Retinol binding protein as early marker of fetal growth restriction in first trimester maternal serum.

BACKGROUND: Serum retinol binding protein (RBP4) is the binding protein for retinol, being delivered into the circulation through the carrier protein transthyretin (TTR) together with thyroxin (T4). RBP4 has also been recently indicated as a new adipokine implicated in insulin resistance and metabolism regulation. OBJECTIVE: To investigate the role of RBP4 as early markers of fetal growth restriction (FGR) and preeclampsia (PE) in maternal serum during the first trimester of pregnancy. MATERIALS AND METHODS: Retrospective case control study in patients between the 12th and the 14th week of gestation. RBP4, TTR and T4 concentration was assessed in maternal serum of three groups of women: 15 and 14 patients later developing respectively FGR and PE were compared with 11 patients having a normal pregnancy. RESULTS: All women were Caucasian and the mean maternal age was 33.62 years (±5.50). RBP4 resulted lower in the FGR than in the control group (11.00 versus 16.00 µg/ml, p < 0.05) and than in the PE group (15.00 µg/ml, p = 0.075), both in bivariate and multivariate analysis. No difference was observed in TTR and T4 concentration. CONCLUSIONS: RBP4 seems to play a role as early marker of FGR but not PE in first trimester maternal serum.

Association of recreational physical activity with homocysteine, folate and lipid markers in young women.

We assessed the influence of recreational physical activity in young healthy women on homocysteine, a potential risk factor for cardiovascular disease (CVD). Participants were 124 23-year-old normal-weight Italian recreational athletes (performing 8.7 +/- 2.46 h week(-1) exercise) and 116 controls. Median blood homocysteine, folate and lipid markers did not differ between athletes and controls. Elevated homocysteine levels at CVD risk > or =12.0 and > or =15.0 micromol l(-1) were not different between groups. Continuous homocysteine was inversely related to folate (P < 0.001), positively associated with age (P = 0.009) and creatinine (P = 0.033), but not associated with hours of exercise, body mass index, and lipid markers. Women with folate depletion (<3.0 microg l(-1)) were 4.5-fold more likely to have homocysteine > or =15.0 micromol l(-1). Recreational physical exercise does not adversely impact homocysteine levels among young women. Only low folate significantly increases the risk for hyperhomocysteinemia in young women.

Effects of third-generation oral contraceptives on high-sensitivity C-reactive protein and homocysteine in young women.

OBJECTIVE: To evaluate the effect of third-generation oral contraceptives on high-sensitivity C-reactive protein (CRP), homocysteine, and lipids levels in a population of young, fertile, nonobese women. METHODS: Blood markers were evaluated in 277 healthy white women (mean age 23 years and mean body-mass index 21 kg/m(2)). Seventy-seven oral contraceptive users were compared with 200 non-oral contraceptive users. Progressive cutoffs of high-sensitivity CRP and homocysteine levels were examined. RESULTS: Levels of high-sensitivity CRP posing a high risk of cardiovascular disease (3.0 to less than 10.0 mg/L) were found in 27.3% of oral contraceptive users and in 8.5% of non-oral contraceptive users (odds ratio 4.04; 95% confidence interval [CI] 1.99-8.18). Levels of high-sensitivity CRP at intermediate risk (1.0 to less than 3.0 mg/L) were found in 32.5% of oral contraceptive users and in 11.0% of non-oral contraceptive users (odds ratio 3.89; 95% CI 2.03-7.46). Notably, non-oral contraceptive users were 8.65 (95% CI 4.39-17.1) times as likely to demonstrate a protective level of high-sensitivity CRP (less than 0.5 mg/L) compared with oral contraceptive users. Oral contraceptive use increased serum triglycerides (P<.001) and total cholesterol P=.001); however, high-density lipoprotein, not low-density lipoprotein, contributed to this increase. A decreased ratio of low-density lipoprotein to high-density lipoprotein cholesterol was observed in oral contraceptive users compared with nonusers (P=.016). Oral contraceptive use did not affect homocysteine levels. CONCLUSION: Third-generation oral contraceptive use increases low-grade inflammatory status measured by high-sensitivity CRP concentrations. Alteration of inflammatory status in oral contraceptive users could affect the risk of venous thromboembolism, cardiovascular disease, and other oral contraceptive-associated adverse conditions in young women.

Evaluation of iron deficiency in young women in relation to oral contraceptive use.

