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 mucus 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 serum osmolality >340 mOsm/kg.

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

HHS, also known as non-ketotic hyperglycemic hyperosmolar syndrome, is characterized by profound hyperglycemia (glucose >600 mg/dL), hyperosmolality (effective serum osmolality ≥320 mOsm/kg), and volume depletion in the absence of significant ketoacidosis (pH >7.3 and HCO3 >15 mEq/L), and is a serious complication of diabetes. HHS may be the first presentation of type 2 diabetes.[1]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43. http://care.diabetesjournals.org/content/32/7/1335.long http://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com

Although HHS and diabetic ketoacidosis (DKA) are often discussed as distinct entities, they represent 2 points on the spectrum of metabolic derangements in diabetes.[2]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 [3]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

HHS and DKA are characterized by relative or absolute insulin deficiency combined with increased counter-regulatory hormones.[1]Kitabchi AE, Umpierrez GE, Miles JM, et al. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009 Jul;32(7):1335-43. http://care.diabetesjournals.org/content/32/7/1335.long http://www.ncbi.nlm.nih.gov/pubmed/19564476?tool=bestpractice.com [4]Wolfsdorf JI, Glaser N, Agus M, et al. ISPAD Clinical Practice Consensus Guidelines 2018: Diabetic ketoacidosis and the hyperglycemic hyperosmolar state. Pediatr Diabetes. 2018 Oct;19 Suppl 27:155-77. https://onlinelibrary.wiley.com/doi/full/10.1111/pedi.12701 http://www.ncbi.nlm.nih.gov/pubmed/29900641?tool=bestpractice.com Approximately one third of patients with hyperglycemic crises present with a mixed picture of DKA and HHS.[5]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.[6]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