Physical activity, gestational weight gain in obese patients with early gestational diabetes and the perinatal outcome - a randomised-controlled trial.

BACKGROUND: Excessive gestational weight gain, especially among women with gestational diabetes, is associated with several adverse perinatal outcomes. Our study aimed to analyse the impact of the use of pedometers to supervise physical activity on maternal health and the obstetric outcomes of pregnant women with obesity and early gestational diabetes. METHODS: 124 pregnant patients were enrolled in the presented research. INCLUSION CRITERIA: singleton pregnancy, age > 18 years, gestational diabetes diagnosed in the first half of pregnancy (< 20th week of pregnancy), obesity according to the American Endocrine Society criteria. Each patient was advised to take at least 5000 steps daily. Patients were randomly assigned to pedometers (N = 62), and were recommended to monitor daily the number of steps. The group without pedometers (N = 62) was not observed. Visit (V1) was scheduled between the 28th and 32nd gestational week (GW), and visit (V2) occurred between the 37th and 39th GW. Anthropometric measurements and blood samples were collected from all patients at each appointment. Foetal and maternal outcomes were analysed at the end of the study. RESULTS: In the group supervised by pedometers, there were significantly fewer newborns with macrosomia (p = 0,03). Only 45% of patients satisfied the recommended physical activity guidelines. Patients who walked more than 5000 steps per day had significantly higher body weight at baseline (p = 0,005), but weight gain was significantly lower than in the group that did not exceed 5000 steps per day (p < 0,001). The perinatal outcome in the group of patients performing more than 5000 steps did not demonstrate significant differences with when compared to less active group. ROC curve for weight gain above the guidelines indicated a statistically substantial cut-off point for this group at the level of 4210 steps/day (p = 0.00001). CONCLUSIONS: Monitoring the activity of pregnant patients with gestational diabetes and obesity by pedometers did not have a significantly impact on their metabolic control and weight gain. However, it contributed to less macrosomia. Furthermore, physical activity over 5,000 steps per day positively affects weight loss, as well as contributes to improved obstetric and neonatal outcomes.

The transcriptome-wide association search for genes and genetic variants which associate with BMI and gestational weight gain in women with type 1 diabetes.

BACKGROUND: Clinical data suggest that BMI and gestational weight gain (GWG) are strongly interconnected phenotypes; however, the genetic basis of the latter is rather unclear. Here we aim to find genes and genetic variants which influence BMI and/or GWG. METHODS: We have genotyped 316 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays. The GIANT, ARIC and T2D-GENES summary statistics were used for TWAS (performed with PrediXcan) in adipose tissue. Next, the analysis of association of imputed expression with BMI in the general and diabetic cohorts (Analysis 1 and 2) or GWG (Analysis 3 and 4) was performed, followed by variant association analysis (1 Mb around identified loci) with the mentioned phenotypes. RESULTS: In Analysis 1 we have found 175 BMI associated genes and 19 variants (p < 10-4) which influenced GWG, with the strongest association for rs11465293 in CCL24 (p = 3.18E-06). Analysis 2, with diabetes included in the model, led to discovery of 1812 BMI associated loci and 207 variants (p < 10-4) influencing GWG, with the strongest association for rs9690213 in PODXL (p = 9.86E-07). In Analysis 3, among 648 GWG associated loci, 2091 variants were associated with BMI (FDR < 0.05). In Analysis 4, 7 variants in GWG associated loci influenced BMI in the ARIC cohort. CONCLUSIONS: Here, we have shown that loci influencing BMI might have an impact on GWG and GWG associated loci might influence BMI, both in the general and T1DM cohorts. The results suggest that both phenotypes are related to insulin signaling, glucose homeostasis, mitochondrial metabolism, ubiquitinoylation and inflammatory responses.

Epidemiology of gestational diabetes mellitus according to IADPSG/WHO 2013 criteria among obese pregnant women in Europe.

