Gestational diabetes mellitus in patients undergoing assisted reproductive techniques or conceiving spontaneously: an analysis on maternal and foetal outcomes.

PURPOSE: With the rise of medically assisted reproductive techniques (ART) the number of pregnancies complicated by gestational diabetes mellitus (GDM) has increased. The aim of this study was to evaluate retrospectively the outcomes of pregnancies complicated by GDM who conceive trough ART (cases) compared to those who conceived spontaneously (controls). METHODS: In 670 women with GDM, 229 cases and 441 controls, followed by the Diabetology of Padua, between 2010-2022, clinical-metabolic maternal characteristics and maternal-foetal outcomes were evaluated. RESULTS: As for the maternal clinical-metabolic characteristics, plasma glucose levels at 60' and 120' under oral glucose tolerance test (OGTT) at time of diagnosis were significantly higher in cases (177.4 ± 31.1 vs 170.9 ± 34.1 mg/dl, p = 0.016; 151.5 ± 32.2 vs 144.0 ± 33.4 mg/dl, p = 0.005 respectively). Furthermore, at diagnosis, cases show higher levels of total cholesterol (257 ± 53 mg/dl vs 246 ± 52 mg/dl; p = 0.012) and triglycerides (199.8 ± 83.2 mg/dl vs 184.9 ± 71.3 mg/dl; p = 0.02) compared to controls. As for maternal outcomes, thyroid disfunction, was recorded in a higher percentage in case (21.4% vs 14.3%; p = 0.008), as well as, the frequency of cesarean section (50.3% vs 41.2%; p = 0.038) and twin pregnancies (16.2% vs 2.5%; p < 0.001). As for neonatal outcomes, there were no statistically significant differences, except for the birth weight of the second twin, which was significantly lower in cases (2268 ± 536 vs 2822 ± 297 g; p = 0.002). No other significant differences were found. CONCLUSION: This study showed no meaningful differences in the outcomes of GDM pregnancies who were conceived with ART compared to that arose spontaneously as the patients were promptly diagnosed and treated.

The unexplored role of sedentary time and physical activity in glucose and lipid metabolism-related placental mRNAs in pregnant women who are obese: the DALI lifestyle randomised controlled trial.

OBJECTIVE: We aimed to explore: (i) the association of sedentary time (ST) and physical activity (PA) during pregnancy with the placental expression of genes related to glucose and lipid metabolism in pregnant women who are obese; (ii) maternal metabolic factors mediating changes in these placental transcripts; and (iii) cord blood markers related to the mRNAs mediating neonatal adiposity. DESIGN: Multicentre randomised controlled trial. SETTING: Hospitals in nine European countries. POPULATION: A cohort of 112 pregnant women with placental tissue. METHODS: Both ST and moderate-to-vigorous PA (MVPA) levels were measured objectively using accelerometry at three time periods during pregnancy. MAIN OUTCOME MEASURES: Placental mRNAs (FATP2, FATP3, FABP4, GLUT1 and PPAR-γ) were measured with NanoString technology. Maternal and fetal metabolic markers and neonatal adiposity were assessed. RESULTS: Longer periods of ST, especially in early to middle pregnancy, was associated with lower placental FATP2 and FATP3 expression (P < 0.05), whereas MVPA at baseline was inversely associated with GLUT1 mRNA (P = 0.02). Although placental FATP2 and FATP3 expression were regulated by the insulin-glucose axis (P < 0.05), no maternal metabolic marker mediated the association of ST/MVPA with placental mRNAs (P > 0.05). Additionally, placental FATP2 expression was inversely associated with cord blood triglycerides and free fatty acids (FFAs; P < 0.01). No cord blood marker mediated neonatal adiposity except for cord blood leptin, which mediated the effects of PPAR-γ on neonatal sum of skinfolds (P < 0.05). CONCLUSIONS: In early to middle pregnancy, ST is associated with the expression of placental genes linked to lipid transport. PA is hardly related to transporter mRNAs. Strategies aimed at reducing sedentary behaviour during pregnancy could modulate placental gene expression, which may help to prevent unfavourable fetal and maternal pregnancy outcomes. TWEETABLE ABSTRACT: Reducing sedentary behaviour in pregnancy might modulate placental expression of genes related to lipid metabolism in women who are obese.

Metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes.

AIMS: To describe the metabolic phenotypes of early gestational diabetes mellitus and their association with adverse pregnancy outcomes. METHODS: We performed a post hoc analysis using data from the Vitamin D And Lifestyle Intervention for gestational diabetes prevention (DALI) trial conducted across nine European countries (2012-2014). In women with a BMI ≥29 kg/m2 , insulin resistance and secretion were estimated from the oral glucose tolerance test values performed before 20 weeks, using homeostatic model assessment of insulin resistance and Stumvoll first-phase indices, respectively. Women with early gestational diabetes, defined by the International Association of Diabetes and Pregnancy Study Groups criteria, were classified into three groups: GDM-R (above-median insulin resistance alone), GDM-S (below-median insulin secretion alone), and GDM-B (combination of both) and the few remaining women were excluded. RESULTS: Compared with women in the normal glucose tolerance group (n = 651), women in the GDM-R group (n = 143) had higher fasting and post-load glucose values and insulin levels, with a greater risk of having large-for-gestational age babies [adjusted odds ratio 3.30 (95% CI 1.50-7.50)] and caesarean section [adjusted odds ratio 2.30 (95% CI 1.20-4.40)]. Women in the GDM-S (n = 37) and GDM-B (n = 56) groups had comparable pregnancy outcomes with those in the normal glucose tolerance group. CONCLUSIONS: In overweight and obese women with early gestational diabetes, higher degree of insulin resistance alone was more likely to be associated with adverse pregnancy outcomes than lower insulin secretion alone or a combination of both.

Innovative clinical pathways for obese pregnant women: design and feasibility of the Padua project (North-Eastern Italy).

BACKGROUND: Obesity during pregnancy can adversely affect the wellbeing of the mother and the newborn, as well as the latter's long-term health. Preconception counseling, careful prenatal management, and strict follow-up during pregnancy are, therefore, essential for obese fertile women in order to prevent the negative effects of obesity. METHODS: In this setting, we developed a project that consisted in creating an integrated network of primary, secondary, and tertiary care providers and designing new clinical pathways for managing pregnancy in obese women. RESULTS: Two distinct pathways were devised: a Pre-Gestational Pathway for programming a pregnancy in obese women; and a Gestational Pathway for the clinical management of their pregnancy. DISCUSSION: Judging from the preliminary results of our study, the latter (Gestational) pathway seems to be successful, since there has been a gradual increase in the number of women using it, and these women have reported having no difficulty in accessing the services involved. It is noteworthy that immigrant women (who accounted for 60% of the women using the pathway) also reported no access issues. The pre-gestational pathway was very little used, however, accounting for only 2% of the appointments made with the services involved. In conclusion, the key to success in managing pregnancy in obese women lies in sharing the various different health care competences required and taking the local resources into account. The prevention of obesity in women of fertile age remains the main problem, however, and further efforts are needed in this setting.

Quality of life in pregnancy and post-partum: a study in diabetic patients.

PURPOSE: We evaluated quality of life in pregnant women with diabetes followed up at Italian diabetes clinics. METHODS: A total of 245 pregnant women (30 type 1 diabetes mellitus (T1DM), 176 gestational diabetes (GDM) and 39 controls) were asked to fill in a questionnaire including the SF-36 Health Survey and the Center for Epidemiological Studies-Depression (CES-D) Scale in third trimester of pregnancy and after delivery. GDM and T1DM also completed two diabetes-specific questionnaires (Diabetes-related stress and Diabetes health distress). Quality of life scores were compared between the groups with the Mann-Whitney U-test, mean changes in scores (after delivery to 3rd trimester) were compared between groups by ANCOVA. RESULTS: Regarding the SF-36 scores in the third trimester of pregnancy, T1DM and GDM women had a better Standardised Physical Component score than controls (P < 0.0001, P = 0.009, respectively). GDM and T1DM pregnant women scored significantly lower for general health perception than controls (P = 0.009 and P = 0.001, respectively). T1DM patients had lower Standardised Mental Component scores than controls (P = 0.03). Compared with the third trimester of pregnancy, the severity of depressive symptoms increased significantly after delivery in both diabetic groups, but not in controls (P < 0.0001). Scores improved in all SF-36 areas in healthy and GDM women, while they all became worse in the T1DM group. CONCLUSIONS: Pregnancy is associated with a perception of poor general health in women with both T1DM and GDM. After delivery, significantly worse depressive symptoms were documented in both groups, while a generally worse physical and psychological well-being was only identified in women with T1DM. These findings have important implications for pregnancy follow-up.