BACKGROUND: The purpose of this study was to identify the optimal measures for diagnosing iron deficiency (ID) in oral contraceptive (OC) users and nonusers, and to estimate ID frequency in relation to OC use. STUDY DESIGN: Conventional biomarkers of iron status - serum ferritin, iron, transferrin (Tf) and transferrin saturation (TfS) - were compared with serum soluble Tf receptor (sTfR) and the sTfR/log ferritin ratio (sTfR-F index). Two hundred two healthy menstruating white Italian women (aged 24+/-4.8 years) were analyzed. Serum ferritin concentrations <12 microg/L were considered as ID. RESULTS: ID was detected in 29.7% (60/202) of the study women. Fifty-nine women were OC users (59/202, 29.2%). OC use did not significantly affect ID prevalence (p=.24). However, OC use markedly increased Tf in OC users, who had an odds ratio (OR) of 9.3 (CI 3.8-22.7, p<.001) for elevated Tf >330 mg/dL. No other iron status measure was affected by OC. Of the markers for ID adjunctive to ferritin, an elevated sTfR-F index >or =1.5 showed the best performance. Specifically in OC users, the elevated sTfR-F index had better sensitivity (81.0% vs. 33.3%), specificity (94.7% vs. 92.1%), efficiency (89.8% vs. 71.2%), positive predictive value (89.5% vs. 70.0%) and negative predictive value (90.0% vs. 71.1%) than a TfS <15%. Additionally, the sTfR-F index allowed the identification of low iron stores in 4.5% (9/202) of women with ferritin > or =12 microg/L. CONCLUSION: Among healthy OC users and non-OC users, the sTfR-F index had the highest performance for diagnosing ID compared with other serum markers adjunctive to ferritin measurements, whereas sTfR by itself had a low sensitivity. We showed that neither the sTfR nor sTfR-F index was affected by third-generation OC use. The sTfR measurement is useful in the diagnosis of ID, especially in women using OC, where Tf and TfS tests may be misleading.

Prolonged exercise in type 1 diabetes: performance of a customizable algorithm to estimate the carbohydrate supplements to minimize glycemic imbalances.

Physical activity in patients with type 1 diabetes (T1DM) is hindered because of the high risk of glycemic imbalances. A recently proposed algorithm (named Ecres) estimates well enough the supplemental carbohydrates for exercises lasting one hour, but its performance for prolonged exercise requires validation. Nine T1DM patients (5M/4F; 35-65 years; HbA1c 54 ± 13 mmol · mol(-1)) performed, under free-life conditions, a 3-h walk at 30% heart rate reserve while insulin concentrations, whole-body carbohydrate oxidation rates (determined by indirect calorimetry) and supplemental carbohydrates (93% sucrose), together with glycemia, were measured every 30 min. Data were subsequently compared with the corresponding values estimated by the algorithm. No significant difference was found between the estimated insulin concentrations and the laboratory-measured values (p = NS). Carbohydrates oxidation rate decreased significantly with time (from 0.84 ± 0.31 to 0.53 ± 0.24 g · min(-1), respectively; p < 0.001), being estimated well enough by the algorithm (p = NS). Estimated carbohydrates requirements were practically equal to the corresponding measured values (p = NS), the difference between the two quantities amounting to -1.0 ± 6.1 g, independent of the elapsed exercise time (time effect, p = NS). Results confirm that Ecres provides a satisfactory estimate of the carbohydrates required to avoid glycemic imbalances during moderate intensity aerobic physical activity, opening the prospect of an intriguing method that could liberate patients from the fear of exercise-induced hypoglycemia.

Oxidative stress in patients with type 1 diabetes mellitus: is it affected by a single bout of prolonged exercise?

Presently, no clear-cut guidelines are available to suggest the more appropriate physical activity for patients with type 1 diabetes mellitus due to paucity of experimental data obtained under patients' usual life conditions. Accordingly, we explored the oxidative stress levels associated with a prolonged moderate intensity, but fatiguing, exercise performed under usual therapy in patients with type 1 diabetes mellitus and matched healthy controls. Eight patients (4 men, 4 women; 49±11 years; Body Mass Index 25.0±3.2 kg·m(-2); HbA1c 57±10 mmol·mol(-1)) and 14 controls (8 men, 6 women; 47±11 years; Body Mass Index 24.3±3.3 kg·m(-2)) performed a 3-h walk at 30% of their heart rate reserve. Venous blood samples were obtained before and at the end of the exercise for clinical chemistry analysis and antioxidant capacity. Capillary blood samples were taken at the start and thereafter every 30 min to determine lipid peroxidation. Patients showed higher oxidative stress values as compared to controls (95.9±9.7 vs. 74.1±12.2 mg·L(-1) H2O2; p<0.001). In both groups, oxidative stress remained constant throughout the exercise (p = NS), while oxidative defence increased significantly at the end of exercise (p<0.02) from 1.16±0.13 to 1.19±0.10 mmol·L(-1) Trolox in patients and from 1.09±0.21 to 1.22±0.14 mmol·L(-1) Trolox in controls, without any significant difference between the two groups. Oxidative stress was positively correlated to HbA1c (p<0.005) and negatively related with uric acid (p<0.005). In conclusion, we were the first to evaluate the oxidative stress in patients with type 1 diabetes exercising under their usual life conditions (i.e. usual therapy and diet). Specifically, we found that the oxidative stress was not exacerbated due to a single bout of prolonged moderate intensity aerobic exercise, a condition simulating several outdoor leisure time physical activities. Oxidative defence increased in both patients and controls, suggesting beneficial effects of prolonged aerobic fatiguing exercise.

