Whipple's triad: Symptoms of hypoglycemia, serum blood glucose level <70 mg/dL (3.9 mmol/L), and resolution of symptoms when blood glucose returns to normal[2]
In type 1 diabetics, mild hypoglycemia occurs twice per week on average, and severe hypoglycemia occurs once per year.[3]
Deaths
In type 1 diabetics, 6–10% will die of hypoglycemia.[3]
Hypoglycemia (American English), also spelledhypoglycaemia orhypoglycæmia (British English), sometimes calledlow blood sugar, is a fall inblood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L).[1][3]Whipple's triad is used to properly identify hypoglycemic episodes.[2] It is defined as blood glucose below 70 mg/dL (3.9 mmol/L), symptoms associated with hypoglycemia, and resolution of symptoms when blood sugar returns to normal.[1] Hypoglycemia may result inheadache, tiredness, clumsiness, trouble talking,confusion,fast heart rate,sweating, shakiness,nervousness, hunger,loss of consciousness,seizures, ordeath.[1][3][2] Symptoms typically come on quickly.[1] Symptoms can persist after blood-glucose levels are restored to normal.
Hypoglycemia is treated by eating a sugary food or drink, for example glucose tablets or gel, apple juice, soft drink, or lollipops.[1][3][2] The person must beconscious and able to swallow.[1][3] The goal is to consume 10–20 grams of a carbohydrate to raise blood glucose levels to a minimum of 70 mg/dL (3.9 mmol/L).[3][2] If a person is not able to take food by mouth,glucagon by injection orinsufflation may help.[1][3][9] The treatment of hypoglycemia unrelated to diabetes includes treating the underlying problem.[3][2]
Among people with diabetes, prevention starts with learning the signs and symptoms of hypoglycemia.[3][2] Diabetes medications, likeinsulin,sulfonylureas, andbiguanides can also be adjusted or stopped to prevent hypoglycemia.[3][2] Frequent and routine blood glucose testing is recommended.[1][3] Some may find continuous glucose monitors withinsulin pumps to be helpful in the management of diabetes and prevention of hypoglycemia.[3]
Hypoglycemia, also calledlow blood sugar orlow blood glucose, is a blood-sugar level below 70 mg/dL (3.9 mmol/L).[3][5]
Blood-sugar levels naturally fluctuate throughout the day, the body normally maintaining levels between 70 and 110 mg/dL (3.9–6.1 mmol/L).[3][2] Although 70 mg/dL (3.9 mmol/L) is the lower limit of normal glucose, symptoms of hypoglycemia usually do not occur until blood sugar has fallen to 55 mg/dL (3.0 mmol/L) or lower.[3][2] The blood-glucose level at which symptoms of hypoglycemia develop in someone with several prior episodes of hypoglycemia may be even lower.[2]
The symptoms of low blood sugar alone are not specific enough to characterize a hypoglycemic episode.[2] A single blood sugar reading below 70 mg/dL is also not specific enough to characterize a hypoglycemic episode.[2]Whipple's triad is a set of three conditions that need to be met to accurately characterize a hypoglycemic episode.[2]
The three conditions are the following:
The signs and symptoms of hypoglycemia are present (see section below onSigns and Symptoms)[2][10]
A low blood glucose measurement is present, typically less than 70 mg/dL (3.9 mmol/L)[2]
The signs and symptoms of hypoglycemia resolve after blood glucose levels have returned to normal[2]
The biggest difference in blood glucose levels between the adult and pediatric population occurs in newborns during the first 48 hours of life.[8] After the first 48 hours of life, the Pediatric Endocrine Society cites that there is little difference in blood glucose level and the use of glucose between adults and children.[8] During the 48-hour neonatal period, the neonate adjustsglucagon andepinephrine levels following birth, which may cause temporary hypoglycemia.[8] As a result, there has been difficulty in developing guidelines on interpretation and treatment of low blood glucose in neonates aged less than 48 hours.[8] Following a data review, the Pediatric Endocrine Society concluded that neonates aged less than 48 hours begin to respond to hypoglycemia at serum glucose levels of 55–65 mg/dL (3.0–3.6 mmol/L).[8] This is contrasted by the value in adults, children, and older infants, which is approximately 80–85 mg/dL (4.4–4.7 mmol/L).[8]
