Resistin is a cysteine-rich adipokine originally described as a molecular link between obesity and insulin resistance in rodents. In this study, we hypothesised that serum resistin concentrations are elevated in patients with gestational diabetes mellitus (GDM) when compared with pregnant women with normal glucose tolerance (NGT) and related to proinflammatory interleukin-6 (IL-6) and other factors conferring insulin resistance. Serum resistin and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA) in 81 women with GDM, 82 women with NGT between 24 and 31 weeks of gestation and 25 healthy non-pregnant women. Resistin concentrations were significantly higher in the GDM (21.9 [17.55-25.40] ng/ml) than in the NGT group (19.03 [15.92-23.91] ng/ml, p = 0.047), as well as in the non-pregnant women (14.8 [13.7-16.6] ng/ml, p < 0.0001). Serum IL-6 levels were elevated in the GDM (1.0 [0.7-1.5] pg/ml) as compared with the NGT group (0.8 [0.5-1.1] pg/ml, p = 0.006) and the non-pregnant controls (0.7 [0.5-1.1] pg/ml, p = 0.04). Multiple regression analysis revealed that in the pregnant women circulating resistin was related to serum IL-6 (beta = 0.33, p = 0.0004) but not to insulin or the index of insulin resistance. It is concluded that the finding of high resistin and IL-6 levels in women with gestational diabetes might confirm a role of low-grade inflammation in the pathogenesis of GDM.

Plasma concentrations of adiponectin, tumor necrosis factor-alpha (TNF-alpha) and its soluble receptors sTNFR-1 and sTNFR-2 were measured in 80 patients with gestational diabetes (GDM) (mean age 29.0 +/- 4.9 years) and 30 pregnant women with normal glucose tolerance (NGT) (mean age 28.2 +/- 6.0 years). We found that GDM patients had significantly lower concentrations of adiponectin (11.28 +/- 5.91 vs. 16.31 +/- 6.04 microg/ml, p = 0.00009) and elevated levels of TNF-alpha (1.71 +/- 0.92 vs. 1.27 +/- 0.42 pg/ml, p = 0.0175) in comparison to NGT women. The differences remained statistically significant after adjusting for BMI. Plasma levels of sTNFR-1 and sTNFR-2 also tended to be higher in GDM patients. In the GDM group TNF-alpha concentrations correlated significantly with sTNFR-1 (r = 0.444, p = 0.00008), sTNFR-2 (r = 0.364, p = 0.0016) and with C-peptide concentrations (r = 0.318, p = 0.016), whereas in women with NGT TNF-alpha correlated only with TG levels (r = 0.50, p = 0.024). Multivariate linear regression analysis revealed that prepregnant BMI was the most predictive indicator of TNF-alpha concentrations in GDM women. TG concentrations as well as BMI before pregnancy and at the time of sampling in pregnant NGT women were significant predictors, explaining 62% of the variance in TNF-alpha concentration. There were also negative correlations between adiponectin concentrations and a pregestational BMI (r = - 0.298, p = 0.009), BMI at the time of sampling (r = - 0.239, p = 0.034) and TG concentrations (r = - 0.379, p = 0.039) in GDM patients, whereas women with NGT showed only a negative correlation between adiponectin and TG concentrations (r = - 0.488, p = 0.025). In a multivariate regression analysis, prepregnancy BMI and TG levels remained significant predictors, explaining 39% of the variation in plasma adiponectin concentration in GDM women. In conclusion, our results suggest that decreased adiponectin concentration in GDM may not simply reflect maternal adiposity and insulin resistant state, but may contribute to the impaired glucose metabolism during pregnancy, with potential implications for screening and prevention of the disease.

