic emergencies.
  • HHS has higher mortality rates than DKA, yet optimal treatment strategies remain undefined.
  • Current DKA protocols are often applied to HHS, lacking HHS-specific evidence.

Purpose of the Study:

  • Compare clinical characteristics and outcomes of HHS and DKA.
  • Identify factors contributing to higher HHS mortality.
  • Inform the development of effective HHS treatment strategies to reduce mortality.

Main Methods:

  • Retrospective analysis of adult patients admitted with HHS or DKA between 2015-2021.
  • Comparison of clinical characteristics and outcomes between HHS and DKA groups.
  • Primary outcome: in-hospital mortality.

Main Results:

  • Study included 608 patients (223 HHS, 385 DKA).
  • HHS patients were older, more frequently had infection as a trigger, and presented with more comorbidities.
  • Univariate analysis showed higher in-hospital mortality in HHS (41.2% vs. 4.7%), but matched multivariate analysis revealed no significant difference.

Conclusions:

  • Metabolic abnormalities alone do not explain worse HHS outcomes compared to DKA.
  • Baseline comorbidities, age, and infection trigger significantly impact outcomes in hyperglycemic emergencies.
  • Further research is needed to elucidate HHS-specific factors influencing mortality.