Inflammation and Endothelial Activation Is Evident at Birth in Offspring of Mothers With Type 1 Diabetes

  1. Scott M. Nelson1,
  2. Naveed Sattar1,2,
  3. Dilys J. Freeman1,
  4. James D. Walker3 and
  5. Robert S. Lindsay2
  1. 1Division of Developmental Medicine, Reproductive and Maternal Medicine, University of Glasgow, Glasgow, U.K
  2. 2British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, U.K
  3. 3Department of Diabetes, St. John's Hospital, Livingston, U.K
  1. Address correspondence and reprint requests to Dr. Scott M. Nelson, Reproductive and Maternal Medicine, Division of Developmental Medicine, University of Glasgow, Glasgow Royal Infirmary, 10 Alexandra Parade, Glasgow, G31 2ER, U.K. E-mail: s.nelson{at}


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).

RESEARCH DESIGN AND 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.


  • Published ahead of print at on 17 August 2007. DOI: 10.2337/db07-0662.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Received May 16, 2007.
    • Accepted August 12, 2007.
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  1. Diabetes vol. 56 no. 11 2697-2704
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