Insulin and glucagon are primary hormones involved in blood glucose (BG) management. One of the main functions of insulin is to lower BG levels by allowing glucose to move into cells and out of the plasma. Alternatively, glucagon increases BG levels by stimulating glycogenolysis and gluconeogenesis as well as by decreasing glucose utilization by peripheral tissues. Insulin and glucagon are in a constant, flexible balance in the healthy individual, thereby maintaining normoglycemia (60-100 mg/dL during a fasting state).
When insufficient insulin is present, either by absence or by cellular resistance to insulin, BG levels rise and hyperglycemia may develop. The imbalance of insulin and glucagon leads to cellular release of fatty acids, which are metabolized to produce ketones, such as beta-hydroxybutyrate. Excessive ketoacids in the bloodstream can cause acidemia (low blood pH), which can result in diabetic ketoacidosis (DKA), a life-threatening emergency, usually in DM type 1. Hyperosmolar hyperglycemic syndrome (HHS) is another life-threatening emergency, usually occurring in those with DM type 2, characterized by severe hyperglycemia (often BGs greater than 500 mg/dL), severe dehydration, and hyperosmolarity without the presence of acidemia or ketonemia.
Other causes of hyperglycemia include intravenous (IV) glucose / dextrose infusion, sampling technique (eg, testing a prandial / nonfasting blood specimen), pancreatic disease (eg, chronic pancreatitis, cystic fibrosis), and endocrine disorders (eg, acromegaly, Cushing syndrome, glucagonoma, pheochromocytoma, polycystic ovary syndrome). Stress hyperglycemia can be seen in the setting of acute illness, such as stroke, traumatic brain injury, myocardial infarction, or severe infection. Certain medications can induce hyperglycemia through a variety of mechanisms, including pancreatic beta-cell toxicity, diminished insulin release, changes to peripheral tissue insulin sensitivity, and increased production of glucose via gluconeogenesis / glycogenolysis. Commonly implicated medications include glucocorticoids, beta blockers, thiazide diuretics, estrogens, protease inhibitors, antipsychotics, chemotherapies, and others (see drug-induced diabetes). Illicit anabolic steroid use may also contribute to insulin resistance and hyperglycemia.
In newborns, hyperglycemia is more often related to IV glucose administration in a sick infant, rather than due to neonatal DM.
Regardless of etiology, hyperglycemia may lead to osmotic diuresis. When filtered in the kidney, glucose levels can exceed the renal tubule's ability to fully reabsorb glucose, leading to glucosuria, excessive urination, electrolyte losses, and dehydration.
Low-grade or acute hyperglycemia is generally asymptomatic. With severe or sustained hyperglycemia, symptoms may develop, including excessive thirst, excessive urination, fatigue, nausea, hemiballism, and blurred vision. Rapid, deep breathing (Kussmaul respirations) and fruity-smelling breath (from ketonemia) can be features of DKA. Confusion or coma can be present with DKA and HHS.
Related topics: diabetes mellitus type 1, diabetes mellitus type 2, maturity-onset diabetes of the young (MODY)
R73.9 – Hyperglycemia, unspecified
80394007 – Hyperglycemia
Differential Diagnosis & Pitfalls
- Diabetes mellitus – type 1, type 2, or other subtypes
- Gestational diabetes – pregnant patients only
- Diabetic ketoacidosis
- Hyperosmolar hyperglycemic syndrome
- Steroid-induced hyperglycemia (see drug-induced diabetes)
- Medication-induced hyperglycemia
- Stress hyperglycemia – "stress" refers to a state of acute illness, often requiring hospitalization, eg, stroke, myocardial infarction, infection
- Endocrine disorders and hormonally active tumors – eg, Cushing syndrome, acromegaly, glucagonoma, polycystic ovary syndrome
- Pancreatic disease – eg, acute or chronic pancreatitis, cystic fibrosis
- Improper POC BG sampling technique – Glucose on the skin surface can cause false elevations on POC BG testing. Excessive pressure (milking) on tissue can also cause inaccurate results. Extreme highs and lows of BG can cause inaccurate readings on POC BG testing as well.
- Hemoglobin A1c (HgbA1c), which is often used to diagnose DM, can be falsely high or low depending on underlying conditions. For example, HgbA1c can be falsely low in conditions of high red blood cell turnover (eg, blood loss anemia, hemolytic anemia), as well as other conditions, such as end-stage renal disease or pregnancy. False elevations can occur in conditions that prolong the life of red blood cells, such as asplenia, as well as other disease states including severe hyperbilirubinemia, severe hypertriglyceridemia, and uremia. HgbA1c cannot be accurately interpreted in patients who recently received red blood cell transfusions. For patients with hemoglobinopathies, such as hemoglobin S and hemoglobin C, HgbA1c should be interpreted with caution as accuracy depends on the specific laboratory assay.