Hyperglycemia
Hyperglycemia is a condition where an unusually high amount of glucose is present in blood. It is defined as blood glucose level exceeding 6.9 mmol/L after fasting for 8 hours or 10 mmol/L 2 hours after eating.
Signs and symptoms
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. During this asymptomatic period, an abnormality in carbohydrate metabolism can occur, which can be tested by measuring plasma glucose.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.
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
- Blurred vision
- Fatigue
- Restlessness
- Weight loss or weight gain
- Poor wound healing
- Dry mouth
- Dry or itchy skin
- Tingling in feet or heels
- Erectile dysfunction
- Recurrent infections, external ear infections
- Delayed gastric emptying
- Cardiac arrhythmia
- Stupor
- Coma
- Seizures
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
- 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
Complications
In contrast to hypoglycemia, 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. Acute hyperglycemia involving glucose levels that are extremely high is a medical emergency and can rapidly produce serious complications. It is most often seen in persons who have uncontrolled insulin-dependent diabetes.Metabolic
In acute hyperglycemia, a condition called ketoacidosis may develop because decreased insulin levels increase the activity of hormone sensitive lipase. 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, nausea and vomiting, and very dry mouth.
Chronic hyperglycemia 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.
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.
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, which are more prevalent in hyperglycemic conditions, can interfere with the normal function of the immune system and contribute to the pathogenesis of infections. 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 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 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 endocrine disorders, sepsis and certain infections, intracranial diseases , 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.Diabetes mellitus
Chronic hyperglycemia that persists even in fasting states is most commonly caused by diabetes mellitus. In fact, chronic hyperglycemia is the defining characteristic of the disease. Intermittent hyperglycemia may be present in prediabetic states. Acute episodes of hyperglycemia without an obvious cause may indicate developing diabetes or a predisposition to the disorder.Diabetes mellitus is usually caused by either low insulin levels or resistance to insulin at the cellular level. Low insulin levels or insulin resistance prevent the body from converting glucose into glycogen, 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.