Your immune system protects you from pathogens like bacteria, viruses, and fungi, as well as abnormal or diseased cells, such as cancer cells. At the same time, your immune system must recognize cells that belong to you. It is a delicate balance to remove damaged or infected cells as quickly as possible while protecting self-cells. Uncontrolled high blood sugar can weaken your immune response, which makes it harder to fight off pathogens.
Immune System Overview
The immune system is a multilayer defense that helps protect you from a wide variety of pathogens. Disease-causing bacteria, viruses, and fungi must first overcome the many barriers your body has in place to protect you. Your skin and mucous membranes (moist membranes that line cavities like your mouth and eyes) protect you from pathogens living on your body. Sebum (an oily substance produced by your sebaceous glands, tears, saliva, and digestive juices all contain enzymes that help disable pathogens and prevent them from entering your bloodstream and body tissue.
The Innate Immune System
The innate immune system is nonspecific but acts quickly. Cells of the innate immune system recognize patterns on the surface of pathogens and attack them. Innate immune cells release chemicals called cytokines that signal other cells to alert them of the presence of an invader. These chemical messages call other immune cells to the area and make blood vessels leakier, so immune cells can leave the bloodstream more easily and enter the body tissue. This response is called inflammation and is responsible for the swelling, redness, warmth, and pain that may occur with an infection.
The innate immune system is made up of the following defenses:
- Mast cells and basophils produce an inflammatory response.
- Monocytes, neutrophils, and macrophages are “phagocytes” or cells that engulf and digest cellular debris and infected cells.
- Complement system or cascade, labels pathogens to make them easier for immune cells to find.
- Cytokines and chemokines are chemical messengers that allow immune cells to communicate.
<p class="pro-tip"><strong>Learn about </strong> <a href="/blog/ways-to-reduce-inflammation">how to reduce inflammation</a>.</p>
The Adaptive Immune System
The adaptive immune system acts slower than the innate immune system but is highly specific and effective when attacking pathogens. Its immune response improves with each repeated exposure to a pathogen.
The adaptive immune system is made up of the following major cell types:
- T-cells (lymphocytes) control the immune response and target body cells and pathogens with an abnormal or foreign surface protein.
- B cells (lymphocytes) produce antibodies that bind to receptors and make it easier for T-lymphocytes to recognize an abnormal cell or pathogen and remove it.
- Natural killer cells target and break down abnormal and infected cells.
The adaptive immune system has memory. Once you have an infection and recover from it, a special colony of B-cells and T-cells remains that recognize that specific pathogen. With a second infection of the same type, these cells can immediately begin reproducing and producing antibodies. This reaction is so quick that you commonly don’t even have symptoms the next time the same pathogen infects you.
Vaccines stimulate the adaptive immune system so a colony of memory B-cells and T-cells can be activated and stored without an infection.
Signs of a weak immune system:
- Frequent infections that take a long time to recover from
- Digestive symptoms such as chronic diarrhea or constipation
- Frequent skin infections
- Delayed wound healing
- Frequent yeast infections
<p class="pro-tip"><strong>Learn about </strong> <a href="/blog/probiotics-gut-health">improving gut health with probiotics</a>.</p>
How And Why Do Blood Sugar Levels Affect the Immune System?
Uncontrolled high blood sugar disrupts your body’s immune response, which makes it more difficult for your immune cells to fight infection. Signs of immune dysfunction may even come before a diabetes diagnosis.
