Editing Hypoglycemia (section)

=== Non-diabetics ===

==== Serious illness ====
Serious illness may result in low blood sugar.<ref name="NIH2008" /><ref name="Jameson_2018" /><ref name="Cry2009" /><ref name=":10">{{Cite book |title=StatPearls |vauthors=Mathew P, Thoppil D |date=2022 |publisher=StatPearls Publishing |location=Treasure Island (FL) |chapter=Hypoglycemia |pmid=30521262 |access-date=24 January 2022 |chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK534841/ |archive-url=https://web.archive.org/web/20210830033137/https://www.ncbi.nlm.nih.gov/books/NBK534841/ |archive-date=30 August 2021 |url-status=live}}</ref> Severe disease of many organ systems can cause hypoglycemia as a secondary problem.<ref name="Jameson_2018" /><ref name="Cry2009" /> Hypoglycemia is especially common in those in the [[intensive care unit]] or those in whom food and drink is withheld as a part of their treatment plan.<ref name="Jameson_2018" /><ref name=":10" />

[[Sepsis]], a common cause of hypoglycemia in serious illness, can lead to hypoglycemia through many ways.<ref name="Jameson_2018" /><ref name=":10" /> In a state of sepsis, the body uses large amounts of glucose for energy.<ref name="Jameson_2018" /><ref name=":10" /> Glucose use is further increased by [[cytokine]] production.<ref name="Jameson_2018" /> [[Cytokine]]s are a protein produced by the body in a state of stress, particularly when fighting an infection.<ref name="Jameson_2018" /> [[Cytokine]]s may inhibit glucose production, further decreasing the body's energy stores.<ref name="Jameson_2018" /> Finally, the [[liver]] and [[kidney]]s 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.<ref name="Jameson_2018" />

Other causes of serious illness that may cause hypoglycemia include liver failure and kidney failure.<ref name="Jameson_2018" /><ref name=":10" /> The [[liver]] is the main site of glucose production in the body, and any liver failure or damage will lead to decreased glucose production.<ref name="Jameson_2018" /><ref name=":10" /> While the [[kidney]]s are also sites of glucose production, their failure of glucose production is not significant enough to cause hypoglycemia.<ref name="Jameson_2018" /> 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.<ref name="Jameson_2018" />

==== Drugs ====
A number of medications have been identified which may cause hypoglycemia, through a variety of ways.<ref name="Jameson_2018" /><ref name="Cry2009" /><ref name=":8">{{Cite journal |display-authors=6 |vauthors=Murad MH, Coto-Yglesias F, Wang AT, Sheidaee N, Mullan RJ, Elamin MB, Erwin PJ, Montori VM |date=March 2009 |title=Clinical review: Drug-induced hypoglycemia: a systematic review |journal=The Journal of Clinical Endocrinology and Metabolism |volume=94 |issue=3 |pages=741–745 |doi=10.1210/jc.2008-1416 |pmid=19088166}}</ref> Moderate quality evidence implicates the [[Nonsteroidal anti-inflammatory drug|non-steroidal anti-inflammatory]] drug [[Indometacin|indomethacin]] and the anti-malarial [[quinine]].<ref name="Jameson_2018" /><ref name="Cry2009" /><ref name=":8" /> Low quality evidence implicates [[Lithium (medication)|lithium]], used for [[bipolar disorder]].<ref name="Cry2009" /><ref name=":8" /> Finally, very low quality evidence implicates a number of [[hypertension]] medications including [[angiotensin converting enzyme inhibitors]] (also called ACE-inhibitors), [[Angiotensin II receptor blocker|angiotensin receptor blockers]] (also called ARBs), and [[Beta blocker|β-adrenergic blockers]] (also called beta blockers).<ref name="Jameson_2018" /><ref name="Cry2009" /><ref name=":8" /> Other medications with very low quality evidence include the antibiotics [[levofloxacin]] and [[Trimethoprim/sulfamethoxazole|trimethoprim-sulfamethoxazole]], [[progesterone blocker]] [[mifepristone]], [[anti-arrhythmic]] [[disopyramide]], [[anti-coagulant]] [[heparin]], and chemotherapeutic [[mercaptopurine]].<ref name="Cry2009" /><ref name=":8" />

If a person without diabetes accidentally takes medications that are traditionally used to treat diabetes, this may also cause hypoglycemia.<ref name="Jameson_2018" /><ref name="Cry2009" /> These medications include [[Insulin (medication)|insulin]], [[Meglitinide|glinides]], and [[sulfonylurea]]s.<ref name="Jameson_2018" /><ref name="Cry2009" /> This may occur through medical errors in a healthcare setting or through pharmacy errors, also called [[Iatrogenesis|iatrogenic]] hypoglycemia.<ref name="Jameson_2018" />

