Explore the intricacies of Hypoglycemic Associated Autonomic Failure (HAAF) and its impact on individuals with insulin resistance and metabolic problems. Learn about the symptoms, risks, and management strategies for this condition characterized by a lack of typical warning signs for low blood sugar, posing challenges in glycemic control and overall health.
Hypoglycemic Associated Autonomic Failure, or HAAF for short, is a condition that happens when someone’s blood sugar level drops too low, also known as hypoglycemia, especially in people who have diabetes. Normally, when your blood sugar gets low, your body has a built-in alarm system that sends signals to raise your sugar levels back to normal. This system involves your autonomic nervous system, which controls things like your heart rate, sweating, and digestion.
Autonomic Dysfunction (AD) is common in Insulin Resistance / Metabolic Syndrome patients, and in those who suffer Iatrogenic Hypoglycemia1Chittineni C, Driver BE, Halverson M, et al. Incidence and Causes of Iatrogenic Hypoglycemia in the Emergency Department. West J Emerg Med. 2019;20(5):833-837.,2Allison MG, McCurdy MT. Alcoholic metabolic emergencies. Emerg Med Clin North Am. 2014;32(2):293–301.,3Khanimov I, Shimonov M, Wainstein J, Leibovitz E. Hypoglycemia, Malnutrition and Body Composition. Adv Exp Med Biol. 2021;1307:71-84. doi: 10.1007/5584_2020_526. Erratum in: Adv Exp Med Biol. 2021;1307:577.,4Cryer PE. Iatrogenic hypoglycemia as a cause of hypoglycemia-associated autonomic failure in IDDM. A vicious cycle. Diabetes. 1992 Mar;41(3):255-60. there is a hypoglycemia-associated autonomic failure (HAAF).5Cryer PE. Hypoglycemia in diabetes: pathophysiological mechanisms and diurnal variation. Prog Brain Res. 2006;153:361–365 This is a result of decreased response of adrenaline and the SNS to hypoglycemia.6Gaab J, Engert V, Heitz V, Schad T, Schürmeyer TH, Ehlert U. Associations between neuroendocrine responses to the Insulin Tolerance Test and patient characteristics in chronic fatigue syndrome. J Psychosom Res. 2004 Apr;56(4):419-24. doi: 10.1016/S0022-3999(03)00625-1. PMID: 15094026. Autonomic Dysfunction (AD) creates hypoglycemic unawareness, and therefore a vicious circle of worsening AD.7Cryer PE. Diverse causes of hypoglycemia-associated autonomic failure in diabetes. N Engl J Med. 2004;350(22):2272–2279.
What are the autonomic symptoms of hypoglycemia?
The surge in autonomic activity in response to low plasma glucose causes sweating, nausea, warmth, anxiety, tremulousness, palpitations, and possibly hunger and paresthesias.
What are the autonomic symptoms of Hypoglycemic Associated Autonomic Failure, or HAAF?
However, in people with HAAF, this alarm system doesn’t work as it should. When they experience low blood sugar, their body doesn’t give them the usual warning signs like feeling shaky, sweaty, or hungry. This can be dangerous because if you don’t realize your blood sugar is low, you might not take action to raise it, which could lead to more severe hypoglycemia.
Hypoglycemic Associated Autonomic Failure
The symptoms of Hypoglycemic Associated Autonomic Failure (HAAF) can vary from person to person, but they often include:
- Lack of typical warning signs: One of the main symptoms of HAAF is the absence of the usual symptoms of low blood sugar (hypoglycemia), such as feeling shaky, sweaty, dizzy, or hungry. This means that someone with HAAF might not realize their blood sugar is low until it becomes more severe.
- Difficulty recognizing low blood sugar: People with HAAF may find it challenging to recognize when their blood sugar is dropping because they don’t experience the typical warning signs. This can make it harder for them to manage their diabetes safely.
- Increased risk of severe hypoglycemia: Because individuals with HAAF don’t receive the usual signals that their blood sugar is low, they are at a higher risk of experiencing severe hypoglycemia, which can lead to confusion, loss of consciousness, seizures, and even coma if left untreated.
- Autonomic symptoms: In some cases, people with HAAF may still experience symptoms related to the autonomic nervous system, such as changes in heart rate, sweating, or digestion, but these symptoms may not be reliable indicators of low blood sugar.
Individuals who adhere to extremely healthy diets, impose chronic dietary restrictions, or suffer from chronic illnesses may inadvertently experience prolonged periods of malnutrition, which can lead to consistently low blood sugar levels. Unfortunately, in such cases, both the affected individuals and their healthcare providers may fail to recognize the connection between high cholesterol levels, elevated LDL (low-density lipoprotein), and conditions like insulin resistance or Hypoglycemic Associated Autonomic Failure (HAAF).8Hoenig MR, Sellke FW. Insulin resistance is associated with increased cholesterol synthesis, decreased cholesterol absorption and enhanced lipid response to statin therapy. Atherosclerosis. 2010 Jul;211(1):260-5. doi: 10.1016/j.atherosclerosis.2010.02.029. Epub 2010 Mar 1. PMID: 20356594.Gylling H, Hallikainen M, Pihlajamäki J, Simonen P, Kuusisto J, Laakso M, Miettinen TA. Insulin sensitivity regulates cholesterol metabolism to a greater extent than obesity: lessons from the METSIM Study. J Lipid Res. 2010 Aug;51(8):2422-7. 9Mingming Hao, W. Steven Head, Subhadra C. Gunawardana, Alyssa H. Hasty, David W. Piston; Direct Effect of Cholesterol on Insulin Secretion: A Novel Mechanism for Pancreatic β-Cell Dysfunction. Diabetes 1 September 2007; 56 (9): 2328–2338.