High Blood Glucose Impacts Cytokine Production
Cytokines are chemical messengers that increase antibody production and T-cell development. They are important cell signaling molecules that allow your immune cells to “talk” to each other. Increased blood glucose levels trigger an increase in cytokine synthesis and release. This may alter the careful balance your body must keep between promoting enough inflammation to quickly fight infection and too much inflammation, which can lead to widespread infection and organ damage.1
There are dozens of cytokines and many factors, including glucose, affect their ability to function. For example, moderately elevated glucose promotes type 1 interferon (a type of cytokine) production, and high glucose suppresses interferon type 1 production.2 Increased glycation (when glucose attaches to proteins and changes their shape) inhibits the production of IL10 and tumor necrosis factor, two key cytokines.3 Other studies in people with and without diabetes showed suppression of cytokines, especially interleukins.1
Reduced Ability to Recruit White Blood Cells
Inflammation is a critical step in fighting an infection. It makes it possible for disease-fighting cells to find the infected tissue and migrate toward it. Inflammatory chemicals dilate blood vessels to increase blood flow to infected tissue and make them leakier, so disease-fighting cells can leave the bloodstream and enter the body tissue.1
Infection-fighting white blood cells roll along blood vessels until they reach signals that tell them to migrate through the blood vessel wall into the body tissue.
Endothelial cells lining the inside of blood vessels maintain blood flow. Excess glucose can attach to proteins and change their shape. When blood glucose levels are persistently high, short-term and long-term changes may occur in blood vessels:1,4
Short-term high blood glucose
- Reduced ability to widen blood vessels to increase blood flow
Long-term high blood glucose
- Increased widespread inflammation
- Increased risk for blood clots
- Decreased ability to bind lipids (fats) in the blood
- Decreased ability to reduce or stop the inflammatory process
- Increased atherosclerotic plaques lining blood vessels
- Reduced ability to activate macrophages
When blood vessels cannot widen, and there are increased fat deposits lining blood vessels (atherosclerosis), disease-fighting white blood cells, nutrients, and oxygen cannot reach the site of infection, which delays healing.
Defects in the Ability to Recognize Pathogens
Infection-fighting cells recognize pathogens by specific pathogen-associated molecular patterns (PAMPs). A specific class of immune cells recognizes and binds to pathogens with specific PAMPs like a lock and key. When a pattern is recognized on the surface of a pathogen, it triggers the innate immune system.5 Persistently high blood glucose levels impair this process. Recognition seems to be impaired in people with diabetes and returns to normal when blood sugar is well-controlled.6 However, more research is needed.7
Neutrophils are part of the innate immune system. They travel through your bloodstream and are typically the first on the scene when a pathogen gets past your barrier defenses. Neutrophils trigger an inflammatory response and start engulfing and eliminating pathogens. The inflammatory response makes it easier for more infection-fighting cells to travel into the body tissue and help fight the infection.
Elevated blood sugar can negatively affect neutrophils, including 1,8
- Reducing their ability to cause inflammation
- Decreasing their ability to move through the body tissue towards the pathogen (chemotaxis)
- Reducing their ability to engulf (phagocytize) pathogens
- Reducing their ability to release bleach-like chemicals to kill pathogens
- Increasing the likelihood of excessive inflammation
- Increasing stickiness between neutrophils and blood vessel walls slows their movement
Even transient changes in blood sugar can impair neutrophil function.9 These changes are reversible. Insulin binds to neutrophils and improves their ability to move, engulf, and kill pathogens.10
Decreased Complement Response
The complement cascade is a key part of the innate immune system. It is made up of proteins whose main function is to make it easier for neutrophils and macrophages to engulf pathogens.
Complement proteins poke holes in pathogens. When pathogens break open and release chemicals, it is easier for disease-fighting cells to find and kill the pathogen. Some studies have shown a decrease in complement in diabetes mellitus, but others suggest that it is not a decrease in complement that is the problem. Instead, it is a reduced response to the signal.11
The Effect of Low Blood Sugar on the Immune System
Low blood sugar (hypoglycemia) can also affect the immune system. When blood sugar is low, it can mobilize monocytes, increase platelet reactivity, and promote interaction between monocytes and platelets. This interaction can increase inflammation and decrease blood vessels’ ability to dilate.
