General Health

Understanding Hyperglycemia beyond Diabetes

High blood sugar is associated with Diabetes mellitus, but that need not always be the case.

Normal blood sugar levels lie below 120 mg of glucose/dL of blood and it can vary from one individual to another based on the metabolism and body type. If the level goes above 160 mg/dL, it is considered as hyperglycemia. The most common reason for hyperglycemia is diabetes mellitus, a metabolic disorder where there is either inadequate production of insulin or cells of the body do not respond properly to insulin. Due to this, the sugar ends up getting trapped in the bloodstream leading to hyperglycemia. 

However, not all patients with hyperglycemia are diabetics. Trauma of any kind triggers a response characterized by enhanced metabolism and hyperglycemia. Administering lesser insulin, under-consuming carbohydrates, stress, insufficient exercise, hormonal fluctuation, and illness can all contribute to hyperglycemia. Using insulin that has expired or lost its effectiveness due to  improper storage can also cause hyperglycemia. 

Hyperglycemia can occur during physically stressful situations such as infections, illnesses, or injuries. It also occurs when a patient while a patient is recovering from a surgery. Emotional stress contributes to hyperglycemia as the stress hormones can cause blood glucose levels to rise. Steroid medication which is used to treat inflammatory and infectious illnesses can lead to transient hyperglycemia. 

Stress induced Hyperglycemia

Stress induced hyperglycemia is commonly seen in critically ill patients and is a marker for disease severity. Claude Bernard, a French physiologist, first observed hyperglycemia during hemorrhagic shock in 1878. Since then, several studies have established that acute illness or injury can result in hyperglycemia, insulin resistance and glucose intolerance. Numerous studies in both ICU and hospitalized non-ICU patients have also demonstrated a correlation between stress hyperglycemia and poor clinical outcomes, including mortality, morbidity, length of stay, infections and overall complications.

The bodily response to any kind of stress involves endocrine, immunological, neurological and hematological systems. Increased pituitary hormone secretions and activation of sympathetic systems can lead to significant hyperglycemia. Cortisol and catecholamine levels correspond to the type and severity of the injury. Stress can result in up to 10 times greater adrenal cortical output causing stress hyperglycemia. Neuroendocrine response to stress is characterized by excessive gluconeogenesis (glucose production), glycogenolysis (glycogen breakdown) and insulin resistance. 

Stress hyperglycemia predominantly occurs due to the increased output of glucose from the liver rather than impaired tissue glucose extraction. Increased levels of cortisol (a glucocorticoid hormone) leads to a concomitant increase in the blood glucose by activating enzymes involved in hepatic glucose production and inhibiting glucose uptake in the skeletal muscles. Adrenaline, another stress hormone, stimulates hepatic gluconeogenesis, and glycogen breakdown. Norepinephrine increases the supply of glycerol to the liver via lipid breakdown. 

Glucose Transporters (GLUT) specifically GLUT-4 enable the entry of glucose from the plasma into the cell across the non-polar cell membrane. During sepsis and thermal injury the number of GLUT receptors increases. During stress and inflammatory conditions the expression of the GLUT-4 receptors on the surface to the membrane reduces. This could be due to the influence of proinflammatory mediators, particularly TNF-α and IL-1 which are also responsible for inducing peripheral insulin resistance. 

Tight glycemic control (targeting a blood glucose of 70 to 110 mg/dL) using intensive insulin therapy needs to be practiced in order to improve patient outcomes. 

Steroid Induced Hyperglycemia: 

Steroids are used extensively to treat a variety of conditions, both acute and chronic. At doses more than the body’s requirement, they reduce the synthesis of pro-inflammatory cytokines, T-cell function, and antibody F-c receptor expression, thus activating anti-inflammatory and immunosuppressive processes. Hence, steroids are very effective in treating numerous inflammatory, infectious and autoimmune diseases. Despite being extremely beneficial, steroids have a variety of side effects with the main one being hyperglycemia. 

Steroids induce insulin resistance by directly interfering with signaling cascades, mainly the GLUT4 transporter, within muscle cells, with the subsequent reduction in insulin-stimulated glucose uptake (30-50% reduction) and glycogen synthesis (70% reduction). Steroids are responsible for the breakdown of proteins hence increasing the serum amino acid levels, which also interfere with insulin signaling in the muscle cell. These drugs also increase lipid breakdown, resulting in an increase in serum free fatty acids and triglycerides.

Doctors should advise their patients who are on steroid treatment to monitor glucose on a daily basis especially when the glucose levels are 180 mg/dL and above. Due to differences in steroid dose and the scheme used, treating steroid induced hyperglycemia should be personalized. Oral hypoglycemic drugs such as metformin, sulphonylureas and TZDs or insulin therapy can be used. 

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