Long-term cardio-metabolic effects after gestational diabetes: a review.

Women with GDM are at high risk of metabolic syndrome and type 2 diabetes (T2DM). A relationship with GDM and future development of cardiovascular disease (CVD) has been also recognized. Pregnancy and postpartum period in women with GDM give us the opportunity to identify the underlying, often unrecognized, CVD risk factors. Ideally, the postpartum follow-up of this women should be done by a multidisciplinary team to evaluate their cardio-metabolic risk and to counseling regarding lifestyle modification (healthy diet and regular physical activity) and breastfeeding that can reduce their risk. Longer follow-up of these women should be individualized, focusing attention on women at medium-high cardio-metabolic risk. The link between GDM and T2DM-CVD offers us a great opportunity for the diseases prevention.

New International Association of the Diabetes and Pregnancy Study Groups (IADPSG) recommendations for diagnosing gestational diabetes compared with former criteria: a retrospective study on pregnancy outcome.

AIMS: The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) Consensus Panel recommends new criteria for diagnosing gestational diabetes. We evaluated the clinical and metabolic characteristics, and pregnancy outcome, in women previously classifiable as 'normal' according to the 4th International Workshop Conference on gestational diabetes criteria, but reclassified as 'abnormal' according to the new recommendations. METHODS: Using the new IADPSG criteria, 3953 pregnancies were retrospectively reclassified as 1815 women with normal glucose tolerance and 2138 with gestational diabetes, 112 (2.8%) of whom would have been classified as normal according to the older criteria. RESULTS: Of the 2138 women classified as abnormal by the new criteria, the 112 women now reclassified as abnormal were younger and had a lower pre-pregnancy BMI than the 2026 women who had also been classified as abnormal by the previous criteria. The 100-g oral glucose tolerance test showed significantly higher glucose levels in these 112 women than in the 1815 women reclassified as normal (P < 0.0001). Caesarean section was significantly more frequent (P < 0.01) and the ponderal index for the newborn significantly higher in these reclassified women than in those classified as normal (P < 0.0001), and their basal glucose levels correlated significantly with the ponderal index (P < 0.05). CONCLUSION: The new criteria for diagnosing gestational diabetes identified a group of women previously classifiable as normal according to the 4th International Workshop Conference criteria, but revealing metabolic characteristics and pregnancy outcomes resembling those of women who would have been considered to have gestational diabetes by the previous criteria.

Vaccination against COVID-19 infection: the need of evidence for diabetic and obese pregnant women.

AIM: The recent availability of vaccines against COVID-19 has sparked national and international debate on the feasibility of administering them to pregnant and lactating women, given that these vaccines have not been tested to assess their safety and efficacy in such women. As concerns the risks of COVID-induced disease, published data show that pregnant women who develop COVID-19 have fewer symptoms than patients who are not pregnant, but they are more likely to need hospitalization in intensive care, and neonatal morbidity. Aim of the present perspective paper is to analyze the current literature regarding the use of the vaccine against COVID-19 infection, in terms of safety and protection, in high risk pregnant women as those affected by diabetes and obesity. METHODS: Analysis of literature about vaccination against COVID-19 infection in pregnancy. RESULTS: The main health organizations and international scientific societies, emphasize that-although data regarding the use of COVID vaccines during pregnancy and lactation are still lacking-vaccination should not be contraindicated. It should be considered for pregnant women at high risk of exposure to COVID-19. For such women, the potential benefits and risks should be assessed by the healthcare professionals caring for them. A recent prospective study to test the immunogenicity and reactogenicity of vaccination with COVID-19 mRNA in pregnant and lactating women, has showed that SARS-CoV-2 mRNA vaccination triggers a robust humoral immunity in pregnant and lactating women; there was also evidence of an immune transfer to their newborn. CONCLUSIONS: We urgently need data on the effect of COVID-19 vaccination, in terms of maternal and fetal outcomes and vaccine related symptoms in high risk women during pregnancy and breastfeeding. It is important to run campaigns to promote vaccination, in particular in pregnant women at high risk to have severe COVID infection as those diabetics and/or obese.

Diabetes related autoimmunity in gestational diabetes mellitus: is it important?

Some GDM women show autoantibody positivity during and after pregnancy and pancreatic autoantibodies can appear for the first time in some patients after delivery. Autoantibody positivity is often accompanied by a high frequency of DR3 and DR4 alleles, which are classically related to the development of type 1 diabetes and, although not all studies agree on this point, by an immunological imbalance expressed by the behaviour of the lymphocyte subpopulation, which can be seen as diabetic anomalies overlapping with the immunological changes that occur during pregnancy. It is worth emphasizing that such patients may develop classical type 1 diabetes during and/or after their pregnancy or they may evolve, often some years after their pregnancy, into cases of latent autoimmune diabetes of adulthood (LADA). Autoimmune GDM accounts for a relatively small number of cases (about 10% of all GDM) but the risk of these women developing type 1 diabetes or LADA is very high, so these patients must be identified in order to prevent the severe maternal and fetal complications of type 1 diabetes developing in pregnancy, or its acute onset afterwards. Since women with autoimmune GDM must be considered at high risk of developing type 1 diabetes in any of its clinical forms, these women should be regarded as future candidates for the immunomodulatory strategies used in type 1 diabetes.

Short- and long-term consequences for offspring exposed to maternal diabetes: a review.

The prevalence of gestational diabetes mellitus is increasing, as is the worldwide prevalence of type 2 diabetes and obesity, even in children and adolescents. Exposure in utero to maternal diabetes carries several short-term consequences due mainly to maternal hyperglycemia, and consequent fetal hyperinsulinemia. Current evidence also supports the hypothesis that adult health and disease have developmental origins, and that disorders in early-life environments prompt metabolic imprinting that results in a greater risk of negative metabolic outcomes later in life. In particular, exposure in utero to maternal diabetes seems to influence long-term metabolic outcomes, carrying a higher risk of obesity and type 2 diabetes, and thus creating a vicious cycle for future generations. In this paper, the short- and long-term consequences of exposure in utero to hyperglycemia are reviewed, focusing particularly on the long-term metabolic consequences, and investigating the possible pathogenic mechanisms involved.

Early detection of insulin sensitivity and beta-cell function with simple tests indicates future derangements in late pregnancy.

OBJECTIVE: Insulin sensitivity and secretion during early and late pregnancy were assessed in women with normal glucose tolerance and gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: The oral glucose tolerance test (OGTT) was performed in 903 women at 16-20th gestational week, of whom 37 had GDM (GDM1 group), and 859 repeated the OGTT at wk 26-30. At the second test, 55 had GDM (GDM2 group); the others remained normotolerant (ND group). Insulin sensitivity from OGTT (as quantitative insulin sensitivity check index and OGTT insulin sensitivity) and beta-cell function (as the ratio of the areas under the insulin and glucose concentration curves, adjusted for insulin sensitivity) were assessed in both tests. RESULTS: In early pregnancy the quantitative insulin sensitivity check index was not different in the three groups, whereas OGTT insulin sensitivity was lowest in GDM2, intermediate in GDM1, and highest in ND. In late pregnancy both indices were reduced in GDM compared with ND and lower than in early pregnancy. In early pregnancy GDM1, but not GDM2, had lower beta-cell function than ND. During the late visit, GDM2 also showed impaired beta-cell function compared with ND; furthermore, the adaptation to the increase to insulin resistance from early to late pregnancy was defective in GDM2. CONCLUSIONS: In early pregnancy insulin sensitivity, as assessed from the OGTT but not from fasting measurements, is impaired in women who developed GDM. beta-Cell function impairment is evident only when GDM is manifest and is characterized by inappropriate adaptation to the pregnancy induced increase in insulin resistance.

