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Introduction: Early diagnosis and adequate care of gestational diabetes is of great importance for both the mother and her fetus. Although several national and international guidelines are known on the methodology for screening gestational diabetes, a not negligible part of the cases remain unrecognized when applying even the most widely used criteria recommended by the World Health Organization (1st recommendation). A connection has been found between the maternal blood glucose values and the prevalence of still-birth, preeclampsia and large for gestational age neonates in several studies, from which the Hyperglycaemia and Adverse Pregnancy Outcomes study has come into prominence. According to conclusions of this study the International Association of Diabetic Pregnancy Study Groups suggested new numeric criteria for the evaluation of the 75-gramm oral glucose tolerance test (2nd rercommendation), which differs from the evaluation used in the afore mentioned screening system. Aims: The aim of the study was to compare the effectiveness of the two screening systems by evaluation of the pregnancy outcomes. Methods: By following non-twin pregnancies of 1107 pregnant mothers (831 with normal glucose tolerance, 276 with gestational diabetes based on any of the applied screening methods) the maternal (pre- and postterminal birth, caesarean section, toxaemia) and newborns pregnancy outcomes (infants small and large for gestational age, hypoglycaemia) were analysed. Results: With the exception of the prevalence of large for gestational age infants – which was higher among women screened by the new evaluation – no substantial difference in the efficacy of the two investigated methods was found. Conclusion: The decision whether the screening of gestational diabetes using the new criteria results in safer recognition of the disturbances of glucose metabolism during pregnancy requires further investigations including a large number of cases. Orv. Hetil., 2013, 154, 776–783.

OBJECTIVE: Human fetuin/alpha(2)-HS-glycoprotein (AHSG) is a 49 kDa serum and tissue protein which is a natural inhibitor of insulin receptor signaling. We investigated serum AHSG levels during pregnancy and whether the protein is involved in insulin resistance observed in healthy pregnant women and patients with gestational diabetes. DESIGN: One hundred and four healthy pregnant women and 23 of their neonates, 30 patients with gestational diabetes and their neonates and 30 healthy age-matched non-pregnant females as a control group were investigated in a case-control cross-sectional study. METHODS: Serum AHSG was determined by radial immunodiffusion. RESULTS: We observed an increase of serum AHSG concentration in the second and third trimesters. Gestational diabetes patients had significantly higher AHSG levels than healthy pregnant women and non-pregnant controls. There was a highly significant positive correlation between serum AHSG concentration and indirect parameters of insulin resistance, i.e. tumor necrosis factor-alpha (TNF-alpha), leptin, C-peptide and C-peptide/blood glucose ratio. There was also a negative correlation between maternal AHSG, TNF-alpha, leptin levels and head circumference, body length and body weight of newborns. CONCLUSION: AHSG, TNF-alpha and leptin may contribute to insulin resistance during normal pregnancy and gestational diabetes. AHSG along with these cytokines may also negatively regulate neonatal skeletal development.

The aim of the study was to investigate the pathophysiological role of the tumor necrosis factor (TNF) system in insulin resistance in patients with gestational diabetes (GDM) and during the course of normal pregnancy.Thirty women with GDM (16-39 gestational weeks), 35 healthy pregnant women (15 first, nine second and 11 third trimester) and 25 healthy age-matched non-pregnant women were studied. Serum TNF-alpha, and its soluble receptors 1 and 2 (sTNFR-1 and -2) were measured.In non-diabetic pregnant women in the third trimester all measures were significantly higher (P0.05 or less) than in the first trimester and in non-pregnant women (BMI 27.6 +/- 4.1 (+/- S.D.), 24.1 +/- 2.6, 22.4 +/- 2.4 kg/m(2)), serum TNF-alpha (4.6 +/- 0.6, 4.1 +/- 0.4, 4.1 +/- 0.4 ng/l), sTNFR-1 (2.7 +/- 0.9, 2.0 +/- 0.5, 2.0 +/- 0.1 microg/l), sTNFR-2 (5.6 +/- 2.6, 4.6 +/- 2.1, 3.3 +/- 0.2 microg/l), C-peptide (3.1 +/- 1.7, 1.1 +/- 0.7, 1.1 +/- 0.8 microg/l), and C-peptide:blood glucose ratio (0.6 +/- 0.2, 0.2 +/- 0.1, 0.2 +/- 0.1 microg/mmol). In GDM these measures were even higher than in any subgroup of healthy pregnant women (BMI) (33.4 +/- 6.4 kg/m(2), TNF-alpha) (6.3 +/- 0.6 microg/l), sTNFR-1 (3.0 +/- 0.5 microg/l), sTNFR-2 (10.0 +/- 6.9 microg/l, C-peptide 6.0 +/- 2.7 microg/l, C-peptide:blood glucose ratio: 1.2 +/- 0.5 microg/mmol, P0.01). Significant (P0.01) positive linear correlations were found in gestational diabetic and non-diabetic women between serum TNF-alpha, C-peptide levels, and BMI. In gestational diabetic women, in multivariate analysis studying the dependency of C-peptide only BMI remained significant (r(2)=0.67, P=0.01).Our observation emphasizes the obesity-related component of insulin resistance driven by adipocytokines, such as TNF-alpha and its receptors during the course of normal pregnancy and GDM.

