Impfen bei Diabetes - warum? - ÖGIT, 21. 6. 2021 - infektiologie.co.at
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Helmut Brath
Diabetes- und Fettstoffwechselambulanz
Gesundheitszentrum Favoriten, Wien
Impfen bei Diabetes –
warum?
ÖGIT, 21. 6. 2021 Brath: DM
Agenda 1. Diabetes & Infektionen: ein wichtiges Thema? 2. Warum? 3. Verlaufen Infektionen laufen bei Diabetes anders 4. Diabetes & Influenza 5. Diabetes & Pneumokokken 6. Diabetes & HPV 7. Diabetes & COVID-19 8. Wirken Impfungen bei Diabetes? 9. Snopsis 10. Diskussion Brath: DM
1.
Diabetes & Infektionen:
ein wichtiges Thema?
Brath: DM
Zeitliche Veränderungen der Komplikationsraten
Participants with T2DM from the Fremantle Diabetes Study Phases I (n=1291
recruited 1993-1996) and II (n=1509 recruited 2008-2011).
Age-, sex- and zip code-matched 1:4 to people without diabetes.
YLL: years of lost life
Wendy A Davis, Edward W Gregg, Timothy M E Davis:
Temporal trends in cardiovascular complications in people with or without type 2 diabetes: The Fremantle Diabetes Study.
The Journal of Clinical Endocrinology & Metabolism, dgaa215, https://doi.org/10.1210/clinem/dgaa215, Apr. 30, 2020 Brath: DM
T2DM & ambulant behandelte Infektionen
69.318 Pat. mit neuer Dg. DM2 zw. 2000 - 2012 in Nord Dänemark
Inzidenz ambulant erworbener Infektionen: 394/1.000 py
Vergleich HbA1c ≥ 10,5 % vs. 5,5 – 6,5 %
HR: 1.19 (95% CI: 1.14, 1.26)
Adjust. HR ratios, by baseline (dotted-dashed line), updated mean (solid line),
updated time-weighted mean (dashed line), and latest updated (dotted line) hemoglobin A1c (HbA1c)
Anil Mor et al, Am J Epidemiol 2017;186(2):227-236 Brath: DM
T2DM & stationär behandelte Infektionen
69.318 Pat. mit neuer Dg. DM2 zw. 2000 - 2012 in Nord Dänemark
Inzidenz ambulant erworbener Infektionen: 394/1.000 py
Vergleich HbA1c ≥ 10,5 % vs. 5,5 – 6,5 %
HR: 1.64 (95% CI: 1.51, 1.79)
Adjust. HR ratios, by baseline (dotted-dashed line), updated mean (solid line),
updated time-weighted mean (dashed line), and latest updated (dotted line) hemoglobin A1c (HbA1c)
Anil Mor et al, Am J Epidemiol 2017;186(2):227-236 Brath: DM
Serumglukosespiegel & Sterberisiko an CAP
b e Prospektive
i
te n H y p e r g ly k ä m ie
“A usm aß der aku r ta li tä ts r is
Kohorten-
ik o ,
h m e In d ik a to r fü r M o studie
Spita ls a u fn a T h e r a p ie .”
b e s o nders in te n s iv e
Patien te n b r a u c h e n
CAP: Community acquired pneumonia
Lepper P et al, BMJ. 2012; 344: e3397. doi: 10.1136/bmj.e3397 Brath: DM
2.
Warum?
Brath: DM
Ursachen f. ↑ Infektmorbidität bei DM
Abwehrschäche:
Glykosilierung von Antikörpern
↓ d. zell. Immunität - Geerlings SE, Hoepelman AIM. Immune dysfunction in ptx
with DM. FEMS Immunol Med Microbiol. 1999;26(3-4):259-
265
↓ d. Phagozytose - Mohan V, Unnikrishnan R, Thomas N, Bhansali A,
Wangnoo SK, Thomas K. Pneumococcal infections and
↓ d. T-Zell Immunität
immunization in diabetic patients. J Postgrad Med.