Outcome of pregnancy in type 1 diabetic patients treated with insulin lispro or regular insulin: an Italian experience.

Some studies have shown that fetal outcome observed in patients using insulin lispro is much the same as in pregnant women using regular insulin. This study aims to analyze the Italian data emerging from a multinational, multicenter, retrospective study on mothers with type 1 diabetes mellitus before pregnancy, comparing those treated with insulin lispro for at least 3 months before and 3 months after conception with those treated with regular insulin. The data collected on pregnant women with diabetes attending 15 Italian centers from 1998 to 2001 included: HbA1c at conception and during the first and third trimesters, frequency of severe hypoglycemic episodes, spontaneous abortions, mode and time of delivery, fetal malformations and mortality. Seventy-two diabetic pregnancies treated with lispro and 298 treated with regular insulin were analyzed, revealing a trend towards fewer hypoglycemic episodes in the former, who also had a significantly greater reduction in HbA1c during the first trimester. The rate of congenital malformations was similar in the offspring of the two groups of women treated with insulin lispro or regular insulin. These findings suggest that insulin lispro could be useful for the treatment of hyperglycemia in type 1 diabetic pregnant women.

Can plasma glucose and HbA1c predict fetal growth in mothers with different glucose tolerance levels?

To assess whether HbA1c and plasma glucose predicts abnormal fetal growth, 758 pregnant women attending 5 Diabetic Centers were screened for gestational diabetes mellitus (GDM). On glucose challenge (GCT) at 24-27 weeks of gestation (g.w.), negative cases formed the normal control group (N1). Positive cases took an oral glucose tolerance test (OGTT): those found negative were classed as false positives screening test (N2); if they had an OGTT result at least as high as their normal glucose levels, they were classed as having one abnormal glucose value (OAV) at OGTT; two values as GDM. HbA1c was assayed on the day of GCT. We considered fetal macrosomia, large for gestational age (LGA), ponderal index and mean growth percentile. Mean age, pre-pregnancy BMI, fasting plasma glucose (FPG) and HbA1c were progressively higher from N1 to GDM patients. The newborn of N2 mothers were heavier than those with N1 or GDM. The mean growth percentile was significantly higher in N2 than in N1. More LGA babies were born to OAV than to N1 or N2 women. Macrosomia and ponderal index did not differ significantly in the four groups. At logistic regression only plasma glucose at GCT could predict LGA babies and a ponderal index above 2.85. At risk analysis, GDM and OAV significantly predicted LGA babies, and GDM a ponderal index >2.85. In conclusion, FPG at GCT could predict fetal overgrowth and plasma glucose >85mg/dl doubles the risk of LGA infants. HbA1c at 24-27g.w. does not predict fetal overgrowth. Mild alterations in glucose tolerance correlate with fetal overgrowth and needs monitoring and treatment.

Plasma phospholipid fatty acid composition and desaturase activity in women with gestational diabetes mellitus before and after delivery.

AIMS: Analyze plasma phospholipid fatty acids (PPFA) composition and desaturase activity in women with gestational diabetes (GDM) and in women with a normal glucose tolerance (NGT) before and after delivery, and to evaluate the possible relationship between desaturase activity and inflammatory parameters. METHODS: PPFA composition was analyzed by gas chromatography in 21 women with GDM and from 21 with NGT, during the third trimester of pregnancy and 6 months after delivery. We used fatty acid product-to-precursor ratios to estimate desaturase activity, and we also measured in all women interleukins six and ten, tumor necrosis factor alpha and C-reactive protein. RESULTS: No significant differences were observed between NGT and GDM women in terms of PPFA composition, both in pregnancy and after pregnancy. Estimated desaturase Δ9-18 activity was significantly higher, and estimated desaturase Δ5 activity was significantly lower during pregnancy in all women. We observed no correlations between inflammatory markers and desaturases activity, during or after pregnancy, in both groups. CONCLUSIONS: Our data suggest that GDM does not influence PPFA composition and desaturase activity during pregnancy. In addition, late pregnancy characterized by hyperinsulinemia appears to upregulate desaturase Δ9-18 activity in NGT and GDM women.

Gestational Diabetes Mellitus and Future Cardiovascular Risk: An Update.

The prevalence of gestational diabetes mellitus is increasing in parallel with the rising prevalence of type 2 diabetes and obesity around the world. Current evidence strongly suggests that women who have had gestational diabetes mellitus are at greater risk of cardiovascular disease later in life. Given the growing prevalence of gestational diabetes mellitus, it is important to identify appropriate reliable markers of cardiovascular disease and specific treatment strategies capable of containing obesity, diabetes, and metabolic syndrome in order to reduce the burden of cardiovascular disease in the women affected.

Antepartum and early postpartum predictors of type 2 diabetes development in women with gestational diabetes mellitus.

OBJECTIVES: This study aimed at identifying ante-partum and early post-partum (one year) clinical and metabolic characteristics capable of predicting the future development of type 2 diabetes in pregnant women of Mediterranea area affected by gestational diabetes mellitus (GDM). MATERIAL AND METHODS: Seventy GDM patients were evaluated: mean age during pregnancy, plasma glucose levels under OGTT (100 gr. glucose), fasting, 1-h post-prandial plasma glucose levels, HbA(1c) at the third trimester, gestational week of GDM diagnosis, insulin therapy, and weight gain were all taken into consideration. Some maternal risk factors such as pre-pregnancy BMI, and maternal and fetal outcome of index pregnancy were also assessed. One year after delivery in the same patients, BMI, fasting and 1-h post-prandial plasma glucose, plasma glucose and insulinemia under OGTT (75 gr. glucose) were measured. We focused our attention on women who presented type 2 diabetes 5 years after pregnancy or IGT and those who, one year after pregnancy, were normal. RESULTS: Five years after pregnancy 49 women were normal, 5 had developed type 1 diabetes and were not considered, 6 had developed IGT, and 10 type 2 diabetes. Analysis of variables during pregnancy showed that those variables predicting type 2 diabetes were pre-pregnancy BMI, gestational week of diagnosis, need for insulin therapy, obesity, and plasma glucose at 60' OGTT. Analysis of variables evaluated one year after pregnancy showed that BMI, fasting and post-prandial plasma glucose, plasma glucose at each point of the OGTT, and plasma insulin at 30' OGTT were predictive of the development of type 2 diabetes. Furthermore, age, post-partum fasting plasma glucose, and plasma glucose under OGTT post-partum were predictive of the development of IGT. Our data show for the first time that, also in a Caucasian Mediterranean population, markers of the future development of diabetes do exist, as reported in literature. They also stress the importance of correct identification of GDM patients, in order to screen those at greater risk of developing diabetes, for whom it is imperative to set up prevention programs.

Evaluation of T-cell receptor CD3+ gamma delta in gestational diabetes mellitus.

Few studies have shown a significant increase of CD3+ T-cell receptor (TCR) gamma delta in the early phases of type 1 diabetes. We wished to determine if CD3+ TCR gamma delta is involved in the pathogenesis of gestational diabetes mellitus (GDM). We studied 29 GDM patients and 21 normal pregnant women. Lymphocyte subpopulations (CD3+ TCR alpha beta, CD3+ TCR gamma delta), islet cell antibodies (ICA), glutamic acid decarboxylase antibodies (GAD) and protein tyrosine phosphatase antibodies (IA2-Ab) were evaluated in all patients. The percentage of CD3+ TCR gamma delta was significantly higher in GDM women than in the control group (5.1 +/- 2.9% vs 3.7 +/- 1.7%; p < 0.05). No abnormalities of the other lymphocyte subpopulations were found. All subjects were negative for ICA; 2 GDM patients were positive for GAD, but no relationship was found between GAD positivity and CD3+ gamma delta levels in these 2 patients. Further follow-up studies of these patients are required to verify if the CD3+ TCR gamma delta receptor is a useful marker for diabetes development.