Whole-body glucose oxidation rate during prolonged exercise in type 1 diabetic patients under usual life conditions.

OBJECTIVE: Fuel oxidation during exercise was studied in type 1 insulin-dependent (T1DM) patients mainly under quite constant insulin and glycemia; these protocols, however, likely do not reflect patients' usual metabolic conditions. The glucose oxidation rate (GLUox) in T1DM patients under usual life conditions was thus investigated during prolonged exercise (3-h) and its behavior was described mathematically. MATERIALS/METHODS: Whole-body GLUox was determined in eight T1DM patients (4/8 M; aged 35-59 years) and eight well-matched healthy subjects. Venous blood was drawn prior to and every 30 min until the end of exercise; glycemia, insulin, cortisol, and growth hormone concentrations were determined. Oxygen consumption, carbon dioxide production, and ventilation were measured at rest and thereafter every 30 min of the exercise. To prevent hypoglycemia, patients were given fruit fudge (93% sucrose) prior to / during exercise. RESULTS: Insulin concentration and glycemia were significantly higher in patients across the entire exercise period (group effect, p<0.001 for both). GLUox decreased significantly with increasing exercise duration (time effect, p<0.001), but no significant difference was detected between the two groups (group effect, p=NS). GLUox, expressed as the percentage of the starting value, was described by an exponential function showing a time constant of 90 min (n=96; mean corrected R(2)=0.666). CONCLUSIONS: GLUox in T1DM patients was not significantly different from the rate observed in the control subjects. The function describing the time course of GLUox may be useful to correct an estimated GLUox for the duration of exercise and help T1DM patients avoiding exercise-induced glycemic imbalances.

Anemia and iron status in young fertile non-professional female athletes.

We evaluated the effects of regular physical exercise on anemia and iron status in young non-professional female athletes. A total of 191 healthy white Italian women (23.5 +/- 4.68 years) were analyzed; 70 were non-professional athletes performing 11.1 +/- 2.63 h week(-1) exercise and 121 were sedentary controls. Blood markers of anemia and iron status-hemoglobin (Hb), hematocrit (Hct), red blood cells (RBC), serum ferritin, iron, transferrin (Tf), transferrin saturation (TfS), soluble transferrin receptor (sTfR), and the sTfR/log ferritin ratio (sTfR-F index)-were evaluated. Anemia threshold was Hb < 120 g l(-1). Ferritin concentrations < 12 microg l(-1) were considered as iron deficiency (ID). Frequency of anemia (15.7 versus 10.7%, P = 0.32), ID (27.1 versus 29.8%, P = 0.70), and ID anemia (8.6 versus 5.8%, P = 0.46) was not different in athletes and controls. However, athletes were threefold more likely than controls (17.1 versus 5.8%) to have serum iron < 50 microg dl(-1) [odds ratio (OR) 3.37, P = 0.012]. Low-TfS (<15%) was found in 25.7% of athletes and in 13.2% of controls, OR 2.27, P = 0.030. Elevated-sTfR (>1.76 mg l(-1)) was found in 24.3% of athletes and in 12.4% of controls, OR 2.27, P = 0.034. Regular non-professional sport activity does not cause an increased rate of anemia or of iron deficiency in fertile women. However, physical exercise has an impact on iron status as it reduces serum iron and transferrin saturation, and elevates sTfR. Nearly one fifth of recreational athletes have anemia and a third have iron deficit, these conditions can decrease their physical performance.

Alcohol-induced endothelial changes are associated with oxidative stress and are rapidly reversed after withdrawal.

BACKGROUND: Although heavy alcohol drinkers are at an increased risk of developing cardiovascular events, moderate alcohol intake is associated with reduced incidence of cardiovascular death. This paradox might reflect a dose-related effect of different alcohol intakes on endothelial function and this, in turn, might depend on changes in oxidative stress. METHODS: We tested the effects of alcohol withdrawal in heavy alcohol consumers and compared the plasma levels of endothelin-1, nitric oxide, plasminogen activator inhibitor-1, von Willebrand factor, malondialdehyde, and intracellular glutathione with those of alcoholics that did not modify their alcohol intake and teetotalers. In human endothelial cells that had been cultured for 2 weeks in the presence of different concentrations of ethanol, we assessed the same parameters after withdrawal of ethanol exposure. RESULTS: Alcohol increased the levels of endothelin-1, nitric oxide, and plasminogen activator inhibitor-1 and decreased the levels of von Willebrand factor both in vivo and in vitro. These changes were dose dependent, rapidly reversed after withdrawal of exposure, and associated with the presence of increased oxidative stress as indicated by increased levels of both malondialdehyde and intracellular glutathione. Blockade of oxidative stress by incubation of endothelial cells in the presence of oxidants' scavengers prevented the alcohol-induced functional modifications of the endothelium. CONCLUSIONS: Alcohol affects endothelial function with an effect that is mediated by an activated oxidative stress and is rapidly reversed after withdrawal. Dose-related endothelial responses to different alcohol intakes might translate in either vascular protection or vascular damage.