Editing Hyperglycemia (section)

==Signs and symptoms==
The degree of hyperglycemia can change over time depending on the metabolic cause, for example, impaired glucose tolerance or fasting glucose, and it can depend on treatment.<ref name="ADA">{{cite journal |title=Diagnosis and Classification of Diabetes Mellitus |journal=Diabetes Care |volume=37 |pages=S81–S90 |year=2014 |author1=American Diabetes Association |pmid=24357215 |doi=10.2337/dc14-s081 |doi-access=free}}</ref> Temporary hyperglycemia is often benign and asymptomatic. Blood glucose levels can rise well above normal and cause pathological and functional changes for significant periods without producing any permanent effects or symptoms.<ref name=ADA/> During this asymptomatic period, an abnormality in carbohydrate metabolism can occur, which can be tested by measuring plasma glucose.<ref name=ADA/> Chronic hyperglycemia at above normal levels can produce a very wide variety of serious complications over a period of years, including kidney damage, neurological damage, cardiovascular damage, [[diabetic retinopathy|damage to the retina]] or damage to feet and legs. [[Diabetic neuropathy]] may be a result of long-term hyperglycemia. Impairment of growth and susceptibility to certain infections can occur as a result of chronic hyperglycemia.<ref name=ADA/>

Acute hyperglycemia involving glucose levels that are extremely high is a medical emergency and can rapidly produce serious complications (such as fluid loss through [[osmotic diuresis]]). It is most often seen in persons who have uncontrolled [[diabetes mellitus type 1|insulin-dependent diabetes]].{{Citation needed|date=November 2020}}

The following symptoms may be associated with acute or chronic hyperglycemia, with the first three composing the classic hyperglycemic triad:<ref>{{cite web |last1=James |first1=Norman |title=Hyperglycemia Symptoms |date=30 March 2019 |publisher=EndocrineWeb |url=https://www.endocrineweb.com/conditions/diabetes/symptoms-hyperglycemia |access-date=24 December 2022<!-- bad https: certificate and moved to https://www.healthcentral.com/condition/hypoglycemia---hyperglycemia -->}}</ref>
* [[Polyphagia]] – frequent hunger, especially pronounced hunger
* [[Polydipsia]] – frequent thirst, especially excessive thirst
* [[Polyuria]] – increased volume of urination (''not'' an increased frequency, although it is a common consequence)<span style="height: 2em; display: inline-block; vertical-align: top"></span>
* [[Blurred vision]]
* [[Fatigue (physical)|Fatigue]]
* [[Psychomotor agitation|Restlessness]]
* [[Weight loss]] or [[weight gain]]
* Poor [[wound]] healing (cuts, scrapes, etc.)
* [[Dry mouth]]
* Dry or itchy [[skin]]
* Tingling in feet or heels
* [[Erectile dysfunction]]
* Recurrent [[infection]]s, external ear infections ([[otitis externa|swimmer's ear]])
* [[Gastroparesis|Delayed gastric emptying]]
* [[Cardiac arrhythmia]]
* [[Stupor]]
* [[Coma]]
* Seizures

Frequent hunger without other symptoms can also indicate that blood sugar levels are too low. This may occur when people who have diabetes take too much oral hypoglycemic medication or insulin for the amount of food they eat. The resulting drop in blood sugar level to below the normal range prompts a hunger response.{{Citation needed|date=November 2020}}

Polydipsia and polyuria occur when blood glucose levels rise high enough to result in excretion of excess glucose via the kidneys, which leads to the presence of [[glycosuria|glucose in the urine]]. This produces an [[osmotic diuresis]].{{Citation needed|date=November 2020}}