Metabolic characteristics of physiological and diabetic pregnancies are discussed. The basic factor of these changes is the increasing insulin resistance throughout pregnancy, which in case of diabetes may result in hyperglycemia with undesirable clinical consequences and complications for both the mother and the fetus. Prevention of these complications by maintaining physiological metabolic state of diabetic pregnant women is possible, which is similar to that of healthy women. The aim of treatment of pregnant diabetics is to achieve normoglycemic state during the whole gestation that is possible by early diagnosis in case of gestational diabetes and by an adequate preconceptional care in case of pregestational diabetes. To obtain desirable glycemic conditions insulin treatment is necessary in most of the cases together with an adequate, quantitative nutrition therapy, while oral antidiabetic drugs during pregnancy and lactation are to be avoided. For adequate care of the cases with diabetes and pregnancy interdisciplinary diabetes centers with well-trained experts are required. Orv. Hetil., 2011, 152, 1635–1640.

To study fasting biologically active serum ghrelin (RIA) and resistin (ELISA) levels in different trimesters of pregnancy (HP, n=45, 15 in each) and in gestational diabetes mellitus (GDM, n=30) compared to non-pregnant healthy women (NP, n=40) in correlation with TNF-alpha, soluble (s)TNF-receptor (R)-1, -2, leptin (ELISA), C-peptide (Cp, RIA) and Cp/blood glucose ratio (bg).Cross-sectional case control study.Acylated ghrelin levels were significantly increased (p0.0001) in the 2nd (377+/-38pg/ml, X+/-S.D.) and decreased in the 3rd trimester (252+/-36) and in GDM (226+/-21) compared to NP controls (309+/-20) and HP women in the 1st trimester (314+/-41). Serum resistin levels were higher in the 1st (8.5+/-2.6ng/ml), 2nd (10.2+/-2.1) and 3rd (13.1+/-3.6) trimesters of pregnancy and in GDM (15.7+/-3.5) than in NP controls (6.5+/-2.3). Significant (p0.01) negative linear correlations were found among fasting serum ghrelin and body mass index (BMI), the fasting C-peptide (Cp) level, C-peptide/blood glucose (Cp/bg) ratio, TNF-alpha, soluble (s)TNFR-2, leptin and resistin concentrations in both, HP and GDM groups. Significant positive correlations were observed between serum acylated ghrelin and adiponectin, and between BMI and fasting Cp, Cp/bg, TNF-alpha, sTNFR-1, -2 and leptin levels in both pregnant groups.Increased fasting serum acylated ghrelin concentrations in the 2nd trimester may associate with weight gain during pregnancy. Hyperresistinemia may also be associated with the pregnancy-induced insulin resistance. A negative regulatory feed-back mechanism between resistin, TNF-alpha and ghrelin may be hypothesized.

Lindsay et al. (1) recently published an article in Diabetes Care that claims adiponectin is present in the cord blood of the offspring of diabetic and nondiabetic pregnant mothers and that its level does not correlate with their birth weight and skinfold thickness. Our data, obtained from a case-control study of nondiabetic women and women with gestational diabetes mellitus (GDM), further support the role of adiponectin in insulin resistance. We observed significantly decreased plasma adiponectin levels (7.55 ± 2.04 μg/ml [means ± SD]) using radioimmunoassay (Linco Research, St. Charles, MO) (intra-assay precision coefficient of variation [CV] 3.86%, interassay CV 8.47%) in 30 women with GDM, all of whom were treated with insulin (aged 28.12 ± 2.71 years, gestational age 27.35 ± 6.15 weeks), compared with 40 nondiabetic pregnant women tested with oral glucose tolerance test (OGTT) (total group 9.91 ± 3.32, P < 0.01, Mann-Whitney, aged 26.91 ± 2.65 years, gestational age …