AIMS/HYPOTHESIS: Accurate prevalence estimates for gestational diabetes mellitus (GDM) among pregnant women in Europe are lacking owing to the use of a multitude of diagnostic criteria and screening strategies in both high-risk women and the general pregnant population. Our aims were to report important risk factors for GDM development and calculate the prevalence of GDM in a cohort of women with BMI ≥29 kg/m2 across 11 centres in Europe using the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)/WHO 2013 diagnostic criteria. METHODS: Pregnant women (n = 1023, 86.3% European ethnicity) with a BMI ≥29.0 kg/m2 enrolled into the Vitamin D and Lifestyle Intervention for GDM Prevention (DALI) pilot, lifestyle and vitamin D studies of this pan-European multicentre trial, attended for an OGTT during pregnancy. Demographic, anthropometric and metabolic data were collected at enrolment and throughout pregnancy. GDM was diagnosed using IADPSG/WHO 2013 criteria. GDM treatment followed local policies. RESULTS: The number of women recruited per country ranged from 80 to 217, and the dropout rate was 7.1%. Overall, 39% of women developed GDM during pregnancy, with no significant differences in prevalence across countries. The prevalence of GDM was high (24%; 242/1023) in early pregnancy. Despite interventions used in the DALI study, a further 14% (94/672) had developed GDM when tested at mid gestation (24-28 weeks) and 13% (59/476) of the remaining cohort at late gestation (35-37 weeks). Demographics and lifestyle factors were similar at baseline between women with GDM and those who maintained normal glucose tolerance. Previous GDM (16.5% vs 7.9%, p = 0.002), congenital malformations (6.4% vs 3.3%, p = 0.045) and a baby with macrosomia (31.4% vs 17.9%, p = 0.001) were reported more frequently in those who developed GDM. Significant anthropometric and metabolic differences were already present in early pregnancy between women who developed GDM and those who did not. CONCLUSIONS/INTERPRETATION: The prevalence of GDM diagnosed by the IADPSG/WHO 2013 GDM criteria in European pregnant women with a BMI ≥29.0 kg/m2 is substantial, and poses a significant health burden to these pregnancies and to the future health of the mother and her offspring. Uniform criteria for GDM diagnosis, supported by robust evidence for the benefits of treatment, are urgently needed to guide modern GDM screening and treatment strategies.

Functional analysis of daily glycemic profiles and excessive fetal growth in pregnant patients with well-controlled type 1 diabetes: Retrospective cohort.

AIMS: The study objective was to compare daily glycemic profiles throughout gestation between the mothers of large-for-gestational-age (LGA) and non-LGA newborns in patients with type 1 diabetes (T1D). METHODS: We selected 102 eligible pregnant women who were treated with sensor-augmented pumps in our single-center retrospective cohort study. We used functional data analysis to compare glycemic control across gestation. RESULTS: Median HbA1c values in the first, second, and third trimester were 6.23 %, 5.49 %, and 5.75 % respectively. Median time-in-range (TIR) exceeded 70 % in each trimester (72.4 %, 72.5 %, and 75.9 %, respectively). From 59 % up to 77 % of women met the criteria for well-controlled T1D defined by the mean HbA1c and TIR in each trimester. Despite that, 27 % (28/102) of pregnancies were complicated by LGA. Mothers of LGA infants had significantly increased HbA1c levels and decreased TIR values in the second and third trimesters. The most significant differences in daily mean glucose values between LGA and non-LGA newborns' mothers occurred between 26 and 32 weeks of pregnancy. These discrepancies were noted in daytime glucose values rather than nocturnal and fasting glucose levels. CONCLUSIONS: Mothers of LGA newborns present significantly worse glycemic control. Our findings may emphasize the need for more rigorous daytime glycemic control.

Multiple daily injections of insulin versus continuous subcutaneous insulin infusion for pregnant women with type 1 diabetes.

AIMS: The aim was to evaluate the outcome of pregnancies with type 1 diabetes (T1DM) treated from the first trimester with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). METHODS: In a retrospective, observational study, we matched 64 CSII patients for age, age at onset and duration of diabetes and HbA1c in the first trimester with 64 MDI pregnancies. We analysed carbohydrate metabolism, insulin requirements, development of PIH, progression of retinopathy and fetal outcome. RESULTS: In CSII group, we found a significantly smaller insulin requirement both at the beginning of pregnancy and before delivery, significant decrease in HbA1c levels and significantly smaller number of hypoglycaemic episodes in the second trimester and significantly more hyperglycaemic episodes in the first trimester. In both groups, maternal, fetal and perinatal outcomes were similar and the number of hypo- and hyperglycaemic episodes decreased throughout pregnancy. CONCLUSION: Continuous subcutaneous insulin infusion (CSII) treatment in pregnant women with type 1 diabetes is associated with a reduced number of hypoglycaemia and decreased insulin requirement. We noted no difference in perinatal outcome comparing women on multiple insulin injections with those on continuous insulin infusion.

Endometriosis is associated with an increased whole-blood thrombogenicity detected by a novel automated microchip flow-chamber system (T-TAS®).

