Etienne Sochett1, Damien Noone2, Michael Grattan3, Cameron Slorach4, Rahim Moineddin5, Yesmino Elia4, Farid H Mahmud4, David B Dunger6, Neil Dalton7, David Cherney8, James Scholey8, Heather Reich8, John Deanfield9. 1. Department of Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada; Division of Endocrinology, Hospital for Sick Children, Toronto, Canada. Electronic address: etienne.sochett@sickkids.ca. 2. Department of Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada; Division of Nephrology, Hospital for Sick Children, Toronto, Canada. 3. Department of Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada; London Health Sciences Centre, Children's Hospital, University of Western Ontario, London, Ontario, Canada. 4. Department of Paediatrics, Hospital for Sick Children, University of Toronto, Toronto, Canada. 5. Department of Family and Community Medicine, University of Toronto, Toronto, Canada. 6. Department of Paediatrics, University of Cambridge, Cambridge, UK Department of Medicine, UK. 7. WellChild Laboratory, Evelina Children's Hospital, St Thomas' Hospital, London, UK. 8. Division of Nephrology, University Health Network, University of Toronto, Toronto, Canada. 9. Institute of Child Health, University College London, London, UK.
Abstract
OBJECTIVE: The contribution of inflammation to endothelial/vascular dysfunction in early Type I Diabetes (T1D) is not well understood. The objective of this study was to examine the interaction between systemic inflammation and vascular function in adolescent's with and without-T1D. METHODS: 51 subjects from our observational cohort of adolescents with T1D (JDRF-CCTN), and 59 healthy controls (HC) were studied. Serum cytokines-chemokines were quantified using Human 41-Plex Array, and vascular function was measured by Flow Mediated Dilatation (FMD), Pulse Wave Velocity (PWV) and Blood Pressure (BP). Factor Analysis was used to identify pro- and anti-inflammatory cytokine-chemokine factors, which were then correlated with vascular outcomes. RESULTS: Three pro-inflammatory factors were identified in HC and three in TID, and a single anti-inflammatory factor in both groups. In HC there was a positive correlation (r=0.33; p=0.01) between control proinflammatory Factor 1 and systolic BP and a negative correlation between control proinflammatory Factor 3(r=-0.29; p=0.02) and diastolic BP. Control proinflammatory Factor 2 correlated positively with PWV. In TID subjects, no correlations were found between any of the pro-inflammatory factors and the vascular measurements. No correlations were found between the anti-inflammatory factors and BP, FMD and PWV in either HC or T1D. Levels of pro-inflammatory analytes, EGF, GRO, PDGF-BB, PDGF-AA and sCD40L were significantly higher in T1D. CONCLUSIONS: The cytokine-chemokine signature in early T1D, prior to the development of arterial disease, is significantly different from that seen in healthy controls. This may be relevant to pathophysiology, determining risk and identifying target cytokines-chemokines for intervention in T1D.
OBJECTIVE: The contribution of inflammation to endothelial/vascular dysfunction in early Type I Diabetes (T1D) is not well understood. The objective of this study was to examine the interaction between systemic inflammation and vascular function in adolescent's with and without-T1D. METHODS: 51 subjects from our observational cohort of adolescents with T1D (JDRF-CCTN), and 59 healthy controls (HC) were studied. Serum cytokines-chemokines were quantified using Human 41-Plex Array, and vascular function was measured by Flow Mediated Dilatation (FMD), Pulse Wave Velocity (PWV) and Blood Pressure (BP). Factor Analysis was used to identify pro- and anti-inflammatory cytokine-chemokine factors, which were then correlated with vascular outcomes. RESULTS: Three pro-inflammatory factors were identified in HC and three in TID, and a single anti-inflammatory factor in both groups. In HC there was a positive correlation (r=0.33; p=0.01) between control proinflammatory Factor 1 and systolic BP and a negative correlation between control proinflammatory Factor 3(r=-0.29; p=0.02) and diastolic BP. Control proinflammatory Factor 2 correlated positively with PWV. In TID subjects, no correlations were found between any of the pro-inflammatory factors and the vascular measurements. No correlations were found between the anti-inflammatory factors and BP, FMD and PWV in either HC or T1D. Levels of pro-inflammatory analytes, EGF, GRO, PDGF-BB, PDGF-AA and sCD40L were significantly higher in T1D. CONCLUSIONS: The cytokine-chemokine signature in early T1D, prior to the development of arterial disease, is significantly different from that seen in healthy controls. This may be relevant to pathophysiology, determining risk and identifying target cytokines-chemokines for intervention in T1D.
Authors: Juma Alkaabi; Charu Sharma; Javed Yasin; Bachar Afandi; Salem A Beshyah; Raya Almazrouei; Ahmed Alkaabi; Sania Al Hamad; Luai A Ahmed; Rami Beiram; Elhadi H Aburawi Journal: Am J Transl Res Date: 2022-07-15 Impact factor: 3.940
Authors: Ida Pastore; Andrea Mario Bolla; Laura Montefusco; Maria Elena Lunati; Antonio Rossi; Emma Assi; Gian Vincenzo Zuccotti; Paolo Fiorina Journal: Int J Mol Sci Date: 2020-07-12 Impact factor: 5.923
Authors: Scott T Chiesa; Marietta Charakida; Eve McLoughlin; Helen C Nguyen; Georgios Georgiopoulos; Laura Motran; Yesmino Elia; M Loredana Marcovecchio; David B Dunger; R Neil Dalton; Denis Daneman; Etienne Sochett; Farid H Mahmud; John E Deanfield Journal: Eur Heart J Date: 2019-11-14 Impact factor: 29.983