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Diabetes Publish Ahead of Print published online ahead of print August 17, 2007
DOI: 10.2337/db07-0662
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Original Research

Inflammation and endothelial activation is evident at birth in offspring of mothers with type 1 diabetes

Scott M. Nelson1, Naveed Sattar1,,2, Dilys J. Freeman1, James D. Walker3, and Robert S. Lindsay2

1Reproductive and Maternal Medicine, University of Glasgow, 10 Alexandra Parade, Glasgow G31 2ER
2BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Place, Glasgow, G12 8TA
3Department of Diabetes, St John's Hospital, Livingston, EH54 6PP

Correspondence: s.nelson{at}clinmed.gla.ac.uk

Objective: Offspring of mothers with diabetes are at risk of obesity and glucose intolerance in later life. In adults markers of subclinical inflammation (CRP, IL-6) and endothelial activation (ICAM-1) are associated with obesity and with higher risk for incident type 2 diabetes. We examined whether these biomarkers were elevated at birth in offspring of mothers with type 1 diabetes (OT1DM).

Research Methods: Umbilical cord plasma CRP, IL-6 and ICAM-1 measured in 139 OT1DM and 48 control offspring, with analysis relative to fetal lipids and hormonal axes.

Results: OT1DM had higher CRP (OT1DM 0.17 [0.13-0.22]mg/l; control 0.14 [0.12-0.17]mg/l; P<0.001: median [inter-quartile range]) and ICAM-1 (OT1DM 180 [151-202]ng/ml; control 166 [145-187]ng/ml, P=0.047). IL-6 was not different after necessary adjustment for mode of delivery. Birthweight was unrelated to inflammatory indices, however, leptin was correlated with CRP (controls r=0.33, p=0.02; OT1DM r=0.41, p<0.001) and with IL-6 (r=0.23, p<0.01) and ICAM-1 (r=0.29, p<0.001) in OT1DM. In OT1DM CRP correlated with maternal glycaemic control (HbA1c at 35-40 weeks; r=0.28, P=0.01). In multivariate analysis leptin was a determinant of CRP (p<0.001), ICAM-1 (p=0.003) and IL-6 (p=0.02) in OT1DM. Inflammatory measures demonstrated positive relationships with triglycerides in OT1DM (CRP, IL-6 and ICAM-1 P<0.05) and controls (ICAM-1 P=0.001).

Conclusions: Inflammatory markers are increased in OT1DM and are related to measures of fetal adiposity- particularly leptin- and to maternal glycaemia. Sub-clinical inflammation is a novel component of the diabetic intra-uterine environment and should be considered as a potential etiological mechanism for in-utero programming of disease.


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