==== Surreptitious insulin use ====
When individuals take insulin without needing it, to purposefully induce hypoglycemia, this is referred to as ''surreptitious insulin use'' or ''factitious hypoglycemia''.<ref name="Jameson_2018" /><ref name="Cry2009" /><ref name=":9">{{Cite book |title=StatPearls |vauthors=Awad DH, Gokarakonda SB, Ilahi M |date=2022 |publisher=StatPearls Publishing |location=Treasure Island (FL) |chapter=Factitious Hypoglycemia |pmid=31194450 |access-date=21 January 2022 |chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK542310/ |archive-url=https://web.archive.org/web/20220126212626/https://www.ncbi.nlm.nih.gov/books/NBK542310/ |archive-date=26 January 2022 |url-status=live}}</ref> Some people may use insulin to induce weight loss, whereas for others this may be due to [[malingering]] or [[factitious disorder]], which is a [[psychiatric disorder]].<ref name=":9" /> 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.<ref name="Jameson_2018" /><ref name=":9" /> The classic way to identify surreptitious insulin use is through blood work revealing high insulin levels with low [[C-peptide]] and [[proinsulin]].<ref name="Jameson_2018" /><ref name=":9" />

==== Alcohol misuse ====
The production of glucose is blocked by alcohol.<ref name="Jameson_2018" /> In those who misuse alcohol, hypoglycemia may be brought on by a several-day alcohol binge associated with little to no food intake.<ref name="NIH2008" /><ref name="Jameson_2018" /> The cause of hypoglycemia is multifactorial, where [[glycogen]] becomes depleted in a state of [[starvation]].<ref name="Jameson_2018" /> Glycogen stores are then unable to be repleted due to the lack of food intake, all compounded the inhibition of glucose production by alcohol.<ref name="Jameson_2018" />

====Hormone deficiency====
Children with primary adrenal failure, also called [[Addison's disease]], may experience hypoglycemia after long periods of [[fasting]].<ref name="Jameson_2018" /> Addison's disease is associated with chronically low levels of the stress hormone [[cortisol]], which leads to decreased glucose production.<ref name="Jameson_2018" />

[[Hypopituitarism]], leading to decreased [[growth hormone]], is another cause of hypoglycemia in children, particularly with long periods of fasting or increased exercise.<ref name="Jameson_2018" />

==== Inborn errors of metabolism ====
Briefly, [[inborn errors of metabolism]] are a group of rare [[genetic disorder]]s that are associated with the improper breakdown or storage of [[protein]]s, [[carbohydrate]]s, or [[fatty acid]]s.<ref name=":11">{{Cite book |title=StatPearls |vauthors=Jeanmonod R, Asuka E, Jeanmonod D |date=2022 |publisher=StatPearls Publishing |location=Treasure Island (FL) |chapter=Inborn Errors Of Metabolism |pmid=29083820 |access-date=24 January 2022 |chapter-url=http://www.ncbi.nlm.nih.gov/books/NBK459183/ |archive-url=https://web.archive.org/web/20211013135517/https://www.ncbi.nlm.nih.gov/books/NBK459183/ |archive-date=13 October 2021 |url-status=live}}</ref> Inborn errors of metabolism may cause infant hypoglycemia, and much less commonly adult hypoglycemia.<ref name=":11" />

Disorders that are related to the breakdown of glycogen, called [[Glycogen storage disease|''glycogen storage diseases'']], may cause hypoglycemia.<ref name="Jameson_2018" /><ref name=":11" /> Normally, breakdown of glycogen leads to increased glucose levels, particularly in a fasting state.<ref name="Jameson_2018" /> In glycogen storage diseases, however, glycogen cannot be properly broken down, leading to inappropriately decreased glucose levels in a fasting state, and thus hypoglycemia.<ref name="Jameson_2018" /> The glycogen storage diseases associated with hypoglycemia include [[Glycogen storage disease type 0|type 0]], [[Glycogen storage disease type I|type I]], [[Glycogen storage disease type III|type III]], and [[Glycogen storage disease type IV|type IV]], as well as [[Fanconi syndrome]].<ref name="Jameson_2018" />

