BACKGROUND/OBJECTIVES:Umbilical cord leptin is increased in infants of women with obesity. We tested the hypothesis that a high cord leptin-to-fat mass ratio might be associated with adverse outcomes at birth and in early childhood. METHODS:A secondary analysis of vitamin D And Lifestyle Intervention for gestational diabetes mellitus prevention (DALI) trial was conducted. Cord leptin-to-fat mass ratios were classified into top (TT), middle, and low (LT) tertiles overall and within sexes. Relationship with neonatal outcomes and offspring BMI z-scores were compared between TT and LT groups. RESULTS:Among 323 infants (maternal pre-pregnancy BMI 33.7 ± 4.2 kg/m2, 52% male) female (vs. male) offspring had higher cord leptin, fat mass percentage, and leptin-to-fat mass ratio (median (IQR): 21.4 (13.4, 30.99) vs. 15.5 (8.3, 25.9), p < 0.001). Compared to the LT group, infants in the TT group (58% females) had higher cord leptin but similar fat mass percentage. Among males (but not in females), the C-peptide-to-glucose ratio was elevated in the TT group (vs. LT) (0.2 (0.1-0.2) vs. 0.1(0.02-0.2), p < 0.001), while birthweight (3.5 ± 0.5 vs. 3.7 ± 0.4 kg, p = 0.045), fat mass percentage (11.1 ± 3.9 vs. 13.0 ± 3.6, p = 0.008), and BMI z-scores (at age 1 only) were lower (median (IQR): -0.15 (-0.67, 0.98) vs. 1.35 (-0.06, 1.67), p = 0.03). CONCLUSIONS:Relative cord hyperleptinaemia was associated with reduced offspring BMI among males.

Bariatric surgery is an established therapeutic option for morbid obesity increasing worldwide, including women of childbearing age, due to improved fertility. From this perspective, several issues related to the management of pregnancy after bariatric surgery will be analyzed and discussed, including alterations in glucose homeostasis, diagnosis of gestational diabetes, postprandial hyperinsulinemic hypoglycemia, and nutritional deficiencies.

This study aimed to investigate the impact of type 2 diabetes (T2D) on muscle and tendon mechanics by comparing individuals with controlled diabetes to a healthy cohort matched for age, BMI, and physical activity level. A secondary aim was to investigate the possible association between muscle-tendon proprieties and glycated haemoglobin (HbA1c) or advanced glycated end products (AGE, RAGE) as determined in blood and skin biopsies. Twenty-eight patients and eighteen controls were recruited for this study. Achilles tendon stiffness (kT), muscle-tendon stiffness (kM, in gastrocnemius medialis) and the rate of torque development (RTD) were evaluated by combining dynamometric and ultrasound data. Diabetic patients showed increased tendon stiffness and reduced tendon elongation compared to controls, but similar RTD and kM values. No differences in advanced glycation end products (in serum or biopsies) were observed between cohorts, but a significant positive correlation was observed between kT and HbA1c (r = 0.610, N = 46, P < 0.001). Our data indicate that muscle, but not tendon, properties can be preserved in controlled and physically active diabetic patients and that higher tendon stiffness does not result in a functional deficit (i.e., same explosive capacity between cohorts). Although this study is cross-sectional and has a limited sample size, our data suggest a potential role of HbA1c as a non-invasive biomarker of altered tendon mechanics in people with diabetes. NCT05585502.