Signs and symptoms of [[diabetic ketoacidosis]] may include:{{Citation needed|date=November 2020}}
* [[Ketoacidosis]]
* [[Kussmaul breathing]] (deep, rapid breathing)
* Confusion or a decreased level of consciousness
* Dehydration due to [[glycosuria]] and osmotic diuresis
* Increased thirst
* 'Fruity' smelling breath odor
* Sweet sensation that is felt into the mouth without a reason
* Nausea and vomiting
* Abdominal pain
* Impairment of cognitive function, along with increased sadness and anxiety<ref>{{cite journal |vauthors=Pais I, Hallschmid M, Jauch-Chara K, etal |title=Mood and cognitive functions during acute euglycaemia and mild hyperglycaemia in type 2 diabetic patients |journal=Exp. Clin. Endocrinol. Diabetes |volume=115 |issue=1 |pages=42–46 |year=2007 |pmid=17286234 |doi=10.1055/s-2007-957348}}</ref><ref>{{cite journal |vauthors=Sommerfield AJ, Deary IJ, Frier BM |title=Acute hyperglycemia alters mood state and impairs cognitive performance in people with type 2 diabetes |journal=Diabetes Care |volume=27 |issue=10 |pages=2335–40 |year=2004 |pmid=15451897 |doi=10.2337/diacare.27.10.2335 |doi-access=free}}</ref>
* Weight loss

Hyperglycemia causes a decrease in cognitive performance, specifically in processing speed, executive function, and performance.<ref name=CP>{{cite journal |title=The Role of Hyperglycemia, Insulin Resistance, and Blood Pressure in Diabetes-Associated Differences in Cognitive Performance—The Maastricht Study |journal=Diabetes Care |volume=40 |issue=11 |pages=1537–1547 |year=2017 |last1=Geijselaers |first1=Stefan L.C. |last2=Sep |first2=Simone J.S. |last3=Claessens |first3=Danny |last4=Schram |first4=Miranda T. |last5=Van Boxtel |first5=Martin P.J. |last6=Henry |first6=Ronald M.A. |last7=Verhey |first7=Frans R.J. |last8=Kroon |first8=Abraham A. |last9=Dagnelie |first9=Pieter C. |last10=Schalkwijk |first10=Casper G. |last11=Van Der Kallen |first11=Carla J.H. |last12=Biessels |first12=Geert Jan |last13=Stehouwer |first13=Coen D.A. |pmid=28842522 |doi=10.2337/dc17-0330 |doi-access=free}}</ref> Decreased cognitive performance may cause forgetfulness and concentration loss.<ref name=CP/>

===Complications===
In untreated hyperglycemia, a condition called [[ketoacidosis]] may develop because decreased [[insulin]] levels increase the activity of [[hormone sensitive lipase]].<ref name="KraemerShen2002">{{cite journal |last1=Kraemer |first1=Fredric B. |last2=Shen |first2=Wen-Jun |title=Hormone-sensitive lipase |journal=Journal of Lipid Research |volume=43 |issue=10 |year=2002 |pages=1585–1594 |issn=0022-2275 |pmid=12364542 |doi=10.1194/jlr.R200009-JLR200 |doi-access=free}}</ref> The degradation of triacylglycerides by hormone-sensitive lipase produces free fatty acids that are eventually converted to acetyl-coA by beta-oxidation.{{Citation needed|date=November 2020}}

Ketoacidosis is a life-threatening condition which requires immediate treatment. Symptoms include: shortness of breath, breath that smells fruity (such as pear drops), nausea and vomiting, and very dry mouth.
Chronic hyperglycemia (high blood sugar) injures the heart in patients without a history of heart disease or diabetes and is strongly associated with heart attacks and death in subjects with no coronary heart disease or history of heart failure.<ref>{{cite web |title=Chronic hyperglycemia may lead to cardiac damage |work=Journal of the American College of Cardiology |date=2012-02-03 |url=https://www.news-medical.net/news/20120203/Chronic-hyperglycemia-may-lead-to-cardiac-damage.aspx |access-date=3 February 2012 |url-status=live |archive-url=https://web.archive.org/web/20131227010650/http://www.news-medical.net/news/20120203/Chronic-hyperglycemia-may-lead-to-cardiac-damage.aspx |archive-date=2013-12-27}}</ref>

Also, a life-threatening consequence of hyperglycemia can be [[hyperosmolar hyperglycemic state|nonketotic hyperosmolar syndrome]].<ref name=ADA/>

