Glucose transporters (GLUT 1, GLUT 3) mRNA in human placenta of diabetic and non-diabetic pregnancies.

Glucose transporters (GLUT) catalyse the transport of glucose in many human tissues, including the placenta. On the other hand glucose concentrations can affect both glucose transport activity and level of GLUT mRNA and protein. Up to now very few studies, concerning GLUT in the placenta appeared and studies in vivo in human diabetic pregnancy are lacking. Therefore we investigated placental GLUT 1 and GLUT 3 mRNA in 10 diabetic (5 IDDM, 2 NIDDM, 3 GDM) and 9 non-diabetic women. GLUT 1 mRNA was found significantly correlated with maternal age (> 30 vs < 30 years: p < 0.025), with placental weight (> 575 vs < 575 g: p < 0.05), while GLUT 3 mRNA decreased significantly in late gestation of diabetic women (38-40 vs < 38 weeks: p < 0.025). In addition GLUT 3 was significantly lower in the diabetic than in non-diabetic women in late gestation. These preliminary results deserve to better elucidate feto-maternal carbohydrate metabolism at the placental level in normal as well as diabetic pregnancy.

Levels of advanced glycosylation end-products (AGE) in sera of pregnant diabetic women: comparison between type 1, type 2 and gestational diabetes mellitus.

The chronic hyperglycemia can lead to an increase of the advanced glycosylation end-products (AGE) levels on proteins and macromolecules. Abnormal levels of AGE in several tissues has been associated with the pathogenesis of late diabetic complications. In diabetic pregnant women, high AGE levels might influence the delicate maternal-fetal balance and therefore alter the pregnancy outcome. In this preliminary study, we have measured the AGE in sera of 44 diabetic women in two trimester. Sixteen sera from non diabetic pregnant women have been used as controls. The AGE have been analyzed by means of an ELISA method with an antiserum anti-RNAse-AGE, produced in the Laboratory of Clinical Biochemistry of the Istituto Superiore di Sanità. Diabetic patients type 1 and type 2, in good metabolic control, showed normal AGE levels at both trimester. Patients with gestational diabetes showed significantly high serum AGE levels (p < 0.05). A more extended study will give better insight on the association between AGE levels and a physiopathology of diabetic pregnancy.

Autoimmune markers of diabetes in diabetic pregnancy.

Gestational diabetes mellitus (GDM) has been described in 1-3% of pregnancies and increases the risk (up to 60-70%) to subsequently developing an overt diabetes (generally of type 2 non insulin-dependent diabetes mellitus (NIDDM)). Several humoral autoimmune phenomena have been described in GDM: islet cell antibodies (ICA) have been found and it was shown that ICA+ patients tend to have a worse glucose tolerance. Recently, autoantibodies against glutamic acid decarboxylase (GAD), were detected in type 1 diabetic sera before or at the onset of the disease; these markers, as well as ICA and insulin antibodies, seem to have a predictive value for the onset of the disease. Aim of our study was to investigate the presence of GAD65 in 83 GDM, 79 NIDDM and 64 pregnant normal women in late gestation. GAD Ab positivity was found (0.035 index as limit) only in GDM and NIDDM (3.6% in GDM, 3.8% in NIDDM, and nothing in control women). These results indicate that GAD positivity in GDM overlaps that of NIDDM, suggesting that the two diabetic populations have the same predisposition to develop a type 1 diabetes mellitus, and likely they share the same disease. Further studies need to clarify whether this prevalence of GAD positivity may unmask type 1 diabetes in both GDM and NIDDM diabetic women.

Glucose transporter (Glut1, Glut3) mRNA in human placenta of diabetic and non-diabetic pregnancies.

Transport of glucose into the cell is catalyzed by glucose transporters (Glut). Glut1 and Glut3 are expressed at various levels in many human tissues, including the placenta. It has been reported that ambient glucose can affect both glucose transport activity and expression of the Glut genes, and protein. To date, very few studies concerning Glut in the placenta have been published, and studies in vivo in human diabetic pregnancy are lacking. We therefore investigated placental Glut1 and Glut3 mRNA by Northern blot analysis in ten diabetic (five insulin dependent diabetes mellitus (IDDM), two non-insulin dependent diabetes mellitus (NIDDM) and three gestational diabetes mellitus (GDM)) and nine non-diabetic women. The quantitative results of specific mRNA/beta-actin ratios were expressed as arbitrary units. The results were evaluated according to metabolic and clinical findings. Glut1 and Glut3 mRNA values in diabetic and non-diabetic pregnant women were similar. The metabolic environment seems to affect the Glut3 mRNA levels in IDDM pregnant women but not the control women. In addition, Glut3 mRNA decreased in late pregnancy in the diabetic but not in the control women. Moreover, Glut1 mRNA levels were correlated with maternal age in the diabetic as well as in the control women (significantly). Finally, an inverse correlation was found between Glut1 mRNA levels and placental weight (in both diabetic and non-diabetic women). These results, although preliminary, shed some light on the function of these glucose transporters in normal as well as in diabetic pregnancies and prompt us to carry out a further investigation to better elucidate fetomaternal metabolic correlation at the placental level.

Amniotic fluid insulin and C peptide levels in diabetic and nondiabetic women during early pregnancy.

Thanks to the widespread use of amniocentesis, glucose, insulin, and C peptide have often been measured in amniotic fluid (AF) during late gestation, but little is known about their concentrations during early pregnancy. To better understand early fetal beta-cell function under normal conditions and in the presence of maternal diabetes, we measured glucose, insulin, and C peptide in the AF collected during weeks 15-22 in 77 healthy and 9 diabetic women undergoing amniocentesis for clinical indications and compared the results with those obtained during late pregnancy (weeks 34-36). The AF C peptide concentration was higher in diabetic women (102 +/- 53 vs. 38 +/- 2 pmol/L), in the women with a family history of diabetes (41 +/- 6 vs. 35 +/- 2 pmol/L), after the 19th week of gestation (46 +/- 5 vs. 35 +/- 2 pmol/L; in the presence of lower glucose concentrations), and in the presence of maternal plasma glucose levels greater than 5.56 mmol/L (42 +/- 3.5 vs. 34 +/- 2 pmol/L). The comparison between early and late gestation showed decreasing glucose and increasing C peptide concentrations in both healthy and diabetic women (in the latter, C peptide values were always 3 times higher), whereas the insulin concentration was increased in late gestation only in diabetic women. The AF C peptide/insulin molar ratio increased throughout pregnancy in both healthy (from 0.97 +/- 0.06 to 4.3 +/- 1.2) and diabetic (from 2.9 +/- 1.1 to 13.2 +/- 1.6) women. These parallel changes suggest that the fetal clearance and/or degradation of insulin and C peptide may greatly change during both normal and diabetic gestation.