INTRODUCTION:Vitamin D (vitD) plays a role in metabolic regulation, including lipid metabolism and insulin sensitivity. During pregnancy, profound physiological changes in lipid handling and ketogenesis occur to support fetal development. However, the extent to which maternal vitamin D status influences these metabolic adaptations and fetal metabolic markers remains unclear. METHODS:In this secondary analysis, we examined lipid distribution throughout pregnancy-from before 20 weeks' gestation to delivery-in women with overweight or obesity, stratified by vitamin D status (deficiency, insufficiency, or sufficiency), assessing both maternal and cord blood. Main inclusion criteria were: age > =18 years, singleton pregnancy, < 20 weeks' gestation, BMI ≥ 29 kg/m2. Women with GDM < 20 weeks' gestation were excluded. In total, 962 pregnant women were divided into vitD deficient (< 30 nmol/L, n = 102), insufficient (30-50 nmol/L, n = 222) and sufficient (> 50 nmol/L, n = 638) groups. VitD levels and lipid concentrations were assessed at < 20, 24-28 and 35-37 weeks' gestation and in cord blood. RESULTS:Compared with vitD sufficient women, women with vitD deficiency had significantly larger increases in LDL-C throughout pregnancy and ß-OH-butyrate at 24-28 weeks' gestation, in adjusted analysis. VitD in cord blood was highest in offspring of mothers with vitD sufficiency. In cord blood, significantly higher ß-OH-butyrate was observed with vitD deficiency; lipid concentrations were similar between groups. CONCLUSIONS:Early vitamin D deficiency before 20 weeks of gestation was associated with altered metabolic trajectories during pregnancy, including greater increases in LDL cholesterol and ketone body concentrations in women with overweight or obesity, as well as higher cord blood ketone levels in their offspring. These findings suggest that early maternal vitamin D status may influence maternal and fetal metabolic adaptations, although causal relationships and clinical implications require further investigation. TRIAL REGISTRATION:Trial registered at ISRCTN registry (https://doi.org/10.1186/ISRCTN70595832) trial number ISRCTN70595832. Registration date 02/12/2011.

INTRODUCTION:The prevalence of preexisting type 1 and type 2 diabetes in pregnancy continues to rise, with women with type 2 facing adverse maternal and fetal outcomes comparable to those with type 1. Despite international guidelines emphasizing a comprehensive, multi-targeted approach to ensure safe pregnancy outcomes, pregnancy-related complications remain substantially elevated in this population. AREAS COVERED:This perspective article examines critical issues in the management of diabetes during pregnancy, identifying key barriers and evidence-based strategies to optimize suitable care. A search of the medical literature was performed, giving priority to randomized controlled trials (RCT), systematic reviews and meta-analyses. By analyzing the current evidence, we address fundamental challenges in preconception counseling, metabolic control optimization and pharmacological management. EXPERT OPINION:The knowledge of these critical points is essential to improving maternal and neonatal outcomes and to reducing predictable complications in pregnant women with preexisting diabetes.

Background/Objectives: Patients with type 2 diabetes (T2D) are at risk of developing multiple complications, and diabetic polyneuropathy (DPN) is by far the most common. The purpose of the present study was to assess the ability of a new algorithm based on artificial intelligence (AI) to identify patients with T2D who are at risk of DPN in order to move on to further instrumental evaluation with the biothesiometer method. Methods: This is a single-centre, cross-sectional study with 201 consecutive T2D patients recruited at the Diabetes Operating Unit of the ULSS 6 of Padua (Northeast Italy). The individual risk of developing DPN was calculated using the AI-based MetaClinic Prediction Algorithm and compared with the DPN diagnosis provided by the digital biothesiometer method, which measures the vibratory perception threshold (VPT) on both feet. Results: Of the enrolled patients, 107 (53.23%) were classified by AI software as having a low probability of developing DPN, 39 (19.40%) as having a moderate probability, 29 (14.43%) as having a high probability, and 26 (12.94%) as having a very high probability. In 63 of the total patients, biothesiometer measurement showed a VPT ≥ 25 V, indicative of DPN, while 138 patients had a non-pathological VPT value (< 25 V) (prevalence of abnormal VPT 31.34%; prevalence of normal VPT 68.66%). The overall agreement between biothesiometer results and AI risk attribution was 65%. Cohen’s κ was 0.162, and Gwet’s AC1 coefficient 0.405. Conclusions: The use of an optimized AI algorithm can help estimate the risk of developing DPN, thereby guiding more targeted and in-depth screening, including instrumental assessment using the biothesiometer method.

