Abstract

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.