This lack of connection can occur because the focus is often placed solely on the immediate symptoms or consequences of malnutrition, rather than considering its broader impacts on metabolic health. Therefore, individuals and their healthcare providers may overlook the potential link between malnutrition-induced hypoglycemia and other metabolic disturbances, such as elevated cholesterol levels or insulin resistance.
It’s crucial for both patients and healthcare professionals to maintain awareness of the complex interplay between nutritional status, metabolic health, and various health conditions. By adopting a comprehensive approach to healthcare that considers the interconnectedness of these factors, individuals can receive more holistic and effective management of their health concerns. This may involve regular monitoring of blood sugar levels, lipid profiles, and other relevant markers, as well as addressing underlying nutritional deficiencies and metabolic dysregulations through appropriate dietary and lifestyle interventions.
It’s essential for individuals with Insulin Resistance and HAAF to be aware of these potential symptoms and work closely with their healthcare team to develop strategies for managing their condition effectively. Regular monitoring of blood sugar levels and close communication with healthcare providers can help prevent severe hypoglycemic episodes and minimize the impact of HAAF on daily life.
What is the first organ to manifest hypoglycemic symptom?
A cardinal manifestation of hypoglycemia arises from inadequate supply of glucose to the brain, where glucose is the primary metabolic fuel. The brain is one of the first organs to be affected by hypoglycemia.10Blaabjerg L, Juhl CB. Hypoglycemia-Induced Changes in the Electroencephalogram: An Overview. J Diabetes Sci Technol. 2016 Nov 1;10(6):1259-1267. Hypoglycemia commonly causes brain fuel deprivation, resulting in functional brain failure, which can be corrected by raising plasma glucose concentrations.11Cryer PE. Hypoglycemia, functional brain failure, and brain death. J Clin Invest. 2007 Apr;117(4):868-70.
HAAF can make it harder for people with diabetes to manage their blood sugar levels because they can’t rely on their body’s normal signals to alert them when they need to eat or drink something sugary to bring their blood sugar back up. It’s important for people with diabetes and HAAF to work closely with their healthcare team to find ways to manage their condition safely and prevent dangerous drops in blood sugar.
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References
- 1Chittineni C, Driver BE, Halverson M, et al. Incidence and Causes of Iatrogenic Hypoglycemia in the Emergency Department. West J Emerg Med. 2019;20(5):833-837.
- 2Allison MG, McCurdy MT. Alcoholic metabolic emergencies. Emerg Med Clin North Am. 2014;32(2):293–301.
- 3Khanimov I, Shimonov M, Wainstein J, Leibovitz E. Hypoglycemia, Malnutrition and Body Composition. Adv Exp Med Biol. 2021;1307:71-84. doi: 10.1007/5584_2020_526. Erratum in: Adv Exp Med Biol. 2021;1307:577.
- 4Cryer PE. Iatrogenic hypoglycemia as a cause of hypoglycemia-associated autonomic failure in IDDM. A vicious cycle. Diabetes. 1992 Mar;41(3):255-60.
- 5Cryer PE. Hypoglycemia in diabetes: pathophysiological mechanisms and diurnal variation. Prog Brain Res. 2006;153:361–365
- 6Gaab J, Engert V, Heitz V, Schad T, Schürmeyer TH, Ehlert U. Associations between neuroendocrine responses to the Insulin Tolerance Test and patient characteristics in chronic fatigue syndrome. J Psychosom Res. 2004 Apr;56(4):419-24. doi: 10.1016/S0022-3999(03)00625-1. PMID: 15094026.
- 7Cryer PE. Diverse causes of hypoglycemia-associated autonomic failure in diabetes. N Engl J Med. 2004;350(22):2272–2279.
- 8Hoenig MR, Sellke FW. Insulin resistance is associated with increased cholesterol synthesis, decreased cholesterol absorption and enhanced lipid response to statin therapy. Atherosclerosis. 2010 Jul;211(1):260-5. doi: 10.1016/j.atherosclerosis.2010.02.029. Epub 2010 Mar 1. PMID: 20356594.Gylling H, Hallikainen M, Pihlajamäki J, Simonen P, Kuusisto J, Laakso M, Miettinen TA. Insulin sensitivity regulates cholesterol metabolism to a greater extent than obesity: lessons from the METSIM Study. J Lipid Res. 2010 Aug;51(8):2422-7.
- 9Mingming Hao, W. Steven Head, Subhadra C. Gunawardana, Alyssa H. Hasty, David W. Piston; Direct Effect of Cholesterol on Insulin Secretion: A Novel Mechanism for Pancreatic β-Cell Dysfunction. Diabetes 1 September 2007; 56 (9): 2328–2338.
- 10Blaabjerg L, Juhl CB. Hypoglycemia-Induced Changes in the Electroencephalogram: An Overview. J Diabetes Sci Technol. 2016 Nov 1;10(6):1259-1267.
- 11Cryer PE. Hypoglycemia, functional brain failure, and brain death. J Clin Invest. 2007 Apr;117(4):868-70.
