scholarly journals Inverse association between use of broad spectrum penicllin with beta-lactamase inhibitors and prevalence of type 1 diabetes mellitus in Europe

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gábor Ternák ◽  
Károly Berényi ◽  
Szilárd Kun ◽  
Nóra Szigeti ◽  
Tamás Decsi ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Environmental Factors ◽  
Broad Spectrum ◽  
International Diabetes Federation ◽  
Inverse Correlation ◽  
Mitochondrial Enzymes ◽  
Inverse Association ◽  
Beta Lactamase ◽  
Narrow Spectrum

AbstractIncreasing incidence of type 1 diabetes is supposed to be induced by environmental factors. Microbiome modulated by antibiotics seems to serve as one of the environmental factors which could influence the development of T1DM. Mitochondria, as autochthonous environmental bacteria living in our cells, and other bacteria share many common enzymes including beta-lactamases and it is supported by evidence that some beta-lactamase inhibitors are able to interact with counterpart enzymes. Thus, antibiotics may utilize two different pathways influencing the development of T1DM; one through modulation of microbiome and a second one via the interaction of mitochondrial enzymes. Data of consumption of penicillin (both narrow and broad spectrum) and beta-lactamase inhibitors in 30 European countries were collected from the database of the European Centre for Disease Prevention and Control. These data were correlated with the prevalence reported by the International Diabetes Federation (2019) referring to type 1 diabetes in Europe. No correlation was found between total penicillin consumption or use of broad spectrum penicillin and the prevalence of type 1 diabetes. Nevertheless, broad spectrum penicillin, in combination with beta-lactamase inhibitor, was in inverse correlation with the prevalence of type 1 diabetes (r = − 0.573, p = 0.001). On the other hand, narrow spectrum penicillin was in positive correlation with type 1 diabetes (r = 0.523, p = 0.003). Prevalence of type 1 diabetes showed an inverse correlation with the use of beta-lactamase inhibitors and a positive one with that of narrow spectrum penicillin. Such a detailed analysis has not so far been provided referring to the penicillin group. In the background of this association either microbiomal or direct mitochondrial effects can be supposed.

scholarly journals Antibiotic Consumption Patterns in European Countries Might Be Associated with the Prevalence of Diabetes Type-1-2 (T1D, T2D)

2021 ◽  
Author(s):  
Gábor Ternák ◽  
Márton Németh ◽  
Martin Rozanovic ◽  
Lajos Bogár
Keyword(s):  
Broad Spectrum ◽  
Antibiotic Consumption ◽  
Diabetes Type ◽  
Variance Analysis ◽  
European Countries ◽  
Diabetes Type 1 ◽  
Beta Lactamase ◽  
Narrow Spectrum ◽  
High Prevalence

Abstract: Several publications have raised the issue that the development of diabetes is preceded by alteration of the microbiome (dysbiosis) and hence, the role of environmental factors, triggering dysbiosis, should be considered. Antibiotics are powerful agents inducing dysbiosis and the authors wanted to explore the possible relationship between the consumption of different major classes of antibiotics and the prevalence of diabetes (type-1, /T1D/, type-2 /T2D/) in thirty European countries. According to our hypothesis, if such association exists, the dominant use of certain major antibiotic classes might be reflected in the prevalence of T1D and T2D in different countries. Comparisons were performed between the prevalence of diabetes (T1D and T2D) estimated for 2019 and featured in the Diabetes Atlas with the average yearly consumption of major antibiotic classes of the previous 10 years (2010-19) extracted from the ECDC yearly reports on antibiotic consumption in Europe. Pearson correlation and variance analysis were used to estimate the possible relationship. Strong, positive (enhancer) associations were found between the prevalence of T1D and the consumption of tetracycline (J01A /p: 0.001/) and the narrow spectrum penicillin (J01CE /p: 0,006/, CF /p: 0.018/). Strong negative (inhibitor) association was observed with broad-spectrum, beta-lactamase resistant penicillin (J01CR /p: 0.003/), macrolide (J01F /p: 0.008/) and quinolone (J01M /p: 0.001/). T2D showed significant positive associations with cephalosporin (J01D /p: 0.048/) and quinolone (J01M /p: 0.025/), and a non-significant negative association was detected with broad-spectrum, beta-lactamase-sensitive penicillin (J01CA /p: 0.67/). Countries with the highest prevalence of diabetes (first 10 positions) showed concordance with the higher consumption of “enhancer” and the lower consumption of “inhibitor” antibiotics (first 10 positions) as indicated by variance analysis. Countries with high prevalence of T1D showed high consumption of tetracycline (p: 0.015), and narrow spectrum, beta-lactamase sensitive penicillin (p: 0.008), and low consumption of “inhibitor” antibiotics (broad-spectrum, beta-lactamase resistant, combination penicillin (p: 0.005), cephalosporin (p: 0.036), and quinolone (p: 0.003). Countries with a high prevalence of T2D consumed more cephalosporin (p: 0.084), quinolone (p: 0.54), and less broad-spectrum, beta-lactamase sensitive penicillin (p: 0.012) than other countries. Conclusion/Interpretation: The development of diabetes-related dysbiosis might be attached to higher consumption of specific classes of antibiotics, showing positive (enhancer) associations with the prevalence of diabetes, and the low consumption of other classes of antibiotics shoving negative (inhibitory) associations. Those groups of antibiotics are different in T1D and T2D