In children who are aged greater than 48 hours, serum glucose on average ranges from 70 to 100 mg/dL (3.9–5.5 mmol/L), similar to adults.[8] Elderly patients and patients who take diabetes pills such as sulfonylureas are more likely to suffer from a severe hypoglycemic episode.[11][12] Whipple's triad is used to identify hypoglycemia in children who can communicate their symptoms.[8]
Hypoglycemic symptoms are divided into two main categories.[3] The first category is symptoms caused by low glucose in the brain, calledneuroglycopenic symptoms.[3] The second category of symptoms is caused by the body's reaction to low glucose in the blood, calledadrenergic symptoms.[3]
Everyone experiences different symptoms of hypoglycemia, so someone with hypoglycemia may not have all of the symptoms listed above.[3][5][4] Symptoms also tend to have quick onset.[5] It is important to quickly obtain a blood glucose measurement in someone presenting with symptoms of hypoglycemia to properly identify the hypoglycemic episode.[5][2]
Hypoglycemia is most common in those with diabetes treated byinsulin,glinides, andsulfonylureas.[3][2] Hypoglycemia is rare in those without diabetes, because there are many regulatory mechanisms in place to appropriately balanceglucose,insulin, andglucagon.[3][2]
The most common cause of hypoglycemia in diabetics is medications used to treat diabetes such asinsulin,sulfonylureas, andbiguanides.[3][2][6] This is often due to excessive doses or poorly timed doses.[3] Sometimes diabetics may take insulin in anticipation of a meal or snack; then forgetting or missing eating that meal or snack can lead to hypoglycemia.[3] This is due to increased insulin without the presence of glucose from the planned meal.[3]
Recurrent episodes of hypoglycemia can lead tohypoglycemic unawareness, or the decreased ability to recognize hypoglycemia.[15][16][17] As diabetics experience more episodes of hypoglycemia, the blood glucose level which triggers symptoms of hypoglycemia decreases.[15][16][17] In other words, peoplewithout hypoglycemic unawareness experience symptoms of hypoglycemia at a blood glucose of about 55 mg/dL (3.0 mmol/L).[3][2] Thosewith hypoglycemic unawareness experience the symptoms of hypoglycemia at far lower levels of blood glucose.[15][16][17] This is dangerous for a number of reasons.[15][16][17] The hypoglycemic person not only gains awareness of hypoglycemia at very low blood glucose levels, but they also require high levels of carbohydrates or glucagon to recover their blood glucose to normal levels.[15][16][17] These individuals are also at far greater risk of severe hypoglycemia.[15][16][17]
While the exact cause of hypoglycemic unawareness is still under research, it is thought that these individuals progressively begin to develop fewer adrenergic-type symptoms, resulting in the loss of neuroglycopenic-type symptoms.[16][17]Neuroglycopenic symptoms are caused by low glucose in the brain, and can result in tiredness, confusion, difficulty with speech, seizures, and loss of consciousness.[3]Adrenergic symptoms are caused by the body's reaction to low glucose in the brain, and can result in fast heart rate, sweating, nervousness, and hunger.[3] See section above onSigns and Symptoms for further explanation of neuroglycopenic symptoms and adrenergic symptoms.
In terms of epidemiology, hypoglycemic unawareness occurs in 20–40% of type 1 diabetics.[15][17][18]
Serious illness may result in low blood sugar.[1][3][2][19] Severe disease of many organ systems can cause hypoglycemia as a secondary problem.[3][2] Hypoglycemia is especially common in those in theintensive care unit or those in whom food and drink is withheld as a part of their treatment plan.[3][19]
Sepsis, a common cause of hypoglycemia in serious illness, can lead to hypoglycemia through many ways.[3][19] In a state of sepsis, the body uses large amounts of glucose for energy.[3][19] Glucose use is further increased bycytokine production.[3]Cytokines are a protein produced by the body in a state of stress, particularly when fighting an infection.[3]Cytokines may inhibit glucose production, further decreasing the body's energy stores.[3] Finally, theliver andkidneys are sites of glucose production, and in a state of sepsis those organs may not receive enough oxygen, leading to decreased glucose production due to organ damage.[3]
Other causes of serious illness that may cause hypoglycemia include liver failure and kidney failure.[3][19] Theliver is the main site of glucose production in the body, and any liver failure or damage will lead to decreased glucose production.[3][19] While thekidneys are also sites of glucose production, their failure of glucose production is not significant enough to cause hypoglycemia.[3] Instead, the kidneys are responsible for removing insulin from the body, and when this function is impaired in kidney failure, the insulin stays in circulation longer, leading to hypoglycemia.[3]
If a person without diabetes accidentally takes medications that are traditionally used to treat diabetes, this may also cause hypoglycemia.[3][2] These medications includeinsulin,glinides, andsulfonylureas.[3][2] This may occur through medical errors in a healthcare setting or through pharmacy errors, also callediatrogenic hypoglycemia.[3]
When individuals take insulin without needing it, to purposefully induce hypoglycemia, this is referred to assurreptitious insulin use orfactitious hypoglycemia.[3][2][21] Some people may use insulin to induce weight loss, whereas for others this may be due tomalingering orfactitious disorder, which is apsychiatric disorder.[21] Inappropriate usage of insulin is most common in people who have had exposure to diabetes management, such as healthcare workers, people who have relatives with diabetes, or people with diabetes themselves.[3][21] The classic way to identify surreptitious insulin use is through blood work revealing high insulin levels with lowC-peptide andproinsulin.[3][21]
The production of glucose is blocked by alcohol.[3] In those who misuse alcohol, hypoglycemia may be brought on by a several-day alcohol binge associated with little to no food intake.[1][3] The cause of hypoglycemia is multifactorial, whereglycogen becomes depleted in a state ofstarvation.[3] Glycogen stores are then unable to be repleted due to the lack of food intake, all compounded the inhibition of glucose production by alcohol.[3]
Children with primary adrenal failure, also calledAddison's disease, may experience hypoglycemia after long periods offasting.[3] Addison's disease is associated with chronically low levels of the stress hormonecortisol, which leads to decreased glucose production.[3]
Hypopituitarism, leading to decreasedgrowth hormone, is another cause of hypoglycemia in children, particularly with long periods of fasting or increased exercise.[3]
Disorders that are related to the breakdown of glycogen, calledglycogen storage diseases, may cause hypoglycemia.[3][22] Normally, breakdown of glycogen leads to increased glucose levels, particularly in a fasting state.[3] In glycogen storage diseases, however, glycogen cannot be properly broken down, leading to inappropriately decreased glucose levels in a fasting state, and thus hypoglycemia.[3] The glycogen storage diseases associated with hypoglycemia includetype 0,type I,type III, andtype IV, as well asFanconi syndrome.[3]
