Why does hypoglycemia (low blood glucose) trigger the release of cortisol and other stress hormones?

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From the Guidelines

Low glucose levels trigger the release of cortisol and other stress hormones as part of the body's survival mechanism to maintain adequate glucose supply to the brain. When blood sugar drops below normal levels, the brain detects this dangerous situation and activates the hypothalamic-pituitary-adrenal (HPA) axis, which signals the adrenal glands to release cortisol, adrenaline, and glucagon, as noted in the context of managing stress levels in diabetes patients 1. These stress hormones work together to raise blood glucose levels through several mechanisms: cortisol increases glucose production in the liver through gluconeogenesis, breaks down muscle protein into amino acids that can be converted to glucose, and reduces glucose uptake by non-essential tissues; adrenaline stimulates the breakdown of glycogen stores in the liver and muscles; and glucagon promotes the conversion of stored glycogen back into glucose. This stress hormone response is essential for maintaining adequate glucose supply to the brain, which requires constant glucose to function properly, and its importance is highlighted in the management of glycemic targets, especially in preventing hypoglycemia and its complications 1. Without this protective mechanism, severe hypoglycemia could lead to confusion, seizures, loss of consciousness, and potentially death, emphasizing the need for patients to understand situations that increase their risk of hypoglycemia and to balance insulin use, carbohydrate intake, and exercise to prevent such outcomes. Key points to consider include:

  • The role of the HPA axis in responding to low blood glucose
  • The mechanisms by which cortisol, adrenaline, and glucagon raise blood glucose levels
  • The importance of preventing hypoglycemia to avoid its complications, as discussed in the context of glycemic targets and standards of medical care in diabetes 1. Overall, the release of cortisol and other stress hormones in response to low glucose levels is a critical survival mechanism that helps maintain brain function and prevent the severe consequences of hypoglycemia.

From the Research

Low Glucose and Stress Hormones

  • Low glucose levels trigger the release of stress hormones, including cortisol, as part of the glucose counterregulatory response 2, 3.
  • This response is mediated by glucose-sensing neurons in the brain, which detect declining plasma glucose levels and stimulate the secretion of hormones such as glucagon, adrenaline, cortisol, and growth hormone to recover from hypoglycemia 2.
  • The release of these hormones helps to increase blood glucose levels and prevent further decreases, which is essential for maintaining normal cerebral metabolism and preventing the consequences of hypoglycemia, such as convulsions, loss of consciousness, and even death 2, 3.

Glucose Counterregulation

  • The glucose counterregulatory system is a complex physiological system that has evolved to maintain blood glucose at a constant level 2.
  • This system involves the detection of declining plasma glucose levels and the secretion of counterregulatory hormones to prevent and correct hypoglycemia 3.
  • The importance of the glucose counterregulatory system is highlighted by the consequences of poor glucose homeostasis, including hyperglycemia-associated cardiovascular disease, neuropathy, and nephropathy, as well as hypoglycemia-associated convulsions, loss of consciousness, and death 2.

Hypoglycemia and Diabetes

  • Hypoglycemia is a major limiting factor to successful glycaemic management in people with diabetes, particularly those with type 1 diabetes and insulin-treated type 2 diabetes 4, 5.
  • The fear of hypoglycemia can lead to delayed initiation of insulin therapy, which can worsen hyperglycemia and increase the risk of complications 5.
  • Education and regular review are essential for people with diabetes and their caregivers to recognize the symptoms, prevention, and treatment of hypoglycemia, and to have ready access to effective treatment for hypoglycemia emergencies 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Physiology of glucose counterregulation to hypoglycemia.

Endocrinology and metabolism clinics of North America, 1999

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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