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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.

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.

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.

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.

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. 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. 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. 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.

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.

Diabet. Med. 28, 1074–1077 (2011) Abstract 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

This study aimed to identify potential immunological markers for predicting type 1 diabetes in patients with gestational diabetes mellitus (GDM) and any immunological impairment in their newborn. In 62 GDM patients and 74 women with normal glucose tolerance (NGT), and their babies, we assessed total lymphocytes, T lymphocyte subsets CD3 and CD8 expressing T cell receptor (TCR) alpha/beta or gamma/delta, CD16 and CD19, pancreatic autoantibodies and cytokines (IL-5, IL-2, soluble receptor IL-2). At delivery, umbilical cord blood samples were taken for lymphocyte subpopulations and cytokine measurements. GDM mothers had higher levels of total lymphocytes, CD8 expressing TCR gamma/delta, and lower levels of CD3 expressing TCR alpha/beta than NGT controls. Insulin-treated GDM mothers had lower CD4 and CD4/CD8 ratios, and higher CD8 and IL-5 than diet-treated GDM or controls. Five women were positive for pancreatic autoantibodies, with lower CD4 (p

It has been demonstrated that good metabolic control maintained throughout pregnancy can reduce maternal and fetal complications in diabetes. To achieve good metabolic control, before conception and throughout pregnancy, insulin therapy needs to be optimized, and, in this context, the new insulins currently on the market may help. We therefore review here what is known about the potential benefits and risks related to the use of these new insulins in pregnancy. Clinical and experimental data on insulin lispro strongly suggest that lispro does not have adverse maternal or fetal effects during pregnancy in women with preexisting diabetes, and also that its use in these women results in improved glycemic control, fewer hypoglycemic episodes, and improved patient satisfaction. In women with gestational diabetes mellitus (GDM), the use of insulin lispro is efficient in reducing postprandial hyperglycemia and some neonatal features related to hyperglycemia, thus stressing its usefulness in this condition. As for insulin aspart, clinical data on GDM patients shows the same efficacy as insulin lispro in lowering postprandial hyperglycemia, indicating that insulin aspart may be used in GDM when this condition is characterized by postprandial hyperglycemia. The results of a multicentric study now in progress on the efficacy and safety of insulin aspart in type 1 pregnant diabetic patients will definitely be useful in establishing whether this insulin is safe in pregnancy. For the moment, the use of insulin glargine during pregnancy is not recommended owing to the lack of data on maternal and fetal effects.

We evaluated the outcome of pregnancies followed between 1990 and 2000 in 93 women with type 1 diabetes, treated with conventional intensive insulin therapy (n=68) or continuous subcutaneous insulin infusion (n=25). We evaluated metabolic control (fasting and 1-hour post-prandial plasma glucose and HbA1c levels), spontaneous or induced abortions, time and mode of delivery, maternal outcome (pregnancy-induced hypertension, preeclampsia, placental insufficiency, hydramnios, hypoglycemic coma, ketoacidosis) and fetal outcome (weight, hypoglycemia, hypocalcemia, hyperbilirubinemia, fetal distress, asphyxia, hyaline membrane disease, polycythemia, shoulder dystocia, malformations). Patients treated with insulin pump more frequently had background retinopathy and clinical neuropathy. No significant differences were observed between the two groups in metabolic control and maternal outcome. Glycemic control, non-optimal in the prepregnancy state, improved significantly during pregnancy, as shown by the progressive reduction in HbA1c levels. As regards fetal outcome, no differences were observed between the two groups in morbidity and especially in malformation rate. Patients with malformed babies did not have optimal metabolic control at conception. Thus, maternal and perinatal outcomes were comparable in patients treated with insulin pump and continuous subcutaneous insulin therapy, and depended on metabolic control. In patients in higher White's class and with more unstable glycemia, we achieved metabolic control and outcomes comparable with those of women of lower White's class and more stable glycemic values using the insulin pump. Our data suggest that insulin pump therapy is useful in problematic, complicated cases of women who want a baby.

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.

Continuous glucose monitoring (CGM) gives a unique insight into magnitude and duration of daily glucose fluctuations. Limited data are available on glucose variability (GV) in pregnancy. We aimed to assess GV in healthy pregnant women and cases of type 1 diabetes mellitus or gestational diabetes (GDM) and its possible association with HbA1c. CGM was performed in 50 pregnant women (20 type 1, 20 GDM, and 10 healthy controls) in all three trimesters of pregnancy. We calculated mean amplitude of glycemic excursions (MAGE), standard deviation (SD), interquartile range (IQR), and continuous overlapping net glycemic action (CONGA), as parameters of GV. The high blood glycemic index (HBGI) and low blood glycemic index (LBGI) were also measured as indicators of hyperhypoglycemic risk. Women with type 1 diabetes showed higher GV, with a 2-fold higher risk of hyperglycemic spikes during the day, than healthy pregnant women or GDM ones. GDM women had only slightly higher GV parameters than healthy controls. HbA1c did not correlate with GV indicators in type 1 diabetes or GDM pregnancies. We provided new evidence of the importance of certain GV indicators in pregnant women with GDM or type 1 diabetes and recommended the use of CGM specifically in these populations.

We evaluated quality of life in pregnant women with diabetes followed up at Italian diabetes clinics.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.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.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.

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.

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 β-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 β-cell function than ND. During the late visit, GDM2 also showed impaired β-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. β-Cell function impairment is evident only when GDM is manifest and is characterized by inappropriate adaptation to the pregnancy induced increase in insulin resistance.

The prevalence of diabetes and impaired glucose tolerance in women of childbearing age is increasing worldwide, particularly among minority youth. As a consequence, in many parts of the world the number of pregnancies complicated by Type 2 diabetes is actually exceeding those complicated by Type 1 diabetes. Moreover, also the prevalence and incidence of gestational diabetes mellitus have been rising over recent years. Although diabetes complicating pregnancy is a cause of maternal and foetal complications, its exact prevalence in pregnancy is yet not well defined and large population studies are still lacking. This article reviews the existing epidemiologic studies on diabetes in pregnancy performed in Italy.

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).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.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.

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%; p0.05). 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.

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. ispartof: DIABETIC MEDICINE vol:38 issue:2 ispartof: location:England status: published