Hyperosmolar hyperglycemic state

Hyperosmolar hyperglycemic state (HHS) occurs most commonly in older patients with type 2 diabetes. Contributes to less than 1% of all diabetes-related admissions. However, mortality is high (5% to 20%).

Presents with polyuria, polydipsia, weakness, weight loss, tachycardia, dry mucous membranes, poor skin turgor, hypotension, and, in severe cases, shock.

Altered sensorium (lethargy, disorientation, stupor) is common and correlates best with effective serum osmolality. Coma is rare and, if seen, is usually associated with a total serum osmolality >340 mOsm/kg.

Treatment includes correction of fluid deficit and electrolyte abnormalities, and intravenous insulin.

HHS, also known as nonketotic hyperglycemic hyperosmolar state, is characterized by profound hyperglycemia (glucose ≥600 mg/dL), hyperosmolality (total serum osmolality >320 mOsm/kg or calculated effective serum osmolality >300 mOsm/kg), and volume depletion in the absence of significant ketoacidosis (pH ≥7.3 and HCO₃ ≥15 mEq/L, beta-hydroxybutyrate <3.0 mmol/L), and is a serious complication of diabetes.[1]Umpierrez GE, Davis GM, ElSayed NA, et al. Hyperglycaemic crises in adults with diabetes: a consensus report. Diabetologia. 2024 Aug;67(8):1455-79. https://pmc.ncbi.nlm.nih.gov/articles/PMC11343900 http://www.ncbi.nlm.nih.gov/pubmed/38907161?tool=bestpractice.com ​​ HHS may be the first presentation of type 2 diabetes.​​​[2]Mustafa OG, Haq M, Dashora U, et al. Management of hyperosmolar hyperglycaemic state (HHS) in adults: an updated guideline from the Joint British Diabetes Societies (JBDS) for inpatient care group. Diabet Med. 2023 Mar;40(3):e15005. https://onlinelibrary.wiley.com/doi/10.1111/dme.15005 http://www.ncbi.nlm.nih.gov/pubmed/36370077?tool=bestpractice.com ​​

HHS and diabetic ketoacidosis (DKA) are often discussed as distinct entities, but they represent opposite ends of the spectrum of metabolic derangements in diabetes, and the conditions can overlap.[3]Stoner GD. Hyperosmolar hyperglycemic state. Am Fam Physician. 2017 Dec 1;96(11):729-36. https://www.aafp.org/afp/2017/1201/p729.html http://www.ncbi.nlm.nih.gov/pubmed/29431405?tool=bestpractice.com [4]Fayfman M, Pasquel FJ, Umpierrez GE. Management of hyperglycemic crises: diabetic ketoacidosis and hyperglycemic hyperosmolar state. Med Clin North Am. 2017 May;101(3):587-606. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6535398 http://www.ncbi.nlm.nih.gov/pubmed/28372715?tool=bestpractice.com [5]Pasquel FJ, Tsegka K, Wang H, et al. Clinical outcomes in patients with isolated or combined diabetic ketoacidosis and hyperosmolar hyperglycemic state: a retrospective, hospital-based cohort study. Diabetes Care. 2020 Feb;43(2):349-57. https://care.diabetesjournals.org/content/43/2/349.long http://www.ncbi.nlm.nih.gov/pubmed/31704689?tool=bestpractice.com

Both HHS and DKA are characterized by relative or absolute insulin deficiency combined with increased counter-regulatory hormones.[1]Umpierrez GE, Davis GM, ElSayed NA, et al. Hyperglycaemic crises in adults with diabetes: a consensus report. Diabetologia. 2024 Aug;67(8):1455-79. https://pmc.ncbi.nlm.nih.gov/articles/PMC11343900 http://www.ncbi.nlm.nih.gov/pubmed/38907161?tool=bestpractice.com ​​​[6]Glaser N, Fritsch M, Priyambada L, et al. ISPAD clinical practice consensus guidelines 2022: diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes. 2022 Nov;23(7):835-56. http://www.ncbi.nlm.nih.gov/pubmed/36250645?tool=bestpractice.com Approximately one third of patients with hyperglycemic crises present with a mixed picture of DKA and HHS.[5]Pasquel FJ, Tsegka K, Wang H, et al. Clinical outcomes in patients with isolated or combined diabetic ketoacidosis and hyperosmolar hyperglycemic state: a retrospective, hospital-based cohort study. Diabetes Care. 2020 Feb;43(2):349-57. https://care.diabetesjournals.org/content/43/2/349.long http://www.ncbi.nlm.nih.gov/pubmed/31704689?tool=bestpractice.com [7]Wachtel TJ, Tetu-Mouradjian LM, Goldman DL, et al. Hyperosmolarity and acidosis in diabetes mellitus: a three-year experience in Rhode Island. J Gen Intern Med. 1991 Nov-Dec;6(6):495-502. http://www.ncbi.nlm.nih.gov/pubmed/1765864?tool=bestpractice.com ​​​​​ Infection is the most common precipitant.[3]Stoner GD. Hyperosmolar hyperglycemic state. Am Fam Physician. 2017 Dec 1;96(11):729-36. https://www.aafp.org/afp/2017/1201/p729.html http://www.ncbi.nlm.nih.gov/pubmed/29431405?tool=bestpractice.com [8]Trence DL, Hirsch IB. Hyperglycemic crises in diabetes mellitus type 2. Endocrinol Metab Clin North Am. 2001 Dec;30(4):817-31. http://www.ncbi.nlm.nih.gov/pubmed/11727401?tool=bestpractice.com [9]Pasquel FJ, Umpierrez GE. Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment. Diabetes Care. 2014 Nov;37(11):3124-31. http://care.diabetesjournals.org/content/37/11/3124.long http://www.ncbi.nlm.nih.gov/pubmed/25342831?tool=bestpractice.com [10]Karslioglu French E, Donihi AC, Korytkowski MT. Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome: review of acute decompensated diabetes in adult patients. BMJ. 2019 May 29;365:l1114. https://www.bmj.com/content/365/bmj.l1114.long http://www.ncbi.nlm.nih.gov/pubmed/31142480?tool=bestpractice.com ​​​​

This topic covers HHS in adults. The International Society for Pediatric and Adolescent Diabetes (ISPAD) publishes guidelines for management in children and adolescents.[6]Glaser N, Fritsch M, Priyambada L, et al. ISPAD clinical practice consensus guidelines 2022: diabetic ketoacidosis and hyperglycemic hyperosmolar state. Pediatr Diabetes. 2022 Nov;23(7):835-56. http://www.ncbi.nlm.nih.gov/pubmed/36250645?tool=bestpractice.com ​​