How Stress and Infection Promote Hyperglycemia in Diabetes

Stress as a Biological Trigger

Stress affects different individuals differently and the human body is designed to detect and react to stress. Stress results in adverse effects such as frustration, exhaustion, dread, and agitation. As a biological reaction, stress is triggered by intrinsic and external stimuli. One of the intrinsic stimuli to stress is infection. Acute stress can be caused by disease and infection, and stress inhibits the body's ability to fight infections.

Hormonal Mechanisms of Stress-Induced Hyperglycemia

Both stress and infections cause hyperglycemia in patients with diabetes, resulting in catecholamines and glucocorticoids as hormonal responses (Vedantam et al., 2022). In the acute phase, these hormones do not lead to side effects but may lead to disturbed glucose homeostasis. The disturbed glucose homeostasis leads to chronic hyperglycemia resulting in insulin resistance and Type II Diabetes.

Glucocorticoids stimulate gluconeogenesis leading to depletion of glycogen. The hormone inhibits white adipose tissue and muscles from absorbing and using glucose, making hyperglycemia a side effect. Chronic stress causes insulin resistance, lean body mass loss, and visceral fat accumulation (Sharma et al., 2022).

The GLUT-4 Pathway and Insulin Resistance

The intake of glucose in the body is regulated by Glucose Transporter Type 4 (GLUT-4), which is stimulated by insulin. In the presence of glucocorticoids, the GLUT-4 effect is blocked, reducing the ability of skeletal muscles to absorb glucose, resulting in elevated blood glucose levels. In white adipose tissue, glucocorticoids boost lipolysis, allowing accumulation of non-esterified fatty acids in muscle cells, leading to declined glucose uptake through interfering with insulin signaling (Sharma et al., 2022).

Catecholamine-Mediated Hyperglycemia

Chronic stress results in increased sympathoadrenal system activity, reducing glucose tolerance and increasing chances of cardiovascular events. The stimulated catecholamines increase glycolysis, gluconeogenesis, and glycogenolysis, suppressing insulin-mediated glycogenesis leading to hyperlactatemia and hyperglycemia (Ingrosso et al., 2023).

During stress, beta-adrenergic receptors, norepinephrine, and epinephrine receptors are activated, resulting in insulin resistance. Stress activates hormone-sensitive lipase encouraging the accumulation of free fatty acids and enhancing ceramide formation. Ceramide increases insulin resistance by curbing the functioning of Protein Kinase B (Sharma et al., 2022).

References

• Ingrosso, D. M. F., et al. (2023). Stress and diabetes mellitus: pathogenetic mechanisms and clinical outcome. Hormone Research in Paediatrics, 96(1), 34-43.
• Sharma, K., et al. (2022). Stress-induced diabetes: a review. Cureus, 14(9).
• Vedantam, D., et al. (2022). Stress-induced hyperglycemia: consequences and management. Cureus, 14(7).