2011;57(1):78-81
- Alves C, Casqueiro J, Casqueiro J. Infections in patients
with DM: A review of pathogenesis. Indian J Endocr Metab.
Lokale Faktoren: 2012;16(7):27–15
Pulmonale Mikroangiopathie
↓ mukocil. Clearance - Yue WL. Nasal mucociliary clearance in patients with
diabetes mellitus. J Laryngol Otol. 1989;103(9):853-855.
- Thomsen RW, Hundborg HH, Lervang H-H et al: Diabetes &
↓ Lungenfunktion outcome of community-acquired pneumococcal
bacteremia: a 10-year population-based cohort study.
Diabetes Care. 2004;27(1):70-76
Brath: DM
Weitere Ursachen
- Hyperglycemia is associated with an increased
susceptibility to viral infections1
- cell-mediated immune deficiencies2
- disturbances in innate immunity, including humoral
immunity (low complement factor 4, decreased
cytokine response after stimulation) and cellular
immunity (chemotaxis, phagocytosis, killing)3
1. Mor A et al: Impact of glycemic control on risk of infections in ptx with T2D: a population-based cohort study. Am J Epidemiol.
2017;186(2):227-236. https://doi.org/10.1093/aje/kwx049
2. Abu-Ashour W et al: The association between DM & incident infections: a systematic review and meta-analysis of
observational studies. BMJ Open Diabetes Res Care. 2017;5(1):e000336. https://doi.org/10.1136/bmjdrc-2016-000336
3. Geerlings SE et al. Immune dysfunction in ptx with DM. FEMS Immunol Med Microbiol. 1999;26:259–265. Brath: DMInfektionen könnten bei älteren
Patienten mit Diabetes zumindest so
viel Einfluss auf Lebensqualität haben
wie makro- & mikrovasculares Risiko.
Pearson-Stuttard J, et al. Lancet Diabetes Endocrinol. 2016 Feb;4(2):148-58 Brath: DM3.
Verlaufen Infektionen bei Diabetes anders?
Brath: DMKlinische Symptome* sind unterschiedlich
Seltener:
akuter Beginn, Husten, gelber Auswurf,
Brustschmerzen
Häufiger:
intrahospitale Komplikationen
Patienten mit Diabetes & Organschäden:
mehr kardiale Komplikationen & höhere
Sterblichkeit
* Community acquired pneumonia
Silvana Di Yacovo et al , Medicine 2013;92:42-50 Brath: DMInfektionen führen zu gravierenden
Diabeteskomplikationen
Häufigsten auslösenden Ursachen von
diabetischer Ketoazidose (DKA)
und hyperglykämischen
hyperosmolarem Status (HHS):
Infektionen
30 – 60 % der Fälle von HHS
15 – 58 % der Fälle von DKA
Umpierrez G, Nat Rev Endocrinol. 2016 Apr;12(4):222-32 Brath: DM4.
Diabetes und Influenza
Brath: DMInfluenza: Risikofaktoren f. schwere Verläufe
Multicenter, retrospective, observational study
Zhejiang, China during a severe influenza epidemic in August 2017-May 2018
Multivariate analysis for risk factors assoc. with Influenza A pneumonia severity
Zou Q et et:
Influenza A-associated severe pneumonia in hospitalized ptx: Risk factors & NAI treatments. Int J Infect Dis. 2020 Mar;92:208-213 Brath: DMÖsterr. Impfplan: Influenza Impfplan Österreich 2021 Brath: DM
5.
Diabetes und Pneumokokken
Brath: DMDiabetes & Inzidenz v. Pneumokokkeninfekt. Shea KM et al, Open Forum Infect Dis. 2014 May 27;1(1):ofu024. doi: 10.1093/ofid/ofu024 Brath: DM
Risiko f. invasive Pneumokokkenerkr.
z. B. Sepsis, Meningitis
Hoek AJ et al, Journal of Infection (2012) 65, 17-24 Brath: DMÖsterr. Impfplan: Pneumokokken Impfplan Österreich 2021 Brath: DM
Österr. Impfplan: Pneumokokken Impfplan Österreich 2021 Brath: DM
6.
