Association Between Diabetes Mellitus and Allergic Diseases Sensitized by Different Allergens and the Potential Mechanism of Diabetes Mellitus Affecting Ovalbumin-Induced Allergic Rhinitis

Abstract

Objective

To investigate the association between diabetes mellitus (DM) and allergic diseases caused by different allergens and explore the mechanism of DM in allergic rhinitis (AR) induced by ovalbumin (OVA).

Methods

We established linear regression models to examine the correlation of specific immunoglobulin E (sIgE) and total immunoglobulin E (TIgE) with glycohemoglobin (A1c) and fasting plasma glucose (FPG) in individuals allergic to different allergens by retrospectively analyzing the 2005-2006 National Health and Nutrition Examination Survey database. Participants were classified into Allergy + DM and Allergy groups based on whether they had allergic disease and DM or only allergic disease. An AR mouse model was established using OVA. Mice were randomly assigned to the control, AR, diabetic (db), or db & AR group, with 6 mice in each group. The expression of GATA3, T-bet, and Foxp3 was detected using immunofluorescence and western blotting. Cytokines, FPG, A1c, and immunoglobulin in serum were detected using enzyme-linked immunosorbent assays.

Results

Based on the database, the TIgE and SIgE levels in participants with perennial allergies were lower in the Allergy + DM group than in the Allergy group, whereas those in participants with food allergies were higher in the Allergy + DM group than in the Allergy group. TIgE was negatively correlated with FPG or A1c in participants with perennial allergies and positively correlated with FPG and A1c in participants with egg allergy (among food allergens). In mice, AR symptoms, eosinophilic infiltration, and OVA-induced IgE levels were more serious in the db & AR group than in the AR group. TIgE was positively correlated with FPG, and interleukin-2 (IL-2) was negatively correlated with FPG; this was most pronounced in db & AR mice. The expression of T-bet and Foxp3 in mice was negatively associated with A1c.

Conclusions

The effect of DM on allergic diseases is related to the type of allergen. Decreased IL-2, T-bet, and Foxp3 levels resulting from elevated FPG and A1c levels may be involved in the association between OVA-induced AR and DM.

Keywords

allergic rhinitis diabetes mellitus immunoglobulin E fasting plasma glucose glycohemoglobin allergic diseases allergen perennial allergen food allergen ovalbumin

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References

Valenta

Karaulov

Niederberger

, et al. Molecular aspects of allergens and allergy. Adv Immunol. 2018;138:195-256.

Fujita

Hemmi

Kajiwara

, et al. Complement-mediated chronic inflammation is associated with diabetic microvascular complication. Diabetes Metab Res Rev. 2013;29(3):220-226.

Ohkura

Sakaguchi

. Transcriptional and epigenetic basis of Treg cell development and function: its genetic anomalies or variations in autoimmune diseases. Cell Res. 2020;30(6):465-474.

Forrester

Kuffova

Delibegovic

. The role of inflammation in diabetic retinopathy. Front Immunol. 2020;11:583687.

George

Ducatman

Conway

. Increased risk of respiratory diseases in adults with type 1 and type 2 diabetes. Diabetes Res Clin Pract. 2018;142:46-55.

Lee

. Hypertension and diabetes mellitus as risk factors for asthma in Korean adults: the sixth Korea national health and nutrition examination survey. Int Health. 2020;12(4):246-252.

Brigham

Keet

Brown

Hansel

McCormack

. Association between prediabetes/diabetes and asthma exacerbations in a claims-based obese asthma cohort. J Allergy Clin Immunol Pract. 2019;7(6):1868–73.e5.

Klamt

Vogel

Kapellen

, et al. Association between IgE-mediated allergies and diabetes mellitus type 1 in children and adolescents. Pediatr Diabetes. 2015;16(7):493-503.

Sokolova

Yankova

Abadjieva

, et al. Association between type 2 diabetes, obesity and key immunological components of IgE-mediated inflammation. Folia Med (Plovdiv). 2017;59(2):159-164.

10.

Hashimoto

Futamura

. Prevalence of allergic rhinitis is lower in subjects with higher levels of fasting plasma glucose. Diabetes Care. 2010;33(11):e143.

11.

Hwang

Lee

Ahn

Lee

. Association between allergic rhinitis and metabolic conditions: a nationwide survey in Korea. Allergy Asthma Clin Immunol. 2016;12:5.

12.

Lee

Jeon

Jung

. Bi-directional association between allergic rhinitis and diabetes mellitus from the national representative data of South Korea. Sci Rep. 2021;11(1):4344.

13.

The prevention of Diabetes Mellitus. JAMA. 2021;325(2):190.

14.

Zhang

Lan

Zhang

. Advances and highlights in allergic rhinitis. Allergy. 2021;76(11):3383-3389.

15.

Guan

Zheng

Sun

, et al. The changing relationship between HbA1c and FPG according to different FPG ranges. J Endocrinol Invest. 2016;39(5):523-528.

16.

Tsuang

Grishin

Grishina

, et al. Endotoxin, food allergen sensitization, and food allergy: a complementary epidemiologic and experimental study. Allergy. 2020;75(3):625-635.

17.

Visness

London

Daniels

, et al. Association of obesity with IgE levels and allergy symptoms in children and adolescents: results from the National Health and Nutrition Examination Survey 2005-2006. J Allergy Clin Immunol. 2009;123(5):1163-1169, 1169.e1-4.

18.

Weir

Jan

. BMI classification percentile and cut off points. 2023 Jun 26. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing LLC; 2025.

19.

Peng

Harlow

Park

. Urinary arsenic and insulin resistance in US adolescents. Int J Hyg Environ Health. 2015;218(4):407-413.

20.

Lee

Min

. Caffeine and caffeine metabolites in relation to insulin resistance and Beta cell function in U.S. Adults. Nutrients. 2020;12(6):1783.

21.

Xie

, et al. Association between triclocarban and triclosan exposures and the risks of type 2 diabetes mellitus and impaired glucose tolerance in the National Health and Nutrition Examination Survey (NHANES 2013-2014). Environ Int. 2020;136:105445.

22.

Van Nguyen

Piao

Fan

, et al. Anti-allergic rhinitis activity of α-lipoic acid via balancing Th17/Treg expression and enhancing Nrf2/HO-1 pathway signaling. Sci Rep. 2020;10(1):12528.

23.

Weaver

Hatton

Mangan

Harrington

. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol. 2007;25:821-852.

24.

Pai

Truitt

. GATA-3 deficiency abrogates the development and maintenance of T helper type 2 cells. Proc Natl Acad Sci U S A. 2004;101(7):1993-1998.

25.

Butcher

Zhu

. Recent advances in understanding the Th1/Th2 effector choice. Fac Rev. 2021;10:30.

26.

Lazarevic

Glimcher

. T-bet in disease. Nat Immunol. 2011;12(7):597-606.

27.

Pritchard

Kedl

Hunter

. The evolving role of T-bet in resistance to infection. Nat Rev Immunol. 2019;19(6):398-410.

28.

Huehn

Polansky

Hamann

. Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage? Nat Rev Immunol. 2009;9(2):83-89.