Hyperglycaemia is a medical condition characterised by high levels of glucose (a type of sugar) in the blood. It is the defining feature of diabetes, and the most common symptoms of hyperglycaemia are increased thirst, frequent urination, and fatigue.
Normally, the body regulates the level of glucose in the blood by releasing insulin, a hormone produced by the pancreas. Insulin helps the body’s cells to use glucose for energy and also helps to store excess glucose in the liver and muscle tissue for later use. In people with diabetes, however, the body is either not able to produce enough insulin (as in type 1 diabetes) or the cells in the body don’t respond properly to insulin (as in type 2 diabetes), leading to high levels of glucose in the blood.
Hyperglycaemia can be caused by a variety of factors, including:
- Not taking enough insulin or oral diabetes medication: People with diabetes who don’t take their medication as prescribed can develop hyperglycaemia.
- Eating too much food: Consuming more carbohydrates than usual can cause hyperglycaemia.
- Skipping meals: Not eating enough food can cause hyperglycaemia.
- Illness or infection: Illness or infection can cause the body to release stress hormones that raise blood sugar levels.
- Certain medications: Some medications can raise blood sugar levels, including corticosteroids and some blood pressure medications.
Hyperglycaemia is a serious condition that can lead to long-term complications if left untreated. People with diabetes need to closely monitor their blood sugar levels and work with their healthcare provider to manage their diabetes and prevent hyperglycaemia.
Pathophysiology
Insulin Resistance
- In individuals with type 2 diabetes or pre-diabetes, insulin resistance is a key factor in the development of hyperglycaemia.
- Insulin resistance refers to reduced responsiveness of target tissues (such as liver, muscle, and adipose tissue) to the effects of insulin.
- Insulin normally facilitates the uptake of glucose into cells, primarily in skeletal muscle and adipose tissue, and suppresses glucose production in the liver.
- In insulin resistance, cells become less sensitive to insulin, leading to impaired glucose uptake and increased hepatic glucose production.
Beta Cell Dysfunction and Insulin Deficiency
- In addition to insulin resistance, impaired function of pancreatic beta cells contributes to hyperglycaemia.
- Beta cells secrete insulin in response to elevated blood glucose levels. However, in individuals with type 2 diabetes, beta cells may not produce enough insulin or may release it in a delayed manner.
- Over time, the beta cells may lose their ability to compensate for insulin resistance, leading to insufficient insulin secretion and relative insulin deficiency.
- In type 1 diabetes, there is an absolute deficiency of insulin due to autoimmune destruction of beta cells.
Increased Hepatic Glucose Production
- Hyperglycemia occurs when the liver produces excessive glucose and releases it into the bloodstream.
- In the absence of sufficient insulin action or insulin deficiency, the liver fails to receive the necessary signals to reduce glucose production.
- As a result, hepatic gluconeogenesis (the production of glucose from non-carbohydrate sources) and glycogenolysis (breakdown of glycogen into glucose) continue unabated, leading to increased hepatic glucose output.
Impaired Glucose Uptake in Peripheral Tissues
- Insulin resistance affects glucose uptake in skeletal muscle and adipose tissue, further contributing to hyperglycaemia.
- Skeletal muscle is a major site of glucose disposal. Impaired insulin signalling in muscle cells hinders glucose transporters (such as GLUT4) from translocating to the cell membrane and facilitating glucose uptake.
- Adipose tissue normally stores excess glucose as triglycerides. Insulin resistance impairs this storage capacity, leading to elevated circulating fatty acids and worsening insulin resistance.
Glucagon Imbalance
- Glucagon, produced by the alpha cells of the pancreas, opposes the effects of insulin and increases blood glucose levels.
- In hyperglycemia, there is often a dysregulation of glucagon secretion.
- The elevated blood glucose levels fail to suppress glucagon secretion adequately, leading to increased hepatic glucose production through glycogen breakdown and gluconeogenesis.
Impaired Renal Glucose Handling
- Normally, the kidneys filter glucose from the bloodstream and reabsorb it back into circulation to prevent its loss in the urine.
- In hyperglycaemia, when blood glucose levels exceed the renal threshold, the kidneys are unable to reabsorb all the filtered glucose.
- Glucose spills into the urine (glucosuria), resulting in increased urine volume and contributing to fluid loss and dehydration.