Hypoglycemia overview
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1], Associate Editor(s)-in-Chief: Mohammed Abdelwahed M.D[2]
Overview
Hypoglycemia is a medical term referring to a pathologic state produced by a lower than normal level of glucose (sugar) in the blood. No single glucose value alone serves to define the medical condition termed hypoglycemia for all people and purposes. Although 60 or 70 mg/dL (3.3 or 3.9 mmol/L) is commonly cited as the lower limit of normal glucose, different values (typically below 40, 50, 60, or 70 mg/dL) have been defined as low for different populations, clinical purposes, or circumstances.
Historical Perspective
Hypoglycemia is a Greek word that means under-sweet blood. In 1922, hypoglycemia was first discovered by James Collip when he was working on purifying insulin. He injected insulininto a rabbit and realized a reduction in blood glucose levels. Collip injected of a large doses of insulin to the rabbit, that lead to coma and death of rabbit.
Classification
Hypoglycemia can be classified based on severity into 5 categories, include Severe hypoglycemia, symptomatic hypoglycemia, asymptomatic hypoglycemia, probable symptomatic hypoglycemia, and pseudo hypoglycemia. It is also can be classified based on severity into mild, moderate and severe forms.
Pathophysiology
The pathophysiology of hypoglycemia depends on the failure of physiological defense mechanisms and hormones such as insulin, glucagon and epinephrine to correct hypoglycemia. Most of these defense mechanisms are hormones that control glycogenolysis and gluconeogenesis.
Causes of hypoglycemia depend on age; neonatal causes are transient neonatal hypoglycemia, Prematurity, intrauterine growth retardation, perinatal asphyxia, sepsis, congenital hypopituitarism, beta sympathomimetic drugs, congenital hyperinsulinism, infant of a diabetic mother, Beckwith-Wiedemann syndrome and inborn errors of carbohydrate metabolism. Causes of adult hypoglycemia are: insulin or insulin secretagogue drugs, alcohol, hepatic, renal, or cardiac failure, sepsis, non-islet cell pancreatic tumors, insulinoma, reactive hypoglycemia, post gastric bypass hypoglycemia, autoimmune hypoglycemia.
Differentiating Hypoglycemia from other Diseases
Hypoglycemia should be differentiated from other causes of autonomic hyperactivity symptoms. Physicians should have history, signs and laboratory results sufficient to help them to identify the cause of hypoglycemia. Neonatal hypoglycemia should be differentiated from other causes of neurological symptoms in neonates such as sepsis, metabolic diseases: urea cycle disorders, and branched-chain organic acidemias, hyponatremia and neonatal asphyxia.
Epidemiology and Demographics
Patients with type 1 diabetes may suffer an average of two episodes of symptomatic hypoglycemia per week, thousands of such episodes over a lifetime of diabetes, and one episode of severe symptoms per year. Hypoglycemia is less frequent in type 2 diabetes than it is in type1. Event rate for severe hypoglycemia range from 40 to 100 percent of those in type 1 diabetes. There is no racial or gender predilection of hypoglycemia.
Risk Factors
Risk factors of hypoglycemia include diabetic patients with excessive insulin doses especially after missed meals or after exercise, nocturnal or with alcohol. Absolute endogenous insulindeficiency is another risk factor.
Screening
Screening of hypoglycemia should be obtained in infants who are at risk for hypoglycemia. Surveillance should be continued every three to six hours for the first 48 hours of life. Treatment should be started immediately after primary blood test and we should not wait for the confirmatory laboratory results due to high risk of the neurological outcome.
Natural History, Complications and Prognosis
If left untreated, patients with hypoglycemia may progress to develop anxiety, nervousness, tremor, palpitations, and sweating. Common complications of hypoglycemia include psychomotor retardation, epilepsy and prematurity in neonates. Complications in adults include increased the risk of dementia, cardiovascular complications and may be death. Prognosis is generally good, and 4-10% of deaths of patients with type 1 diabetes are due to hypoglycemia.
Diagnosis
Diagnostic criteria
Diagnostic criteria of hypoglycemia include symptoms of hypoglycemia, a low plasma glucose concentration correlated with symptoms, and correction of glucose level relieves symptoms. These criteria called Whipple's triad. Neonatal hypoglycemia can be diagnosed by measuring multiple metabolic panels include plasma insulin, plasma C-peptide, beta-hydroxybutyrate, blood pH, bicarbonate, lactate, free fatty acids, acylcarnitine profile, plasma free and total carnitine levels.
History and Symptoms
Hypoglycemic symptoms and manifestations can be divided into those produced by the counter-regulatory hormones: adrenergic Manifestations: anxiety, nervousness, tremor, Palpitations, Sweating, coldness. Glucagon Manifestations: Hunger, nausea, vomiting. Neuroglycopenic Manifestations: irritability, weakness, apathy, lethargy Confusion, amnesia.
Physical Examination
Main signs of hypoglycemia are tachycardia and ventricular arrhythmia. Neurological manifestations include altered mental status, hypotonia, focal or general motor deficit and jerks. Neonatal hypoglycemia signs include large for gestational age, hepatomegaly in Beckwith-Wiedemann syndrome and glycogen storage diseases. Ambiguous genitalia, hypertension, hyponatremia, and hyperkalemia are found in congenital adrenal insufficiency.
Laboratory Findings
Laboratory investigations of hypoglycemia depend on many tests: plasma glucose should be <55 mg/dL, insulin, c-peptide, proinsulin, sulfonylurea screen, beta-hydroxybutyrate, 24-hour fasting glucose level and identifying the cause after that.
Electrocardiogram
On EKG, hypoglycemia is characterized by sinus tachycardia and supraventricular tachycardia.
Chest X Ray
There is no x-ray findings in hypoglycemia.
CT
Ultrasound, Computed tomography and MRI can differentiate between insulinoma and islet-cell hypertrophy.
MRI
MRI scan is helpful in the diagnosis of insulinoma in the case of failed CT. It shows enhancement.
Echocardiography or Ultrasound
Other Imaging Findings
There are no other imaging findings associated with hypoglycemia.
Other Diagnostic Studies
Other tests include: injection of calcium gluconate into splanchnic arteries and venous sampling searching for insulin.
Treatment
Medical Therapy
Medical treatment of hypoglycemia depends on the severity of symptoms and the cause. If asymptomatic, repeating the measurement in short time and avoiding critical tasks. Twenty grams of gucose is usually sufficient to raise the blood glucose in a severe hypoglycemic and symptomatic patients. Glucose should be administered subcutaneously or intramuscularly or 25% of dextrose serum should be given intravenously. In case of postprandial hypoglycemia, patient should have frequent small meals or snacks and foods should be high in fiber, avoiding foods high in sugar. Surgery is the best treatment for insulinoma.
Surgery
Surgical removal of the insulinoma is the treatment of choice and resection of metastatic liver disease.
Primary Prevention
The main issue is patient education about nature, symptoms, how to measure glucose level and how to treat. Reactive hypoglycemia prevention depends on changing eating patterns smaller meals and avoiding excessive sugar.
Secondary Prevention
Secondary Prevention is the same as primary prevention.