Some [[Organic acidemia|organic]] and amino acid acidemias, especially those involving the [[Fatty-acid metabolism disorder|oxidation of fatty acids]], can lead to the symptom of intermittent hypoglycemia,<ref name=":14">{{Cite journal |last=Ozand |first=Pinar T. |date=2000 |title=Hypoglycemia in association with various organic and amino acid disorders |url=https://linkinghub.elsevier.com/retrieve/pii/S0146000500800324 |journal=Seminars in Perinatology |language=en |volume=24 |issue=2 |pages=172–193 |doi=10.1053/sp.2000.6367 |pmid=10805172}}</ref><ref>{{Cite journal |last=Baker |first=Joshua J |last2=Burton |first2=Barbara K |date=November 2021 |title=Diagnosis and Clinical Management of Long-chain Fatty-acid Oxidation Disorders: A Review |journal=TouchREVIEWS in Endocrinology |volume=17 |issue=2 |pages=108–111 |doi=10.17925/EE.2021.17.2.108 |issn=2752-5457 |pmc=8676101 |pmid=35118456}}</ref> as for example in [[combined malonic and methylmalonic aciduria]] (CMAMMA),<ref>{{Cite journal |last=NIH Intramural Sequencing Center Group |last2=Sloan |first2=Jennifer L |last3=Johnston |first3=Jennifer J |last4=Manoli |first4=Irini |last5=Chandler |first5=Randy J |last6=Krause |first6=Caitlin |last7=Carrillo-Carrasco |first7=Nuria |last8=Chandrasekaran |first8=Suma D |last9=Sysol |first9=Justin R |last10=O'Brien |first10=Kevin |last11=Hauser |first11=Natalie S |last12=Sapp |first12=Julie C |last13=Dorward |first13=Heidi M |last14=Huizing |first14=Marjan |last15=Barshop |first15=Bruce A |date=2011 |title=Exome sequencing identifies ACSF3 as a cause of combined malonic and methylmalonic aciduria |journal=Nature Genetics |language=en |volume=43 |issue=9 |pages=883–886 |doi=10.1038/ng.908 |issn=1061-4036 |pmc=3163731 |pmid=21841779}}</ref><ref>{{Cite journal |last=Wehbe |first=Zeinab |last2=Behringer |first2=Sidney |last3=Alatibi |first3=Khaled |last4=Watkins |first4=David |last5=Rosenblatt |first5=David |last6=Spiekerkoetter |first6=Ute |last7=Tucci |first7=Sara |date=2019 |title=The emerging role of the mitochondrial fatty-acid synthase (mtFASII) in the regulation of energy metabolism |url=https://linkinghub.elsevier.com/retrieve/pii/S1388198119301349 |journal=Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids |language=en |volume=1864 |issue=11 |pages=1629–1643 |doi=10.1016/j.bbalip.2019.07.012 |pmid=31376476 |s2cid=199404906}}</ref><ref>{{Cite journal |last=Levtova |first=Alina |last2=Waters |first2=Paula J. |last3=Buhas |first3=Daniela |last4=Lévesque |first4=Sébastien |last5=Auray-Blais |first5=Christiane |author-link5=Christiane Auray |last6=Clarke |first6=Joe T.R. |last7=Laframboise |first7=Rachel |last8=Maranda |first8=Bruno |last9=Mitchell |first9=Grant A. |last10=Brunel-Guitton |first10=Catherine |last11=Braverman |first11=Nancy E. |date=2019 |title=Combined malonic and methylmalonic aciduria due to ACSF3 mutations: Benign clinical course in an unselected cohort |url=https://onlinelibrary.wiley.com/doi/10.1002/jimd.12032 |journal=Journal of Inherited Metabolic Disease |language=en |volume=42 |issue=1 |pages=107–116 |doi=10.1002/jimd.12032 |issn=0141-8955 |pmid=30740739 |s2cid=73436689}}</ref> [[propionic acidemia]]<ref name=":15">{{Citation |last=Ozand |first=Pinar T. |title=Disorders of Organic Acid and Amino Acid Metabolism |date=2012 |work=Textbook of Clinical Pediatrics |pages=451–514 |editor-last=Elzouki |editor-first=Abdelaziz Y. |editor-last2=Harfi |editor-first2=Harb A. |editor-last3=Nazer |editor-first3=Hisham M. |editor-last4=Stapleton |editor-first4=F. Bruder |url=http://link.springer.com/10.1007/978-3-642-02202-9_38 |place=Berlin, Heidelberg |publisher=Springer Berlin Heidelberg |language=en |doi=10.1007/978-3-642-02202-9_38 |isbn=978-3-642-02201-2 |last2=Al-Essa |first2=Mohammed }}</ref><ref name=":14" /> or isolated [[methylmalonic acidemia]].<ref name=":15" /><ref name=":14" />

