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==Overview==
==Overview==


Hypoglycemia is a [[Pathology|pathologic]] state produced by a lower than normal level of [[glucose]] in the blood. It happens usually when blood [[glucose]] level is less than  60 or 70 mg/dL, different values (typically below 40, 50, 60, or 70 mg/dL) have been defined as low for different populations, clinical purposes, or circumstances. Patients with [[Diabetes mellitus type 1|type 1 diabetes]] may suffer an average of two episodes of symptomatic hypoglycemia per week, thousands of such episodes over a lifetime of [[Diabetes mellitus|diabetes]], and one episode of severe symptoms per year. Causes of hypoglycemia depend on age; neonatal causes are transient neonatal hypoglycemia, [[Prematurity]], [[intrauterine growth retardation]], [[perinatal asphyxia]], [[Sepsis|sepsis,]] congenital [[hypopituitarism]], beta sympathomimetic drugs[[Congenital hyperinsulinism|, congenital hyperinsulinism]], [[Infant of diabetic mother (patient information)|infant of a diabetic mother]][[Beckwith-Wiedemann syndrome|, Beckwith-Wiedemann syndrome]] and [[Inborn error of metabolism|inborn errors of carbohydrate metabolism]]. Adult hypoglycemia caused mainly by [[insulin]] or insulin secretagogue drugs, [[alcohol]], [[Hepatic failure|hepatic]], [[Renal insufficiency|renal]], or [[cardiac failure]], [[sepsis]], non-islet cell [[Pancreatic cancer|pancreatic tumors]], [[insulinoma]], and reactive hypoglycemia. 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|gluconeogenesis.]] No single value alone serves to define the hypoglycemia. So, diagnostic criteria [[Whipple's triad|(Whipple's triad]]) is needed to diagnose hypoglycemia. Complications in adults include increased the risk of [[dementia]], [[cardiovascular]] complications and maybe death. Prognosis is generally good, and 4-10% of deaths of patients with [[Diabetes mellitus type 1|type 1 diabetes]] are due to hypoglycemia. 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. 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 [[glucose]] 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, the 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|insulinoma.]]
Hypoglycemia is a [[Pathology|pathologic]] state produced by a lower than normal level of [[glucose]] in the [[blood]]. It happens usually when blood [[glucose]] level is less than  60 or 70 mg/dL, different values (typically below 40, 50, 60, or 70 mg/dL) have been defined as low. Patients with [[Diabetes mellitus type 1|type 1 diabetes]] may suffer an average of two episodes of symptomatic hypoglycemia per week, thousands of such episodes over a lifetime of [[Diabetes mellitus|diabetes]], and one episode of severe symptoms per year. Causes of hypoglycemia depend on age; [[neonatal]] causes are transient neonatal hypoglycemia, [[Prematurity]], [[intrauterine growth retardation]], [[perinatal asphyxia]], [[Sepsis|sepsis,]] [[Congenital disorder|congenital]] [[hypopituitarism]][[Congenital hyperinsulinism|, congenital hyperinsulinism]], [[Infant of diabetic mother (patient information)|infant of a diabetic mother]][[Beckwith-Wiedemann syndrome|, Beckwith-Wiedemann syndrome]] and [[Inborn error of metabolism|inborn errors of carbohydrate metabolism]]. Adult hypoglycemia caused mainly by [[insulin]] or insulin secretagogue drugs, [[alcohol]], [[Hepatic failure|hepatic]], [[Renal insufficiency|renal]], or [[cardiac failure]], [[sepsis]], non-islet cell [[Pancreatic cancer|pancreatic tumors]], [[insulinoma]], and reactive hypoglycemia. 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|gluconeogenesis.]] No single value alone serves to define the hypoglycemia. So, diagnostic criteria [[Whipple's triad|(Whipple's triad]]) is needed to diagnose hypoglycemia. Complications in adults include increased the risk of [[dementia]], [[cardiovascular]] complications and maybe death. Prognosis is generally good, and 4-10% of deaths of patients with [[Diabetes mellitus type 1|type 1 diabetes]] are due to hypoglycemia. 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. 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 [[glucose]] 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, the 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|insulinoma.]]


==Historical Perspective==
==Historical Perspective==
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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|gluconeogenesis.]]
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|gluconeogenesis.]]


