Enhancement of Endothelial Function by Pregnancy

Enhancement of Endothelial Function by Pregnancy Inadequate response in women with type 1 diabetes Jane E. Ramsay , MRCOG 1 , Roslyn J. Simms 2 , William R. Ferrell , PHD 2 , Lynn Crawford , PHD 3 , Ian A. Greer , MD 1 , Mary-Anne Lumsden , MD 1 and Naveed Sattar , PHD 1 3 1 University Department of Obstetrics and Gynaecology, Glasgow Royal Infirmary, Glasgow, Scotland, U.K. 2 University Department of Medicine, Glasgow Royal Infirmary, Glasgow, Scotland, U.K. 3 University Department of Pathological Biochemistry, Glasgow Royal Infirmary, Glasgow, Scotland, U.K. Abstract OBJECTIVE —Pregnant women with type 1 diabetes have a substantially increased risk of vascular complications. Our aim was to study vascular function and metabolic and inflammatory risk factors during the antenatal and postpartum periods in women with type 1 diabetes compared with healthy control subjects. RESEARCH DESIGN AND METHODS —A total of 15 women with diabetes and 30 control subjects were recruited in the third trimester of pregnancy. Of these women, 9 case subjects and 16 control subjects were reinvestigated in the postnatal period. Blood samples were collected and microvascular skin perfusion was assessed in vivo using laser Doppler imaging and iontophoretic administration of endothelial-dependent (acetylcholine [ACH]) and endothelial-independent (sodium nitroprusside [SNP]) vasodilators. RESULTS —Microvascular responses in both control subjects (ACH, P = 0.018; SNP, P = 0.01) and diabetic women (ACH, P = 0.029; SNP, P = 0.105) were better during pregnancy than in the postnatal period, although responses in women with diabetes were significantly inferior to those in control subjects during both periods (all P < 0.001, two-way ANOVA). This dysfunction existed despite similar lipoprotein profiles. The difference in vascular responsivity between case and control subjects was significantly attenuated by adjustment for differences in HbA 1c but not C-reactive protein concentrations in the two groups. CONCLUSIONS —Pregnancy enhances microvascular function, but in women with diabetes, such improvements are insufficient to attain responses seen in healthy nonpregnant women. This suggests a persistent vascular defect in young women with type 1 diabetes that may contribute to adverse pregnancy outcome. Our data suggest a role for the chronic effects of hyperglycemia in the impaired vascular responsiveness in such women. ACH, acetylcholine AUC, area under the perfusion time curve CRP, C-reacti