This study aimed to evaluate the predictive performance of an artificial intelligence (AI)-based algorithm in estimating the risk of cardio-cerebrovascular complications in patients with type 2 diabetes mellitus (T2D). Medical records of 532 T2D patients from the Diabetology Unit in Padova, Italy, were analyzed using the Metaclinic AI Prediction Module, which estimates the probability of heart and cerebrovascular organ damage. For patients identified as “Very high” (n = 63) or “Low” (n = 122) risk for heart disease, additional clinical and instrumental data on their cardiac history were collected. The level of agreement between AI predictions and traditional clinical-instrumental diagnostics was assessed using Cohen’s κ coefficient. In the “Very high” risk group, the agreement between AI predictions and clinical diagnostics for heart disease was poor (κ = 0.00), while prediction for cerebrovascular disease showed excellent agreement (κ = 0.89). Similarly, in the “Low” risk group, agreement for heart disease remained poor (κ = 0.00), but agreement for cerebrovascular disease was again high (κ = 0.83). A marked difference was observed in the algorithm’s performance. While the AI showed strong predictive ability for cerebrovascular complications, it failed to reliably predict heart disease risk. These results suggest that the algorithm may be clinically valuable for cerebrovascular risk assessment but needs refinement for cardiac prediction.

BACKGROUND:Preexisting diabetes (PDM) increases the risk of maternal and perinatal mortality and morbidity. Reduction of maternal hyperglycemia prior to and during pregnancy can reduce these risks. Despite compelling evidence that preconception care (PCC), which includes achieving strict glycemic goals, reduces the risk of congenital malformations and other adverse pregnancy outcomes, only a minority of individuals receive PCC. Suboptimal pregnancy outcomes demonstrated in real-world data highlight the need to further optimize prenatal glycemia. New evolving technology shows promise in helping to achieve that goal. Dysglycemia is not the only driver of poor pregnancy outcomes in PDM. The increasing impact of obesity on pregnancy outcomes underscores the importance of optimal nutrition and management of insulin sensitizing medications during prenatal care for PDM. OBJECTIVE:To provide recommendations for the care of individuals with PDM that lead to a reduction in maternal and neonatal adverse outcomes. METHODS:The Guideline Development Panel (GDP) composed of a multidisciplinary panel of clinical experts, along with experts in guideline methodology and systematic literature review, identified and prioritized 10 clinically relevant questions related to the care of individuals with diabetes before, during and after pregnancy. The GDP prioritized randomized controlled trials (RCTs) evaluating the effects of different interventions (eg, PCC, nutrition, treatment options, delivery) during the reproductive life cycle of individuals with diabetes, including type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Systematic reviews queried electronic databases for publications related to these 10 clinical questions. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was used to assess the certainty of evidence and develop recommendations. The approach incorporated perspectives from 2 patient representatives and considered patient values, costs and resources required, acceptability and feasibility, and impact on health equity of the proposed recommendations. RESULTS:In individuals with diabetes mellitus who have the possibility of becoming pregnant, we suggest asking a screening question about pregnancy intention at every reproductive, diabetes, and primary care visit. Screening for pregnancy intent is also suggested at urgent care/emergency room visits when clinically appropriate (2 | ⊕OOO). This was suggested based on indirect evidence demonstrating a strong association between PCC and both reduced glycated hemoglobin (HbA1c) at the first prenatal visit and congenital malformations.In individuals with diabetes mellitus who have the possibility of becoming pregnant, we suggest use of contraception when pregnancy is not desired (2 | ⊕⊕OO). This was suggested based on indirect evidence in women with diabetes, where PCC-including contraception as a key component-showed a clinically significant association with improvements in first-trimester HbA1c and the rate of congenital