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Plasma levels of mannan-binding lectin-associated serine proteases are increased in type 1 diabetes patients with insulin resistance

Kietsiriroje, Noppadol, Scott, Georgia E, Ajjan, RA, Brož, Jan, Schroeder, Verena and Campbell, Matthew (2023) Plasma levels of mannan-binding lectin-associated serine proteases are increased in type 1 diabetes patients with insulin resistance. Clinical and Experimental Immunology, 215 (1). pp. 58-64. ISSN 0009-9104

Item Type: Article


Activation of the lectin pathway of the complement system, as demonstrated by elevated levels of mannan-binding lectin proteins (MBL), contributes to vascular pathology in type 1 diabetes (T1D). Vascular complications are greatest in T1D individuals with concomitant insulin resistance (IR), however, whether IR amplifies activiation of the lectin pathway in T1D is unknown. We pooled pre-treatment data from two RCTs and performed a cross-sectional analysis on 46 T1D individuals. We employed estimated glucose disposal rate (eGDR), a validated IR surrogate with cut-points of: <5.1, 5.1 – 8.7, and >8.7 mg/kg/min to determine IR status, with lower eGDR values conferring higher degrees of IR. Plasma levels of MBL-associated proteases (MASP-1, MASP-2, MASP-3) and their regulatory protein MAp44 were compared among eGDR classifications. In a subset of 14 individuals, we assessed change in MASPs and MAp44 following improvement in IR. We found that MASP-1, MASP-2, MASP-3, and MAp44 levels increased in a stepwise fashion across eGDR thresholds with elevated MASPs and MAp44 levels conferring greater degrees of IR. In a subset of 14 patients, improvement in IR was associated with significant reductions in MASPs, but not MAp44, levels. In conclusion, IR in T1D amplifies levels of MASP-1/2/3 and their regulator MAp44, and improvement of IR normalises MASP-1/2/3 levels. Given that elevated levels of these proteins contribute to vascular pathology, amplification of the lectin pathway of the complement system may offer mechanistic insight into the relationship between IR and vascular complications in T1D.

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More Information

Depositing User: Matthew Campbell


Item ID: 16604
Identification Number:
ISSN: 0009-9104
Official URL:

Users with ORCIDS

ORCID for Noppadol Kietsiriroje: ORCID iD
ORCID for Jan Brož: ORCID iD
ORCID for Matthew Campbell: ORCID iD

Catalogue record

Date Deposited: 19 Sep 2023 13:02
Last Modified: 10 Apr 2024 11:15


Author: Noppadol Kietsiriroje ORCID iD
Author: Jan Brož ORCID iD
Author: Matthew Campbell ORCID iD
Author: Georgia E Scott
Author: RA Ajjan
Author: Verena Schroeder

University Divisions

Faculty of Health Sciences and Wellbeing > School of Nursing and Health Sciences


Sciences > Biomedical Sciences
Sciences > Health Sciences

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