Low blood sugar can have the following effects on the immune system:12
- Decrease natural killer cell number
- Decrease natural killer cell activity
- Decrease cytokine secretion
- Decreased T cell numbers and proliferation
- Decreased ability to secrete bleach-like enzymes to kill pathogens
Low blood sugar increases inflammation and narrows blood vessels, which can delay healing.
Does Sugar Consumption Suppress the Immune System?
Increasing amounts of glucose progressively lower neutrophil function. Glucose concentrations over 200 mg/dL for 30 minutes may be enough to decrease neutrophil function, and concentrations over 500 mg/dL decrease innate defenses at sites of infection.1 Fructose, in the form of high-fructose corn syrup, may reduce pattern recognition in the innate immune system.5 More research is needed to determine the effect of isolated glucose spikes or short-term hyperglycemia on the immune system.
The average American consumes 125 grams of sucrose daily, plus 50 grams of other refined sugars.13 Excess sugar consumption increases the risk of obesity and insulin resistance, which increases the risk of type 2 diabetes. The links between type 2 diabetes and changes in the immune system are becoming better understood. Try to reduce your risk of type 2 diabetes to optimize your immune function.
How Does Prediabetes/Insulin Resistance/Type 2/Type 1 Affect the Immune System?
Diabetes is a major risk factor for poor outcomes from bacterial and viral infections. Even in the early stages of diabetes, there are changes in T cells in the adaptive immune system.14
Hyperglycemia is a common feature in insulin resistance, prediabetes, and uncontrolled type 1 and type 2 diabetes mellitus. Prolonged hyperglycemia causes multiple changes in both the innate and adaptive immune systems.11 As a result, infections are much more common in people with diabetes.15 More research is needed to determine the mechanism linking diabetes mellitus and an increased risk of infections.11
Consuming too much sugar increases your risk of obesity and insulin resistance. Insulin resistance and obesity both increase the release of inflammatory cytokines. Chronic inflammation makes it more difficult for the immune system to mount a quick and effective attack on invading pathogens. And inflammation may play a role in developing diabetes mellitus. The relationship is complex, and experts are investigating the potential links because they may provide new and better ways to treat or prevent diabetes mellitus.16
Insulin resistance, prediabetes, and type 2 diabetes are all reversible.
<p class="pro-tip"><strong>Learn more about </strong> <a href="/blog/insulin-resistance-vs-prediabetes">insulin resistance vs pre diabetes</a>.</p>
Do People Without Diabetes Need to Worry About Sugar Consumption Affecting Their Immune System?
Yes, processed sugar negatively affects everyone’s immune system by causing glucose spikes. However, it is not as simple as a direct relationship between sugar consumption and immune function, and the negative effect of sugar on the immune system does not apply to all carbohydrates, suggesting that hyperglycemia, not sugar, is the link. Hospitalized patients with episodes of hyperglycemia are at increased risk of infection, which suggests that even episodic hyperglycemia can adversely affect the innate and adaptive immune system.1
One study conducted in the 1970s showed that as little as 75 grams of sugar could weaken the immune response. Once immune function is compromised, the effects can last for about five hours.17 As a reference, there are 39 grams of sugar in a 12 oz can of Cola-Cola. However, the immune system is very complex, and inaccurate assumptions can be made when studying one immune process in isolation.
How the western diet affects the immune system is not completely understood. However, it is clear that obesity and insulin resistance are risk factors for type 2 diabetes, and the immune system is compromised in both type 1 and type 2 diabetes.
What Can Someone Without Diabetes Do to Support Their Immune System?
Like any body system, your immune system needs nutrients to ensure its cells can reproduce and repair themselves. To provide your immune system with the support it needs:18,19
- Eat foods high in antioxidants, zinc, and selenium. Antioxidants reduce inflammation.
- Avoid ultra-processed foods, fats, sugars, salt, and excess alcohol.
- Eat more fiber. It slows sugar absorption and can help protect against blood sugar spikes.
- Spend 20 minutes in the sun two to three days per week. UV light is an ideal source of vitamin D. Vitamin D is important for proper immune function and glucose metabolism.