A primary B-celltumor, such as aninsulinoma, is associated with hypoglycemia.[3] This is a tumor located in thepancreas.[3] An insulinoma producesinsulin, which in turn decreases glucose levels, causing hypoglycemia.[3] Normal regulatory mechanisms are not in place, which prevent insulin levels from falling during states of low blood glucose.[3] During an episode of hypoglycemia, plasmainsulin,C-peptide, andproinsulin will be inappropriately high.[3]
Hypoglycemia may occur in people with non-B celltumors such ashepatomas, adrenocorticoid carcinomas,[29] andcarcinoid tumors.[3] These tumors lead to a state of increased insulin, specifically increasedinsulin-like growth factor II, which decreases glucose levels.[3]
TheRoux-en-Y gastric bypass, is a weight-loss surgery performed on the stomach, and has been associated with hypoglycemia, calledpost-gastric bypasspostprandial hypoglycemia.[3] Although the entire mechanism of hypoglycemia following this surgery is not fully understood, it is thought that meals cause very high levels ofglucagon-like peptide-1 (also called GLP-1), a hormone that increases insulin, causing glucose levels to drop.[3]
Antibodies can be formed against insulin, leading toautoimmune hypoglycemia.[3][30]Antibodies are immune proteins produced by the body, that normally attack bacteria and viruses, but sometimes can attack normal human cells, leading to anautoimmune disorder.[31] In autoimmune hypoglycemia, there are two possible mechanisms.[3][30] In one instance, antibodies bind to insulin following its release associated with a meal, resulting in insulin being non-functional.[3][30] At a later time, the antibodies fall off insulin, causing insulin to be functional again leading late hypoglycemia after a meal, calledlate postprandial hypoglycemia.[3][30] Another mechanism causing hypoglycemia is due to antibodies formed against insulinreceptors, calledinsulin receptor antibodies.[3][30] The antibodies attach to insulin receptors and prevent insulin breakdown, or degradation, leading to inappropriately high insulin levels and low glucose levels.[3][30]
Low blood sugar may occur in healthyneonates aged less than 48 hours who have not eaten for a few hours.[8] During the 48-hour neonatal period, the neonate adjustsglucagon andepinephrine levels following birth, which may trigger transient hypoglycemia.[8] In children who are aged greater than 48 hours, serum glucose on average ranges from 70 to 100 mg/dL (3.9–5.5 mmol/L), similar to adults, with hypoglycemia being far less common.[8]
Glucose is the main source of energy for the brain, and a number of mechanisms are in place to prevent hypoglycemia and protect energy supply to the brain.[3][19] The body can adjustinsulin production and release, adjust glucose production by theliver, and adjust glucose use by the body.[3][19] The body naturally produces the hormoneinsulin, in an organ called thepancreas.[3] Insulin helps to regulate the amount of glucose in the body, especially after meals.[3]Glucagon is another hormone involved in regulating blood glucose levels, and can be thought of as the opposite of insulin.[3] Glucagon helps to increase blood glucose levels, especially in states of hunger.[3]
Once blood glucose levels fall out of the normal range, additional protective mechanisms work to prevent hypoglycemia.[3][19] Thepancreas is signaled to releaseglucagon, ahormone that increases glucose production by the liver and kidneys, and increases muscle and fat breakdown to supplygluconeogenesis.[3][32] If increased glucagon does not raise blood sugar levels to normal, the adrenal glands releaseepinephrine.[3][19]Epinephrine works to also increasegluconeogenesis andglycogenolysis, while also decreasing the use of glucose by organs, protecting the brain's glucose supply.[3][19]
After hypoglycemia has been prolonged,cortisol andgrowth hormone are released to continuegluconeogenesis andglycogenolysis, while also preventing the use of glucose by other organs.[3][19] The effects of cortisol and growth hormone are far less effective than epinephrine.[3][19] In a state of hypoglycemia, the brain also signals a sense of hunger and drives the person to eat, in an attempt to increase glucose.[3][19]
