Obstetric results of the multicenter, nationwide, scientific-educational program for pregnant women with gestational diabetes mellitus (GDM).

OBJECTIVES: The aim of the present study was to compare the obstetric results in women with GDM in a Polish population based on the criterion for the diagnosis of GDM. MATERIAL AND METHODS: The study was a questionnaire study covering the data of 2853 patients with GDM treated in centers nationwide in the years 2011-2013. The principles of self-control, glycemic targets and treatment were based on the then-current PDA guidelines. Analysis of the collected data included an assessment of obstetric results based on the diagnostic criteria for GDM. Depending on the result of the glucose tolerance test, the patients were divided into subgroups. RESULTS: 6.28% of births were preterm, and 47% were caesarean. A significant difference was observed in the number of preterm births between a subgroups: PDA(+) meeting only criterion 0' and a PDA(+)meeting only criterion 120' (16.67% vs. 5.83%); and between WHO(+) subgroup meeting only criterion 0' with respect to the subgroup PDA(+) meeting only criterion 0' (4.69% vs. 16.67%). Significant difference was found in the frequency of LGA between the WHO(-)PDA(+) and WHO(+)PDA(-) subgroups (6,57% vs. 14.93%), and between the WHO(-)PDA(+) group and a group of isolated hyperglycemia in 60'(6.57% vs. 12.5%). Also a significant positive correlation was observed between birth weight, the occurrence of LGA and macrosomia, and maternal weight and BMI before pregnancy. CONCLUSIONS: The results of the analysis indicate the new criteria have greater sensitivity in the prediction of prematurity and birth weight. However, it cannot be ruled out that the final results were affected by the therapeutic intervention employed.

Family, anthropometric and biochemical factors affecting birth weight of infants born to GDM women.

OBJECTIVES: Gestational diabetes mellitus (GDM) affects up to 25% of all pregnancies worldwide. If untreated, GDM leads to increased complication rates both, in the mother and the fetus. Early diagnosis and adequate management of GDM are essential to avoid macrosomia. Nonetheless, neonates born to GDM mothers often have high birth weight. The aim of the study was to evaluate selected factors which can affect neonatal birth weight. MATERIAL AND METHODS: The study included 152 women with GDM and 58 healthy pregnant controls. Anthropometric data of both parents, maternal biochemical parameters, and neonatal birth weight were collected. RESULTS: The independent factors influencing neonatal birth weight were pregnancy duration, maternal smoking, as well as birth weight and current weight of the father. The risk of delivering a large for gestational age (LGA) infant increases with the diagnosis of GDM, higher maternal pre-pregnancy weight, and higher fasting glycaemia. No correlation between maternal fasting glycaemia, HbA1c, 1,5-AG, lipids and neonatal birth weight was found. CONCLUSIONS: Risk factors for LGA include gestational diabetes, high maternal pre-pregnancy weight, and current body weight of the father. Neither HbA1c nor 1,5-AG were reliable predictors of neonatal birth weight and occurrence of LGA in the studied population.

Continuous subcutaneous insulin infusion does not correspond with pregnancy outcomes despite better glycemic control as compared to multiple daily injections in type 1 diabetes - Significance of pregnancy planning and prepregnancy HbA1c.

