Endothelium-derived nitric oxide metabolites and soluble intercellular adhesion molecule-1 in diabetic and normal pregnancies.

OBJECTIVE: Endothelial dysfunction has been demonstrated in adult subjects with diabetes. We studied if maternal diabetes is associated with altered endothelial function in the fetus, as this might shed light on mechanisms by which adult diseases are programmed in utero. STUDY DESIGN: Total nitrate/nitrite (NOx) concentration was measured spectrophotometrically with the Griess reagent method. Soluble intercellular adhesion molecule-1 (sICAM-1) concentration was measured by enzyme-linked immunoassay. RESULTS: Venous cord serum NOx concentration at birth was highest in pregnancies complicated by type 1 diabetes (29.5+/-1.8 micromol/l, n=63) (P<0.0001 versus controls) and lowest in normal pregnancies (19.0+/-1.0 micromol/l, n=56). The concentration was intermediate in pregnancies complicated by gestational diabetes (23.9+/-2.7 micromol/l, n=24), but not significantly higher than in normal pregnancies (P=0.172). Venous cord serum sICAM-1 concentration did not differ between the three groups (P=0.191). Maternal serum NOx concentration in the third trimester was higher in pregnancies complicated by type 1 diabetes (22.9+/-3.4 micromol/l, n=22) than in normal pregnancies (15.4+/-1.4 micromol/l, n=21) (P=0.049). CONCLUSIONS: : Increased cord serum NOx but unaltered sICAM-1 concentration in diabetic pregnancies indicates that maternal diabetes does not cause a general alteration in fetal endothelial function. The increase in cord serum and maternal serum NOx concentration in diabetic pregnancies may be due to abnormalities in insulin-induced nitric oxide release or to a diminished reactivity of the vasculature to the effects of nitric oxide.

Reduced IGFBP-1 is associated with thickening of the carotid wall in type 2 diabetes.

OBJECTIVE: The aim of the present study was to assess the role of the insulin-like growth factor (IGF) system and lipids in predicting the carotid intima-media thickness (IMT) in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 239 type 2 diabetic participants in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study (76 women) aged 50-75 years were examined before fenofibrate intervention. Patients underwent carotid ultrasonography for determination of IMT. IGF-I, IGF binding protein 1 (IGFBP-1), IGFBP-3, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein B (apoB), lipoprotein(a) (Lp(a)), glucose, HbA(1c), and C-peptide were measured in fasting samples. Patients were divided in groups without (n = 168) and with (n = 71) clinical cardiovascular disease (CVD). RESULTS: Partial correlations adjusted for age, sex, BMI, and diabetes duration showed an inverse association of IGFBP-1 with C-peptide (r = -0. 24, P = 0.018) and with maximal IMT (r = -0.42, P < 0.001), whereas IGF I and IGFBP-3 correlated positively with several risk-promoting lipid parameters. In linear regression analysis controlling for age, sex, BMI, diabetes duration, and presence or absence of oral antihyperglycemic or insulin medication, determinants of IMT were age, IGFBP-1, pulse pressure, Lp(a), diabetes duration, and insulin treatment. IGFBP-1 persisted in the model for subjects with CVD. CONCLUSIONS: In summary, a decrease in IGFBP-1 is a marker of carotid IMT thickening in patients with type 2 diabetes.