Hyperglycemia

Hyperglycemia may be asymptomatic. Blood glucose levels can rise above normal and cause pathological and functional changes for significant periods without producing any permanent effects or symptoms. The following symptoms may be associated with acute or chronic hyperglycemia, with the first three composing the classic hyperglycemic triad: • 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) • Blurred vision • Fatigue • Restlessness • Weight loss or weight gain • Poor wound healing (cuts, scrapes,slashes, etc.) • Dry mouth • Dry or itchy skin • Tingling in feet or heels • Erectile dysfunction • Recurrent infections, external ear infections (swimmer's ear) • 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. 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 glucose in the urine. This produces an osmotic diuresis. Signs and symptoms of diabetic ketoacidosis may include: • 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 • Weight loss Hyperglycemia causes a decrease in cognitive performance, specifically in processing speed, executive function, and performance. Decreased cognitive performance may cause forgetfulness and concentration loss. ==Complications==

In contrast to hypoglycemia (a low level of blood glucose), hyperglycemia often poses a subtle and long-term threat to health. Chronic hyperglycemia over a period of years can produce serious complications, including kidney damage, neurological damage, cardiovascular damage, 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. The degradation of triacylglycerides by hormone-sensitive lipase produces free fatty acids that are eventually converted to acetyl-coA by beta-oxidation. 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. Another life-threatening consequence of hyperglycemia is nonketotic hyperosmolar syndrome. Perioperative 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. Immune system and infection Furthermore, hyperglycemia has been linked to increased susceptibility to a range of 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 infections and vulnerability to pathogens. 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 neutrophils, 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. 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 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. 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. 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 mmol/L (155 mg/dL) at 1-h are associated with T2DM-related complications, which worsen as the degree of hyperglycemia increases. ==Causes==

Hyperglycemia may be caused by: diabetes, various (non-diabetic) endocrine disorders (insulin resistance and thyroid, adrenal, pancreatic, and pituitary disorders), sepsis and certain infections, intracranial diseases (e.g. encephalitis, brain tumors (especially if near the pituitary gland), brain haemorrhages, and meningitis) (frequently overlooked), convulsions, end-stage terminal disease, prolonged/major surgeries, stress, and excessive eating of carbohydrates. Endocrine Chronic, persistent hyperglycaemia is most often a result of diabetes. Several hormones act to increase blood glucose levels and may thus cause hyperglycaemia when present in excess, including: cortisol, catecholamines, growth hormone, glucagon, and thyroid hormones. Hyperglycaemia may thus be seen in: Cushing's syndrome, pheochromocytoma, acromegaly, hyperglucagonemia, and hyperthyroidism. Low insulin levels or insulin resistance prevent the body from converting glucose into glycogen (a starch-like source of energy stored mostly in the liver), which in turn makes it difficult or impossible to remove excess glucose from the blood. With normal glucose levels, the total amount of glucose in the blood at any given moment is only enough to provide energy to the body for 20–30 minutes, and so glucose levels must be precisely maintained by the body's internal control mechanisms. When the mechanisms fail in a way that allows glucose to rise to abnormal levels, hyperglycemia is the result. Ketoacidosis may be the first symptom of type 1 diabetes, particularly in children and adolescents. Also, patients with type 1 diabetes can change from modest fasting hyperglycemia to severe hyperglycemia and even ketoacidosis as a result of stress or an infection. Values of blood glucose higher than 160 mg/dL are classified as 'very high' hyperglycemia, a condition in which an excessive amount of glucose (glucotoxicity) circulates in the blood plasma. These values are higher than the renal threshold of 10 mmol/L (180 mg/dL) up to which glucose reabsorption is preserved at physiological rates and insulin therapy is not necessary. Blood glucose values higher than the cutoff level of 11.1 mmol/L (200 mg/dL) are used to diagnose T2DM and strongly associated with metabolic disturbances, although symptoms may not start to become noticeable until even higher values such as 13.9–16.7 mmol/L (~250–300 mg/dL). A subject with a consistent fasting blood glucose range between 5.6–7 mmol/L (~100–126 mg/dL) (American Diabetes Association guidelines) is considered slightly hyperglycemic, and above 7 mmol/L (126 mg/dL) is generally held to have diabetes. For diabetics, glucose levels that are considered to be too hyperglycemic can vary from person to person, mainly due to the person's renal threshold of glucose and overall glucose tolerance. On average, however, chronic levels above 10–12 mmol/L (180–216 mg/dL) can produce noticeable organ damage over time. Insulin resistance Obesity has been contributing to increased insulin resistance in the global population. Insulin resistance increases hyperglycemia because the body becomes over saturated by glucose. Insulin resistance desensitizes insulin receptors, preventing insulin from lowering blood sugar levels. The leading cause of hyperglycemia in type 2 diabetes is the failure of insulin to suppress glucose production by glycogenolysis and gluconeogenesis due to insulin resistance. Insulin normally inhibits glycogenolysis, but fails to do so in a condition of insulin resistance, resulting in increased glucose production. In the liver, FOXO6 normally promotes gluconeogenesis in the fasted state, but insulin blocks Fox06 upon feeding. In a condition of insulin resistance insulin fails to block Fox06, resulting in continued gluconeogenesis even upon feeding., statins and antipsychotics. The administration of amphetamines initially produces hyperglycemia but later produces hypoglycemia. Thiazides are used to treat hypertension in type 2 diabetes but also may cause hyperglycemia. Somatostatinomas and aldosteronoma-induced hypokalemia can cause hyperglycemia but usually disappears after the removal of the tumour. Hormones such as the growth hormone, glucagon, cortisol, and catecholamines, can cause hyperglycemia when they are present in the body in excess amounts. ==Diagnosis==

