A serious metabolic complication of diabetes characterized by severe hyperglycemia, hyperosmolality, and volume depletion, in the absence of severe ketoacidosis.
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 15%).
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 IV insulin.
Hyperosmolar hyperglycemic syndrome (HHS), also known as non-ketotic hyperglycemic hyperosmolar syndrome (NKHS), 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.   Although both HHS and diabetic ketoacidosis (DKA) are often discussed as distinct entities, they represent 2 points on the spectrum of metabolic derangements in diabetes,  both HHS and DKA being characterized by relative or absolute insulin deficiency combined with increased counter-regulatory hormones.   Approximately one third of patients with hyperglycemic crises present with a mixed picture of DKA and HHS. 
Joslin Diabetes Clinic
NK declares that she has no competing interests.
Professor of Medicine
Emory University School of Medicine
GU is supported by research grants from the American Diabetes Association and the National Institutes of Health, and has received research funds from Sanofi-Aventis, Novo Nordisk, Takeda, and GlaxoSmithKline. GU is an author of a number of references cited in this monograph.
Beta Cell Unit
Chelsea and Westminster NHS Trust
DM declares that he has no competing interests.
Department of Medicine
Division of Endocrinology and Metabolism
University of Florida
MCL has received speaker fees from Sanofi-Aventis and Novo Nordisk, makers of insulin products.
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