- Get at least 8 hours of restful sleep.
- Stop smoking. Smoking increases oxidative stress on cells and inflammation.
- Practice relaxation techniques to manage stress.
- Moderate alcohol consumption.
- Lose any excess pounds. Body fat can trigger inflammation, which affects immune function.
- Increase physical activity. Exercise can reduce stress and increase blood flow which can improve immune function.
- Eat healthy sources of fat. Omega-3 fatty acids can reduce inflammation and promote wound healing.
- Stay up to date on all your vaccines.
- Look for hidden sugar in foods and drinks.
- Exercise to help with blood sugar control and weight management.
- Use a CGM to track blood sugar spikes.
Your immune system is a complex system of cells and chemicals. Maintaining optimal metabolic health is the best way to support immune function. Since the immune system must maintain a careful balance between enough inflammation to fight infection without overdoing it and causing organ and tissue damage, there is no way to boost its function.
Allergies are an example of when the immune system overreacts to a harmless protein. Read more about Seasonal Allergies and Blood Sugar Spikes.
<p class="pro-tip"><strong>Learn more about </strong> <a href="/blog/four-healthy-habits-to-bolster-your-immune-system-an-interview-with-dr-heather-moday">healthy habits to bolster your immune system</a>.</p>
Can A CGM Be Helpful for Those Who Want to Control Blood Sugar Spikes to Improve Their Immune System?
Both high and low glycemic conditions can affect the immune system. Undernourishment can depress immune function, and obesity and hyperglycemia can compromise immune function. Immune cells require a lot of energy and are most affected by diet, especially glucose, exercise, and hormones.20
Your blood sugar levels will spike after consuming a large quantity of sugar. A healthy pancreas will respond to this blood sugar spike with an insulin burst. Insulin moves glucose out of the bloodstream into muscle and liver cells. Fluctuating blood glucose levels can trigger inflammation, which can affect the immune system.
Use your CGM to watch for blood glucose spikes and identify triggers. Added sugar can be found in foods you would not suspect, such as salad dressings, ketchup, protein bars, and cereal. Minimizing glucose spikes can reduce insulin resistance, which may promote better immune function.
<p class="pro-tip"><strong>Learn more about </strong> <a href="/blog/weight-immune-system">how your weight can affect your immune system</a>.</p>
Topics discussed in this article:
- Jafar N, Edriss H, Nugent K. The Effect of Short-Term Hyperglycemia on the Innate Immune System. Am J Med Sci. Feb 2016;351(2):201-11. doi:10.1016/j.amjms.2015.11.011
- Hu R, Xia CQ, Butfiloski E, Clare-Salzler M. Effect of high glucose on cytokine production by human peripheral blood immune cells and type I interferon signaling in monocytes: Implications for the role of hyperglycemia in the diabetes inflammatory process and host defense against infection. Clin Immunol. Oct 2018;195:139-148. doi:10.1016/j.clim.2018.06.003
- Pavlou S, Lindsay J, Ingram R, Xu H, Chen M. Sustained high glucose exposure sensitizes macrophage responses to cytokine stimuli but reduces their phagocytic activity. BMC Immunology. 2018/07/11 2018;19(1):24. doi:10.1186/s12865-018-0261-0
- Daryabor G, Atashzar MR, Kabelitz D, Meri S, Kalantar K. The Effects of Type 2 Diabetes Mellitus on Organ Metabolism and the Immune System. Front Immunol. 2020;11:1582. doi:10.3389/fimmu.2020.01582