scholarly journals Környezeti hatások a gyermekkori kezdetű, 1-es típusú diabetes epidemiológiai változásainak hátterében

2021 ◽  
Vol 162 (1) ◽  
pp. 13-22
Author(s):  
Krisztina Lukács ◽  
Pál Pánczél ◽  
Nóra Hosszúfalusi
Keyword(s):  
Type 1 Diabetes ◽  
Environmental Factors ◽  
Genetic Load ◽  
International Diabetes Federation ◽  
Population Level ◽  
Incidence Rates ◽  
Climatic Conditions ◽  
Number Of Patients ◽  
Rate Of Increase

Összefoglaló. A Nemzetközi Diabetes Szövetség (International Diabetes Federation, IDF) legutóbbi becslése szerint napjainkban több mint 600 000, 15 év alatti 1-es típusú cukorbeteg gyermek él a világon, az új esetek száma pedig évi 98 200-ra tehető. Az elmúlt évtizedekben az 1-es típusú diabetes incidenciája világszerte jelentősen nőtt ebben a korosztályban: Európában az 1989 és 2013 közötti periódusban átlagosan évi 3,4%-kal, ami 20 éven belül a betegek számának duplázódását vetíti előre a kontinensen. Az epidemiológiai vizsgálatok kezdete óta nyilvánvaló, hogy a gyermekkori kezdetű, 1-es típusú diabetes előfordulási gyakorisága széles határok között ingadozik, amit egyaránt befolyásolnak geográfiai és klímaviszonyok, etnikai és demográfiai hatások. Bár az 1-es típusú cukorbetegség kialakulása során az autoimmunitás primer kockázati tényezője a genetikai háttér, mégsem a genetikai terheltség populációszintű fokozódása okozza az incidencia robbanásszerű növekedését, hanem a környezeti tényezőknek a betegség penetranciáját megváltoztató hatása. A környezeti hatások oki tényezőkként, akcelerátorokként és védőfaktorokként is hozzájárulhatnak mindehhez, sőt akár a betegség patogenezisében egyszerre több ponton, több mechanizmussal is részt vehetnek. Ugyanakkor a nemzetközi kutatások ellenére a legnépszerűbb háttérelméletek (például vírusinfekció, higiéniahipotézis, bélmikrobiom, áteresztő bél, D-vitamin-hiány) máig nem szolgálnak kielégítő magyarázattal az epidemiológiai észlelések többségére (például földrajzi régiónként jelentősen eltérő incidenciaértékek, geográfiai „forrópontok”, az új esetek megjelenésének szezonális ingadozása, az incidenciacsúcsok ciklicitása). Összefoglalónk célja a gyermekkori 1-es típusú diabetes epidemiológiájára vonatkozó aktuális adatok és háttérelméletek áttekintése. Orv Hetil. 2021; 162(1): 13–22. Summary. According to the latest report of the IDF (International Diabetes Federation), more than 600 000 children under the age of 15 years are living with type 1 diabetes in the world and the number of new cases is estimated to be 98 200 annually. In recent decades, a significant increase in the incidence has been observed globally: during 1989–2013, the annual rate of increase was 3.4% in Europe, suggesting a doubling in the number of patients within approximately 20 years on the continent. The wide variation in incidence has been well documented by epidemiological studies and influenced by geographical and climatic conditions, ethnic and demographic factors. Although the genetic background is the primary risk factor for beta-cell autoimmunity, such dynamic changes in incidence are more likely to be associated with the higher environmental pressure than the increase in genetic load at population level. Environmental factors can also contribute to the pathogenesis of type 1 diabetes as accelerators, causal or protective factors, moreover may even be involved at several points and with several mechanisms at the same time. However, despite the extensive international research on environmental factors, the most popular hypotheses associated with them (e.g., virus infections, hygiene hypothesis, intestinal microbiota, leaky gut, lack of vitamin D) have not yet provided a satisfactory explanation for most epidemiological observations (e.g., geographically significant variability of incidence rates, geographical “hotspots”, seasonal fluctuations in new cases, cyclical trends of incidence peaks). In this article, recent data and hypotheses about the epidemiology of childhood type 1 diabetes are summarized. Orv Hetil. 2021; 162(1): 13–22.

