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How Diabetics Taking Beta Blockers Still Sweat with Hypoglycemia

Summary:

  • Diabetic patients are known to have a 2 to 4 fold greater risk of cardiac heart disease and stroke where the use of beta blockers has been proven beneficial. Thus these drugs are likely to be used frequently in this population.
  • Diabetics being treated with insulin or certain antihyperglycemic drugs are at potential risk for developing a hypoglycemic episode.   Some symptoms that are reflective of the release of norepinephrine and epinephrine as a result of the activation of the sympathetic nervous system are tachycardia, tremor, shakes, hunger are generally experienced during hypoglycemic episodes.
  • While most physiologic responses to sympathetic activation are mediated by the release of norepinephrine, sweating is mediated by the release of acetylcholine, which then activates nicotinic receptors on the sweat gland.
  • As a result, beta blockers will not inhibit sweating during the "fight-or-flight" or acute stress response. This may allow diabetic patients the ability to recognize a hypoglycemic episode needing treatment by the presence of increased sweating alone.

Editor-in-Chief: Anthony J. Busti, MD, PharmD, FNLA, FAHA
Reviewers: 
Jon D. Herrington, PharmD, BCPS, BCOP and Donad S. Nuzum, PharmD, BCACP, CDE
Last Reviewed:
October 2015

Explanation

  • There are 23.6 million children and adults (7.8 percent of the population) in the United States alone that have diabetes mellitus (DM).1  Unfortunately, 65 percent of the deaths in diabetic patients are due to heart disease and stroke.  In fact, adults with DM are 2 to 4 times more likely to have heart disease and/or a stroke than adults without diabetes.2  The elevated cardiovascular risk in diabetics is partially due to the high prevalence (about 73 percent of all diabetics) of hypertension (defined as > 130/80 mm Hg) for which treatment with beta blockers is indicated. 2  Thus, the use of beta blocking agents is relatively common in those living with DM.

    Beta blockers, such as atenolol (Tenormin), metoprolol (Toprol; Toprol XL), carvedilol (Coreg; Coreg CR) and many others, are known to be antagonists of the noradrenergic response that results from the release of catecholamines by the sympathetic nervous system.4-6  The sympathetic branch of the autonomic system is activated primarily during an acute stress response ("fight or flight") and  releases the predominant neurotransmitter, norepinephrine, from post-ganglionic sympathetic nerve fibers.7,8  In addition, the sympathetic nervous system also causes the adrenal glands to release both epinephrine (80%) and norepinephrine (20%).   Norepinephrine and epinephrine may then activate the adrenergic receptors of various organs, such as beta-1 receptors in the heart which results in tachycardia (increase pulse).7,8  This acute stress response can be activated by hypoglycemia (low blood sugar) which may occur episodically in diabetic patients.  Hypoglycemia generally occurs in diabetics when the blood glucose level falls below 70 mg/dL and is most often observed in patients receiving insulin or those being treated with tight glucose control.8   During a hypoglycemic episode, most patients will commonly experience tachycardia, tremors, shakes, and sweating that can serve as a warning sign to the patient and encourage treatment with glucose. 

    As mentioned previously, the use of beta-blockers in DM is common. Beta blocker use is also very likely in this population since evidence suggests that diabetic patients may receive greater cardioprotective benefits compared to nondiabetic patients.9-11   However, many clinicians  remain reluctant to use beta blockers in those with DM because of concerns that these drugs might block the effects of sympathetic (noradrenergic) activation that occurs during hypoglycemic episodes.  Therefore,  these patients might fail to recognize key symptoms of a hypoglycemic state and may neglect to treat themselves appropriately.4-6  

    How can sweating be a possible sign of hypoglycemia while on a beta blocker when sweating is also mediated by the sympathetic nervous system?

    The autonomic nervous system is under subconscious control by sympathetic and parasympathetic nerve cell bodies found in the medulla of the central nervous system.7  In particular, catecholamines (norepinephrine and epinephrine) are released by the following mechanisms from the sympathetic nervous system.  In the both mechanisms, sympathetic nerve cell bodies located in the intermediolateral cell column (IMLCC) of the spinal cord (T1 - L3) have preganglionic nerve axons that release acetylcholine in the sympathetic ganglion that then activates nicotinic (or "ionotropic") receptors to initiate an action potential on the postganglionic sympathetic nerve axon, or directly acts on the adrenal gland to secrete epinephrine (80%) and norepinephrine (20%) into the circulation.7  Outside of the adrenal glands, in nearly all cases, the postganglionic sympathetic nerve fiber will release norepinephrine at various target organs (such as smooth and cardiac muscle) which can activate various adrenergic receptors (such as alpha-1, alpha-2, beta-1, beta-2) needed for the acute stress response.7  While this is true for most organs innervated by the sympathetic nervous system, it is not the case for sweat glands.  Instead, sympathetic postganglionic nerve axons release acetylcholine, notnorepinephrine.  The released acetylcholine then activates nicotinic receptors (ionotropic) located on the sweat glands, which are needed to help control body temperature that is likely to increase during a fight-or-flight response.  Therefore, beta-blockers are not able to inhibit sweating, but can still inhibit tachycardia and tremors, thus "masking" important signs and symptoms that diabetic patients use to recognize hypoglycemic episodes.  

                     Beta Blockers Effects on Sweating in Diabetics 

    Since sweating during the activation of the sympathetic nervous system is mediated by the release of acetylcholine via activation of a nicotinic receptor and not by norepinephrine via an adrenergic receptor, diabetic patients taking beta blockers may only be able to recognize sweating as a sign of a hypoglycemic episode.  Due to a number of variables, the exact percentage of diabetic patients experiencing this problem is not known, but should be considered since untreated hypoglycemia can be life-threatening.

    References:

    1. American Diabetes Association.  All About Diabetes. Accessed on 12/8/2009.         
    2. American Diabetes Association.  
    3. Hunt SA et al.  ACC/AHA 2005 Guideline update for the diagnosis and management of chronic heart failure in the adult.  A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure.  J Am Coll Cardiol   2005;46:e1-82.  
    4. AstraZeneca LP.  Tenormin (atenolol) product  insert.  Wilmington, DE. April  2003.  Linked last accessed on 12/8/2008
    5. AstraZeneca LP.  Toprol XL (metoprolol succinate) product insert.  Wilmington, DE. July 2007.  Linked last accessed on 12/8/2008
    6. GlaxoSmithKline.  Coreg CR (carvedilol phosphate) product insert.  Research Triangle Park, NC.  April 2008.  Last accessed on 12/8/2008
    7. Elfvin LG, Lindh B, Hokfelt T.  The chemical neuroanatomy of sympathetic ganglia.  Ann Rev Neurosci  1993;16:471-507.  
    8. Zammitt NN, Frier BM.  Hypoglycemia in type 2 diabetes: pathophysiology, frequency, and effects of different treatment modalities. Diabetes Care  2005;28:2948-61.  
    9. Kjekshus J, Gilpin E, Cali G et al.  Diabetic patients and beta-blockers after acute myocardial infarction.  Eur Heart J  1990;11:43-50.   
    10. Mykkanen L, Kuusisto J, Pyorala K et al.  Increased risk of non-insulin-dependent diabetes mellitus in elderly hypertensive subjects.  J Hypertens  1994;12:1425-32.   
    11. Cruickshank JM.  Beta blockers continue to surprise us.  Eur Heart J   2000;21:354-64.

MESH Terms & Keywords

  • Diabetes Mellitus, Beta Blockers, Hypoglycemia and Sweating, Beta Blocker Use in Diabetics