Perioperative hyperglycemia has been associated with immunosuppression, increased infections, osmotic diuresis, delayed wound healing, delayed gastric emptying, sympatho-adrenergic stimulation, and increased mortality. In addition, it reduces skin graft success, exacerbates brain, spinal cord, and renal damage by ischemia, worsens neurologic outcomes in traumatic head injuries, and is associated with postoperative cognitive dysfunction following CABG.<ref>Miller, Miller's Anesthesia, 7th edition, pp. 1716, 2674, 2809.</ref>

Furthermore, hyperglycemia has been linked to increased susceptibility to a range of [[list of infectious diseases|infectious diseases]]. This susceptibility can be attributed to the impairment of the immune system's response, which is often compromised in hyperglycemic conditions. Hyperglycemia also leads to biochemical changes in the body; both of these factors result in increased severity of [[respiratory tract infection|respiratory infections]] and vulnerability to pathogens.<ref name=":2">{{cite journal |last1=Chávez-Reyes |first1=Jesús |last2=Escárcega-González |first2=Carlos E. |last3=Chavira-Suárez |first3=Erika |last4=León-Buitimea |first4=Angel |last5=Vázquez-León |first5=Priscila |last6=Morones-Ramírez |first6=José R. |last7=Villalón |first7=Carlos M. |last8=Quintanar-Stephano |first8=Andrés |last9=Marichal-Cancino |first9=Bruno A. |date=2021 |title=Susceptibility for Some Infectious Diseases in Patients With Diabetes: The Key Role of Glycemia |journal=Frontiers in Public Health |volume=9 |issn=2296-2565 |pmid=33665182 |doi=10.3389/fpubh.2021.559595 |doi-access=free |pmc=7921169|bibcode=2021FrPH....959595C }}</ref> Hyperglycemic individuals face the most pronounced risk from such types of ailments, including tuberculosis, the flu, and COVID-19. These risks can be compounded even further by the effects of physiological stress.

Importantly, hyperglycemia affects the function of [[neutrophil]]s, which are white blood cells responsible for responding to infection. In hyperglycemic individuals, the ability for neutrophils to move toward infection sites, ingest bacteria, and kill them are often impaired, leading to reduced effectiveness in combating infections.<ref>{{cite journal |last1=Ngo |first1=Minh Dao |last2=Bartlett |first2=Stacey |last3=Ronacher |first3=Katharina |date=November 2021 |title=Diabetes-Associated Susceptibility to Tuberculosis: Contribution of Hyperglycemia vs. Dyslipidemia |journal=Microorganisms |language=en |volume=9 |issue=11 |pages=2282 |issn=2076-2607 |pmid=34835407 |doi=10.3390/microorganisms9112282 |doi-access=free |pmc=8620310}}</ref>

Hyperglycemia also creates microbiological changes within the body: hyperglycemia can lead to rapid changes in blood pH and cell viscosity, weakening the cells and making it more conducive for infectious agents to thrive and dampen [[inflammation|inflammatory responses]]. This is because hyperglycemia impacts a few factors such as microenvironment of immune cells, or even bacteria's supply of energy, adding on stress to the bacterial proliferation metabolism.<ref name=":2"/>

The chronic inflammatory state induced by high glucose levels can also lead to dysfunction in various parts of the [[immune system]]. For example, advanced glycation end products (AGEs), which are more prevalent in hyperglycemic conditions, can interfere with the normal function of the immune system and contribute to the pathogenesis of infections.<ref>{{cite web |last=CDC |title=Your Immune System and Diabetes |date=2024-05-14 |website=Centers for Disease Control and Prevention |language=en-us |url=https://www.cdc.gov/diabetes/diabetes-complications/diabetes-immune-system.html |access-date=2025-01-09}}</ref> AGEs, whose cross-links are permanent will continue to harm the surrounding tissue until the proteins are destroyed. In addition, they can interact with the RAGE receptor to cause oxidative stress, apoptosis, and inflammation.