- Takahashi K, Chang W-C, Moyo P, et al. Dietary sugars inhibit biologic functions of the pattern recognition molecule, mannose-binding lectin. Open Journal of Immunology. 2011;01(02):41-49. doi:10.4236/oji.2011.12005
- Gupta S, Maratha A, Siednienko J, et al. Analysis of inflammatory cytokine and TLR expression levels in Type 2 Diabetes with complications. Sci Rep. 2017/08/09 2017;7(1):7633. doi:10.1038/s41598-017-07230-8
- Berbudi A, Rahmadika N, Tjahjadi AI, Ruslami R. Type 2 Diabetes and its Impact on the Immune System. Curr Diabetes Rev. 2020;16(5):442-449. doi:10.2174/1573399815666191024085838
- Hosseini B, Berthon BS, Saedisomeolia A, et al. Effects of fruit and vegetable consumption on inflammatory biomarkers and immune cell populations: a systematic literature review and meta-analysis. Am J Clin Nutr. Jul 1 2018;108(1):136-155. doi:10.1093/ajcn/nqy082
- Kjersem H, Hilsted J, Madsbad S, Wandall JH, Johansen KS, Borregaard N. Polymorphonuclear leucocyte dysfunction during short term metabolic changes from normo- to hyperglycemia in type 1 (insulin dependent) diabetic patients. Infection. Jul-Aug 1988;16(4):215-21. doi:10.1007/bf01650754
- Rassias AJ, Givan AL, Marrin CA, Whalen K, Pahl J, Yeager MP. Insulin increases neutrophil count and phagocytic capacity after cardiac surgery. Anesth Analg. May 2002;94(5):1113-9, table of contents. doi:10.1097/00000539-200205000-00010
- Casqueiro J, Casqueiro J, Alves C. Infections in patients with diabetes mellitus: A review of pathogenesis. Indian Journal of Endocrinology and Metabolism. 2012;16(Suppl1):S27-S36. doi:10.4103/2230-8210.94253
- Iqbal A, Prince LR, Novodvorsky P, et al. Effect of Hypoglycemia on Inflammatory Responses and the Response to Low-Dose Endotoxemia in Humans. J Clin Endocrinol Metab. Apr 1 2019;104(4):1187-1199. doi:10.1210/jc.2018-01168
- Murray MaN, J. . Textbook of Natural Medicine. Elsevier, Inc.; 2021.
- Giese I-M, Schilloks M-C, Degroote RL, et al. Chronic Hyperglycemia Drives Functional Impairment of Lymphocytes in Diabetic INSC94Y Transgenic Pigs. Original Research. Frontiers in Immunology. 2021-January-22 2021;11doi:10.3389/fimmu.2020.607473
- Carey IM, Critchley JA, DeWilde S, Harris T, Hosking FJ, Cook DG. Risk of Infection in Type 1 and Type 2 Diabetes Compared With the General Population: A Matched Cohort Study. Diabetes Care. Mar 2018;41(3):513-521. doi:10.2337/dc17-2131
- Donath MY, Shoelson SE. Type 2 diabetes as an inflammatory disease. Nat Rev Immunol. Feb 2011;11(2):98-107. doi:10.1038/nri2925
- Sanchez A, Reeser JL, Lau HS, et al. Role of sugars in human neutrophilic phagocytosis. The American Journal of Clinical Nutrition. 1973;26(11):1180-1184. doi:10.1093/ajcn/26.11.1180
- Alexander JW, Supp DM. Role of Arginine and Omega-3 Fatty Acids in Wound Healing and Infection. Advances in Wound Care. 2014/11/01 2013;3(11):682-690. doi:10.1089/wound.2013.0469
- Heiser P, Dickhaus B, Opper C, et al. Alterations of Host Defence System after Sleep Deprivation are followed by Impaired Mood and Psychosocial Functioning. The World Journal of Biological Psychiatry. 2001/01/01 2001;2(2):89-94. doi:10.3109/15622970109027498
- Von Ah Morano AE, Dorneles GP, Peres A, Lira FS. The role of glucose homeostasis on immune function in response to exercise: The impact of low or higher energetic conditions. Journal of Cellular Physiology. 2020;235(4):3169-3188. doi:https://doi.org/10.1002/jcp.29228