Diabetes & HPV
Brath: DMDiabetes & Inzidenz v. HPV assoz. (Prä-)Karzinome
Register-based cohort study, estimation of incid. of HPV-related anogenital precancer & cancer in women with & without
diabetes. Subjects: all women living in DK born 1916 - 2001 (n = 2 508 321). Used (individual-level) information: diabetes
(Type 1 or 2), diag. of cervical, vaginal, vulvar & anal intraepithelial neoplasia Grade 2 or 3 and cancer. Adjusted for
attained age, subsequently further adjusted for educational level, HPV vaccination status and calendar period.
vulvar intraepithelial neoplasia grade 2/3 (IRR = 1.63; 95% CI: 1.41-1.88)
anal intraepithelial neoplasia grade 2/3 (IRR = 1.18; 95% CI, 0.88-1.58)
cervical intraep. neoplasia grade 2/3 (IRR = 0.79; 95% CI, 0.74-0.84)
vaginal intraep. neoplasia grade 2/3 (IRR = 0.79; 95% CI, 0.44-1.43)
Incidence/100.000 patient years
IRR: incidence rate ratio
HPV: human papilloma virus
K Reinholdt et al, Int. J. Cancer. 2021;148:2090–2101 (Unit of Virus, Lifestyle, and Genes, Danish Cancer Society Research Center) Brath: DMDiabetes & Inzidenz v. HPV assoz. Karzinome
Vaginal cancer (IRR = 1.69; 95% CI: 1.20-2.39)
Vulvar cancer (IRR = 1.72; 95% CI, 1.45-2.04)
Cervical cancer (IRR = 1.13; 95% CI, 1.00-1.28)
Anal cancer (IRR = 1.17; 95% CI, 0.92-1.48)
Incidence/100.000 patient years
IRR: incidence rate ratio
K Reinholdt et al, Int. J. Cancer. 2021;148:2090–2101 Brath: DMDiabetes & Inzidenz v. HPV assoz. (Prä-)Karzinome1
Weitere relevante Aussagen
1) Patterns generally similar in women with T1D and T2D, although cancer
rates were higher in women with T2D
2) Women with T2D participated less in screening than women without T2D
(all ages: 75.8% vs 63.6% unscreened person years)
Women with T1D vs. without diabetes: no difference
(all ages: 62.9% vs 63.6% unscreened person-years).
3) Frühere Metaanalye (19 Studien): sign. erhöhtes Risiko für Zervixkarzinom
für Frauen mit Diabetes, wenn Alters- und BMI adjustier:
RR: 1.34 (95% CI, 1.10-1.63)
1. K Reinholdt et al, Int. J. Cancer. 2021;148:2090–2101 (Unit of Virus, Lifestyle, and Genes, Danish Cancer Society Research Center)
2. Starup-Linde et al. CARING (CAncer Risk & INsulin analoGues): assoc. of DM & cancer risk with focus on possible
determinants - a syst- review & meta-analysis. Curr Drug Saf. 2013;8(5):296-332. https://doi. org/10.2174/15748863113086660071 Brath: DMDiabetes & Inzidenz v. HPV assoz. (Prä-)Karzinome1
Conclusion
1) Efforts should be made to promote cervical cancer
screening in women with diabetes,
2) Implementation of HPV vaccination for adolescent
girls remains an important priority to prevent
HPV-related cancers.
K Reinholdt et al, Int. J. Cancer. 2021;148:2090–2101 Brath: DM7a.
