The Coincidence of Diabetes Mellitus and Asthma, Their Probable Causal Relationships and Therapeutic Opportunities

Kosmalski, Marcin; Różycka-Kosmalska, Monika; Pietras, Tadeusz

doi:10.5603/arm.a2020.0168

Cited by 6 publications

(4 citation statements)

References 44 publications

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“…The incidence and prevalence of both childhood asthma and T1DM have been increasing over the past decades, 1,3 suggesting common susceptibility factors. 4 A meta-analysis published in 2003 suggested a weak inverse association between childhood asthma and T1DM. 5 However, majority of the studies included in the meta-analysis are case-control studies.…”

Section: Introductionmentioning

confidence: 99%

Childhood Asthma and Type 1 Diabetes Mellitus: A Meta-analysis and Bidirectional Mendelian Randomization Study

Zhang,

Xie,

Chen

et al. 2024

Preprint

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Objectives: World-wide incidence and prevalence of both asthma and type 1 diabetes mellitus (T1DM) has been increasing in past decades. Association between the two diseases has been found in some but not other studies. We conducted a meta-analysis to verify such an association, and bidirectional Mendelian randomization analysis to examine the potential cause-effect relationships. Methods: Three databases(PubMed, Embase and Web of Science) were searched from their inception to February 1, 2021. Pooled hazard ratios (HR) or odds ratios (OR), and 95% confidence intervals, were calculated. Associations between single-nucleotide polymorphisms with childhood asthma and T1DM were selected based on genome-wide association studies. The outcome datasets were obtained from FinnGen study. We used the inverse variance-weighted, weighted median and MR-Egger methods to estimate causal effects. To assess robustness and horizontal pleiotropy, MR-Egger regression and MR pleiotropy residual sum and outlier test was conducted. Results: In meta-analysis, childhood asthma was associated with an increased risk of T1DM (HR=1.30, 95% CI 1.05–1.61, P=0.014), whereas T1DM was not associated with the risk of asthma (HR=0.98, 95% CI 0.64–1.51, P=0.941; OR=0.84, 95% CI 0.65–1.08, P=0.168). MR analysis indicated increased genetic risk of T1DM in children with asthma (OR=1.308; 95% CI 1.030-1.661; P =0.028). Analysis using the IVW method indicated decreased genetic risk of asthma in children with T1DM (OR = 0.937, 95%CI 0.881-0.996, P = 0.037). Conclusions: Childhood asthma is a risk factor for T1DM; T1DM is a possible protective factor for childhood asthma.

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Section: Introductionmentioning

confidence: 99%

Childhood Asthma and Type 1 Diabetes Mellitus: A Meta-analysis and Bidirectional Mendelian Randomization Study

Zhang,

Xie,

Chen

et al. 2024

Preprint

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“…Epidemiological data and conventional medical practice reveal the active progression of various types of diabetes mellitus (DM) in patients with bronchial asthma [ 5 ]. A statistical analysis demonstrated a significant correlation between carbohydrate metabolism and the risk of bronchial asthma progression [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of Comorbidity of Bronchial Asthma and Type 2 Diabetes Mellitus on the Expression and Functional Activity of TLR2 and TLR4 Receptors