OBJECTIVE: The aim of the study was to compare pregnancy outcomes with glycemic control, total increase in insulin requirement, and body weight gain in the women with Type 1 Diabetes Mellitus (T1DM) using continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). MATERIAL AND METHODS: This was a single center retrospective observational study involving 209 pregnant Caucasian women. Among the study participants, 95 subjects were treated with MDI and 114 patients were using CSII therapy. The primary outcomes were pregnancy results, while secondary ones were HbA1c, increase in daily dose of insulin (DDI), and body weight gain. RESULTS: At baseline, the CSII users were older (P = 0.0373), they were diagnosed with T1DM at a younger age (P = 0.047), and more often planned pregnancy (P = 0.032). A majority of the women were classified as class D, according to the White classification. Among the CSII users, a significantly higher proportion of the subjects in class B was noted than in the MDI users, with no differences in the proportion of the remaining White classes. Prepregnancy HbA1c was insignificantly lower in the CSII group, however, a significantly higher proportion of the CSII users reached the target value of HbA1c (P = 0.008). A prepregnancy daily dose of insulin (both total and per kg of body weight), body weight, and body mass index (BMI) did not differ between the groups. The 1st and 2nd trimester HbA1c was lower among the CSII users (6.83 ± 1.38 vs 7.52 ± 2.11%, P = 0.01 and 6.17 ± 0.9 vs 6.57 ± 1.12%, P = 0.009, respectively), while the 3rd trimester HbA1c as well as the total change in HbA1c were comparable. Neither DDI and body weight in concecutive trimesters, nor their total gestational increase, differed between the groups. The rate of pregnancy loss, such as abortions, fetal and neonatal death did not differ between the groups. As regards composite pregnancy loss, prepregnancy HbA1c was 8.41%±2.81% among the MDI cohort vs 7.22%±1.31% in the CSII users (P = 0.517). No differences were found in the gestational age at delivery, the mode of delivery, neonatal birth weight, the rate of macrosomy, LGA or SGA. A higher Apgar score was noted among the CSII users (8.63 ± 1.63 vs 8.03 ± 2.49%, P = 0.047), however, the proportion of neonates with an Apgar score lower than 7 points was similar. In the women planning pregnancy, as compared to the subjects who did not, HbA1c was significantly lower in the 1st trimester, together with a significantly higher rate of the women achieving the target HbA1c value during planning as well as in the 1st trimester. In the group of women planning pregnancy, significantly lower 1st trimester HbA1c and composite outcome of pregnancy loss were observed in the CSII users vs the MDI treated women. Lack of pregnancy planning and a high HbA1c level in the 1st trimester were independent predictors of both LGA (OR = 4.99 [95%CI 1.12-21.0], P = 0.033 and OR = 3.02 [95%CI 1.19-7.65], P = 0.019, respectively) and macrosomia (OR = 8.43 [95%CI 1.36-51.93], P = 0.021 and OR = 5.47 [95%CI 1.77-16.87], P = 0.003, respectively). CONCLUSIONS: The course of pregnancy and obstetric outcomes were not dependent on the mode of insulin delivery, but only on pregnancy planning and HbA1c in early pregnancy. Further studies are needed to explore more precise parameters describing both glycemic control in pregnant women as well as perinatal infant well-being.

Parity does not affect diabetes complications in women with type 1 diabetes.

INTRODUCTION: The problem concerning the impact of pregnancy on diabetic complications is a matter for discussion as there is some evidence suggesting that pregnancy may trigger development or progression of diabetic chronic complications. However, currently available data concerning this issue is still controversial. OBJECTIVE: The aim of the study was to evaluate the impact of obstetric history on the development of chronic microangiopatic and macroangiopatic complications in type 1 diabetic women. MATERIAL AND METHODS: The retrospective study comprised 226 white Caucasian type 1 diabetic women, including 190 parous and 36 nulliparous women. Anthropometric data, information concerning the course of the disease, including metabolic control and chronic complications, together with obstetric history, were registered. RESULTS: Parous women were older (p<0.001), but did not differ significantly regarding metabolic control in the course of the disease (p>0.05) and diabetes duration (p>0.05) from nulliparous subjects. There were no significant differences in the incidence (p>0.05) nor onset (p>0.05) of chronic diabetes complications between the groups. The number of deliveries did not correlate with either the incidence nor the onset of chronic complications. Longer DM duration at the moment of first delivery was related to the higher incidence of retinopathy (p<0.01), nephropathy (p<0.05) and neuropathy (p<0.001). CONCLUSIONS: The incidence of chronic diabetic complications does not differ between parous women and the subjects that were never pregnant, and is not related to the number of pregnancies.