scholarly journals Environmental Factors and the Risk of Type 1 Diabetes Mellitus-A Case-Control Study

2017 ◽  
Vol 08 (02) ◽  
Author(s):  
Basma Abdelmoez Ali ◽  
Mostafa Ahmed Elfoly ◽  
Eman Ramadan Ghazawy ◽  
Rania Rashad Bersom
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Environmental Factors ◽  
Type 1 Diabetes Mellitus ◽  
Case Control Study ◽  
Case Control ◽  
Control Study

ALLERGIC DISEASES IN TYPE 1 DIABETIC PATIENTS: A BRIEF REVIEW

2015 ◽  
Vol 18 (2-3) ◽  
pp. 65-71
Author(s):  
Alina Gabriela Dutu ◽  
◽  
Silviu Albu ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Autoimmune Disease ◽  
Type 1 Diabetes Mellitus ◽  
Allergic Diseases ◽  
Developed Countries ◽  
Diabetic Patients ◽  
Inverse Association ◽  
Stepping Stones

Type 1 diabetes mellitus is considered an autoimmune disease mediated by Th1 lymphocytes, while allergic diseases are characterized by Th2-mediated immune response. Their incidence is rising in developed countries and the interaction between autoimmune and atopic diseases has been a subject of interest for decades. There are many controversies about the association or mutual exclusion of these diseases, but classical paradigm based on the assumption that diseases mediated by Th1 and Th2 should be mutually exclusive, has been revised considering both the role of regulatory T cells Threg, and the environmental factors involved. The aim of this review is to investigate the association of allergic diseases (rhinitis, asthma, dermatitis) in patient diagnosed with type 1 diabetes mellitus. The studies that attempted to shed light on this topic had surprisingly varied results. These ranged from statistically significant proof of an inverse association between an autoimmune disease and one or several atopic ones to other implying positive associations. Although up to now studies on this subject present seemingly discordant results, each attempt raises new questions and sheds light on new factors involved in the interaction of these diseases. They present much needed stepping stones for future studies to learn from and adapt.

scholarly journals Glutathione peroxidase 4 functional variant rs713041 modulates the risk for cardiovascular autonomic neuropathy in individuals with type 1 diabetes

2019 ◽  
Vol 16 (3) ◽  
pp. 297-299 ◽  
Author(s):  
Sharon Nina Admoni ◽  
Daniele Pereira Santos-Bezerra ◽  
Ricardo Vesoni Perez ◽  
Thiago Andrade Patente ◽  
Maria Beatriz Monteiro ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Glutathione Peroxidase ◽  
Autonomic Neuropathy ◽  
Microvascular Complications ◽  
Diabetic Complication ◽  
Cardiac Autonomic Neuropathy ◽  
Inverse Association ◽  
Gene Encoding ◽  
Functional Variant

Cardiac autonomic neuropathy is a neglected diabetic chronic complication for which genetic predictors are rarely reported. Oxidative stress is implicated in the pathogenesis of microvascular complications, and glutathione peroxidase 4 is involved in the detoxification of peroxides and of reactive oxygen species. Thus, the association of a functional variant in the gene encoding glutathione peroxidase 4 (rs713041) with this diabetic complication was investigated in 341 individuals with type 1 diabetes evaluated for cardiac autonomic neuropathy status (61.7% women, 34 [27–42] years old; diabetes duration: 21 [15–27] years; HbA1c: 8.3% [7.4–9.4]; as median [interquartile interval]). Cardiac autonomic neuropathy was present in 29% of the participants. There was an inverse association of the minor T allele of rs713041 with cardiac autonomic neuropathy (odds ratio = 0.39; 95% confidence interval = 0.17–0.90; p  = 0.0271) after adjustment for potential confounders. The functional glutathione peroxidase 4 variant rs713041 modulated the risk for cardiac autonomic neuropathy in the studied population with type 1 diabetes.