Radzyukevich

Kosyakova

Прохоренко

2023

Life

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Epidemiological data indicate the active progression of various forms of diabetes mellitus in patients with bronchial asthma (BA), but little is known about the mechanisms of comorbidity formation. TLR2 and TLR4 are involved in the progression of asthma and type 2 diabetes mellitus (T2DM). These receptors are involved in the inflammatory response to Gram(+) and Gram(−) bacteria, respectively, so changes in their expression may affect the predisposition of patients to bacteremia. The aim of this study was to analyze the expression and functional activity of toll-like receptor 2 and 4 (TLR2 and TLR4) on peripheral blood cells of patients with BA, T2DM, and BA + T2DM. The expression of TLR2 and TLR4 was analyzed by flow cytometry. Whole blood samples were incubated with lipopolysaccharides from E. coli (LPS) and lipoteichoic acid from S. pyogenes (LTA). The concentration of cytokines and soluble blood proteins was determined by ELISA. Patients with comorbid diseases showed a statistically significant increase in TLR2 expression on both monocytes and neutrophils compared with healthy donors and patients with BA. We found increased expression of TLR4 on the surface of blood monocytes from patients compared to donors. The activation of blood cells of patients and donors with LPS or LTA led to an increase in the expression of “fast” pro-inflammatory cytokines (TNF-α, IL-6). In patients with BA, the average production of TNF-α in response to endotoxin was two times higher than in other studied groups. The reactions of blood cells in patients with T2DM and BA + T2DM did not differ significantly. The expression and functional activity of TLR2 and TLR4 on the blood cells of patients with comorbid disease were similar to those only in patients with T2DM. The greatest increase in the synthesis of the pro-inflammatory cytokine TNF-α in response to LPS and LTA was observed in patients with BA, which can lead to an inadequate response to bacteremia.

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Section: Introductionmentioning

confidence: 99%

“…Type 1 diabetes mellitus (T1DM) occurs at an incidence of 8–20 per 100,000 each year 3 and is one of the most common immune‐related diseases in children. The incidence and prevalence of both childhood asthma and T1DM have been increasing over the past decades, 1,3 suggesting common susceptibility factors 4 …”

Section: Introductionmentioning

confidence: 99%

Childhood asthma and type 1 diabetes mellitus: A meta‐analysis and bidirectional Mendelian randomization study

Xie

Chen

Liang

et al. 2022

Pediatric Allergy Immunology

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Background: Worldwide incidence and prevalence of both asthma and type 1 diabetes mellitus (T1DM) in children have been increasing in past decades. Association between the two diseases has been found in some but not in other studies. Objective:We conducted a meta-analysis to verify such an association, and bidirectional Mendelian randomization analysis to examine the potential cause-effect relationships.Methods: Three databases (PubMed, Embase, and Web of Science) were searched from their inception to February 1, 2021. Pooled hazard ratios (HR) or odds ratios (OR), and 95% confidence intervals, were calculated. Associations between singlenucleotide polymorphisms with childhood asthma and T1DM were selected based on genome-wide association studies. The outcome datasets were obtained from FinnGen study. We used the inverse-variance-weighted (IVW), weighted median and MR-Egger methods to estimate causal effects. To assess robustness and horizontal pleiotropy, MR-Egger regression and MR pleiotropy residual sum and outlier test were conducted. Results:In meta-analysis, childhood asthma was associated with an increased risk of T1DM (HR = 1.30, 95% CI 1.05-1.61, P = .014), whereas T1DM was not associated with the risk of asthma (HR = 0.98, 95% CI 0.64-1.51, P = .941; OR = 0.84, 95% CI 0.65-1.08, P = .168). MR analysis indicated increased genetic risk of T1DM in children with asthma (OR = 1.308; 95% CI 1.030-1.661; P = .028). Analysis using the IVW method indicated no association between T1DM and genetic risk of asthma (OR = 1.027, 95%CI 0.970-1.089, P = .358). Conclusion:Both meta-analysis and MR study suggested that childhood asthma was a risk factor for T1DM. No epidemiological or genetic evidence was found for an association of T1DM with asthma incidence. Further studies could be carried out to leverage

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The Coincidence of Diabetes Mellitus and Asthma, Their Probable Causal Relationships and Therapeutic Opportunities

Cited by 6 publications

References 44 publications

Childhood Asthma and Type 1 Diabetes Mellitus: A Meta-analysis and Bidirectional Mendelian Randomization Study

Childhood Asthma and Type 1 Diabetes Mellitus: A Meta-analysis and Bidirectional Mendelian Randomization Study

Impact of Comorbidity of Bronchial Asthma and Type 2 Diabetes Mellitus on the Expression and Functional Activity of TLR2 and TLR4 Receptors

Childhood asthma and type 1 diabetes mellitus: A meta‐analysis and bidirectional Mendelian randomization study

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