Hyperglykämie & Karzinome
Brath: DMCancer risk
in Diabetes
(results of different
metaanalyses)
Nicolucci A, Acta Diabetol 2010;47:87-95Possible causal relations betw. T2DM & Cancer
1 Insulin Resistance, Hyperinsulinemia
Hyperglycemia
2
Common Causes: Obesity, Smoking,
3 Nutrition…
Special, with Diabetes
4 assoc. Pathomechanisms
Brath: DMStudies performed
DIAPLANT – Studie
Oxidative stress
Dietary intervention Oxidative DNA damage
Genomic instabilities
MIKRODIAB – Studie
Oxidative stress
Oxidative DNA damage Glycemic control (HbA1c)
DNA repair Diabetes Duration
Genomic instabilities MedicationStudies performed
1
DIAPLANT – Studie
Oxidative stress
Dietary intervention Oxidative DNA damage
Genomic instabilitiesDNA Strand breaks
9
8
7
6
% DNA in tail
5
4
3
2
1
-19% -23% -20% +2% +4% +4%
0
wk 0 wk 4 wk 8 wk 16 wk 0 wk 4 wk 8 wk 16
Intervention Information
Müllner E, Brath H, …., Wagner KH, Mol Nutr Food Res. 2013 Feb;57(2):328-38Switzeny OJ, Müllner E, Wagner KH, Brath H et al, Clin. Epigenetics 2012:4:19 Brath: DM
Glycemic Control & Chromosom. Damage (Micronuclei) Müllner E, Brath H, …., Wagner KH: Genome damage in periph blood lymphocytes of diabetic and non-diabetic individuals after intervention with vegetables and plant oil. Mutagenesis. 2013 Jan 21. [Epub ahead of print] Brath: DM
Studies performed
2
MIKRODIAB – Studie
Oxidative stress
Oxidative DNA damage Glycemic control (HbA1c)
DNA repair Diabetes Duration
Genomic instabilities MedicationMikrodiab-Study –
Chromosomal Damage
20 20 20
r = 0.529*** HbA1c > 7.5 % HbA1c ≤ 7.5 %
r = 0.356***
r = 0.735*** r = 0.247*
15 15 15
FPG [mmol/L]
HbA1c [%]
HbA1c [%]
10 10 10
5 5
5
0 0
0 0 1 2 3 4 5 6 0 1 2 3 4 5 6
0 1 2 3 4 5 6
Total MN [‰] Total MN [‰]
Total MN [‰]
Grindel A, Brath H….. Wagner KH. Sci Rep. 2017 Feb 2;7:41985. doi: 10.1038/srep41985Oxidative Stress & DNA-Damage in T2DM
Oxidative Stress
Hyperglycemia
Cell Death
Healthy Cell with
Cell damaged
DNA
Cell with
chromosomal
Damage
DNA Repair
8-oxodG
Brath: DMMethods
! Oxidative damage to DNA/RNA
o Comet Assay (Lysis, FPG-sensitive sites, 100 µM H2O2)
o 8-oxodG and 8-oxoGuo in urine (UPLC with tandem MS)
! Chromosomal damage
o BMCyt Assay in buccal cells
o CBMN-Assay in lymphocytes
Brath: DM7.
Diabetes & COVID-19
Brath: DMProbability of COVID-19 – positive hospitalization by age,
categorized by diabetes type, adjusted to a BMI of 26 kg/m2
JM Gregory et al: COVID-19 Severity Is Tripled in the Diabetes Community: A Prospective Analysis of the Pandemic’s Impact in
Type 1 and Type 2 Diabetes. Diabetes Care 2020 Dec; dc202260.https://doi.org/10.2337/dc20-2260 Brath: DMOR plot displaying adjusted ORs and 95% CIs for independent
variables associated with hospitalization with COVID-19 within
14 days of a positive test.
JM Gregory et al: COVID-19 Severity Is Tripled in the Diabetes Community: A Prospective Analysis of the Pandemic’s Impact in
Type 1 and Type 2 Diabetes. Diabetes Care 2020 Dec; dc202260.https://doi.org/10.2337/dc20-2260 Brath: DMUnrecognized diabetes in critically ill
COVID-19 patients in Tyrol
N = 44, 4 ICUs d. Uni Klinik Innsbruck, 11. 3. – 29. 4. 2020
24 (54.5%): Diabetes mellitus (HbA1c ≥ 6.5%)
16 (36.3%): Prädiabetes (HbA1c ≥ 5.7% < 6.5%)
4 (9%): kein Diabetes (HbA1c < 5.7%)
7 (15.9%): anamnestisch bekannter Diabetes
5 (11.4%) hatten zuvor antidiabetische Therapie
Keiner zuvor insulinpflichtig
Höhere HbA1c Werte: höhere maximale CRP and IL-6 Spiegel
Höhere HbA1c Werte: tendentiell höhere intramurale Mortalität
Klein, S.J., Fries, D., Kaser, S. et al. Unrecognized diabetes in critically ill COVID-19 patients.