Causes of hypoglycemia depend on age; neonatal causes are transient neonatal hypoglycemia, [[Prematurity]], [[intrauterine growth retardation]], [[perinatal asphyxia]], [[Sepsis|sepsis,]] congenital [[hypopituitarism]], beta sympathomimetic drugs[[Congenital hyperinsulinism|, congenital hyperinsulinism]], [[Infant of diabetic mother (patient information)|infant of a diabetic mother]][[Beckwith-Wiedemann syndrome|, Beckwith-Wiedemann syndrome]] and [[Inborn error of metabolism|inborn errors of carbohydrate metabolism]]. Causes of adult hypoglycemia are [[insulin]] or insulin secretagogue drugs, [[alcohol]], [[Hepatic failure|hepatic]], [[Renal insufficiency|renal]], or [[cardiac failure]], [[sepsis]], non-islet cell [[Pancreatic cancer|pancreatic tumors]], [[insulinoma]], reactive hypoglycemia, post [[Gastric bypass surgery|gastric bypass]] hypoglycemia, [[Autoimmune|autoimmun]]<nowiki/>e hypoglycemia.
Causes of hypoglycemia depend on age; neonatal causes are transient neonatal hypoglycemia, [[Prematurity]], [[intrauterine growth retardation]], [[perinatal asphyxia]], [[Sepsis|sepsis,]] congenital [[hypopituitarism]], [[Sympathomimetic drug|sympathomimetic drugs]][[Congenital hyperinsulinism|, congenital hyperinsulinism]], [[Infant of diabetic mother (patient information)|infant of a diabetic mother]][[Beckwith-Wiedemann syndrome|, Beckwith-Wiedemann syndrome]] and [[Inborn error of metabolism|inborn errors of carbohydrate metabolism]]. Causes of adult hypoglycemia are [[insulin]] or insulin secretagogue drugs, [[alcohol]], [[Hepatic failure|hepatic]], [[Renal insufficiency|renal]], or [[cardiac failure]], [[sepsis]], non-islet cell [[Pancreatic cancer|pancreatic tumors]], [[insulinoma]], reactive hypoglycemia, post [[Gastric bypass surgery|gastric bypass]] hypoglycemia, [[Autoimmune|autoimmun]]<nowiki/>e hypoglycemia.


==Differentiating Hypoglycemia from other Diseases==
==Differentiating Hypoglycemia from other Diseases==
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===Medical Therapy===
===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 are 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. The 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|insulinoma.]]
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 glucose 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. The 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|insulinoma.]]


===Surgery===
===Surgery===

Revision as of 14:20, 2 October 2017

Hypoglycemia Microchapters

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Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Hypoglycemia from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic criteria

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

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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 pathologic state produced by a lower than normal level of glucose in the blood. It happens usually when blood glucose level is less than 60 or 70 mg/dL, different values (typically below 40, 50, 60, or 70 mg/dL) have been defined as low. 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. Causes of hypoglycemia depend on age; neonatal causes are transient neonatal hypoglycemia, Prematurityintrauterine growth retardationperinatal asphyxiasepsis, congenital hypopituitarism, congenital hyperinsulinisminfant of a diabetic mother, Beckwith-Wiedemann syndrome and inborn errors of carbohydrate metabolism. Adult hypoglycemia caused mainly by insulin or insulin secretagogue drugs, alcoholhepaticrenal, or cardiac failuresepsis, non-islet cell pancreatic tumorsinsulinoma, and reactive hypoglycemia. The pathophysiology of hypoglycemia depends on the failure of physiological defense mechanisms and hormones such as insulinglucagon, and epinephrine to correct hypoglycemia. Most of these defense mechanisms are hormones that control glycogenolysis and gluconeogenesis. No single value alone serves to define the hypoglycemia. So, diagnostic criteria (Whipple's triad) is needed to diagnose hypoglycemia. Complications in adults include increased the risk of dementia, cardiovascular complications and maybe death. Prognosis is generally good, and 4-10% of deaths of patients with type 1 diabetes are due to hypoglycemia. 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. 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 glucose 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, the 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.

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 insulin into a rabbit and realized a reduction in blood glucose levels. Collip injected a large dose of insulin to the rabbit, that lead to coma and death of the 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.

Pathophysiology

The pathophysiology of hypoglycemia depends on the failure of physiological defense mechanisms and hormones such as insulinglucagon, 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, Prematurityintrauterine growth retardationperinatal asphyxiasepsis, congenital hypopituitarism, sympathomimetic drugs, congenital hyperinsulinisminfant of a diabetic mother, Beckwith-Wiedemann syndrome and inborn errors of carbohydrate metabolism. Causes of adult hypoglycemia are insulin or insulin secretagogue drugs, alcoholhepaticrenal, or cardiac failuresepsis, non-islet cell pancreatic tumorsinsulinoma, 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 acidemiashyponatremia 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 insulin deficiency 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 anxietynervousnesstremor, 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 maybe 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 acidsacylcarnitine 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: anxietynervousnesstremorPalpitationsSweating, coldness. Glucagon Manifestations: Hunger, nauseavomiting. Neuroglycopenic Manifestations: irritabilityweaknessapathylethargy Confusionamnesia.

Physical Examination

Main signs of hypoglycemia are tachycardia and ventricular arrhythmia. Neurological manifestations include altered mental statushypotonia, focal or general motor deficit and jerks. Neonatal hypoglycemia signs include large for gestational agehepatomegaly in Beckwith-Wiedemann syndrome and glycogen storage diseasesAmbiguous genitalia, hypertensionhyponatremia, 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-peptideproinsulinsulfonylurea 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 are 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.

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 glucose 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. The 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.

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

References


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