In this study we measured serum concentrations of proinflammatory interleukin-6, interleukin-8, and interleukin-18 as well as anti-inflammatory interleukin-10 in 30 pregnant women with normal glucose tolerance, in 32 women with abnormal results of a 50-g glucose challenge test, and in 57 patients with gestational diabetes mellitus. Patients with gestational diabetes had significantly higher IL-6 (median 1.0 [0.7-1.5] vs. 0.7 [0.4-0.8] pg/ml, p=0.001), IL-8 (2.1 [1.1-4.2] pg/ml vs. 0.7 [0.4-0.9] pg/ml, p<0.0001), and IL-18 (249.3 [188.5-318.7] pg/ml vs. 186.7 [139.9-243.9] pg/ml, p=0.005) as well as lower IL-10 levels than healthy pregnant women (0.6 [0.5-1.5] pg/ml vs. 2.9 [1.8-3.2] pg/ml, p<0.0001). After adjusting for glucose, insulin, and BMI values, the differences in IL-8 and IL-18 became insignificant, whereas the differences in IL-6 and IL-10 levels remained highly significant (p<0.0001). The subjects with abnormal glucose challenge test results had higher IL-6 levels (0.9 [0.7-1.3] pg/ml, p=0.005) and similar levels of other cytokines as compared with the women with normal glucose tolerance. Our results suggest an impaired balance between circulating pro- and anti-inflammatory cytokines in patients with gestational diabetes; however, a significant contribution of maternal obesity to the increased levels of IL-8 and IL-18 should be underlined.

The aim of this study was to evaluate lipid peroxidation and scavenging enzyme activity in streptozotocin-induced diabetes, and then to establish whether moderate doses of nonenzymatic antioxidant vitamin E play a role in the antioxidant defence system in diabetic pregnant rats and their offspring. The study group consisted of 30 normal female Wistar rats, which were given a single dose of streptozotocin (40 mg/kg) and were mated 7 days later. Subsequently, the diabetic animals were divided into two matched groups: the first supplemented with vitamin E (30 mg/100 g chow), and the other fed with a standard diet lacking vitamin E. Controls consisted of 15 pregnant rats. On the first day after delivery, the rats were decapitated and homogenates of maternal liver and uterus as well as neonatal lungs and liver were prepared. Then the following parameters were measured: malondialdehyde (MDA) concentrations in the homogenates and blood serum, glutathione (GSH) levels, the activity of CuZn-superoxide dismutase (SOD) and glutathione peroxidase (GPx), and glycaemia. The neonates of diabetic rats were smaller than the healthy ones and serum glucose concentration was markedly higher in the diabetic animals. MDA levels were significantly increased, whereas GSH, SOD and GPx were markedly diminished in the diabetic adult rats and their offspring in comparison to the control group. In the animals supplemented with alpha-tocopherol, MDA concentrations were significantly lower, GSH content and SOD activities were markedly elevated most tissues studied, whereas GPx remained unchanged. We conclude that, by monitoring the activity of selected scavenging enzymes, information on ongoing biological oxidative stress and thereby on the fetus/neonate status may be obtained. Our results suggest that diabetic pregnant rats and their neonates are exposed to an increased oxidative stress and that vitamin E supplementation may reduce its detrimental effects.

OBJECTIVE -In some studies, fasting and postload glycemia are a strong predictor of coronary events and cardiac death. Therefore, we investigated the relationship between fasting and postload glucose concentrations and coronary status in 363 men referred for coronary arteriography without a previous history of diabetes.RESEARCH DESIGN AND METHODS -A total of 363 men (mean age 53.0 Ϯ 9.1 years, mean BMI 27.9 Ϯ 3.7 kg/m 2 ) with positive results of exercise testing were included in the study. A standard oral glucose tolerance test (OGTT) with glucose and insulin estimations was performed on all subjects. The concentrations of total cholesterol, HDL cholesterol, triglycerides, and HbA 1c were also measured. All patients were divided into four groups, according to coronary status: no changes in coronary arteries (group 0, n ϭ 61), one-vessel disease (group I, n ϭ 113), two-vessel disease (group II, n ϭ 116), and three-vessel disease (group III, n ϭ 73).RESULTS -The highest postload glucose concentrations were observed in group III. Also, insulin concentrations and HbA 1c increased with the progression of atherosclerotic lesions in the coronary arteries. Based on results of the OGTT, 16% of the patients (n ϭ 59) fulfilled the World Health Organization criteria for type 2 diabetes and 36% of the patients (n ϭ 131) met criteria for impaired glucose tolerance. Significant correlations were observed between the number of involved vessels and postload glycemia, HbA 1c , fasting insulin, and postload insulin. The multiple stepwise regression analysis showed that age, total cholesterol, and HDL cholesterol independently correlated with the number of involved vessels. CONCLUSIONS -We conclude that patients with advanced changes in the coronary arteries experience more pronounced metabolic disturbances. Postload glycemia could be an important predictor of nondiagnosed disturbances of glucose metabolism.

