These days have revealed a heightened interest from the public for immune health. Among factors playing a role in an optimal immune balance, glycemic health is now under the spotlight.
This white paper aims at reviewing the connection between diabetes and immunity, concentrating on key mechanisms and evidence from recent clinical and epidemiological studies.
Click to download the full technical note.
Despite progress due to the development of antibiotic and antiviral therapies, infectious disease remain one of the most important cause of mortality worldwide (1).
Immune supplements have been around for decades and their popularity has always fluctuated alongside the sense of alertness of the population. Immunity supplements are all about prevention, and unfortunately prevention can difficultly be proven.
Did I not catch a cold for the echinacea I’m taking, or was I just lucky this year? Our immune system was not built solely from our past encounters with bacteria and viruses. It also relies on our general metabolism to provide the optimal background for its flawless functioning.
As global obesity and diabetes rates are rising, our poor metabolic background predisposes us to more frequent infections having heavier consequences, while those who choose to preserve their metabolic health should benefits from the full advantages of their optimal immune system.
Review of recent data
Epidemiological data shows that elderly people and the ones with CVDs, diabetes, hypertension, chronic kidney or lung disease and cancer patients are generally more at risk of complications from infections.
Particularly, diabetes seems to act as a facilitator of wound and urinary tract infections, but also as an elicitor of sepsis from common infections (2).
With diabetes rates between 6.3% and 11.1%, and prediabetes affecting 23% to 33% of adults in developed countries of North America and Europe (3), the path is laid for infectious diseases to take advantages of the population’s increased susceptibility to complications.
As a chronic disease, diabetes generates systemic inflammation that affects our response to pathogens (4). High blood glucose and insulin resistance facilitate the accumulation of advanced glycation end products (AGEs) and pro-inflammatory cytokines such as TNF-α (5).
Hyperglycemia also induces oxidative stress and promotes the production of adhesion molecules that mediate tissue inflammation (4, 6).
This inflammatory process may compose the underlying mechanism that leads to a higher propensity to infections, with worse outcomes thereof in patients with diabetes (4).
Finally, diabetes fragilizes blood vessels including capillaries, and affects overall immunity against common infections, increasing the severity and frequency of influenza and pneumonia (7).
Frequent increases in blood glucose levels have been associated with an inhibition of lymphocyte proliferative response to various triggers (8), as well as to an impairment of monocyte and neutrophil functions (4).
There have also been descriptions of abnormal delayed type hypersensitivity reactions (9) and complement system activation dysfunction (10) in patients with diabetes.
In vitro, pulmonary epithelial cells exposed to high glucose concentrations are significantly more sensitive to influenza virus infection and replication, indicating that hyperglycemia may contribute to viral replication in vivo (11).
Animal models have demonstrated significant alterations of the pulmonary architecture with diabetes, leading to an increased vasculature permeability and collapsing of alveolar epithelium (12).
While underlying mechanisms are diverse and remain to be further elucidated, epidemiological studies bring conclusive support that diabetic patients suffer from a weaker immune system.
In a fine research, Carey et al. compared the overall incidence rates ratio (IRR) of 19 common infections over 7 years in 96,630 type II diabetics compared with 191,822 matched controls.
They found a significant increase in infection rates for all infections, with the largest increases in bone and joint infections (IRR 4.93), sepsis (IRR 2.25), candidiasis (IRR 2.11), cellulitis (IRR 2.03), and endocarditis (IRR 1.84).
Diabetic patients were also at higher risk of being prescribed medication for their infection (IRR 1.47), to be hospitalized (IRR 1.88) or die from their infection (IRR 1.92) (13).
Nutritional interventions aiming to support optimal immunity thus cannot be complete if it does not also include an effective support of glycemic health.
Some well-researched dietary supplement ingredients have proven their safety and efficacy at supporting healthy blood glucose levels and glycemic health, some even showing the added capacity to reduce systemic inflammation in well-designed clinical trials.
The epidemiological data presented herein teaches us to view immunity as a downstream component of glycemic health.
2. Frydrych LM, Bian G, O’Lone DE, Ward PA, Delano MJ. Obesity and type 2 diabetes mellitus drive immune dysfunction, infection development, and sepsis mortality. J Leukoc Biol. 2018 Sep;104(3):525-534.
3. International Diabetes Federation. IDF Diabetes Atlas, 9th edn. Brussels, Belgium: 2019. Available at: https://www.diabetesatlas.org
4. Knapp S. Diabetes and infection: is there a link? – A mini-review. Gerontology. 2013;59(2):99–104.
5. Swaroop JJ, Rajarajeswari D, Naidu JN. Association of TNF-α with insulin resistance in type 2 diabetes mellitus. Indian J Med Res. 2012;135(1):127‐130.
6. Petrie JR., Guzik TJ., Touyz RM. Diabetes, hypertension, and cardiovascular disease: clinical insights and vascular mechanisms. Canadian J Cardiol. 2018;34(5):575–584.
7. Pearson-Stuttard J, Blundell S, Harris T, Cook DG, Critchley J. Diabetes and infection: assessing the association with glycaemic control in population-based studies. Lancet Diabetes Endocrinol. 2016;4(2):148–158.
8. Moutschen MP, Scheen AJ, Lefebvre PJ. Impaired immune responses in diabetes mellitus: analysis of thefactors and mechanisms involved. Relevance to the increased susceptibility of diabetic patients to specific infections. Diabete Metab. 1992;18(3):187–201.
9. Geerlings SE, Hoepelman AI. Immune dysfunction in patients with diabetes mellitus (DM) FEMS Immunol Med Microbiol. 1999;26(3–4):259–265.
10. Ilyas R, Wallis R, Soilleux EJ, Townsend P, Zehnder D, Tan BK. High glucose disrupts oligosaccharide recognition function via competitive inhibition: a potential mechanism for immune dysregulation in diabetes mellitus. Immunobiology. 2011;216(1–2):126–131.
11. Kohio HP, Adamson AL. Glycolytic control of vacuolar-type ATPase activity: a mechanism to regulate influenza viral infection. Virology. 2013;444(1-2):301–309.
12. Popov D, Simionescu M. Alterations of lung structure in experimental diabetes, and diabetes associated with hyperlipidaemia in hamsters. Eur Respir J. 1997;10(8):1850–1858.
13. 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. 2018 Mar;41(3):513-521