Crit Care 24, 406 (2020). https://doi.org/10.1186/s13054-020-03139-3 Brath: DMBrath: DM
Other laboratory tests of patients with and without diabetes
A. Blood test results of the patients
with and without diabetes
B. Inflammation-related laboratory
results of the patients with and
without diabetes
C. Coagulation-related laboratory
results of the patients with and
without diabetes
PGlukosespiegel & COVID-19-Verlauf
Blood glucose levels on admission to hospital and after 24 h for patients with
(n = 60) and without severe disease (n = 72) at 20 days after hospitalisation.
C Sardu et al: Hyperglycaemia on admission to hospital and COVID-19. Diabetologia volume 63, pages2486–2487(2020) Brath: DMGlukosespiegel & COVID-19-Verlauf
Blood glucose levels on admission to hospital and after 24 h for patients with
(n = 60) and without severe disease (n = 72) at 20 days after hospitalisation.
o n tr o l m a y b e a s u it able
“Early glycaemic c p o o r o u tc o m e s in
o p ti o n to r e d u ce th e
therap e u ti c p a ti e n ts w ith
g ly c a e m ic C O V ID -1 9
hospita li s e d h y p e r
d ia b e te s d ia g n o s is ”
s
or without a previou
C Sardu et al: Hyperglycaemia on admission to hospital and COVID-19. Diabetologia volume 63, pages2486–2487(2020) Brath: DMPre-infection HbA1c and risk of developing severe
COVID-19 among patients with T2DM
CI, confidence
interval; COVID-
19, coronavirus
disease-2019;
HbA1c, glycated
haemoglobin;
T2DM, type 2
diabetes
mellitus.
Samah Hayek et al, doi: 10.1111/dom.14393 Brath: DMCOVID-19 fatality prediction in people with diabetes and
prediabetes using a simple score upon hospital admission
Sourij H et al: COVID-19 fatality prediction in people with diabetes and prediabetes using a simple score upon
hospital admission. DOM 23, Issue: 2, p 589-598, First published: 16 November 2020, DOI: (10.1111/dom.14256) Brath: DMKrankheitsverlauf bei Menschen mit DM1 und COVID-19
r e H y p e r g ly k ä m ie is t
e r w e it ig n ic h t e r k lä rba
An d fe k ti o n u n d s ollte
ic h e n e in e r aku te n In
wichtig s te s Z e
r A b k lä r u n g fü h r e n .
zu
OA Ebekozien et al: Diabetes Care Publish Ahead of Print, published online June 5, 2020 Brath: DMÖDG, Nationales Impfgremium:
Menschen mit Diabetes sind
Hochrisikopatienten
www.oedg.org Brath: DMCovid-Schutzimpfung bei Diabetes Rimesh Pal et al: COVID-19 vaccination in patients with diabetes mellitus: Current concepts, uncertainties and challenges Diabetes Metab Syndr. Mar-Apr 2021;15(2):505-508. doi: 10.1016/j.dsx.2021.02.026 Brath: DM
8.
Wirken Impfungen bei Diabetes
Brath: DMImpfung gegen Influenza wirkt
bei Personen mit Diabetes gleich gut
Results of influenza vaccination measured by hemagglutination inhibition assay (HIA)
among healthy elderly and elderly patients with T2DM
Janet E McElhaney et al. BMJ Open Diab Res Care 2015;3:e000140 Brath: DMImpferfolg unabhängig von metabol. Parametern
Comparison of clinical and functional parameters among non-responders
and responders among healthy elderly and elderly patients with T2DM.