We studied 374 pregnant diabetic women to determine the value of various ultrasound parameters in the prediction of fetal macrosomia. The correlation between ultrasonographic signs and maternal glycaemia in the development of fetal macrosomia was also studied. Significant correlation was observed between the accurence of hydramnios and future macrosomia during the second-trimester (p less than 0.001). Serum fructosamine levels as an index of maternal glycaemia in patients of macrosomic fetuses were significantly higher throughout the pregnancy as compared with mothers of infants with normal birth weight (p less than 0.001). These data suggest: 1. The presence of hydramnios in the second trimester is a useful predictor of macrosomia in diabetic patients (specificity: 86%, negative predictive value: 88%). 2. Maternal diabetic control during pregnancy has a significant influence on fetal growth and contributes to the development of fetal macrosomia. 3. The lack of correlation between the frequency of hydramnios and fructosamine levels suggests that a mechanism other than carbohydrate metabolism also plays an important role in the development of fetal macrosomia.

A method has been worked out for the intensive care of pregnant diabetics with the object of preventing damage both to the mother and the fetus. The method requires close cooperation between a team of doctors including obstetrician, internist and pediatrician. The present paper reports the experience of the first two years of application of the method and refers to a total of 75 women. The main point consists in an attempt to maintain a normal blood glucose level by administering increasing doses of insulin. Periods of inpatient management alternated with close outpatient control. Of the 75 insulin-dependent diabetics 45% had severe diabetes (White classes D-F); nevertheless, perinatal mortality was only 5.78 per cent. It is worth stressing that the 25 diabetics who came under intensive care before conception or in the early stages of pregnancy all gave birth to live healthy babies.

The longitudinal examination of 132 pregnant diabetic women under care showed a 96.2% prevalence of gingivitis. The intensity of gingivitis was most marked in weeks 11 to 15, and 24 to 26 of pregnancy, and the correlation with changes in oral hygiene was statistically significant (p less than 0.001). On the other hand, the severity of diabetes had no effect on the degree of gingival inflammation. As for caries, the mean DMF values increased during diabetic pregnancy, the number of carious (D) and filled (F) teeth to a higher, that of extracted (M) teeth to a lesser degree, than in diabetic non-pregnant women.

Serum C-peptide concentrations at delivery and neonatal complications were investigated in a group of diabetic mothers and in their infants (IDM, n = 29). Furthermore, the changes in B-cell function and in daily insulin demand was followed up in 12 pregnant diabetics (of them 8 with long-term and 4 with short-term and "mild" diabetes) during pregnancy. All these diabetic mothers were under an intensive metabolic control with the aim to achieve normoglycaemia mainly in the second part of pregnancy. Mean cord blood C-peptide level of 29 IDM was 0,58 +/- 0,43 nmol/l, being not significantly higher than either the average C-peptide concentration of our adult control group (0,50 +/- 0,15 nmol/l, n = 24) or that of seven infants born to healthy mothers (0,58 +/- 0,37 nmol/l). Early hypoglycaemia was observed in five, macrosomia in three and IRDS in one neonate, resp. mothers coming to our intensive care after the 13th week of gestation gave birth with a higher incidence of neonatal complications than those controlled already in the first trimester or even preconceptionally. In 20 of 25 mothers studied venous C-peptide concentrations at delivery were undetectably low, in spite of their infants having cord blood C-peptide levels in the measurable range. In 8 of the 12 diabetic mothers with long-term diabetes C-peptide levels remained under the detection limit of the assay throughout pregnancy. In the 4 other cases with "mild" diabetes (and, hence, with a late start of intensive control) C-peptide values increased in the course of pregnancy; however, 3 of the four mothers gave birth with neonatal complications. These results indicate that (1) early--preferably preconceptional--intensive metabolic control of pregnant diabetics may reduce the incidence of neonatal complications; (2) fetal C-peptide can neither during pregnancy nor at birth pass through the placental barrier, and (3) mothers with "mild" diabetes require the same early and strict metabolic control as the more severe cases to avoid neonatal complications.

ZusammenfassungDie Autoren berichten über eine Gelfiltrationsmethode zwecks paralleler, gleichzeitiger Bestimmung des sogenannten „freien“ markierten Trijodthyronins und Thyroxins. Die praktischen Ergebnisse werden mit Daten über die „freie“ 131J-Trijodthyronin-Menge verglichen, die an einem größeren Krankengut gewonnen wurden.