Monitoring It is critical for patients who monitor glucose levels at home to be aware of which units of measurement their glucose meter uses. Glucose levels are measured in either: • Millimoles per liter (mmol/L) is the SI standard unit used in most countries around the world. • Milligrams per deciliter (mg/dL) is used in some countries such as the United States, Japan, France, Egypt, and Colombia. Scientific journals are moving toward using mmol/L; some journals now use mmol/L as the primary unit but quote mg/dL in parentheses. Glucose levels vary before and after meals, and at various times of day; the definition of "normal" varies among medical professionals. In general, the normal range for most people (fasting adults) is about 4 to 6 mmol/L or 80 to 110 mg/dL. (where 4 mmol/L or 80 mg/dL is "optimal".) A subject with a consistent range above 7 mmol/L or 126 mg/dL is generally held to have hyperglycemia, whereas a consistent range below 4 mmol/L or 70 mg/dL is considered hypoglycemic. In fasting adults, blood plasma glucose should not exceed 7 mmol/L or 126 mg/dL. Sustained higher levels of blood sugar cause damage to the blood vessels and to the organs they supply, leading to the complications of diabetes. Chronic hyperglycemia can be measured via the HbA1c test. The definition of acute hyperglycemia varies by study, with mmol/L levels from 8 to 15 (mg/dL levels from 144 to 270). Defects in insulin secretion, insulin action, or both, results in hyperglycemia. ==Treatment==

Treatment of hyperglycemia requires elimination of the underlying cause, such as diabetes. Acute hyperglycemia can be treated by direct administration of insulin in most cases and may be lessened by the intake of some natural compounds. For example, a single dose of raw cinnamon before a meal containing complex carbohydrates decreases the postprandial hyperglycemia (higher than 140 mg/dL; >7.8 mmol/L) in patients with type II diabetes. Severe hyperglycemia can be treated with oral hypoglycemic therapy and lifestyle modification. In diabetes mellitus (by far the most common cause of chronic hyperglycemia), treatment aims at maintaining blood glucose at a level as close to normal as possible, in order to avoid serious long-term complications. This is done by a combination of proper diet, regular exercise, and insulin or other medication such as metformin. Those with hyperglycaemia can be treated using sulphonylureas or metformin or both. These drugs help by improving glycaemic control. Dipeptidyl peptidase-4 inhibitor alone or in combination with basal insulin can be used as a treatment for hyperglycemia with patients still in hospital. Calorie monitoring, with restriction as necessary, can reduce over-eating, which contributes to hyperglycemia. Diets higher in healthy unsaturated fats and whole-wheat carbohydrates such as the Mediterranean diet can help reduce carbohydrate intake to better control hyperglycemia. Diets such as intermittent fasting and ketogenic diet help reduce calorie consumption which could significantly reduce hyperglycemia. Carbohydrates are the main cause for hyperglycemia. Non-whole-wheat items should be substituted by whole-wheat items. Although fruits can be nutritious, fruit intake should be limited due to high sugar content. ==Epidemiology==

Environmental factors Hyperglycemia is lower in higher income groups since there is access to better education, healthcare, and resources. Low-middle income groups are more likely to develop hyperglycemia, due in part to a limited access to education and a reduced availability of healthy food options. Living in warmer climates can reduce hyperglycemia due to increased physical activity while people are less active in colder climates. Population Hyperglycemia is one of the main symptoms of diabetes and it has substantially affected the population making it an epidemic due to the population's increased calorie consumption. Healthcare providers are trying to work more closely with people allowing them more freedom with interventions that suit their lifestyle. As physical inactivity and calorie consumption increases it makes individuals more susceptible to developing hyperglycemia. Hyperglycemia is caused by type 1 diabetes and non-whites have a higher susceptibility for it. ==Etymology==

The origin of the term is Greek: prefix ὑπέρ- hyper- "over-", γλυκός glycos "sweet wine, must", αἷμα haima "blood", -ία, -εια -ia suffix for abstract nouns of feminine gender. ==See also==