OBJECTIVES: Potential thrombotic and antifibrinolytic influence of endometriosis on haemostasis has been recently reported in the literature, as well as increased cardiovascular morbidity in women suffering from the disease. We performed a pilot study to assess the influence of endometriosis on the thrombus formation process under in vitro flow conditions. MATERIAL AND METHODS: This study compared women with confirmed endometriosis (n = 23) surgically and control healthy subjects (n = 10). In both groups, the same exclusion criteria were used: a prior episode of thrombosis diagnosed as acquired or inherited thrombophilia, neoplasm, and an uncertain family history of thrombosis. We evaluated the whole blood thrombogenicity using T-TAS® at a shear rate of 240 s-1 (Total-Thrombus Analysis System, Zacros, Japan). RESULTS: The blood clot formation initiation time (T10) and occlusion time (OT) were significantly shortened in the endometriosis group (p < 0.05). The area under the curve (AUC30) of blood clot time formation values (BCTF) was substantially higher in the patients suffering from a disease (p = 0.03). An increase in AUC (TTAS) values by 100 increases the risk of developing endometriosis by 1.56-fold [adjusted OR = 1.56 (p = 0.01); (95% CI: 1.10-2.18)]. Inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), and the leucocyte, neutrophil, basophil, and neutrophil concentrations) were also substantially higher in the endometriosis group (p < 0.05). CONCLUSIONS: The alteration of the T-TAS® and NLR values supports the thesis of a shift of the equilibrium towards thrombosis in women who have endometriosis. This phenomenon links to a state of chronic inflammation. It is detectable using a novel system for the quantitative assessment of the platelet thrombus formation process under flow conditions in vitro.

Continuous glucose monitoring parameters in pregnancy-related complications in patients with type 1 diabetes: a retrospective cohort study.

INTRODUCTION: Continuous glucose monitoring (CGM) improves pregnancy outcomes in patients with type 1 diabetes (T1D). OBJECTIVES: The primary study objective was to analyze associations between numerous novel CGM parameters and neonatal complications, such as large­for­gestational­age (LGA) neonates, hypoglycemia, hyperbilirubinemia, transient breathing disorders, preterm births, as well as pre­eclampsia. PATIENTS AND METHODS: In this single­center retrospective cohort study, we recruited 102 eligible pregnant women with T1D who were treated with sensor­augmented pumps with suspend­before­low function from the first trimester. The pregnant patients were admitted for at least 1 control hospital visit in each trimester of gestation for anthropometric and laboratory measurements and collection of sensor data. RESULTS: The median (interquartile range) percentage values for glycated hemoglobin (HbA1c) (first trimester, 6.23 [5.91-6.9]; second trimester, 5.49 [5.16-5.9]; third trimester, 5.75 [5.39-6.29]) and for time­in­range (first trimester, 72.4 [67.3-80.3]; second trimester, 72.5 [64.7-79.6]; third trimester, 75.9 [67.1-81.4] met the criteria of well­controlled T1D in each trimester of pregnancy. Nonetheless, we noted 27% of LGA births, 25% of neonatal hypoglycemia, 33% of hyperbilirubinemia, and 13% of preterm births. Worse glycemic control and more glycemic fluctuations in the second and third trimesters were mainly associated with increased risk of LGA at birth, transient breathing disorders, and hyperbilirubinemia. CONCLUSIONS: CGM parameters (mean of daily differences, high blood glucose index, glycemic risk assessment in diabetes equation, or continuous overall net glycemic action) in the patients with T1D are significantly associated with the increased risk of LGA at birth and neonatal transient breathing disorders and hyperbilirubinemia. However, we did not find evidence that novel CGM indices could be more effective in predicting those events than the commonly used CGM parameters or HbA1c levels.

Corin-The Early Marker of Preeclampsia in Pregestational Diabetes Mellitus.

Preeclampsia (PE) is one of the leading causes of mortality and morbidity in pregnant women. Pregestational diabetes (PGDM) patients are prone to vascular complications and preeclampsia, whereas vascular exposure to hyperglycemia induces inflammation, vascular remodeling, and arterial stiffness. Corin is a serine protease, converting inactive pro-atrial natriuretic peptide (pro-ANP) into an active form. It also promotes salt and water excretion by activating atrial natriuretic peptide (ANP), and significantly increases trophoblast invasion. The study aimed to determine whether corin may be a predictor of PE in a high-risk group-women with long-term PGDM. The nested case-control prospective study involved 63 patients with long-term pregestational type 1 diabetes (PGDM). In total, 17 patients developed preeclampsia (the study group), whereas 43 patients without PE constituted the control group. To assess corin concentration, blood samples were collected at two time points: between 18th-22nd week of gestation and 28th-32nd week of gestation. PE patients presented significantly higher mid-gestation corin levels, urine protein loss in each trimester, serum creatinine in the third trimester, and lower creatinine clearance in the third trimester. The results of our study indicate that serum corin assessment may play a role in predicting preeclampsia. Thus, it may be included in the PE risk calculator, initially in high-risk groups, such as patients with PGDM.

Novel Continuous Glucose Monitoring Metrics and Large-for-Gestational-Age Risk: An Exploratory Retrospective Cohort Study in Pregnancies with Type 1 Diabetes.

Background: Continuous glucose monitoring (CGM) improves pregnancy outcomes in patients with type 1 diabetes (T1D). We aimed to assess the between-group differences in glycated hemoglobin (HbA1c) and the incidence of large-for-gestational-age (LGA) neonates in CGM and glucometer users and analyze the potential association of novel CGM metrics with LGA risk in T1D pregnancies. Materials and Methods: Our retrospective study cohort included 134 women with T1D treated with insulin pumps-75 of them used CGM and 59 patients measured their glucose concentrations using glucometers only. As part of our study, we matched the CGM users and patients who preferred the self-monitoring of blood glucose (SMBG) according to their baseline HbA1c and White's diabetes class at a 1:1 ratio. After the matching, both groups included 42 pregnancies. Results: We did not find any difference in changes in HbA1c and perinatal outcomes between CGM and SMBG users; however, we achieved a limited statistical power, and there were more cases of diabetic nephropathy in the SMBG group. Mothers of LGA infants had higher first-trimester HbA1c, time above target, and mean glucose concentrations in each trimester of pregnancy. Other CGM metrics reflecting glucose fluctuations attributed to hyperglycemia were associated with an increased risk of LGA. Despite optimal maternal HbA1c, 39% of neonates demonstrated LGA. Conclusions: Although participants reached the target HbA1c concentrations, mothers of LGA newborns had higher first-trimester HbA1c, as well as higher time above target range, higher mean glucose concentrations, and more glycemic fluctuations, suggesting that several CGM metrics associated with maternal hyperglycemia are associated with LGA in pregnancies with T1D.

[Maternal body mass index and gestational weight gain and their association with perinatal outcome in women with gestational diabetes]. / Matczyny BMI oraz przyrost masy ciala w ciazy i ich wplyw na wyniki poloznicze u kobiet z cukrzyca ciazowa.

OBJECTIVES: Maternal overweight and obesity constitute the most important factors causing perinatal complications. The purpose of the study was to analyze obstetrical results in overweight/obese pregnant women with gestational diabetes in relation to Institute of Health recommendations concerning gestational weight gain and assessment of the role of prepregnancy BMI in prediction of macrosomia, pregnancy induced hypertension and cesarean deliveries. MATERIAL AND METHODS: Retrospective analysis of 209 overweight and obese pregnant women with gestational diabetes divided into 4 subgroups according to The National Institute of Health (USA) recommendations. The following data were included in the analysis: gestational week in which GDM was diagnosed; HbA1c level in the first and third trimester just before delivery; incidence of pregnancy induced hypertension; incidence of cesarean deliveries; incidence of macrosomia. The following data of II, III, IV subgroups were compared to these found in I subgroup which was classified as the control group. Selected obstetric parameters were also compared between subgroups II, III, IV RESULTS: The selected parameters of subgroups II, III, IV were not significantly different from these of subgroup I. Pregnancy induced hypertension was diagnosed more frequently among subgroup II in comparison to subgroup III. Using ROC curves analysis, the role of pre-pregnancy BMI was found in the prognosis of: birth weight greater than 4300 g, pregnancy induced hypertension, cesarean delivery CONCLUSIONS: 1. The application of the National Institute of Health recommendations on gestational weight gain is limited in case of overweight or obese pregnant women with gestational diabetes mellitus. 2. Excessive weight gain during pregnancy according to National Health Institute recommendations may increase the risk of developing pregnancy induced hypertension in comparison to a pregnant women with weight gain less than recommended, but greater than zero. 3. Increased prepregnancy BMI has a role in prediction of birth weight greater than 4300 g, pregnancy induced hypertension, cesarean delivery

Serum Metabolomics in PCOS Women with Different Body Mass Index.

Polycystic ovary syndrome (PCOS) is the most prevalent endocrine and metabolic disorder, affecting 5-10% of women of reproductive age. It results from complex environmental factors, genetic predisposition, hyperinsulinemia, hormonal imbalance, neuroendocrine abnormalities, chronic inflammation, and autoimmune disorders. PCOS impacts menstrual regularities, fertility, and dermatological complications, and may induce metabolic disturbances, diabetes, and coronary heart disease. Comprehensive metabolic profiling of patients with PCOS may be a big step in understanding and treating the disease. The study aimed to search for potential differences in metabolites concentrations among women with PCOS according to different body mass index (BMI) in comparison to healthy controls. We used broad-spectrum targeted metabolomics to evaluate metabolites' serum concentrations in PCOS patients and compared them with healthy controls. The measurements were performed using high-performance liquid chromatography coupled with the triple quadrupole tandem mass spectrometry technique, which has highly selective multiple reaction monitoring modes. The main differences were found in glycerophospholipid concentrations, with no specific tendency to up-or down-regulation. Insulin resistance and elevated body weight influence acylcarnitine C2 levels more than PCOS itself. Sphingomyelin (SM) C18:1 should be more intensively observed and examined in future studies and maybe serve as one of the PCOS biomarkers. No significant correlations were observed between anthropometric and hormonal parameters and metabolome results.

Diagnosis of preeclampsia in women with diabetic kidney disease.

Objective: assessing the incidence of preeclampisa (PE) in women with diabetic kidney disease (DKD) and analyzing the significance of clinical characteristics and changes in laboratory findings throughout the pregnancy on the onset of PE.Methods: the study included 79 patients with DKD. All patients had elevated urinary protein loss (30-299 mg/24 h) or proteinuria (≥300 mg/24 h) in the first trimester of pregnancy. PE was diagnosed in 22,8% patients with DKD.Results: women with proteinuria and/or proliferative retinopathy at the admission developed preeclampsia significantly more frequently than those without these findings. The degree of proteinuria was significantly associated with the risk of PE development in each trimester of pregnancy. Patients with chronic hypertension developed PE significantly more frequently than those who had no chronic hypertension.Conclusion: chronic hypertension and the degree of primary kidney injury and dysfunction are crucial determinants of PE development in women with DKD. Proteinuria seems to be the best renal predictive factors of PE.

Poor glycaemic control contributes to a shift towards prothrombotic and antifibrinolytic state in pregnant women with type 1 diabetes mellitus.

OJECTIVES: Thrombotic and antifibrinolytic influence of Diabetes mellitus type 1 (T1DM) on haemostasis have been well demonstrated. There has been no research assessing the influence of poor glycemic control on thrombus formation under flow conditions in vitro or in pregnant type 1 diabetic women to date. PATIENTS/METHODS: This study compared singleton pregnant T1DM women (n = 21) and control pregnant subjects without any metabolic disease (n = 15). The T1DM group was divided into two subgroups of sufficient (SGC-DM; HbA1c ≤6,5%,n = 15) and poor glycaemic control (PGC-DM; HbA1c >6,5%,n = 6). Evaluation of the whole blood thrombogenicity we assessed using T-TAS® at a shear rate of 240 s-1 (Total-Thrombus Analysis System, Zacros, Japan). RESULTS: Blood clot formation initiation time (T10) was significantly shortened in PGC-DM subgroup when compared to SGC-DM subgroup (p = 0,03). The area under the curve (AUC30) of blood clot time formation and the MPV (mean platelet volume) values were substantially higher in the PGC-DM subgroup in comparison to the SGC-DM group (p = 0,03). Negative correlations were noted between HbA1c and T10 values (p = 0,02) and between T10 and MPV values in the T1DM group (p = 0,04). CONCLUSIONS: Poor glycaemic control in T1DM subjects triggers a shift towards a prothrombotic and antifibrinolytic state. This phenomenon can be detected using the novel system for quantitative assessment of the platelet thrombus formation process under flow conditions in vitro. The alteration of T-TAS values in PGC-DM subgroup proves that a poor glycemic control-related shift of the equilibrium toward thrombogenesis occurs in this group of patients. Our findings need a further elucidation in research on more massive data sets to be confirmed.

Pregnancy Outcomes in Women with Long-Duration Type 1 Diabetes-25 Years of Experience.

AIMS: Our study aimed to examine the pregnancy outcomes (maternal and fetal) concerning different models of antenatal care across a period of over 25 years (1993-2018) in 459 women with type 1 diabetes. Data from patients with a history of the condition lasting at least 15 years were considered eligible for analysis. METHODS: The study group was divided into three cohorts based on the different models of treatment used in Poznan University Hospital, Poland: 1993-2000 (cohort I, n = 91), 2001-2005 (cohort II, n = 83), 2006-2018 (cohort III, n = 284). To identify predictors for the selected dichotomous outcomes, we calculated the risks for fetal or maternal complications as dependent variables for cohorts II and III against cohort I, using multivariate logistic regression analysis. RESULTS: The mean gestational age was 36.8 ± 2.4 weeks in the total cohort. The percentages of deliveries before the 33rd and the 37th weeks was high. We observed a decreasing percentage during the following periods, from 41.5% in the first period to 30.4% in the third group. There was a tendency for newborn weight to show a gradual increase across three time periods (2850, 3189, 3321 g, p < 0.0001). In the last period, we noticed significantly more newborns delivered after 36 weeks with a weight above 4000 g and below 2500 g. Caesarean section was performed in 88% of patients from the whole group, but in the subsequent periods this number visibly decreased (from 97.6%, 86.7%, to 71%, p = 0.001). The number of emergency caesarean sections was lowest in the third period (27.5%, 16.7%, 11.2%, p = 0.006). We observed a decreasing number of "small for gestational age" newborns (SGA) in consecutive periods of treatment (from 24.4% to 8.7%, p = 0.002), but also a higher percentage of "large for gestational age" (LGA) newborns (from 6.1% to 21.6%, p = 0.001). Modification of treatment might be associated with the gradual reduction of SGA rates (cohort I 3.6%, cohort III 2.3% p < 0,0005). CONCLUSIONS: Strict glycemic and blood pressure control from the very beginning of pregnancy, as well as modern fetal surveillance techniques, may contribute to the improvement of perinatal outcomes in women with long-duration type 1 diabetes.

Early Screening for Gestational Diabetes Using IADPSG Criteria May Be a Useful Predictor for Congenital Anomalies: Preliminary Data from a High-Risk Population.

BACKGROUND: Our aim was to investigate whether the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) glycemic thresholds used for detecting hyperglycemia in pregnancy can be predictive for malformations in women with hyperglycemia detected in early pregnancy. METHODS: a single-center, retrospective observational trial of 125 mother-infant pairs from singleton pregnancies with hyperglycemia according to the IADPSG criteria diagnosed at the gestational age below 16 weeks. Glucose values obtained from 75-g OGTT (oral glucose tolerance test) were investigated as predictors for congenital malformations in newborns. RESULTS: Characteristics of the cohort: maternal age: 31.5 ± 5.2, pre-pregnancy body mass index (BMI) ≥ 30 kg/m2: 42.0%, gestational age at diagnosis (weeks): 12.0 ± 4.0, and newborns with congenital malformations: 8.8%. Fasting blood glycemia (FBG) and HbA1c (Haemoglobin A1c) at baseline significantly predicted the outcome (expB: 1.06 (1.02-1.1), p = 0.007 and expB: 2.05 (1.24-3.38), p = 0.005, respectively). Both the fasting blood glucose (FBG) value of 5.1 mmol/dL (diagnostic for gestational diabetes mellitus (GDM)) and 5.5 mmol/dL (upper limit for normoglycemia in the general population) significantly increased the likelihood ratio (LR) for fetal malformations: 1.3 (1.1; 1.4) and 1.5 (1.0; 2.4), respectively. CONCLUSIONS: (1) Fasting glycemia diagnostic for GDM measured in early pregnancy is associated with a significantly elevated risk for congenital malformations. (2) Our data suggest that women at elevated risks of GDM/diabetes in pregnancy (DiP) should have their fasting blood glucose assessed before becoming pregnant, and the optimization of glycemic control should be considered if the FBG exceeds 5.1 mmol/dL.

Mitochondrial GWAS and association of nuclear - mitochondrial epistasis with BMI in T1DM patients.

BACKGROUND: BMI is a strong indicator of complications from type I diabetes, especially under intensive treatment. METHODS: We have genotyped 435 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays and performed mitoGWAS on BMI. We identified additive interactions between mitochondrial and nuclear variants in genes associated with mitochondrial functioning MitoCarta2.0 and confirmed and refined the results on external cohorts: the Framingham Heart Study (FHS) and GTEx data. Linear mixed model analysis was performed using the GENESIS package in R/Bioconductor. RESULTS: We find a borderline significant association between the mitochondrial variant rs28357980, localized to MT-ND2, and BMI (ß = - 0.69, p = 0.056). This BMI association was confirmed on 1889 patients from FHS cohort (ß = - 0.312, p = 0.047). Next, we searched for additive interactions between mitochondrial and nuclear variants. MT-ND2 variants interacted with variants in the genes SIRT3, ATP5B, CYCS, TFB2M and POLRMT. TFB2M is a mitochondrial transcription factor and together with TFAM creates a transcription promoter complex for the mitochondrial polymerase POLRMT. We have found an interaction between rs3021088 in MT-ND2 and rs6701836 in TFB2M leading to BMI decrease (inter_pval = 0.0241), while interaction of rs3021088 in MT-ND2 and rs41542013 in POLRMT led to BMI increase (inter_pval = 0.0004). The influence of these interactions on BMI was confirmed in external cohorts. CONCLUSIONS: Here, we have shown that variants in the mitochondrial genome as well as additive interactions between mitochondrial and nuclear SNPs influence BMI in T1DM and general cohorts.

Maternal risk factors for neonatal acidosis in women with type 1 diabetes.

INTRODUCTION Type 1 diabetes in the mother is associated with high risk of adverse neonatal outcomes. OBJECTIVES The aim of this study was to identify maternal factors associated with low arterial pH values (pH <7.10) in infants of mothers with type 1 diabetes. PATIENTS AND METHODS Data from 789 women were included in the analysis. Based on pH values in the umbilical arteries of infants, women were divided into 2 groups: those with normal pH, defined as pH of 7.1 or higher, and those with low pH, defined as pH lower than 7.1. A logistic regression analysis was used to identify the determinants of low pH in the umbilical artery, with data presented as odds ratios and 95% CIs. RESULTS Low umbilical artery pH was observed in 72 infants (9.1%). There was an association between maternal glycated hemoglobin A1c (HbA1c) levels measured before delivery and low umbilical artery pH (odds ratio [OR] 1.40; 95% CI, 1.11-1.78; P = 0.01). A similar association was found for HbA1c levels measured between 20 and 24 weeks' gestation (OR 1.29; 95% CI, 1.03-1.63; P = 0.03). There was no association between the levels of HbA1c in the first trimester or lack of preconception care and low umbilical artery pH. In logistic regression, urgent cesarean section was associated with low umbilical artery pH (OR, 1.64; 95% CI, 1.11-2.44; P = 0.01), and this association was independent of HbA1c levels measured before delivery. CONCLUSIONS Lack of sufficient glycemic control in pregnancy is the strongest predictor of neonatal acidosis in women with type 1 diabetes.

Continuous subcutaneous insulin infusion reduces neonatal risk in pregnant women with type 1 diabetes mellitus.

OBJECTIVES: An attempt was made to demonstrate the superiority of the treatment model using continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) of insulin in achieving a successful pregnancy outcome and good newborn's condition in patients with type 1 diabetes. MATERIAL AND METHODS: The study included 297 infants born to type 1 diabetic patients; 175 patients were treated with MDI and 122 with CSII. Maternal metabolic control during pregnancy, gestational weight gain, insulin requirements, pregnancy outcome and neonatal status were compared between MDI and CSII arm. The composite adverse neonatal outcome was diagnosed if at least one of the following was found: abnormal birth weight (LGA or SGA), congenital malformation, miscarriage, intrauterine fetal death, emergency CS due to fetal risk, iatrogenic prematurity, RDS, hypoglycemia, hyperbilirubinemia, and the postpartum pH in the umbilical artery ≤ 7.1. RESULTS: The studied groups did not differ regarding gestational week at delivery, a proportion of births at full term, preterm births, miscarriages, or late pregnancy losses (intrauterine fetal death > 22 weeks). Newborns of mothers treated with CSII showed lower incidence of neonatal complications (composite adverse neonatal outcome) compared to those of mothers treated with MDI (60% vs 74%, respectively; p = 0.01). We did not find any association between the mode of treatment and composite adverse maternal outcome. CONCLUSIONS: The use of CSII in the treatment of pregnant women with type 1 diabetes was associated with reduced number of neonatal complications presented as neonatal composite outcome but had no influence on maternal outcome.

Nutritional Lifestyle Intervention in Obese Pregnant Women, Including Lower Carbohydrate Intake, Is Associated With Increased Maternal Free Fatty Acids, 3-ß-Hydroxybutyrate, and Fasting Glucose Concentrations: A Secondary Factorial Analysis of the European Multicenter, Randomized Controlled DALI Lifestyle Intervention Trial.

