ISSN 1662-4009 (online)

ey0019.10-4 | Mechanisms | ESPEYB19

10.4. Childhood body size directly increases type 1 diabetes risk based on a lifecourse Mendelian randomization approach

TG Richardson , DJM Crouch , GM Power , F Morales-Berstein , E Hazelwood , S Fang , Y Cho , JRJ Inshaw , CC Robertson , C Sidore , F Cucca , SS Rich , JA Todd , Smith G Davey

Nat Commun. 2022 Apr 28;13(1):2337. Summary: This Mendelian randomization study analysed genetic data from 454,023 individuals from the UK Biobank and 15,573 type 1 diabetes (T1D) cases from other cohorts and provides strong evidence that larger childhood body size increases T1D risk, independently from body size at birth and during adulthood.<...

ey0019.10-7 | New paradigms | ESPEYB19

10.7. Circulating C-peptide levels in living children and young people and pancreatic beta cell loss in pancreas donors across type 1 diabetes disease duration

ALJ Carr , JRJ Inshaw , CS Flaxman , P Leete , RC Wyatt , LA Russell , M Palmer , D Prasolov , T Worthington , B Hull , LS Wicker , DB Dunger , RA Oram , NG Morgan , JA Todd , SJ Richardson , REJ Besser

Diabetes. 2022;71:1591-1596. Summary: This cross-sectional study compared trends in plasma C-peptide decline in 4,076 young people with type 1 diabetes (T1D), with trends in beta-cell loss in 235 pancreas donors. As expected, C-peptide declined over time, and this was particularly marked in children with T1D younger than 7 years. Of interest, p...

ey0020.8-9 | New Paradigms | ESPEYB20

8.9. Elevations in blood glucose before and after the appearance of islet autoantibodies in children

K Warncke , A Weiss , P Achenbach , T von dem Berge , R Berner , K Casteels , L Groele , K Hatzikotoulas , A Hommel , O Kordonouri , H Elding Larsson , M Lundgren , BA Marcus , MD Snape , A Szypowska , JA Todd , E Bonifacio , AG Ziegler , GPPAD POInT Study Groups

Brief summary: In this longitudinal study, blood glucose trajectories and their relationship with autoantibodies appearance were assessed in 1050 children with high genetic risk of type 1 diabetes (T1D) between 4 months and 3.6 years. Post-prandial blood glucose levels increased around 2 months prior to autoantibody seroconversion, with further increases thereafter, suggesting that islet autoimmunity co-occurs or follows insults on the β-cells.This ...

ey0020.8-13 | New Mechanisms | ESPEYB20

8.13. Low-dose IL-2 reduces IL-21(+) T cell frequency and induces anti-inflammatory gene expression in type 1 diabetes

JY Zhang , F Hamey , D Trzupek , M Mickunas , M Lee , L Godfrey , JHM Yang , ML Pekalski , J Kennet , F Waldron-Lynch , ML Evans , TIM Tree , LS Wicker , JA Todd , RC Ferreira

Brief summary: This study used high-resolution single-cell multiomics and flow cytometry on blood samples from patients with type 1 diabetes (T1D) to examine the effects of low-dose recombinant IL-2 (iLD-IL-2). Administration of iLD-IL-2 expanded thymic-derived FOXP3+HELIOS+ Tregs and CD56bright NK cells, reduced frequency of IL-21-producing CD4+T cells, and induced long-lived anti-inflammatory transcriptional changes in all T and NK...

ey0019.10-16 | Genetics | ESPEYB19

10.16. Fine-mapping, trans-ancestral and genomic analyses identify causal variants, cells, genes and drug targets for type 1 diabetes

CC Robertson , JRJ Inshaw , S Onengut-Gumuscu , WM Chen , Cruz DF Santa , H Yang , AJ Cutler , DJM Crouch , E Farber , SL Jr Bridges , JC Edberg , RP Kimberly , JH Buckner , P Deloukas , J Divers , D Dabelea , JM Lawrence , S Marcovina , AS Shah , CJ Greenbaum , MA Atkinson , PK Gregersen , JR Oksenberg , F Pociot , MJ Rewers , AK Steck , DB; Type 1 Diabetes Genetics Consortium Dunger , LS Wicker , P Concannon , JA Todd , SS Rich

Nat Genet. 2021 Jul;53(7):962-971. Summary: The authors report the largest and most diverse genome-wide association study (GWAS) of type 1 diabetes (T1D) to date, including 61,427 participants from different ancestries. It identified 78 significant genomic regions associated with T1D, of which 36 were new. The integration of genetic evidence, f...