==== Insulinomas ====
A primary B-cell [[Neoplasm|tumor]], such as an [[insulinoma]], is associated with hypoglycemia.<ref name="Jameson_2018" /> This is a tumor located in the [[pancreas]].<ref name="Jameson_2018" /> An insulinoma produces [[insulin]], which in turn decreases glucose levels, causing hypoglycemia.<ref name="Jameson_2018" /> Normal regulatory mechanisms are not in place, which prevent insulin levels from falling during states of low blood glucose.<ref name="Jameson_2018" /> During an episode of hypoglycemia, plasma [[insulin]], [[C-peptide]], and [[proinsulin]] will be inappropriately high.<ref name="Jameson_2018" />

==== Non-B cell tumors ====
Hypoglycemia may occur in people with non-B cell [[Neoplasm|tumors]] such as [[hepatoma]]s, adrenocorticoid carcinomas,<ref>{{Cite web |date=2007-07-06 |title=Adrenocortical Carcinoma Treatment - NCI |url=https://www.cancer.gov/types/adrenocortical/patient/adrenocortical-treatment-pdq |access-date=2024-08-16 |website=www.cancer.gov |language=en}}</ref> and [[carcinoid]] tumors.<ref name="Jameson_2018" /> These tumors lead to a state of increased insulin, specifically increased [[Insulin-like growth factor 2|insulin-like growth factor II]], which decreases glucose levels.<ref name="Jameson_2018" />

==== Post-gastric bypass postprandial hypoglycemia ====
The [[Gastric bypass surgery|Roux-en-Y gastric bypass]], is a weight-loss surgery performed on the stomach, and has been associated with hypoglycemia, called ''post-gastric bypass [[postprandial hypoglycemia]]''.<ref name="Jameson_2018" /> Although the entire mechanism of hypoglycemia following this surgery is not fully understood, it is thought that meals cause very high levels of [[glucagon-like peptide-1]] (also called GLP-1), a hormone that increases insulin, causing glucose levels to drop.<ref name="Jameson_2018" />

==== Autoimmune hypoglycemia ====
[[Antibody|Antibodies]] can be formed against insulin, leading to [[Autoimmunity|autoimmune]] hypoglycemia.<ref name="Jameson_2018" /><ref name=":12">{{Cite journal |vauthors=Lupsa BC, Chong AY, Cochran EK, Soos MA, Semple RK, Gorden P |date=May 2009 |title=Autoimmune forms of hypoglycemia |journal=Medicine |language=en-US |volume=88 |issue=3 |pages=141–153 |doi=10.1097/MD.0b013e3181a5b42e |pmid=19440117 |s2cid=34429211 |doi-access=free}}</ref> [[Antibody|Antibodies]] are immune cells produced by the body, that normally attack bacteria and viruses, but sometimes can attack normal human cells, leading to an [[Autoimmune disease|autoimmune disorder]].<ref>{{Cite web |title=Antibody |url=https://www.genome.gov/genetics-glossary/Antibody |url-status=live |archive-url=https://web.archive.org/web/20201009141818/https://www.genome.gov/genetics-glossary/Antibody |archive-date=9 October 2020 |access-date=24 January 2022 |website=Genome.gov |language=en}}</ref> In autoimmune hypoglycemia, there are two possible mechanisms.<ref name="Jameson_2018" /><ref name=":12" /> In one instance, antibodies bind to insulin following its release associated with a meal, resulting in insulin being non-functional.<ref name="Jameson_2018" /><ref name=":12" /> At a later time, the antibodies fall off insulin, causing insulin to be functional again leading late hypoglycemia after a meal, called ''late postprandial hypoglycemia''.<ref name="Jameson_2018" /><ref name=":12" /> Another mechanism causing hypoglycemia is due to antibodies formed against insulin [[Receptor (biochemistry)|receptors]], called ''insulin receptor antibodies''.<ref name="Jameson_2018" /><ref name=":12" /> The antibodies attach to insulin receptors and prevent insulin breakdown, or degradation, leading to inappropriately high insulin levels and low glucose levels.<ref name="Jameson_2018" /><ref name=":12" />

==== Neonatal hypoglycemia ====
Low blood sugar may occur in healthy [[Infant|neonates]] aged less than 48 hours who have not eaten for a few hours.<ref name=":7" /> During the 48-hour neonatal period, the neonate adjusts [[glucagon]] and [[Adrenaline|epinephrine]] levels following birth, which may trigger transient hypoglycemia.<ref name=":7" /> In children who are aged greater than 48 hours, serum glucose on average ranges from 70 to 100&nbsp;mg/dL (3.9–5.5&nbsp;mmol/L), similar to adults, with hypoglycemia being far less common.<ref name=":7" />