What is the relationship between hyperinsulinemia and agitation?

From the Guidelines

High insulin levels can cause agitation primarily through their effect on blood glucose, leading to hypoglycemia, which triggers the release of stress hormones and affects mood regulation and cognitive function. When insulin is elevated, it rapidly removes glucose from the bloodstream, potentially leading to hypoglycemia (low blood sugar) 1. This drop in blood glucose triggers the release of stress hormones like adrenaline and cortisol, which can manifest as feelings of anxiety, irritability, nervousness, and agitation. The brain is particularly sensitive to glucose fluctuations since it relies heavily on glucose for energy. When glucose levels fall too quickly, the resulting neurochemical changes can affect mood regulation and cognitive function. Additionally, insulin can influence neurotransmitter activity in the brain, potentially altering serotonin and dopamine levels, which further impacts emotional regulation. People with diabetes who use insulin medication may experience this phenomenon if they take too much insulin relative to their carbohydrate intake or physical activity level.

Key Points to Consider

• Hypoglycemia is a medical emergency that can be caused by high insulin levels, and its signs and symptoms can be confused with intoxication or withdrawal 1.
• Correctional institutions and hospitals should have systems in place to identify patients at greater risk for hypoglycemia and to ensure early detection and treatment 1.
• To prevent insulin-induced agitation, maintaining stable blood glucose levels through balanced meals, regular eating schedules, appropriate insulin dosing, and glucose monitoring is essential.
• If experiencing symptoms of agitation with high insulin levels, consuming fast-acting carbohydrates like juice or glucose tablets can help restore blood sugar balance and alleviate the psychological symptoms.

Prevention and Management

• Algorithms to predict episodes of hypoglycemia in the inpatient setting have been developed, and models such as these could provide a valuable tool to reduce rates of hypoglycemia in the hospital 1.
• A fasting blood glucose of <100 mg/dL was shown to be a predictor of next-day hypoglycemia in one retrospective cohort study data 1.
• Acute kidney injury is an important risk factor for hypoglycemia in people with diabetes in the ambulatory setting, and this relationship also holds true for people with diabetes in the inpatient setting 1.

From the Research

High Insulin and Agitation

• High insulin levels can lead to hypoglycemia, which is associated with unpleasant symptoms, deterioration in cognitive-motor functions, and negative changes in affect and social behavior, including feelings of tension and anger 2.
• The physical symptoms and cognitive impairment that occur with hypoglycemia are caused primarily by hormonal changes and neuroglycopenia, which can also cause negative changes in emotional status and social behavior 2.
• Patients with high insulin levels may experience hypoglycemic episodes, which can lead to agitation, embarrassment, accidents, unconsciousness, seizures, and even death 2, 3.

Mechanism of Agitation in High Insulin Levels

• The intraislet insulin hypothesis suggests that a decrease in arterial glucose leads to a decrease in beta-cell insulin secretion, which in turn leads to a decrease in tonic alpha-cell inhibition by insulin, resulting in an increase in alpha-cell glucagon secretion 4.
• However, in insulin-deficient diabetes, the loss of the decrement in intraislet insulin plausibly explains the loss of the glucagon response to hypoglycemia, leading to impaired glucose regulation and potentially agitation 4.
• Partial inhibition of insulin secretion can result in glucose intolerance but not hyperglucagonemia, suggesting that the primary glucoregulatory role of insulin is not the only regulator of alpha-cell glucagon secretion 5.

Clinical Implications

• ICU patients with extremely high dose insulin infusions are more likely to experience hypoglycemia, longer time to glucose control, and higher mortality, highlighting the need for individualized management approaches 6.
• The use of glucagon as an emergency drug in hypoglycemia can be effective, but its ineffectiveness can occur, and a second dose can be administered in case of failure 3.