A comparison of the effectiveness, tolerability and safety of high and low carbohydrate diets in women with gestational diabetes.

INTRODUCTION: Nutrition therapy is an integral part of the management of gestational diabetes mellitus (GDM). Most women with GDM are treated by nutritional management alone. The goal of our study was to compare low and high carbohydrate diets in their effectiveness, safety and tolerability in women with GDM. MATERIAL AND METHODS: The study group consisted of 30 Caucasian women newly diagnosed with GDM, with a mean age of 28.7 +/- 3.7 years and pregnancy duration of 29.2 +/- 5.4 weeks. The patients were randomised into two groups: those on a low and those on a high carbohydrate diet (45% vs. 65% respectively of energy supply coming from carbohydrates). The presence of urine ketones was controlled every day. After two weeks daily glucose profiles and compliance with the recommended diets were analysed. RESULTS: Glucose concentration before implementation of the diet regimen did not differ between groups. No changes in fasting blood glucose were noticed in the group that had followed a low carbohydrate diet, although a significant decrease in glucose concentration was observed after breakfast (102 +/- 16 vs. 94 +/- 11 mg/dl), lunch (105 +/- 12 vs. 99 +/- 9 mg/dl) and dinner (112 +/- 16 vs. 103 +/- 13 mg/dl) (p < 0.05). In the high carbohydrate diet group fasting and after-breakfast glucose concentration did not change. A significant decrease in glycaemia was noticed after lunch (106 +/- 15 vs. 96 +/- 7 mg/dl) and dinner (107 +/- 12 vs. 97 +/- 7 mg/dl) (p < 0.05). Ketonuria was not observed in either group. Obstetrical outcomes did not differ between groups. CONCLUSIONS: Both high and low carbohydrate diets are effective and safe. A diet with carbohydrate limitation should be recommended to women who experience the highest glycaemia levels after breakfast.

Molecular chaperones in the acquisition of cancer cell chemoresistance with mutated TP53 and MDM2 up-regulation.

Utilizing the TCGA PANCAN12 dataset we discovered that cancer patients with mutations in TP53 tumor suppressor and overexpression of MDM2 oncogene exhibited decreased survival post treatment. Interestingly, in the case of breast cancer patients, this phenomenon correlated with high expression level of several molecular chaperones belonging to the HSPA, DNAJB and HSPC families. To verify the hypothesis that such a genetic background may promote chaperone-mediated chemoresistance, we employed breast and lung cancer cell lines that constitutively overexpressed heat shock proteins and have shown that HSPA1A/HSP70 and DNAJB1/HSP40 facilitated the binding of mutated p53 to the TAp73α protein. This chaperone-mediated mutated p53-TAp73α complex induced chemoresistance to DNA damaging reagents, like Cisplatin, Doxorubicin, Etoposide or Camptothecin. Importantly, when the MDM2 oncogene was overexpressed, heat shock proteins were displaced and a stable multiprotein complex comprising of mutated p53-TAp73α-MDM2 was formed, additionally amplifying cancer cells chemoresistance. Our findings demonstrate that molecular chaperones aid cancer cells in surviving the cytotoxic effect of chemotherapeutics and may have therapeutic implications.

TRIM28 and Interacting KRAB-ZNFs Control Self-Renewal of Human Pluripotent Stem Cells through Epigenetic Repression of Pro-differentiation Genes.

Reprogramming to induced pluripotent stem cells (iPSCs) and differentiation of pluripotent stem cells (PSCs) are regulated by epigenetic machinery. Tripartite motif protein 28 (TRIM28), a universal mediator of Krüppel-associated box domain zinc fingers (KRAB-ZNFs), is known to regulate both processes; however, the exact mechanism and identity of participating KRAB-ZNF genes remain unknown. Here, using a reporter system, we show that TRIM28/KRAB-ZNFs alter DNA methylation patterns in addition to H3K9me3 to cause stable gene repression during reprogramming. Using several expression datasets, we identified KRAB-ZNFs (ZNF114, ZNF483, ZNF589) in the human genome that maintain pluripotency. Moreover, we identified target genes repressed by these KRAB-ZNFs. Mechanistically, we demonstrated that these KRAB-ZNFs directly alter gene expression of important developmental genes by modulating H3K9me3 and DNA methylation of their promoters. In summary, TRIM28 employs KRAB-ZNFs to evoke epigenetic silencing of its target differentiation genes via H3K9me3 and DNA methylation.