malformations, together with indirect evidence from the general population regarding the reduction of unplanned pregnancies and pregnancy terminations with the use of contraception.In individuals with T2DM, we suggest discontinuation of glucagon-like peptide-1 receptor agonist (GLP-1RA) before conception rather than discontinuation between the start of pregnancy and the end of the first trimester (2 | ⊕OOO). This was suggested based on limited data on risk of exposure to GLP-1RA receptor agonists during pregnancy.In pregnant individuals with T2DM already on insulin, we suggest against routine addition of metformin (2 | ⊕OOO). This was suggested based on the GDP judgment that the benefit of adding metformin to insulin to achieve decrease in rates of large for gestational age infants did not outweigh the potential harm of increasing the risk of small for gestational age infants or adverse childhood outcomes related to changes in body composition.In individuals with PDM, we suggest either a carbohydrate-restricted diet (<175 g/day) or usual diet (>175 g/day) during pregnancy (2 | ⊕OOO). This was suggested based on the GDP judgment that the available evidence was limited and very indirect, resulting in significant uncertainty about the net benefits or harms. As such, the evidence was insufficient to support a recommendation either for or against a carbohydrate intake cutoff of 175 g/day.In pregnant individuals with T2DM, we suggest either the use of a continuous glucose monitor (CGM) or self-monitoring of blood glucose (SMBG) (2 | ⊕OOO). There is lack of direct evidence supporting superiority of CGM use over SMBG for T2DM during pregnancy. There is indirect evidence supporting improved glucometrics with the use of CGM for individuals with T2DM outside of pregnancy, substantial improvements in neonatal outcomes for individuals with T1DM using CGM during pregnancy and the potential for decreasing adverse pregnancy outcomes with improved glucometrics in individuals with T2DM.In individuals with PDM using a CGM, we suggest against the use of a single 24-hour CGM target <140 mg/dL (7.8 mmol/L) in place of standard-of-care pregnancy glucose targets of fasting <95 mg/dL (5.3 mmol/L), 1-hour postprandial <140 mg/dL (7.8 mmol/L), and 2-hour postprandial < 120 mg/dL (6.7 mmol/L) (2 | ⊕OOO). This was suggested based on indirect evidence that associated adverse pregnancy outcomes with a fasting glucose > 126 mg/dL (7 mmol/L).In individuals with T1DM who are pregnant, we suggest the use of a hybrid closed-loop pump (pump adjusting automatically based on CGM) rather than an insulin pump with CGM (without an algorithm) or multiple daily insulin injections with CGM (2 | ⊕OOO). This was suggested based on a meta-analysis of RCTs which demonstrated improvement in glucometrics with increased time in range (MD +3.81%; CI -4.24 to 11.86) and reduced time below range (MD -0.85%; CI -1.98 to 0.28) with the use of hybrid closed-loop pump technology.In individuals with PDM, we suggest early delivery based on risk assessment rather than expectant management (2 | ⊕OOO). This was suggested based on indirect evidence that risks may outweigh benefits of expectant management beyond 38 weeks gestation and that risk assessment criteria may be useful to inform ideal delivery timing.In individuals with PDM (including those with pregnancy loss or termination), we suggest postpartum endocrine care (diabetes management), in addition to usual obstetric care (2 | ⊕OOO). As the postpartum period frequently overlaps with preconception, this was suggested based on indirect evidence demonstrating a strong association between PCC and both reduced HbA1c at the first prenatal visit and congenital malformations. CONCLUSION:The data supporting these recommendations were of very low to low certainty, highlighting the urgent need for research designed to provide high certainty evidence to support the care of individuals with diabetes before, during, and after pregnancy. Investment in implementation science for PCC is crucial to prevent significant mortality and morbidity for individuals with PDM and their children. RCTs to further define glycemic targets in pregnancy and refinement of emerging technology to achieve those targets can lead to significant reduction of harm and in the burden of diabetes care. Data on optimal nutrition and obesity management in pregnancy are lacking. More research on timing of delivery in women with PDM is also needed.

