Inflammation and endothelial activation is evident at birth in offspring of mothers with type 1 diabetes.
OBJECTIVE
Offspring of mothers with diabetes are at risk of obesity and glucose intolerance in later life. In adults, markers of subclinical inflammation (C-reactive protein [CRP] and interleukin [IL]-6) and endothelial activation (intracellular adhesion molecule [ICAM]-1) are associated with obesity and higher risk for incident type 2 diabetes. We examined whether these biomarkers were elevated at birth in offspring of type 1 diabetic mothers (OT1DM).


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


RESULTS
OT1DM had higher median (interquartile range) CRP (OT1DM 0.17 mg/l [0.13-0.22] vs. control subjects 0.14 mg/l [0.12-0.17], P < 0.001) and ICAM-1 (OT1DM 180 ng/ml [151-202] vs. control subjects 166 ng/ml [145-187], P = 0.047). IL-6 was not different after necessary adjustment for mode of delivery. Birth weight was unrelated to inflammatory indexes; however, leptin was correlated with CRP (control subjects 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 glycemic control (A1C 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 control subjects (ICAM-1 P = 0.001).


CONCLUSIONS
Inflammatory markers are increased in OT1DM and are related to measures of fetal adiposity, particularly leptin, and maternal glycemia. Subclinical inflammation is a novel component of the diabetic intrauterine environment and should be considered a potential etiological mechanism for in utero programming of disease.
Nelson
Scott M
SM
Division of Developmental Medicine, University of Glasgow, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow, G31 2ER, UK. s.nelson@clinmed.gla.ac.uk
Sattar
Naveed
N
Freeman
Dilys J
DJ
Walker
James D
JD
Lindsay
Robert S
RS
D002097:C-Reactive Protein / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D018149:Glucose Intolerance / Q000235:genetics; D006728:Hormones / Q000097:blood; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000209:etiology / Q000503:physiopathology*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008055:Lipids / Q000097:blood; D009765:Obesity / Q000235:genetics; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology*; D012016:Reference Values
D006728:Hormones; D015850:Interleukin-6; D008055:Lipids; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein