Glucose control during pregnancy in patients with type 1 diabetes correlates with fetal hemodynamics: a prospective longitudinal study.

BACKGROUND: Maternal diabetes adversely affects fetal cardiovascular system development. Previous studies have reported that the fetuses of mothers with diabetes exhibit both structural and functional changes; nevertheless, prior studies have not examined the association between glucose control and fetal cardiac morphology and performance. Thus, the objective was to determine the association between fetal cardiac morphology and function and maternal glucose control in type 1 diabetes and to compare the differences in measured cardiac parameters between the fetuses of mothers with diabetes and healthy controls. METHODS: In this prospective, longitudinal case-control study - including 62 pregnant women with type 1 diabetes mellitus and 30 healthy pregnant women - fetal cardiac assessment using B-mode, M-mode, and spectral pulsed-wave Doppler was performed in the second and third trimesters. In women with T1DM, glycated hemoglobin and data obtained from glucose sensors - including the percentage of time in, below, and above the range (TIR, TBR, and TAR, respectively), and coefficient of variation (CV) - were analyzed across three time periods: the last menstrual period to 13 (V1), 14-22 (V2), and 23-32 weeks (V3) of gestation. Fetal cardiac indices were compared between groups, and the correlation between glucose control and fetal cardiac indices was assessed. RESULTS: At 28-32 weeks, the fetuses of women with T1DM exhibited increased left ventricular end-diastolic length, relative interventricular septum thickness, right ventricular cardiac output, and pulmonary valve peak systolic velocity compared with healthy controls. At 18-22 weeks, pulmonary and aortic valve diameters, left and right ventricular stroke volumes, and left cardiac output inversely correlated with the CV and glycated hemoglobin levels at V1 and V2. Furthermore, at 28-32 weeks, pulmonary and aortic valve diameters, left ventricular stroke volume, cardiac output, and right/left atrioventricular valve ratio inversely correlated with the TBR at V1, V2, and V3. Moreover, diastolic functional parameters correlated with the TAR and glycated hemoglobin levels, particularly after the first trimester. CONCLUSION: In women with T1DM, maternal hyperglycemia during pregnancy correlates with fetal diastolic function, whereas glucose variability and hypoglycemia inversely correlate with fetal left ventricular systolic function in the second and third trimesters.

Preeclampsia and diabetes mellitus.

OBJECTIVE: The purpose of this paper is to provide a review of recent research on the relationship between preeclampsia and diabetes mellitus in pregnancy. METHODOLOGY: A structured search for literary sources in PubMed and ScienceDirect databases using keywords, followed by a selection of papers based on solid methodology. RESULTS: Preeclampsia is a serious condition, which complicates 2-7% of pregnancies. It causes maternal complications (organ dysfunction) and fetal complications (pathological haemodynamic parameters of the uteroplacental unit and fetal growth restriction). Pregnant women with pregestational diabetes have a 2- and 4-times higher risk of developing preeclampsia and the ones with gestational diabetes have 1.3-times higher risk. The main identified risk factors are inadequate compensation of diabetes, diabetic nephropathy, retinopathy and the duration of diabetes. To minimalize the risk of developing preeclampsia, a composite screening has been implemented. With a positive result a preventive use of acetylsalicylic acid from at the latest 16 and up until the 36th week is advised. Preeclampsia is also a risk factor for developing diabetes mellitus and other cardiovascular diseases later in life. For that reason, a long-term dispensary of women who had preeclampsia in pregnancy is recommended.

Establishing the Optimal Time for Induction of Labor in Women with Diet-Controlled Gestational Diabetes Mellitus: A Single-Center Observational Study.

To determine the optimal week for labor induction in women with diet-controlled gestational diabetes mellitus by comparing differences in perinatal and neonatal outcomes of labor induction to expectant management at different gestational weeks. Methods: This was a retrospective analysis of a prospectively recruited cohort of 797 singleton pregnancies complicated by diet-controlled gestational diabetes mellitus that were diagnosed, treated, and delivered after 37 weeks in a tertiary, university-affiliated perinatal center between January 2016 and December 2021. Results: The incidence of neonatal complications was highest when delivery occurred at 37 weeks, whereas fetal macrosomia occurred mostly at 41 weeks (20.7%); the frequency of large for gestational age infants did not differ between the groups. Conversely, the best neonatal outcomes were observed at 40 weeks due to the lowest number of neonates requiring phototherapy for neonatal jaundice (1.7%) and the smallest proportion of neonates experiencing composite adverse neonatal outcomes defined as neonatal hypoglycemia, phototherapy, clavicle fracture, or umbilical artery pH < 7.15 (10.4%). Compared with expectant management, the risk for neonatal hypoglycemia was increased for induction at 39 weeks (adjusted odds ratio 12.29, 95% confidence interval 1.35−111.75, p = 0.026) and that for fetal macrosomia was decreased for induction at 40 weeks (adjusted odds ratio 0.11, 95% confidence interval 0.01−0.92, p = 0.041), after adjusting for maternal pre-pregnancy body mass index, nulliparity, and mean pregnancy A1c. Conclusions: The lowest rate of neonatal complications was observed at 40 weeks. Labor induction at 40 weeks prevented fetal macrosomia.

Association between gestational diabetes mellitus and bioavailability of insulin-like growth factors and role of their binding proteins.

OBJECTIVE: Insulin-like growth factors (IGFs) are involved in regulating growth and metabolism and increase insulin sensitivity, improve glucose metabolism, and are potentially related to gestational diabetes mellitus (GDM) and its complications for mothers and fetuses. DESIGN: This study aimed to assess serum levels and cord blood levels of IGF system components in pregnant women with (39 participants) and without GDM (22 participants). Blood samples were obtained at 28-32 and 36-38 weeks of gestation and 6-12 months after delivery. Cord blood samples were obtained during delivery. Results between both groups as well as between single visits were statistically compared. RESULTS: Both IGF1 and IGF2 maternal serum levels did not differ between the GDM and non-GDM groups. However, levels of IGF-binding proteins (IGFBPs) were different. IGFBP4 levels were decreased during pregnancy and after delivery in women with GDM, while IGFBP7 levels were increased during pregnancy in women with GDM. Cord blood IGFBP3 and IGFBP7 levels were increased (p < 0.001 for IGFBP3, p = 0.003 for IGFBP7), while IGFBP4 levels were decreased (p < 0.001) in the GDM group compared with the non-GDM group. CONCLUSIONS: Although IGF levels did not differ, changes in their function level could still persist possibly because of the effects of the binding proteins, especially their promoting or inhibitory effects on IGFs. These results should be considered in interpretation of IGF levels.

The rs10830963 Polymorphism of the MTNR1B Gene: Association With Abnormal Glucose, Insulin and C-peptide Kinetics.

Background: The MTNR1B gene encodes a receptor for melatonin, a hormone regulating biorhythms. Disruptions in biorhythms contribute to the development of type 2 diabetes mellitus (T2DM). Genetic studies suggest that variability in the MTNR1B gene affects T2DM development. Our aim was to compare the distribution of the genetic variant rs10830963 between persons differing in glucose tolerance in a sample of the Czech population (N=1206). We also evaluated possible associations of the polymorphism with insulin sensitivity, beta cell function, with the shape of glucose, insulin and C-peptide trajectories measured 7 times during a 3-hour oral glucose tolerance test (OGTT) and with glucagon response. In a subgroup of 268 volunteers we also evaluated sleep patterns and biorhythm. Results: 13 persons were diagnosed with T2DM, 119 had impaired fasting blood glucose (IFG) and/or impaired glucose tolerance (IGT). 1074 participants showed normal results and formed a control group. A higher frequency of minor allele G was found in the IFG/IGT group in comparison with controls. The GG constellation was present in 23% of diabetics, in 17% of IFG/IGT probands and in 11% of controls. Compared to CC and CG genotypes, GG homozygotes showed higher stimulated glycemia levels during the OGTT. Homozygous as well as heterozygous carriers of the G allele showed lower very early phase of insulin and C-peptide secretion with unchanged insulin sensitivity. These differences remained significant after excluding diabetics and the IFG/IGT group from the analysis. No associations of the genotype with the shape of OGTT-based trajectories, with glucagon or with chronobiological patterns were observed. However, the shape of the trajectories differed significantly between men and women. Conclusion: In a representative sample of the Czech population, the G allele of the rs10830963 polymorphism is associated with impaired early phase of beta cell function, and this is evident even in healthy individuals.

Altered Steroidome in Women with Gestational Diabetes Mellitus: Focus on Neuroactive and Immunomodulatory Steroids from the 24th Week of Pregnancy to Labor.

Gestational diabetes mellitus (GDM) is a complication in pregnancy, but studies focused on the steroidome in patients with GDM are not available in the public domain. This article evaluates the steroidome in GDM+ and GDM- women and its changes from 24 weeks (± of gestation) to labor. The study included GDM+ (n = 44) and GDM- women (n = 33), in weeks 24-28, 30-36 of gestation and at labor and mixed umbilical blood after delivery. Steroidomic data (101 steroids quantified by GC-MS/MS) support the concept that the increasing diabetogenic effects with the approaching term are associated with mounting progesterone levels. The GDM+ group showed lower levels of testosterone (due to reduced AKR1C3 activity), estradiol (due to a shift from the HSD17B1 towards HSD17B2 activity), 7-oxygenated androgens (competing with cortisone for HSD11B1 and shifting the balance from diabetogenic cortisol towards the inactive cortisone), reduced activities of SRD5As, and CYP17A1 in the hydroxylase but higher CYP17A1 activity in the lyase step. With the approaching term, the authors found rising activities of CYP3A7, AKR1C1, CYP17A1 in its hydroxylase step, but a decline in its lyase step, rising conjugation of neuroinhibitory and pregnancy-stabilizing steroids and weakening AKR1D1 activity.

Pregnancy of women with type 1 diabetes mellitus - the effect of preconception care on perinatal results. Ten years of experience.

INTRODUCTION: Despite the ever-improving medical care, pregnancies of women with type 1 diabetes mellitus (T1DM) are at increased risk of complications for both mother and child. Optimal compensation of diabetes before and during pregnancy is an essential protective factor reducing the risk of congenital malformations, pregnancy loss, and other complications. The pregnancy of women with T1DM should be planned, ideally at a time of optimal diabetes compensation. Target glycated hemoglobin (HbA1c) values until the range of 42-48 mmol/mol should be achieved at least three months before pregnancy. Our work aimed to evaluate the perinatal results of pregnancies in women with T1DM and the eff ect of preconception counseling and adequate T1DM compensation before pregnancy on perinatal outcomes. METHODS AND RESULTS: Retrospective analysis of pregnancy and perinatal outcomes of women with T1DM were followed up at the Department of Gynecology and Obstetrics, General University Hospital in Prague and First Faculty of Medicine, Charles University between 2008 to 2018. A total of 221 women with T1DM were included in the analysis. Adequate (HbA1c  48 mmol/mol at least 3 months before conception) and inadequate diabetes compensation at the beginning of the pregnancy had 59 (26.7%) and 162 (72.3%) women, respectively. Pregnancies of women with adequate diabetes compensation were more often planned (55.9 vs. 24.7%; P  95th percentile; 22.0 vs. 35.8%; P = 0.027). CONCLUSION: The pregnancy of women with T1DM is burdened by a number of perinatal and neonatal complications. In the study group, most women with T1DM became pregnant unintentionally at a time of inadequate diabetes compensation. Women who achieved adequate diabetes compensation before pregnancy had a lower incidence of perinatal complications. Therefore, it is advised that women with T1DM should plan their pregnancy, attend preconception and antenatal care, and give birth in perinatal centers, which provide coordinated care from diabetologists, gynecologists, obstetricians, and neonatologists.

Screening for gestational diabetes mellitus.

A brief summarization of guidelines for screening for gestational diabetes mellitus in pregancy.

The possible role of endocrine dysfunction of adipose tissue in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is diabetes that is first diagnosed in the second or third trimester of pregnancy in patients who did not have a history of diabetes before pregnancy. Consequences of GDM include increased risk of macrosomia and birth complications in the infant and an increased risk of maternal type 2 diabetes mellitus (T2DM) after pregnancy. There is also a longer-term risk of obesity, T2DM, and cardiovascular diseases in the child. GDM is the result of impaired glucose tolerance due to pancreatic ß-cell dysfunction on a background of insulin resistance that physiologically increases during pregnancy. The strongest clinical predictors of GDM are overweight and obesity. The fact that women with GDM are more likely to be overweight or obese suggests that adipose tissue dysfunction may be involved in the pathogenesis of GDM, similarly to T2DM. Adipose tissue is not only involved in energy storage but also functions as an active endocrine organ secreting adipokines (specific hormones and cytokines) with the ability to alter insulin sensitivity. Recent evidence points to a crucial role of numerous adipokines produced by fat in the development of GDM. The following text summarizes the current knowledge about a possible role of selected adipokines in the development of GDM.

Subclinical Inflammation and Adipose Tissue Lymphocytes in Pregnant Females With Gestational Diabetes Mellitus.

CONTEXT: Gestational diabetes mellitus (GDM) is accompanied by subclinical inflammation; however, little is known about local inflammation in adipose tissue and placenta. OBJECTIVE: To analyze systemic and local subclinical inflammation and adipose tissue lymphocyte content and phenotype in pregnant women with and without GDM. DESIGN: Observational study. SETTINGS: Academic hospital. PATIENTS: Twenty-one pregnant women with GDM (GDM group), 16 pregnant women without GDM (non-GDM group) and 15 nonpregnant control women (N group). INTERVENTIONS: Serum samples taken at 28 to 32 (visit 1 [V1]) and 36 to 38 (V2) gestational weeks and 6 to 12 months after delivery (V3) in the GDM and non-GDM group and before elective gynecological surgery in the N group. Subcutaneous (SAT) and visceral adipose tissue (VAT) obtained during cesarean delivery or surgery. MAIN OUTCOME MEASURES: Serum levels and adipose tissue expression of proinflammatory cytokines, adipose tissue lymphocyte content and phenotype (for a subset of GDM and non-GDM subjects). RESULTS: Accented proinflammatory state in GDM was documented by increased circulating tumor necrosis factor-α (TNF-α) levels. In both groups of pregnant females total lymphocytes were higher in VAT compared to SAT. In GDM subjects B cells and NKT cells were higher in SAT compared to VAT and T helper cells were increased relative to SAT of non-GDM group, while no intercompartmental adipose tissue differences were seen in non-GDM women. CONCLUSIONS: Pregnant females had higher total lymphocyte count in VAT relative to SAT regardless of GDM. In addition to increased systemic subclinical inflammation, GDM was associated with significant differences in lymphocyte composition between subcutaneous and visceral adipose tissue depots.

The role of obesity and adipose tissue dysfunction in gestational diabetes mellitus.

Gestational diabetes mellitus is defined as diabetes diagnosed in the second or third trimester of pregnancy in patients with no history of diabetes prior to gestation. It is the most common complication of pregnancy. The underlying pathophysiology shares some common features with type 2 diabetes mellitus (T2DM) combining relatively insufficient insulin secretion with increased peripheral insulin resistance. While a certain degree of insulin resistance is the physiological characteristics of the second half of pregnancy, it is significantly more pronounced in patients with gestational diabetes. Adipose tissue dysfunction and subclinical inflammation in obesity are well-described causes of increased insulin resistance in non-pregnant subjects and are often observed in individuals with T2DM. Emerging evidence of altered adipokine expression and local inflammation in adipose tissue in patients with gestational diabetes suggests an important involvement of adipose tissue in its etiopathogenesis. This review aims to summarize current knowledge of adipose tissue dysfunction and its role in the development of gestational diabetes. We specifically focus on the significance of alterations of adipokines and immunocompetent cells number and phenotype in fat. Detailed understanding of the role of adipose tissue in gestational diabetes may provide new insights into its pathophysiology and open new possibilities of its prevention and treatment.

Blood glucose control by a model predictive control algorithm with variable sampling rate versus a routine glucose management protocol in cardiac surgery patients: a randomized controlled trial.

CONTEXT: Elevated blood glucose levels occur frequently in the critically ill. Tight glucose control by intensive insulin treatment markedly improves clinical outcome. OBJECTIVE AND DESIGN: This is a randomized controlled trial comparing blood glucose control by a laptop-based model predictive control algorithm with a variable sampling rate [enhanced model predictive control (eMPC); version 1.04.03] against a routine glucose management protocol (RMP) during the peri- and postoperative periods. SETTING: The study was performed at the Department of Cardiac Surgery, University Hospital. PATIENTS: A total of 60 elective cardiac surgery patients were included in the study. INTERVENTIONS: Elective cardiac surgery and treatment with continuous insulin infusion (eMPC) or continuous insulin infusion combined with iv insulin boluses (RMP) to maintain euglycemia (target range 4.4-6.1 mmol/liter) were performed. There were 30 patients randomized for eMPC and 30 for RMP treatment. Blood glucose was measured in 1- to 4-h intervals as requested by each algorithm during surgery and postoperatively over 24 h. MAIN OUTCOME MEASURES: Mean blood glucose, percentage of time in target range, and hypoglycemia events were used. RESULTS: Mean blood glucose was 6.2 +/- 1.1 mmol/liter in the eMPC vs. 7.2 +/- 1.1 mmol/liter in the RMP group (P < 0.05); percentage of time in the target range was 60.4 +/- 22.8% for the eMPC vs. 27.5 +/- 16.2% for the RMP group (P < 0.05). No severe hypoglycemia (blood glucose < 2.9 mmol/liter) occurred during the study. Mean insulin infusion rate was 4.7 +/- 3.3 IU/h in the eMPC vs. 2.6 +/- 1.7 IU/h in the RMP group (P < 0.05). Mean sampling interval was 1.5 +/- 0.3 h in the eMPC vs. 2.1 +/- 0.2 h in the RMP group (P < 0.05). CONCLUSIONS: Compared with RMP, the eMPC algorithm was more effective and comparably safe in maintaining euglycemia in cardiac surgery patients.

Increased subcutaneous and epicardial adipose tissue production of proinflammatory cytokines in cardiac surgery patients: possible role in postoperative insulin resistance.

CONTEXT: Hyperglycemia and insulin resistance frequently occur in critically ill patients even without a history of diabetes. OBJECTIVE: Our objective was to study the role of adipose tissue hormonal production in the development of insulin resistance in cardiac surgery patients. PARTICIPANTS, INTERVENTIONS, AND SETTINGS: Fifteen patients with elective cardiac surgery underwent blood sampling before, at the end, and 6, 12, 24, 48, and 120 h after the end of their operation. Epicardial and sc adipose tissue sampling was done at the beginning and at the end of surgery in the Department of Cardiac Surgery. MAIN OUTCOME MEASURES: We measured serum concentrations and sc and epicardial adipose tissue mRNA expression of IL-6, monocyte chemoattractant protein-1 (MCP-1), TNF-alpha, leptin, resistin, and adiponectin and sc and epicardial adipose tissue mRNA expression of CD14, CD45, and CD68. RESULTS: The rate of insulin infusion required to maintain euglycemia increased up to 7-fold 12 h after the operation, suggesting the development of insulin resistance. Serum IL-6 levels increased 43-fold 12 h after surgery. MCP-1 peaked 6-fold at the end of surgery. Smaller peaks of TNF-alpha and leptin appeared 6 and 12 h after surgery, respectively. Resistin levels peaked 4-fold 24 h after surgery, but adiponectin levels were not significantly affected. TNF-alpha and CD45 mRNA expression increased markedly during the operation in sc adipose tissue. IL-6, resistin, and MCP-1 mRNA expression increased in both sc and epicardial adipose tissue. Leptin, adiponectin, CD14, and CD68 mRNA expression did not change significantly. CONCLUSIONS: Both sc and epicardial adipose tissue is a source of proinflammatory cytokines in cardiac surgery patients and may contribute to the development of postoperative insulin resistance.

Serum adiponectin and resistin concentrations in patients with restrictive and binge/purge form of anorexia nervosa and bulimia nervosa.

To study the role of adipose tissue-derived hormones in the pathophysiology of eating disorders, circulating levels of adiponectin, resistin, and other hormonal and metabolic parameters were measured in 16 females with the restrictive subtype of anorexia nervosa (R-AN), 10 females with the binge/purge subtype of anorexia nervosa (P-AN), 15 females with bulimia nervosa (BN), and 12 age-matched healthy females (C). Body mass index (BMI), body fat content, and serum leptin levels were severely decreased in R-AN and moderately decreased in P-AN patients, whereas the BN group did not differ from C in these parameters. Serum soluble leptin receptor levels were increased in R-AN and P-AN and unchanged in BN patients. Circulating adiponectin levels were inversely related to BMI and were unchanged in BN patients and increased by 53% in P-AN and by 96% in R-AN relative to C group, respectively. In contrast, resistin levels in malnourished R-AN and P-AN were not different from either C or BN groups and showed no significant relationship to BMI or body fat content. We suggest that increased adiponectin levels reflect decreased body fat content in AN patients. In contrast, circulating resistin levels do not appear to be closely related to the nutritional status.

Soluble leptin receptor and leptin levels in pregnant women before and after delivery.

Soluble leptin receptor is an extracellular domain of the leptin receptor that serves as the main leptin-binding protein and may play a role in the regulation of leptin tissue effects. The aim of our study was to assess serum concentrations of leptin, soluble leptin receptor, and other hormones involved in the regulation of leptin secretion in pregnant women before and after delivery. Serum leptin, cortisol, and tumor necrosis factor alpha (TNF-alpha) concentrations in 19 pregnant women before delivery were significantly higher than in healthy nonpregnant women (33.3+/-21.0 vs. 7.9+/-3.5 ng/mL, 1068.9+/-442.2 vs. 546.6+/-165.3 nmol/L, 4.4+/-1.1 vs. 3.4+/-1.2 ng/mL, respectively). In contrast, no differences between these groups were found in soluble leptin receptor levels. Delivery significantly decreased serum leptin and cortisol levels and increased soluble leptin receptor levels (12.3+/-9.1 ng/mL, 749.6+/-205.3 nmol/L, 23.3+/-7.9 U/mL, respectively). Soluble leptin receptor levels after delivery became higher than in the control group. We conclude that serum leptin and serum soluble leptin-receptor levels are significantly affected by pregnancy and delivery. The regulation of leptin levels in this group of patients appears to be distinct and independent of soluble leptin-receptor levels.