INTRODUCTION Lipid peroxidation (LPO) results from oxidative damage to membrane lipids. Whereas LPO rises in normal pregnancy, the effect of gestational diabetes mellitus (GDM) on this process has not been clearly defined. MATERIALS AND METHOD Fasting blood concentrations of malondialdehyde+4-hydroxyalkenals (MDA+4-HDA), as LPO index, TNFa soluble receptors (sTNF-R1 and sTNF-R2), and soluble adhesion molecules (sICAM-1, sVCAM-1), were measured in 51 women at 28 weeks of gestation. The women were divided according to the results of 50.0 g glucose challenge test (GCT) and 75.0 g oral glucose tolerance test (OGTT): Controls (n=20), normal responses to both GCT and OGTT; Intermediate Group (IG) (n=15), abnormal GCT but normal OGTT; GDM group (n=16), abnormal both GCT and OGTT. RESULTS Glucose concentrations in women diagnosed with GDM were within the range of impaired glucose tolerance. There were no significant differences in concentrations of either TNF a soluble receptors R1 and R2, or sICAM-1 or sVCAM-1. LPO concentrations [MDA+4-HDA (nmol/mg protein)] were significantly higher in women with GDM than in the other two groups [64.1±24.3 (mean±SD), 39.3±23.1, 47.0±18.1, for GDM, IG and Controls, respectively; p<0.05]. In multivariate analysis, the only significant independent correlation was between LPO level and glucose at 120 minutes of OGTT (rs=0.42; p=0.009). CONCLUSIONS Oxidative damage to membrane lipids is increased in GDM and might result directly from hyperglycaemia. Physiological significance of this phenomenon remains to be elucidated.

Methods. Fasting serum levels of MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured in 26th-28th week of gestation in 51 women divided according to their response to a 50-g glucose challenge test (GCT) and a 75-g OGTT: controls (n = 20): both tests normal; the GDM group (n = 16) both tests abnormal; the intermediate group (IG; n = 15) abnormal GCT and normal OGTT. MMPs and TIMPs were correlated with the parameters of IR: homeostasis model assessment (HOMA) and insulin resistance index (IRI).Results. MMP-9, MMP-2, TIMP-1 and MMP-9/TIMP-1 ratio were not different among the groups. TIMP-2 levels were significantly higher in the GDM and IG groups than in controls (p < 0.01). MMP-2/TIMP-2 ratio was lower in the GDM group than in the other groups (p < 0.01) and was correlated to HOMA and IRI (r = -0.465 and r = -0.43 respectively, p < 0.01).Conclusions. Serum MMP levels do not reflect inflammation in GDM. Elevated TIMP-2 and consequently lower MMP-2/TIMP-2 levels in GDM need to be clarified, but are unlikely to be a consequence of inflammation.

Background. Retinol-binding protein-4 (RBP-4) may increase insulin resistance (IR) in animals, with elevated levels reported in humans with obesity and type 2 diabetes. There are, however, few data on concentrations of RBP-4 in gestational diabetes mellitus (GDM).Methods. We measured fasting serum levels of RBP-4, soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in 50 women at 28 weeks of gestation, divided according to the results of a 50g glucose challenge test (GCT) and a 75g oral glucose tolerance test (OGTT): (1) controls (n=20), normal responses to both GCT and OGTT; (2) intermediate group (IG) (n=15): false positive GCT, but normal OGTT; and (3) GDM group (n=15), both GCT and OGTT abnormal. IR was assessed by homeostasis model assessment (HOMA-IR) and by insulin resistance index (IRI) based on glycemia and insulinemia during OGTT.Results. All groups were matched for age and body mass index (BMI). RBP-4 levels (g/ml, meanstandard deviation) were higher in women with GDM vs. controls (53.917.9 vs. 29.713.9, p0.001), with a trend towards higher RBP-4 in GDM compared with IG (38.019.3, p=0.07). There was no significant correlation between RBP-4 and age, BMI, insulin, IRI or HOMA-IR, but there was a moderate, significant negative correlation between RBP-4 and sVCAM-1 (r2=0.20, p=0.001).Conclusions. RBP-4 levels are elevated in women with GDM, but do not correlate with IR indices and correlate negatively with sVCAM-1. The physiological significance of RBP-4 rise in women with GDM remains to be elucidated.

The objective of this study was to examine the retinal and pregnancy outcomes of pregnancies complicated by advanced diabetic retinopathy. Twenty pregnancies complicated by advanced diabetic retinopathy were included in this retrospective study. The data were analyzed to determine trends in perinatal outcome and to document the ophthalmologic performance. Ophthalmologic management included frequent funduscopic examinations by ophthalmologists of the Yale Retina Center. Among the 20 pregnancies, spontaneous abortion occurred in 2 (10%) and stillbirth in 1 (5%); the remaining 17 (85%) pregnancies culminated in live births at a mean gestational age of 36 weeks (+/- 2.3 SD), with a mean birth weight of 2,620 g (+/- 834 SD). The perinatal survival rate was 94%. Photocoagulation therapy was necessary prior to pregnancy in 45%, during pregnancy in 60% and postpartum in 65%. No pregnancies were terminated because of progressive visual changes that did not respond to photocoagulation therapy. Retinal status should not preclude pregnancy since contemporary methods of management can result in satisfactory retinal and pregnancy outcomes even in the presence of advanced diabetic microvascular disease.

Intensive treatment of insulin-dependent diabetes mellitus during pregnancy often normalizes plasma glucose levels. However, it is unclear whether this adversely affects other metabolic fuels that are essential to normal fetal growth and development. Metabolic studies were conducted after the subjects ingested a standardized mixed meal during each trimester in 7 normal and 15 insulin-dependent diabetic pregnant women. The latter were treated with continuous subcutaneous insulin infusion or multiple injections, which were adjusted to achieve strict glucose control throughout pregnancy. Insulin, alanine, branched-chain amino acids, triglycerides, free fatty acids, and ketones were measured every 15 to 30 minutes before a standardized breakfast and for 150 minutes after the breakfast. Patients with insulin-dependent diabetes mellitus were studied while they received their unusual insulin dosages. Fasting glucose levels (87 +/- 7 mg/dl) and glucose levels 150 minutes after the meal (112 +/- 11 mg/dl) were near normal. However, normoglycemia was achieved at the expense of increased plasma insulin levels (area under insulin response curves, p less than 0.01, vs nondiabetic curves). Nevertheless, fasting and post-prandial plasma branched-chain amino acids, alanine, and free fatty acids were similar in both groups. Fasting cholesterol, triglyceride, and ketone levels were also normalized. We conclude that normalization of circulating amino acids and lipids in conjunction with correction of hyperglycemia may contribute to favorable outcomes in infants of intensively treated diabetic mothers.

Although the 1-hour 50 gm blood glucose screening test is an effective way of detecting diabetes in pregnancy, the taste of available glucose drinks often creates gastrointestinal symptoms and leads to refusal of the patient to be tested. The efficacy of a virtually tasteless glucose polymer in testing carbohydrate tolerance in pregnancy was determined. Sixty-one pregnant patients undergoing screening for gestational diabetes underwent a 1-hour carbohydrate tolerance test of both glucose and a glucose polymer within 3 days of each other. Analysis of the data revealed a high degree of agreement between the results of the 1-hour carbohydrate tolerance test (k = 0.62, p < 0.0001). These data suggest that glucose polymer can be used effectively in screening for gestational diabetes.