Abstract The Centenary of the first person receiving insulin treatment was celebrated in 2022. This was a huge breakthrough in the management of type 1 diabetes, which had previously been a fatal condition. Over the last one hundred years, there have been considerable developments in the treatment of both type 1 and type 2 diabetes, with continuous glucose monitoring and closed loop insulin pumps (the “artificial pancreas”) a reality in type 1 diabetes. In type 2 diabetes over the last 20 years there has also been rapid progress, with a proliferation of new treatments including the GLP-1 agonists and SGLT-2 inhibitors, with positive effects on cardiovascular risk, renal disease and glucose concentrations. The first detailed description of diabetes coma was in the 1820s, and in the 1880s a form of diabetic coma distinct from diabetic ketoacidosis was first described: profound hyperglycaemia was present but without the distinctive “Kussmaul” breathing. However, this was met with scepticism until the 1950s, when the osmotic diuresis, polyuria and progressive water deficit of hyperosmolar hyperglycaemic state or hyperosmolar, non-ketotic coma (HONK), as it was previously known were described. With the discovery of insulin came the possibility of treating diabetes coma. Initially in the 1920s high-dose insulin, 20–100 units every hour was given according to urine testing, and very high doses of insulin continued to be used for decades. Landmark studies in the 1970s showed that diabetic ketoacidosis and hyperosmolar hyperglycaemic state could be successfully treated with lower doses of insulin, with 5–10 units hourly either intravenously or intramuscularly. While there is no definite diagnostic criteria for hyperosmolar hyperglycaemic state, United Kingdom guidelines describe the classic features of hyperosmolar hyperglycaemic state as: hyperglycaemia with glucose greater than 30 mmol/l, hypovolaemia, hypernatraemia, calculated osmolality more than 320 msom/kg, with the absence of significant ketonaemia or acidosis. The classic presentation of hyperosmolar hyperglycaemic state is most commonly seen in older adults with co-morbidities and has a gradual onset. It may be precipitated by infection or other severe illness, or sometimes by medication like corticosteroids. However, often a mixed diabetic ketoacidosis/hyperosmolar hyperglycaemic state picture is seen with hyperglycaemia and hyperosmolality, and ketonaemia and acidosis. Studies suggest that the mortality rate of mixed diabetic ketoacidosis/hyperosmolar hyperglycaemic state presentation is higher than that of diabetic ketoacidosis or hyperosmolar hyperglycaemic state. The principles of management of hyperosmolar hyperglycaemic state are to normalize the osmolality, replace fluid and electrolyte losses, normalize the glucose concentration and treat and/or prevent other complications. The vital signs, electrolytes, osmolality, pH and Glasgow Coma Scale are used to assess severity, with a low threshold for Intensive care admission due to the risk of mortality and need for careful fluid and electrolyte monitoring and replacement. United Kingdom Guidelines suggest fluid replacement with 0.9% sodium chloride, with careful monitoring, aiming for a gradual decline in the sodium concentration and osmolality, to reduce central fluid shifts. Fluid replacement often leads to a reduction in glucose concentrations, so it is recommended that an insulin infusion is not started until glucose concentrations plateau. Then a low-dose fixed-rate intravenous insulin infusion should be started at 0.05 units/kg/h. This contrasts with the management of diabetic ketoacidosis, when the recommended insulin infusion rate is 0.1 units/kg/h, and this is started immediately. Again, a gradual reduction in glucose is suggested to minimise fluid shift, aiming to stabilize at 10–15 mmol/L. Ongoing fluid and electrolyte replacement is guided by close monitoring and assessment. Other important considerations are treating infection and precipitating causes, venous thromboembolism prevention, monitoring for cerebral oedema and prevention of foot ulceration. When there is a mixed diabetic ketoacidosis/hyperosmolar hyperglycaemic state presentation, United Kingdom Guidelines suggest starting fixed rate intravenous insulin infusion immediately, using 0.05 units/kg/h, if blood ketones are between 1 mmol/L and 3 mmol/L, and the higher, diabetic ketoacidosis protocol dose of 0.1 units/kg/h if blood ketones are greater than 3 mmol/L or pH is less than 7.3. However, the evidence base guiding management is limited and local guidelines may differ. In summary, there have been great advances in the management of diabetes over the last one hundred years, and this is reflected in the management of diabetic hyperglycaemic emergencies. The acute management principles of hyperosmolar hyperglycaemic state are similar to those of the 1970s, but the ability to easily monitor blood glucose concentrations and ketones in and out of hospital, as well as advances in hospital care have undoubtedly improved care. References 1. Dhatariya K, Mustafa O, Stathi D. Hyperglycemic Crises. Updated 10 June 2025. In: Feingold KR, Adler RA, Ahmed SF, et al., editors. Endotext Internet. South Dartmouth (MA): MDText.com, Inc.; 2000-. 2. Mustafa OG, Haq M, Dashora U, Castro E, Dhatariya KK; Joint British Diabetes Societies (JBDS) for Inpatient Care Group. 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;40(3):e15005. 3. Pasquel FJ, Tsegka K, Wang H, Cardona S, Galindo RJ, Fayfman M, Davis G, Vellanki P, Migdal A, Gujral U, Narayan KM, Umpierrez GE. Clinical outcomes in patients with isolated or combined diabetic ketoacidosis and hyperosmolar hyperglycemic state: A retrospective, hospital-based cohort study. Diabetes Care 2020; 43:349–357. 4. Pasquel FJ, Umpierrez GE. Hyperosmolar hyperglycemic state: a historic review of the clinical presentation, diagnosis, and treatment. Diabetes Care 2014; 37:3124–31.
Anna Brackenridge (Wed,) studied this question.