The most reliable method of identifying hypoglycemia is through identifyingWhipple's triad.[3][2] The components ofWhipple's triad are a blood sugar level below 70 mg/dL (3.9 mmol/L), symptoms related to low blood sugar, and improvement of symptoms when blood sugar is restored to normal.[3][2] IdentifyingWhipple's triad in a patient helps to avoid unnecessarydiagnostic testing and decreaseshealthcare costs.[2]
In those with a history of diabetes treated withinsulin,glinides, orsulfonylurea, who demonstrate Whipple's triad, it is reasonable to assume the cause of hypoglycemia is due to insulin, glinides, or sulfonylurea use.[2] In those without a history of diabetes with hypoglycemia, further diagnostic testing is necessary to identify the cause.[2] Testing, during an episode of hypoglycemia, should include the following:
If necessary, a diagnostic hypoglycemic episode can be produced in an inpatient or outpatient setting.[3] This is called a diagnosticfast, in which a patient undergoes an observed fast to cause a hypoglycemic episode, allowing for appropriate blood work to be drawn.[3] In some, the hypoglycemic episode may be reproduced simply after a missed meal, whereas in others a fast may last up to 72 hours.[3][2]
After hypoglycemia in a person is identified, rapid treatment is necessary and can be life-saving.[1] The main goal of treatment is to raise blood glucose back to normal levels, which is done through various ways of administering glucose, depending on the severity of the hypoglycemia, what is on-hand to treat, and who is administering the treatment.[1][3] A general rule used by theAmerican Diabetes Association is the "15-15 Rule," which suggests consuming or administering 15 grams of acarbohydrate, followed by a 15-minute wait and re-measurement of blood glucose level to assess if blood glucose has returned to normal levels.[5]
If an individual recognizes the symptoms of hypoglycemia coming on, blood sugar should promptly be measured, and a sugary food or drink should be consumed.[1] The person must beconscious and able to swallow.[1][3] The goal is to consume 10–20 grams of a carbohydrate to raise blood glucose levels to a minimum of 70 mg/dL (3.9 mmol/L).[3][2]
Examples of products to consume are:
Glucose tabs or gel (refer to instructions on packet)[1][2]
Juice containing sugar like apple, grape, or cranberry juice, 1/2 cup (~120 mL)[1][2]
Soda or a soft-drink, 1/2 cup (~120 mL) (not diet soda)[2]
Improvement in blood sugar levels and symptoms are expected to occur in 15–20 minutes, at which point blood sugar should be measured again.[3][2] If the repeat blood sugar level is not above 70 mg/dL (3.9 mmol/L), consume another 10–20 grams of a carbohydrate and remeasure blood sugar levels after 15–20 minutes.[3][2] Repeat until blood glucose levels have returned to normal levels.[3][2] The greatest improvements in blood glucose will be seen if the carbohydrate is chewed or drunk, and then swallowed.[35] This results in the greatestbioavailability of glucose, meaning the greatest amount of glucose enters the body producing the best possible improvements in blood glucose levels.[35] A 2019 systematic review suggests, based on very limited evidence, thatoral administration of glucose leads to a bigger improvement in blood glucose levels when compared tobuccal administration.[36] This same review reported that, based on limited evidence, no difference was found in plasma glucose when administering combined oral and buccal glucose (via dextrose gel) compared to only oral administration.[36] The second best way to consume a carbohydrate it to allow it to dissolve under the tongue, also referred to assublingual administration.[35] For example, a hard candy can be dissolved under the tongue, however the best improvements in blood glucose will occur if the hard candy is chewed and crushed, then swallowed.[35]
After correcting blood glucose levels, people may consume a full meal within one hour to replenish glycogen stores.[2]
Family, friends, and co-workers of a person with diabetes may provide life-saving treatment in the case of a hypoglycemic episode.[1] It is important for these people to receive training on how to recognize hypoglycemia, what foods to help the hypoglycemic eat, how to administer injectable or intra-nasalglucagon, and how to use aglucose meter.[1]
