Chapter 222

The hyperosmolar hyperglycemic state (HHS) is characterized by progressive hyperglycemia and hyperosmolarity typically found in a debilitated patient with poorly controlled or undiagnosed type II diabetes mellitus (DM), limited access to water, and commonly, a precipitating medical event. In view of its frequent association with concurrent illnesses and prevalence in debilitated patients, mortality estimates for HHS are significantly higher than diabetic ketoacidosis (DKA). Readers are likely to encounter a host of nomenclatures used to describe this disease state that may include the terms hyperosmotic, non-ketotic, hyperglycemic, and coma. The syndrome does not necessarily include ketosis and coma. This chapter uses the terminology adopted by the American Diabetes Association, “Hyperosmolar Hyperglycemic State (HHS).”

The basic epidemiology of diabetes is discussed in Chapter 218, Type 1 Diabetes Mellitus, and Chapter 219, Type 2 Diabetes Mellitus. Prevalence rates for type 2 diabetes are estimated to be doubling every 10 years in developed countries worldwide, with prevalence rates in the U.S. for those >60 years old to be 20.9%.2 Over the past few decades, with advances in monitoring, treatment, and education, mortality rates from hyperglycemic crises appear to have declined by half, although mortality rates remain unacceptably high.3 In view of its frequent association with concurrent illnesses and prevalence in debilitated patients, mortality estimates for HHS are significantly higher than DKA, which is estimated to be at 2.4%.4

The basic pathophysiology of DM is discussed in Chapter 218, Type 1 Diabetes Mellitus, and Chapter 219, Type 2 Diabetes Mellitus. The development of HHS is attributed to three main factors: (1) insulin resistance or deficiency, or both; (2) increased hepatic gluconeogenesis and glycogenolysis; and (3) osmotic diuresis and dehydration followed by impaired renal excretion of glucose.

In a patient with type 2 DM, physiologic stresses combined with inadequate water intake in an environment of insulin resistance or deficiency leads to HHS. Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle, and liver cells. Insulin deficiency is the secretion of less insulin than necessary. Regardless of whether the state is insufficiency or resistance, the result is impaired peripheral utilization of glucose, increase in hepatic glucose production, and hyperglycemia. As serum glucose concentration increases, an osmotic gradient develops, attracting water from the intracellular space into the intravascular compartment. This initial increase in intravascular volume is accompanied by a temporary increase in the glomerular filtration rate. As serum glucose concentration increases >180 milligrams/dL, the capacity of the kidneys to reabsorb glucose is exceeded, and glucosuria and a profound osmotic diuresis occur.

Patients with easy access to water are often able to prevent profound volume depletion by replacing fluid losses with large free water intake. If this water requirement is not met (as may occur in a nonambulatory nursing home patient), profound volume depletion occurs. During osmotic ...

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