CONTEXT:Women with preexisting diabetes mellitus (PDM) are at increased risk of pregnancy-related complications. OBJECTIVE:To summarize the available supporting evidence for the Endocrine Society guidelines about management of PDM in pregnancy. DATA SOURCES:MEDLINE, EMBASE, Scopus, and other sources through February 2025. STUDY SELECTION:Studies were selected by pairs of independent reviewers. DATA EXTRACTION:Data were extracted by pairs of independent reviewers. DATA SYNTHESIS:We included 17 studies. Meta-analysis showed no significant difference between hybrid closed-loop insulin pump (HCL) and standard of care regarding time in range (TIR), time above range (TAR), and time below range (TBR). HCL had better overnight TIR and TBR. For women with type 2 diabetes mellitus (T2DM), intermittent use of continuous glucose monitoring (CGM) was not associated with a significant change in the risk of large for gestational age (LGA) neonates (2 randomized controlled trials [RCTs], 102 patients). Adding metformin to insulin was associated with a lower risk of LGA (2 RCTs, 1126 patients). Three retrospective studies (1724 patients) suggested increased neonatal complications when delivery was induced before 39 weeks of gestation (particularly before 38 weeks) in women with preexisting type 1 (T1DM) and T2DM, although this evidence was subject to likely confounding. One retrospective study showed no increase in neonatal complications with periconceptional exposure to glucagon-like peptide-1 receptor agonists. We could not identify comparative studies assessing a screening question about the possibility of pregnancy or a carbohydrate restrictive diet. CONCLUSION:This systematic review addresses various aspects of managing PDM in pregnancy and will support the development of the Endocrine Society guidelines.

Proper nutrition is essential during pregnancy to ensure an adequate supply of nutrients to the foetus and adequate maternal weight gain. In pregnancy complicated by diabetes (both gestational and pre-gestational), diet in terms of both the intake and quality of carbohydrates is an essential factor in glycaemic control. Maternal BMI at conception defines the correct weight increase during gestation in order to reduce maternal-foetal complications related to hypo- or hyper-nutrition. The recommendations presented here, which are based on national and international guidelines and the most recently published data on nutrition in physiological pregnancy and pregnancy complicated by hyperglycaemia and/or obesity, are designed to help healthcare professionals prescribe suitable eating patterns to safeguard the health of the mother and the foetus.

Introduction and Objective: Cord blood leptin is high in neonates with high adiposity; however, little is known about the association of these levels with childhood adiposity. We compare the BMI of children with and without relative cord hyperleptinemia born to mothers with overweight/obesity in the Vitamin D and Lifestyle Intervention for Gestational Diabetes Mellitus Prevention (DALI) study. Methods: DALI mothers were contacted annually for available offspring weight and height over 5 years. Neonatal fat mass was calculated using Deierlein’s formula. Cord leptin-to-fat mass ratios were classified into low (LT), middle, and top (TT) tertiles overall and within sexes. Relationship with birthweight, cord C-peptide-to-glucose ratio, and offspring BMI were compared between LT and TT groups. Results: Among 324 babies (31% of total: maternal pre-pregnancy BMI 33.7±4.2 kg/m2, 83% European ethnicity, 52% boys, median cord leptin 8.3 (4.5-13.6) ng/ml), the median (IQR) cord leptin-to-fat mass ratio was 21.07 (12.0-34.8). Female (vs male) offspring had higher cord leptin (10.6 (5.6-16.3) vs. 6.7 (4.0-11.2), p<0.001) but lower fat mass % (10.4±3.8 vs. 12.4± 3.7, p<0.001), with similar cord C-peptide-to-glucose ratios at birth. Infants in the TT group (72% girls) had higher cord leptin (14.8 (10.7-20.7) vs. 4.0 (2.5-5.5), p<0.001) and lower fat mass % (9.8±3.5 vs. 12.6±3.9, p<0.001) and birthweight (kg) (3.4±0.5 vs. 3.6±0.5, p=0.002) compared to the LT group. Among boys, but not girls, the C-peptide-to-glucose ratio was elevated in the TT group (0.19±0.1 vs. 0.12±0.1, p<0.001). There was a trend of lower BMI in the TT group from age 1 through age 5, with a significant difference at age 2 (17.7±1.9 vs 16.5±1.4 (kg/m2), p=0.01). The trend was more remarkable in boys than girls. Conclusion: Relative cord hyperleptinemia in the offspring of women who are overweight/obese is associated with lower birthweight and BMI into early childhood. Longitudinal studies are needed to determine the long-term implications of these associations. J. Immanuel: None. S. Chirayath: None. G. Desoye: None. M. van Poppel: None. R. Corcoy: None. J. Harreiter: None. P. Damm: None. A. Kautzky-Willer: None. A. Lapolla: None. A. Bertolotto: None. D.J. Hill: None. D. Simmons: Research Support; Novo Nordisk, AMSL. Other Relationship; Abbott, Abbott, Boehringer-Ingelheim. Speaker's Bureau; Ascensia Diabetes Care. This project received funding from the European Community’s 7th Framework Program(FP7/2007–2013; grant agreement no. 242187). In the Netherlands, additional funding wasprovided by the Netherlands Organization for Health Research and Development (ZonMW) (Grant nr 200310013). In the UK, the DALI team acknowledges the support received from theNIHR Clinical Research Network: Eastern, especially the local diabetes clinical and research teams based in Cambridge. In Spain, additional funding was provided by CAIBER 1527–B–226.

