Endocrinology

Hyperglycemic Emergencies: Overview

Background

1. Definition
   • High blood sugar with symptoms
   • ADA Standards of Medical Care in Diabetes
     • Fasting plasma glucose (FPG) ≥ 126 mg/dL (7.0 mmol/L)
     • Random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis
     • 2-hour plasma glucose (PG) ≥ 200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test (OGTT)
     • Hemoglobin A1c ≥ 6.5% (48 mmol/mol)
2. Synopsis
   • Hyperglycemic emergencies are commonly due to uncontrolled Diabetes Mellitus (DM)
     • Transient hyperglycemia often asymptomatic/benign (i.e. after a meal/candy)
     • Chronic hyperglycemia (i.e. uncontrolled DM) will have serious complications with slight increases
   • Hyperglycemia can be a result of many etiologies (i.e. surgery, food, etc), but hyperglycemic crisis mainly due to DM
     • Insulin-Dependent DM (IDDM) or Type 1 DM can develop Diabetic Ketoacidosis (DKA)
     • Non-Insulin-Dependent DM (NIDDM) or Type 2 DM can develop Diabetic Hyperosmolar Hyperglycemic State (HHS) or Non-Ketotic Hyperosmolar Coma

Pathophysiology

1. Mechanism
   • Imbalance between glucose production and utilization
   • Ketoacidosis may develop if uncontrolled in Type 1 DM (rare in Type 2 DM)
     • Insulin deficiency with hyperglycemia, dehydration, ketone production > 5 mEq/L with blood-glucose > 250 mg/dL and pH < 7.3
     • Enhanced gluconeogenesis, increased glycolysis, lack of metabolism and peripheral utilization of glucose
     • Leads to osmotic diuresis, increased lipolysis and fatty acids converted into ketones
     • DKA can be classified as mild, moderate, or severe based on the severity of metabolic acidosis and altered mental status
       • Over 30% of patients have features of both DKA and HHS
       • Most recent evidence confirming that about 1 out of 4 patients will have both conditions at the time of presentation with hyperglycemic crisis
   • Hyperosmolar hyperglycemic state may develop in uncontrolled Type 2 DM (Type 1 less common)
     • Plasma glucose > 600 mg/dL, serum osmolality > 320 mOsm/kg with pH > 7.3
       • Bicarbonate level > 2 0 mEq/L
       • Negative ketone bodies in plasma and urine (unless mixed with DKA)
     • Similar pathogenesis as DKA with lowered GFR and decreased glucose excretion via urine
   • Major cause of water deficit in DKA and HHS (View image)
     • Glucose-mediated osmotic diuresis
     • Leads to loss of water in excess of electrolytes
2. Etiology/Risk Factors
   • Hyperglycemia-associated disorders
     • DM
     • Stress: infection, surgery, trauma, psychosocial
     • Hyperosmolar states, Hypernatremic dehydration, Hypokalemic states
     • Uremia
     • Pancreatic disease: pancreatitis, trauma, neoplasm
     • Obesity: primary, Prader-Willi syndrome, achondroplasia
     • Pregnancy
     • Hypoinsulinemic states
     • Hyperinsulinemic/insulin-resistant states
     • Genetic syndromes
     • Drugs (steroids)
     • Antipsychotic medications
3. Epidemiology
   • Incidence/Prevalence
     • DKA: young, women (< 65 years old) > men
       • HHS: elderly, men > women
     • As population ages, prevalence of diabetes continues to rise
       • Prevalence of hyperglycemia is high in the elderly (> 65 years old)
     • CDC reported estimate of 120,000 DKA patients in hospitals in 2005 compared to 62,000 in 1980
     • CDC estimates hospital admission rates HHS < DKA, though no pop-based data available for HHS specifically
   • Mortality/Morbidity
     • CDC reported DKA mortality has declined from 1985-2005, especially in the elderly
       • Mortality for HHS in elderly higher than DKA (5-20%)

Related Topics

• DKA Treatment
• Non-Ketotic Hyperosmolar Coma Treatment

References

1. American Diabetes Association (ADA). Standards of Medical Care in Diabetes- 2022. Available at: https://diabetesjournals.org/care/issue/45/Supplement_1. [Accessed April 2022]
2. American Diabetes A. Standards of Medical Care in Diabetes-2018. Diabetes Care. Jan 2018;41(Suppl 1):S1-S159
3. Gosmanov AR, Gosmanova EO, Kitabchi AE. Hyperglycemic Crises: Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar State. Endotext [Internet]. Available at: https://www.ncbi.nlm.nih.gov/books/NBK279052/. [Accessed April 2022]
4. Kitabchi AE, Umpierrez GE, Murphy MB, et al. Management of hyperglycemic crises in patients with diabetes. Diabetes Care. Jan 2001;24(1):pp.131-153
5. Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. Jul 2009;32(7):pp.1335-1343
6. Fishbein HA, Palumbo PJ. Acute metabolic complications in diabetes. Diabetes in America, 2nd ed, National Diabetes Data Group, National Institutes of Health, Bethesda, MD;95(1468):Chapter 13
7. Matz R. Management of the Hyperosmolar Hyperglycemic Syndrome. Am Fam Physician. Oct 1 1999;60(5):pp.1468-1476
8. Nathan DM, Buse JB, Davidson MB, et al. Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy. Diabetes Care. Jan 2009;32(1):pp.193-203

Contributor(s)

1. Ho, Nghia, MD

Updated/Reviewed: April 2022