Due to neutrophil changes, microbiological changes, and chronic inflammation, patients with hyperglycemia are thus more prone to severe respiratory infections. This increased risk is particularly pronounced with pathogens like [[Mycobacterium tuberculosis]] (the bacterium responsible for tuberculosis) and the flu.<ref>{{citation |last=Baccouch |first=Mahboub |title=A Brief Summary of the Finite Element Method for Differential Equations |date=2021-02-17 |work=Finite Element Methods and Their Applications |publisher=IntechOpen |language=en |isbn=978-1-83962-342-4 |url=https://www.intechopen.com/chapters/75281 |access-date=2024-05-06}}</ref> In recent history, hyperglycemic individuals have also responded more severely to the symptoms of COVID-19. Another example is diabetes. Hyperglycemia and risk of severe infectious outcomes can even further be complicated by physiological stress. For instance, elevated blood glucose levels can actively contribute to pathophysiology of this disease, by exacerbating existing inflammation, impairing cellular immune responses, and increasing oxidative stress, which can also lead to more severe infection. In addition, patients with acute hyperglycemia who don't have a history of diabetes can experience higher rates of mortality and complications.

Postprandial hyperglycemic levels as high as 8.6&nbsp;mmol/L (155&nbsp;mg/dL) at 1-h are associated with T2DM-related complications, which worsen as the degree of hyperglycemia increases.<ref name="Ralph A 2020">{{cite journal |last1=Bergman |first1=Michael |last2=Abdul-Ghani |first2=Muhammad |last3=DeFronzo |first3=Ralph A. |last4=Manco |first4=Melania |last5=Sesti |first5=Giorgio |last6=Fiorentino |first6=Teresa Vanessa |last7=Ceriello |first7=Antonio |last8=Rhee |first8=Mary |last9=Phillips |first9=Lawrence S. |last10=Chung |first10=Stephanie |last11=Cravalho |first11=Celeste |last12=Jagannathan |first12=Ram |last13=Monnier |first13=Louis |last14=Colette |first14=Claude |last15=Owens |first15=David |date=July 2020 |title=Review of methods for detecting glycemic disorders |journal=Diabetes Research and Clinical Practice |language=en |volume=165 |pages=108233 |pmid=32497744 |doi=10.1016/j.diabres.2020.108233 |pmc=7977482}}</ref><ref>{{cite journal |last1=Bergman |first1=Michael |last2=Manco |first2=Melania |last3=Sesti |first3=Giorgio |last4=Dankner |first4=Rachel |last5=Pareek |first5=Manan |last6=Jagannathan |first6=Ram |last7=Chetrit |first7=Angela |last8=Abdul-Ghani |first8=Muhammad |last9=Buysschaert |first9=Martin |last10=Olsen |first10=Michael H. |last11=Nilsson |first11=Peter M. |last12=Medina |first12=José Luis |last13=Roth |first13=Jesse |last14=Groop |first14=Leif |last15=del Prato |first15=Stefano |date=December 2018 |title=Petition to replace current OGTT criteria for diagnosing prediabetes with the 1-hour post-load plasma glucose ≥ 155 mg/dl (8.6 mmol/L) |journal=Diabetes Research and Clinical Practice |language=en |volume=146 |pages=18–33 |pmid=30273707 |doi=10.1016/j.diabres.2018.09.017 |url=https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(18)31463-3/abstract}}</ref><ref>{{cite journal |last=Bergman |first=Michael |date=2021-09-07 |title=The 1-Hour Plasma Glucose: Common Link Across the Glycemic Spectrum |journal=Frontiers in Endocrinology |volume=12 |issn=1664-2392 |pmid=34557166 |doi=10.3389/fendo.2021.752329 |doi-access=free |pmc=8453142}}</ref><ref name="ReferenceA">{{cite journal |last1=Chawla |first1=Rajeev |last2=Mukherjee |first2=Jagat Jyoti |last3=Chawla |first3=Manoj |last4=Kanungo |first4=Alok |last5=Shunmugavelu |first5=Meenakshi Sundaram |last6=Das |first6=Ashok Kumar |date=2021-05-28 |title=Expert Group Recommendations on the Effective Use of Bolus Insulin in the Management of Type 2 Diabetes Mellitus |journal=Medical Sciences |language=en |volume=9 |issue=2 |pages=38 |issn=2076-3271 |pmid=34071359 |doi=10.3390/medsci9020038 |doi-access=free |pmc=8162981}}</ref>