OBJECTIVE: In our randomized controlled trial, we investigated the impact of healthy eating (HE) aiming for restricted gestational weight gain (GWG) and physical activity (PA) interventions on maternal and neonatal lipid metabolism. RESEARCH DESIGN AND METHODS: Obese pregnant women (n = 436) were included before 20 weeks' gestation and underwent glucose testing (oral glucose tolerance test) and lipid profiling at baseline and 24-28 and 35-37 gestational weeks after an at least 10-h overnight fast. This secondary analysis had a factorial design with comparison of HE (n = 221) versus no HE (n = 215) and PA (n = 218) versus no PA (n = 218). Maternal changes in triglycerides (TG), LDL cholesterol, HDL cholesterol, free fatty acids (FFAs), and leptin from baseline to end of pregnancy and neonatal outcomes were analyzed using general linear models with adjustment for relevant parameters. RESULTS: At 24-28 weeks' gestation, FFAs (mean ± SD, 0.60 ± 0.19 vs. 0.55 ± 0.17 mmol/L, P < 0.01) were increased after adjustment for FFA at baseline, maternal age, BMI at time of examination, gestational week, insulin resistance, self-reported food intake, self-reported physical activity, and maternal smoking, and GWG was lower (3.3 ± 2.6 vs. 4.3 ± 2.8 kg, P < 0.001, adjusted mean differences -1.0 [95% CI -1.5; -0.5]) in HE versus no HE. Fasting glucose levels (4.7 ± 0.4 vs. 4.6 ± 0.4 mmol/L, P < 0.05) and 3-ß-hydroxybutyrate (3BHB) (0.082 ± 0.065 vs. 0.068 ± 0.067 mmol/L, P < 0.05) were higher in HE. Significant negative associations between carbohydrate intake and FFA, 3BHB, and fasting glucose at 24-28 weeks' gestation were observed. No differences between groups were found in oral glucose tolerance test or leptin or TG levels at any time. Furthermore, in PA versus no PA, no similar changes were found. In cord blood, elevated FFA levels were found in HE after full adjustment (0.34 ± 0.22 vs. 0.29 ± 0.16 mmol/L, P = 0.01). CONCLUSIONS: HE intervention was associated with reduced GWG, higher FFAs, higher 3BHB, and higher fasting glucose at 24-28 weeks of gestation, suggesting induction of lipolysis. Increased FFA was negatively associated with carbohydrate intake and was also observed in cord blood. These findings support the hypothesis that maternal antenatal dietary restriction including carbohydrates is associated with increased FFA mobilization.

Risk factors for hyperglycemia in pregnancy in the DALI study differ by period of pregnancy and OGTT time point.

OBJECTIVE: Risk factors are widely used to identify women at risk for gestational diabetes mellitus (GDM) without clear distinction by pregnancy period or oral glucose tolerance test (OGTT) time points. We aimed to assess the clinical risk factors for Hyperglycemia in pregnancy (HiP) differentiating by these two aspects. DESIGN AND METHODS: Nine hundred seventy-one overweight/obese pregnant women, enrolled in the DALI study for preventing GDM. OGTTs were performed at ≤19 + 6, 24-28 and 35-37 weeks (IADPSG/WHO2013 criteria). Women with GDM or overt diabetes at one time point did not proceed to further OGTTs. Potential independent variables included baseline maternal and current pregnancy characteristics. STATISTICAL ANALYSIS: Multivariate logistic regression. RESULTS: Clinical characteristics independently associated with GDM/overt diabetes were at ≤19 + 6 weeks, previous abnormal glucose tolerance (odds ratio (OR): 3.11; 95% CI: 1.41-6.85), previous GDM (OR: 2.22; 95% CI: 1.20-4.11), neck circumference (NC) (OR: 1.58; 95% CI: 1.06-2.36 for the upper tertile), resting heart rate (RHR, OR: 1.99; 95% CI: 1.31-3.00 for the upper tertile) and recruitment site; at 24-28 weeks, previous stillbirth (OR: 2.92; 95% CI: 1.18-7.22), RHR (OR: 3.32; 95% CI: 1.70-6.49 for the upper tertile) and recruitment site; at 35-37 weeks, maternal height (OR: 0.41; 95% CI: 0.20-0.87 for upper tertile). Clinical characteristics independently associated with GDM/overt diabetes differed by OGTT time point (e.g. at ≤19 + 6 weeks, NC was associated with abnormal fasting but not postchallenge glucose). CONCLUSION: In this population, most clinical characteristics associated with GDM/overt diabetes were non-modifiable and differed by pregnancy period and OGTT time point. The identified risk factors can help define the target population for future intervention trials.