Diabetes control and pregnancy outcomes in women with type 1 diabetes treated during pregnancy with continuous subcutaneous insulin infusion or multiple daily insulin injections.

OBJECTIVES: The aim of the study was to compare diabetes control and obstetrical outcomes in pregnant women with type 1 diabetes treated during pregnancy with either continuous subcutaneous insulin infusion (CSII) or multiple daily insulin injections (MDII). PATIENTS AND METHODS: It was a descriptive, retrospective, observational study of 116 Caucasian pregnant women with type 1 diabetes mellitus. Thirty women were treated during pregnancy with continuous subcutaneous insulin infusion (CSII group) and 86 with multiple daily insulin injections (MDII group). RESULTS: Mean age and body mass index did not differ between groups (p >0.05). Duration of diabetes was longer in CSII than in MDII group, 12.7 +/- 7.20 vs. 7.71 +/- 6.13 years, respectively (p = 0.0005). There were no differences between the studied groups in glycated hemoglobin (HbA(1c)) levels in the I, II and III trimesters of pregnancy - in CSII group 7.41 +/- 1.75, 6.57 +/- 1.09 and 6.46 +/- 0.87, respectively, in MDII group - 7.71 +/- 2.37, 6.65 +/- 1.18 and 6.75 +/- 1.21, respectively (p >0.05). There were no severe hypoglycemia and diabetic coma. Mean duration of pregnancy, rate of premature deliveries, newborn birth weight, incidence of SGA and LGA, and the frequency of neonatal hypoglycemia did not differ between groups (p >0.05). The total malformation rate was 5.13%, including 2 terminated pregnancies and the frequency did not differ between groups (p >0.05). The rate of spontaneous abortions was 16.7% in CSII group and 10.3% in MDII (p >0.05). CONCLUSIONS: No apparent relationships between mode of insulin therapy and pregnancy outcome were found in type 1 diabetes patients.

Self-monitoring of blood glucose and treatment outcomes in type 2 diabetic patients.

OBJECTIVES: The aim of the study was to evaluate an association between the frequency of blood glucose self-monitoring (SMBG) and glycemic control assessed by glycated hemoglobin (HbA1C) levels. PATIENTS AND METHODS: A group of 600 type 2 diabetic patients aged 63.4 +/- 9 years (32 to 85 years) and with a mean diabetes duration of 11.4 +/- 7.7 years (min. 1 year, max. 38 years) were asked to perform weekly blood glucose self-monitoring with an 8-point glucose profile on a chosen day. They were also asked to declare their self-monitoring frequency. HbA1C levels were measured in all the patients. RESULTS: Most of the patients reported that they performed their SMBG 1-2 times a day (44.3%) or 1-2 times a week (31.8%). All of them measured their blood glucose after an overnight fast and after breakfast. Most patients performed their measurements also after lunch and dinner. Less than 50% of patients did their measurements at night-time. The mean HbA1C level was 7.45 +/- 1.08%. Only 20% of patients achieved metabolic control of diabetes recommended by the Polish Diabetic Society (HbA1C < 6.5%). No severe hypoglycemia episodes were obsered. Glycated hemoglobin levels did not differ between the SMBG frequency groups. There was no correlation between HbA1C levels and the frequency of self-monitoring in any group. CONCLUSIONS: There was no correlation between the frequency of SMBG and HbA1C, which questions the need for multiple daily measurements of blood glucose in all type 2 diabetic patients.