Hyperosmolar hyperglycemic state historical perspective

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Husnain Shaukat, M.D [2]

Overview

The first cases of the hyperosmolar hyperglycemic state were described by Von Frerichs and Dreschfeld in the 1880s in some patients with unusual diabetic coma. In 1971, Aerieff and Carroll proposed the diagnostic criteria for patients presenting with diabetic coma and named it as a hyperosmolar hyperglycemic nonketotic state. In the recent times, the term has been changed to the hyperosmolar hyperglycemic state as most of the patients present without coma and with minimal ketosis. Before the discovery of insulin in 1922, it was rare for the patient of diabetes with an episode of diabetic coma to survive for more than a few months. With the discovery of insulin, the development of diabetic coma in patients with diabetes became less frequent. The management of hyperosmolar hyperglycemic state has evolved over the years with the use of insulin and adjustment of doses of insulin to achieve optimum control of the disease.

Historical Perspective

The notable events regarding the history of hyperosmolar hyperglycemic state include:

• The known history of diabetes dates back to the Egyptian era and the first documented evidence was found in an Egyptian papyrus dating back to 1552 BC.
• In 1828, Von Stosch for the first time described diabetic coma in detail.
• In 1857, Petters discovered acetone in the urine of patients with diabetes.
• In 1865, Gerhardt discovered acetoacetic acid in the urine of patients with diabetes.
• In 1874, Kussmaul also described diabetic coma in detail.
• In 1878, Foster described some cases of diabetic coma and ketonemia.
• In 1883–1884, Stadelmann, Külz, Minkowski found out that in addition to acetone patients with diabetic coma also have β-hydroxybutyric acid.
• In 1884–1886, Von Frerichs and Dreschfeld described some cases of patients with diabetic coma but without kussmaul breathing or ketones.
• In 1922, insulin was discovered and isolated by Banting and Best.
• In 1909–1923, Lépine, Revillet, McCaskey and Bock et al also described some cases of patients with diabetic coma without ketonuria.
• In 1930–1935, Lawrence and Joslin described the management of diabetic coma.
• In 1957, Sament, Schwartz, Graeff, and Lips also described some case reports of diabetic coma without ketones and hyperosmolality.
• In 1962, Singer et al explained the relationship of hyperglycemia and osmolality.
• In 1971, Arieff, Carroll and Gerich et al described the modern definition and initial criteria of the hyperosmolar hyperglycemic state which they called hyperosmolar hyperglycemic non-ketotic state.
• In 1973, Arieff and Kleeman explained the mechanism of cerebral edema in the treatment of hyperosmolar hyperglycemic state.
• In 1976–1977, Alberti, Hockaday and Kitabchi et al described the low-dose insulin protocols.
• In 2004–2009, American Diabetes Association has consensus for the management of the hyperosmolar hyperglycemic state in adults.
• In 2011, Pediatric Endocrine Society guidelines for treatment of HHS in children were published.

Landmark Events in the Development of Treatment Strategies

The landmark events in the treatment of hyperosmolar hyperglycemic state are:

Preinsulin era •The treatment modalities used for diabetic coma include blood transfusion, castor oil with potassium citrate, and saline solutions with sodium carbonate among other therapies.

1930–1950 •The usual practice was to use insulin in 20–100 units i.v. or s.c. bolus followed by 20 units s.c. every 30–60 min depending on glucosuria.

1950–1970s • In that period, the insulin was given as 2 units/kg bolus of crystalline insulin; up to 920 units in the first 7 h.

Early 1970s • Insulin was given as low-dose insulin regimens with Regular insulin 0.1 units/kg i.v. followed by 0.1–0.3 units/h i.v., s.c., or i.m.

1990s • Insulin was administered as 0.1 units/kg i.v. bolus, then 0.1 units/kg/h as continuous infusion until glucose level <13.8 mmol/L (250 mg/dL)

2004–2009 • ADA consensus for treatment of DKA and HHS in adult patients according to which Initial bolus (0.1 units/kg i.v.), followed by 0.1 units/kg/h until glucose <250 mg/dL, then reduce insulin by 50%