Family, friends, and co-workers of those with hypoglycemia are often first to identify hypoglycemic episodes, and may offer help.[3] Upon recognizing the signs and symptoms of hypoglycemia in a diabetic, a blood sugar level should first be measured using aglucose meter.[1] If blood glucose is below 70 mg/dL (3.9 mmol/L), treatment will depend on whether the person is conscious and can swallow safely.[3][2] If the person is conscious and able to swallow, the family, friend, or co-worker can help the hypoglycemic consume 10–20 grams of acarbohydrate to raise blood glucose levels to a minimum of 70 mg/dL (3.9 mmol/L).[2] Improvement in blood sugar level and symptoms is expected to occur in 15–20 minutes, at which point blood sugar is measured again.[3][2] If the repeat blood sugar level is not above 70 mg/dL (3.9 mmol/L), the hypoglycemic should consume another 10–20 grams of a carbohydrate and with remeasurement of blood sugar levels after 15–20 minutes.[3][2] Repeat until blood glucose levels have returned to normal levels, or call emergency services for further assistance.[2]
If the person is unconscious, aglucagon kit may be used to treat severe hypoglycemia, which delivers glucagon either by injection into a muscle or through nasal inhalation.[2][3][19] In the United States, glucacon kits are available by prescription for diabetic patients to carry in case of an episode of severe hypoglycemia.[37][38] Emergency services should be called for further assistance.[2]
In a healthcare setting, treatment depends on the severity of symptoms andintravenous access.[39] If a patient is conscious and able to swallow safely, food or drink may be administered, as well as glucose tabs or gel.[39] In those with intravenous access, 25 grams of 50% dextrose is commonly administered.[39] When there is no intravenous access,intramuscular orintra-nasal glucagon may be administered.[39]
While the treatment of hypoglycemia is typically managed with carbohydrate consumption, glucagon injection, ordextrose administration, there are some other treatments available.[3] Medications likediazoxide andoctreotide decrease insulin levels, increasing blood glucose levels.[3]Dasiglucagon was approved for medical use in the United States in March 2021, to treat severe hypoglycemia.[40] Dasiglucagon (brand name Zegalogue) is unique because it is glucagon in a prefilled syringe or auto-injector pen, as opposed to traditional glucagon kits that require mixing powdered glucagon with a liquid.[40]
Due to its original formulation containing large amounts of glucose, the soft drinkLucozade was recommended by diabetes charities in theUnited Kingdom as an immediate treatment for hypoglycemia; however, as the drink was reformulated to replace much of its glucose content withartificial sweeteners, this is no longer recommended.[41]
The prevention of hypoglycemia depends on the cause.[1][3][2] In those with diabetes treated byinsulin,glinides, orsulfonylurea, the prevention of hypoglycemia has a large focus on patient education and medication adjustments.[1][3][2] The foundation of diabetes education is learning how to recognize the signs and symptoms of hypoglycemia, as well as learning how to act quickly to prevent worsening of an episode.[2] Another cornerstone of prevention is strong self-monitoring of blood glucose, with consistent and frequent measurements.[2] Research has shown that patients with type 1 diabetes who usecontinuous glucose monitoring systems withinsulin pumps significantly improve blood glucose control.[42][43][44] Insulin pumps help to prevent high glucose spikes, and help prevent inappropriate insulin dosing.[43][44][45]Continuous glucose monitors can sound alarms when blood glucose is too low or too high, especially helping those with nocturnal hypoglycemia or hypoglycemic unawareness.[43][44][45] In terms of medication adjustments, medication doses and timing can be adjusted to prevent hypoglycemia, or a medication can be stopped altogether.[3][2]