Janet E McElhaney et al. BMJ Open Diab Res Care 2015;3:e000140 Brath: DMGrippeimpfung reduziert Mortalität deutlich
Danish register data: ptx with DM during 9 consecutive influenza seasons 2007–2016.
241,551 patients monitored for a 4 seasons (range: 2 - 8); 425,318 personyears.
Vaccine coverage: 24% - 36%. 8,207 patients died of all causes (3.4%), 4,127 of CV causes (1.7%).
Adjustment for confounders.
D Modin et al. Diabetes Care 2020;43:2226–2233; https://doi.org/10.2337/dc20-0229 Brath: DMImpfung gegen Pneumokokken wirkt
bei Personen mit Diabetes zumindest gleich gut
4 Publikationen: Vergleich d. Immunantwort auf Pneumokkenimpfungen +/- Diabetes
Janet E McElhaney et al. BMJ Open Diab Res Care 2015;3:e000140 Brath: DMImpfung gegen Pneumokokken & Morbidität/Mortalität
bei Personen sehr hohem Risiko od. etablierter CV-Erkrankung
Systematic review & meta-analysis of impact of pneumococcal vaccination in adults with a history
of at a very high risk (incl. Diabetes with organ damage) for CV disease. Prim. Outcome: all-cause
mortality. No RCTs were found. 7 observational studies were included for analyses. N = 163 756.
MM Antunes et al. Eur Heart J - Quality of Care & Clin. Outcomes, Vol 7, Iss 1, Jan 2021, 97–106, https://doi.org/10.1093/ehjqcco/qcaa030 Brath: DMImpfung gegen Hepatitis B abgeschwächt
15 von 16 Studien: reduzierte Immunogenität (4% bis 60% )
der Hepatitis B Impfung bei Personen mit vs. ohne Diabetes B
Janet E McElhaney et al. BMJ Open Diab Res Care 2015;3:e000140 Brath: DMImpfung gegen Hepatitis B abgeschwächt
Warum? Klinische Bedeutung?fung bei Personen mit vs. ohne
Diabetes B
- Altersabhängig: 4/4 Studien mit Kindern,
aber “nur” 5/12 Studien mit Erwachsenen
- Keine Studie über klinische Wirkung von
Hepatitis B vorliegend im Vergleich mit und ohne
Diabetes vorliegend
Janet E McElhaney et al. BMJ Open Diab Res Care 2015;3:e000140 Brath: DMImpfung gegen Varicellen-Zoster wirkt
bei Personen mit Diabetes gleich gut
“Finally, we identified one study which assessed the
effectiveness of a varicella-zoster vaccine by DM status
and found no difference [54].”
1. Janet E McElhaney et al. BMJ Open Diab Res Care 2015;3:e000140
2. Langan S et al. Zoster vaccination is associated with a reduction of zoster in elderly patients with chronic kidney
disease. Nephrol Dial Transplant. 2016;31:2095–2098 Brath: DM9.
Synopsis
Brath: DMMenschen mit Diabetes sind eine sehr wichtige
Risikogruppe für (respiratorische) Infektionen, da
Diabetes häufig
Erkrankungsrisiko erhöht
Komplikationsrate erhöht
Hospitalisierungsrate erhöht
Sterbewahrscheinlichkeit erhöht
Infektionen: wichig(st)e Ursache f. akute Hyperglykämie
und deren Folgen
Brath: DMImpfungen bei Menschen mit Diabetes:
wirken
sind sicher
reduzieren Mortalität beträchtlich
alle Impfungen lt. österr. Impfplan zu empfehlen
besondere Erwähnung: Influenza, Pneumokokken, COVID
Brath: DMDiabetes –
Was sind die heutigen Therapieziele
Optimierung der Zusätzlicher
glykämischen Kontrolle: Organschutz
(SGLT-2 I, GLP-1 RA, Pioglitazon)
- Infektionen
- mikrovask. Schäden Impfungen! - Herzinsuffizienz
- renale Insuffizienz
- Kognition
- KHK
- langfristig makrovask. - Insult
- Lunge
Brath: DMYou can also read