Irisin is a novel myokine and adipokine which induces an increase in total body energy expenditure, improving insulin sensitivity and glucose tolerance in experimental animals. In the present study, serum irisin concentration was measured by an enzyme immunoassay in 130 women with gestational diabetes mellitus (GDM) and 140 BMI-matched patients with normal glucose tolerance (NGT). Median irisin level was significantly lower in the patients with GDM than in the NGT subjects (1703.3 [1354.8-2097.9 ng/ml] versus 1873.8 [1519.8-2294.8 ng/ml], p = 0.01); however, 3 months after childbirth its concentrations did not differ markedly between the two groups (1165.9 [872.1-1497.5] ng/ml versus 1139.0 [984.0-1376.7] ng/ml). In the whole group, irisin concentration correlated negatively with 2 h glucose level (R = -0.14, p = 0.03). In the women with NGT, irisin concentration correlated positively with IS(OGTT) (R = 0.22, p = 0.04) and the disposition index (DI(120)) (R = 0.24, p = 0.03), as well as negatively with 2 h insulin level (R = -0.23, p = 0.03) and HOMA-IR (R = -0.24, p = 0.02). Multiple regression analysis revealed that 2 h glucose and DI(120) were the only variables significantly influencing serum irisin (β = 0.158, p = 0.03 and β = 0.159, p = 0.02, respectively). Our results suggest that serum irisin concentration increases markedly in pregnant women, but this increase seems to be significantly lower in patients with GDM.

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AimThe aim of the study was to compare maternal and cord blood levels of betatrophin – a new peptide potentially controlling beta cell growth - as well as in its mRNA expression in subcutaneous adipose tissue, visceral adipose tissue and placental tissue obtained from pregnant women with normal glucose tolerance (NGT) and gestational diabetes (GDM).MethodsSerum betatrophin and irisin concentrations were measured by ELISA in 93 patients with GDM and 97 women with NGT between 24 and 28 week of gestation. Additionally, maternal and cord blood betatrophin and irisin, as well as their genes (C19orf80 and Fndc5) expression were evaluated in 20 patients with GDM and 20 women with NGT at term.ResultsIn both groups, serum betatrophin concentrations were significantly higher in the patients with GDM than in the controls (1.91 [1.40-2.60] ng/ml vs 1.63 [1.21-2.22] ng/ml, p=0.03 and 3.45 [2.77-6.53] ng/ml vs 2.78 [2.16-3.65] ng/ml, p=0.03, respectively). Cord blood betatrophin levels were also higher in the GDM than in the NGT group (20.43 [12.97-28.80] ng/ml vs 15.06 [10.11-21.36] ng/ml, p=0.03). In both groups betatrophin concentrations in arterial cord blood were significantly higher than in maternal serum (p=0.0001). Serum irisin levels were significantly lower in the patients with GDM (1679 [1308-2171] ng/ml) than in the healthy women between 24 and 28 week of pregnancy (1880 [1519-2312] ng/ml, p=0.03). Both C19orf80 and Fndc5 mRNA expression in fat and placental tissue did not differ significantly between the groups studied.ConclusionsOur results suggest that an increase in maternal and cord blood betatrophin might be a compensatory mechanism for enhanced insulin demand in GDM.