Metformin is the most prescribed glucose-lowering drug worldwide; globally, over 100 million patients are prescribed this drug annually. Some different action mechanisms have been proposed for this drug, but, surprisingly, no metabolite of metformin has ever been described. It was considered interesting to investigate the possible reaction of metformin with glucose following the Maillard reaction pattern. The reaction was first performed in in vitro conditions, showing the formation of two adducts that originated by the condensation of the two molecular species with the losses of one or two water molecules. Their structures were investigated by liquid chromatography coupled with mass spectrometry (HPLC-MS), tandem mass spectrometry (MS/MS) and accurate mass measurements (HRMS). The species originated via the reaction of glucose and metformin and were called metformose and dehydrometformose, and some structural hypotheses were conducted. It is worth to emphasize that they were detected in urine samples from a diabetic patient treated with metformin and consequently they must be considered metabolites of the drug, which has never been identified before now. The glucose-related substructure of these compounds could reflect an improved transfer across cell membranes and, consequently, new hypotheses could be made about the biological targets of metformin.

Background: Different specific surfactant proteins (SPs) have been associated with various pathological conditions, not only of the respiratory system, but also more recently with cardiovascular diseases, such as heart failure. The aim of the present study was to evaluate the role of SP-A, SP-D, and the precursor protein of SP-B (proSP-B) in the pathogenesis of cardiovascular damage in patients affected by type 2 diabetes (T2D). Methods: The study considered 31 patients with T2D (DN group), 34 patients with both T2D and coronary heart disease (CHD) (DC group), and 30 patients without diabetes but with a diagnosis of CHD (NC group). SP-A, SP-D, and proSP-B concentrations were determined in plasma samples, and were statistically compared using parametric and multivariate methods. Results: Higher plasma concentrations of SP-D and proSP-B were found in patients affected by both T2D and CHD (DC group), and in patients with CHD without diabetes (NC group), in comparison to T2D patients (DN group). A significant correlation, both with linear regression (r = 0.3565, p = 0.001) and Principal Component Analysis (PCA), was found between the plasma levels of SP-D and proSP-B in the overall cohort of patients. No differences in SP-A were observed among the three groups of subjects. Conclusion: The present study extends the knowledge on the role of plasma SPs’ levels as possible indicators of the risk of CHD being linked to T2D disease progression.