scholarly journals Recent advances in understanding Type 1 Diabetes

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 110 ◽  
Author(s):  
Gustaf Christoffersson ◽  
Teresa Rodriguez-Calvo ◽  
Matthias von Herrath
Keyword(s):  
Type 1 Diabetes ◽  
Environmental Factors ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Diabetes Research ◽  
Mhc I ◽  
Dependence Versus ◽  
Genetic And Environmental Factors ◽  
P Type

Type 1 diabetes is a multifactorial disease in which genetic and environmental factors play a key role. The triggering event is still obscure, and so are many of the immune events that follow. In this brief review, we discuss the possible role of potential environmental factors and which triggers are believed to have a role in the disease. In addition, as the disease evolves, beta cells are lost and this occurs in a very heterogeneous fashion. Our knowledge of how beta cell mass declines and our view of the disease’s pathogenesis are also debated. We highlight the major hallmarks of disease, among which are MHC-I (major histocompatibility complex class I) expression and insulitis. The dependence versus independence of antigen for the immune infiltrate is also discussed, as both the influence from bystander T cells and the formation of neo-epitopes through post-translational modifications are thought to influence the course of the disease. As human studies are proliferating, our understanding of the disease’s pathogenesis will increase exponentially. This article aims to shed light on some of the burning questions in type 1 diabetes research.

scholarly journals Children with type 1 diabetes of early age at onset – immune and metabolic phenotypes

2019 ◽  
Vol 32 (9) ◽  
pp. 935-941
Author(s):  
Madalena Sales Luis ◽  
Margarida Alcafache ◽  
Sara Ferreira ◽  
Ana Laura Fitas ◽  
Joana Simões Pereira ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Age At Onset ◽  
Disease Onset ◽  
Inverse Correlation ◽  
Early Age ◽  
Insulin Requirements ◽  
Age Related ◽  
One Year ◽  
Immune Imbalance

Abstract Objectives We aimed to evaluate children with type 1 diabetes (T1D) with early age at onset (EAO) for clinical, immune and metabolic features in order to identify age-related disease phenotypes. Methods Comparative study of two groups of T1D children: EAO (≤5 years) and later age at onset (LAO; >5 years), regarding the presence of other autoimmune (AI) diseases, diabetes ketoacidosis and immunologic profile at onset and metabolic data 1 year after diagnosis. Statistical analysis was performed with significance set for p < 0.05. Results The study included 137 children (EAO = 52, mean age 3.6 ± 1.5 [mean ± standard deviation (SD)] and LAO = 85, mean age 10.4 ± 2.9). EAO was more associated with concomitant AI diseases (p = 0.032). Despite no differences in disease onset, EAO presented with lower C-peptide levels (p = 0.01) and higher absolute lymphocyte number (p < 0.0001), with an inverse correlation between these two variables (p = 0.028). Additionally, the EAO group had a higher frequency of serum detection of three antibodies (Abs) (p = 0.0008), specifically insulin Abs (p = 0.0001). One year after diagnosis, EAO had higher total daily insulin (TDI) dose (p = 0.008), despite similar hemoglobin A1c (HbA1c). Conclusions Our data show an association of EAO T1D with more AI diseases, higher number of Abs, lower initial insulin reservoir and higher insulin requirements 1 year after diagnosis. In this group, immune imbalance seems more evident and disease progression faster, probably reflecting distinct “immune environment” with different ages at disease onset. Further studies in the field of immunogenetics and immune tolerance are required, to improve patient stratification and find novel targets for therapeutic intervention.

scholarly journals Response to Dahlquist: Environmental factors and type 1 diabetes

Diabetes Care ◽  
2001 ◽  
Vol 24 (1) ◽  
pp. 181-182 ◽  
Author(s):  
M. Hummel ◽  
A.-G. Ziegler
Keyword(s):  
Type 1 Diabetes ◽  
Environmental Factors
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