In those with hypoglycemia who do not have diabetes, there are a number of preventative measures dependent on the cause.[1][3][2] Hypoglycemia caused by hormonal dysfunction like lack ofcortisol inAddison's disease or lack ofgrowth hormone inhypopituitarism can be prevented with appropriate hormone replacement.[3][2] The hypoglycemic episodes associated with non-B cell tumors can be decreased following surgical removal of the tumor, as well as followingradiotherapy orchemotherapy to reduce the size of thetumor.[3][2] In some cases, those with non-B cell tumors may havehormone therapy withgrowth hormone,glucocorticoid, oroctreotide to also lessen hypoglycemic episodes.[3][2] Post-gastric bypass hypoglycemia can be prevented by eating smaller, more frequent meals, avoiding sugar-filled foods, as well as medical treatment with analpha-glucosidase inhibitor,diazoxide, oroctreotide.[3][2]
Some causes of hypoglycemia require treatment of the underlying cause to best prevent hypoglycemia.[2] This is the case forinsulinomas which often require surgical removal of the tumor for hypoglycemia to remit.[2] In patients who cannot undergo surgery for removal of the insulinoma,diazoxide oroctreotide may be used.[2]
Hypoglycemia is common in people withtype 1 diabetes, and in people withtype 2 diabetes takinginsulin,glinides, orsulfonylurea.[1][3] It is estimated that type 1 diabetics experience two mild, symptomatic episodes of hypoglycemiaper week.[3] Additionally, people with type 1 diabetes have at least one severe hypoglyemic episodeper year, requiring treatment assistance.[3] In terms ofmortality, hypoglycemia causes death in 6–10% of type 1 diabetics.[3][verification needed]
Hypoglycemia was first discovered byJames Collip when he was working withFrederick Banting on purifying insulin in 1922.[46] Collip was asked to develop an assay to measure the activity of insulin.[46] He first injected insulin into a rabbit, and then measured the reduction in blood-glucose levels.[46] Measuring blood glucose was a time-consuming step.[46] Collip observed that if he injected rabbits with a too large a dose of insulin, the rabbits began convulsing, went into a coma, and then died.[46] This observation simplified his assay.[46] He defined one unit of insulin as the amount necessary to induce this convulsing hypoglycemic reaction in a rabbit.[46] Collip later found he could save money, and rabbits, by injecting them with glucose once they were convulsing.[46]
The wordhypoglycemia isalso spelledhypoglycaemia orhypoglycæmia. The term means 'low blood sugar' fromGreek ὑπογλυκαιμία, from ὑπο-hypo- 'under' + γλυκύςglykys 'sweet' + αἷμᾰhaima 'blood'.[47]
^Ling S, Zaccardi F, Lawson C, Seidu SI, Davies MJ, Khunti K (1 April 2021). "Glucose Control, Sulfonylureas, and Insulin Treatment in Elderly People With Type 2 Diabetes and Risk of Severe Hypoglycemia and Death: An Observational Study".Diabetes Care.44 (4):915–924.doi:10.2337/dc20-0876.ISSN1935-5548.PMID33541857.
^abcdefgJohnson-Rabbett B, Seaquist ER (September 2019). "Hypoglycemia in diabetes: The dark side of diabetes treatment. A patient-centered review".Journal of Diabetes.11 (9):711–718.doi:10.1111/1753-0407.12933.PMID30983138.S2CID115202581.
^abcdeMurad MH, Coto-Yglesias F, Wang AT, Sheidaee N, Mullan RJ, Elamin MB, et al. (March 2009). "Clinical review: Drug-induced hypoglycemia: a systematic review".The Journal of Clinical Endocrinology and Metabolism.94 (3):741–745.doi:10.1210/jc.2008-1416.PMID19088166.
^abcdAwad DH, Gokarakonda SB, Ilahi M (2022)."Factitious Hypoglycemia".StatPearls. Treasure Island (FL): StatPearls Publishing.PMID31194450.Archived from the original on 26 January 2022. Retrieved21 January 2022.
^abcJeanmonod R, Asuka E, Jeanmonod D (2022)."Inborn Errors Of Metabolism".StatPearls. Treasure Island (FL): StatPearls Publishing.PMID29083820.Archived from the original on 13 October 2021. Retrieved24 January 2022.
^"Antibody".Genome.gov.Archived from the original on 9 October 2020. Retrieved24 January 2022.
^Rix I, Nexøe-Larsen C, Bergmann NC, Lund A, Knop FK (2000)."Glucagon Physiology". In Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dhatariya K, et al. (eds.).Endotext.PMID25905350.Archived from the original on 15 January 2021.
^abcMian Z, Hermayer KL, Jenkins A (November 2019). "Continuous Glucose Monitoring: Review of an Innovation in Diabetes Management".The American Journal of the Medical Sciences.358 (5):332–339.doi:10.1016/j.amjms.2019.07.003.PMID31402042.S2CID199047204.