Background Type 2 diabetes mellitus (T2DM) increases the risk of coronary heart disease (CHD) by 2–4 fold, and is associated with endothelial dysfunction, dyslipidaemia, insulin resistance, and chronic hyperglycaemia. The aim of this investigation was to assess, by a multimarker mass spectrometry approach, the predictive role of circulating proteins as biomarkers of cardiovascular damage progression associated with diabetes mellitus. Methods The study considered 34 patients with both T2DM and CHD, 31 patients with T2DM and without CHD, and 30 patients without diabetes with a diagnosis of CHD. Plasma samples of subjects were analysed through a multiplexed targeted liquid chromatography mass spectrometry (LC-MS)-based assay, namely Multiple Reaction Monitoring (MRM), allowing the simultaneous detection of peptides derived from a protein of interest. Gene Ontology (GO) Analysis was employed to identify enriched GO terms in the biological process, molecular function, or cellular component categories. Non-parametric multivariate methods were used to classify samples from patients and evaluate the relevance of the analysed proteins’ panel. Results A total of 81 proteins were successfully quantified in the human plasma samples. Gene Ontology analysis assessed terms related to blood microparticles, extracellular exosomes and collagen-containing extracellular matrix. Preliminary evaluation using analysis of variance (ANOVA) of the differences in the proteomic profile among patient groups identified 13 out of the 81 proteins as significantly different. Multivariate analysis, including cluster analysis and principal component analysis, identified relevant grouping of the 13 proteins. The first main cluster comprises apolipoprotein C-III, apolipoprotein C-II, apolipoprotein A-IV, retinol-binding protein 4, lysozyme C and cystatin-C; the second one includes, albeit with sub-grouping, alpha 2 macroglobulin, afamin, kininogen 1, vitronectin, vitamin K-dependent protein S, complement factor B and mannan-binding lectin serine protease 2. Receiver operating characteristic (ROC) curves obtained with the 13 selected proteins using a nominal logistic regression indicated a significant overall distinction ( p < 0.001) among the three groups of subjects, with area under the ROC curve (AUC) ranging 0.91–0.97, and sensitivity and specificity ranging from 85 to 100%. Conclusions Targeted mass spectrometry approach indicated 13 multiple circulating proteins as possible biomarkers of cardiovascular damage progression associated with T2DM, with excellent classification results in terms of sensitivity and specificity.

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). 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. 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

Background: Pregestational diabetes mellitus, if not well controlled, determines maternal and fetal complications. According to the new diagnostic criteria for gestational diabetes, the diagnosis of diabetes mellitus can also occur in early pregnancy (overt diabetes). Aim: This study aims to determine pregnancy outcomes in women with overt diabetes compared to women with pre-existing type 2 diabetes. Methods: In this retrospective study, we selected women with pre-existing type 2 and overt diabetes who had at least one pregnancy in the 2010–2022 period at the Diabetic Care Unit of Padova. Results: We analyzed 83 pregnancies, and overt diabetes was diagnosed in 18 pregnancies. In total, 95.5% of patients with overt diabetes and 48% of T2DM patients were immigrants (p < 0.143). No patients with overt diabetes planned their pregnancy, while pregnancy was planned in 26.3% of patients with pre-exiting type 2 diabetes (p < 0.05). Periconception and first-trimester glycemic control were the worst in patients with overt diabetes (HbA1c 9.7 ± 3.1% vs. 7.3% ± 2.3%, p < 0.044, at first visit; 8.1 ± 1.9% and 7.0 ± 1.6%, p < 0.037 in the first trimester) with respect to patients with pre-existing type 2 diabetes. As for maternal outcomes, 16.6% of pregnancies ended in miscarriage, and 5.5% of women developed gestational hypertension; as for newborn outcomes, 16.6% of newborns were LGA, and 11.1% were affected by congenital anomalies without any significant difference with respect to women with pre-existing type 2 diabetes. The high rate of congenital malformations in pregnancies of women with overt diabetes is probably a result of the poor, metabolic control observed during the periconception period when the organogenesis of the fetus takes place. Conclusions: It is essential to utilize procedures for diabetes screening in women of childbearing age not only at the beginning of the pregnancy, but also during the preconception phase or the postmenarcheal period when strong risk factors for diabetes onset are present, such as a high BMI, glycemic disorders, and those who fall under high-risk ethnicity categories.