Background/Objectives: This population-based observational study with a repeated cross-sectional design included singleton live births occurring in Tuscany, Italy, between 2010 and 2021, identified through regional Delivery Assistance Certificates (CeDAP) and linked with administrative healthcare databases. The study aimed to assess temporal trends in the prevalence of gestational diabetes mellitus (GDM) and to evaluate the contribution of major risk factors-particularly pregestational obesity, maternal age, parity, and origin from high-pressure migration countries (HPMC)-to GDM and related maternal-neonatal outcomes. The rationale for the study derives from the increasing worldwide prevalence of GDM, driven by changes in diagnostic criteria as well as evolving maternal demographic and metabolic risk profiles. Methods: The study included 266,394 singleton live births. GDM was identified using a previously validated algorithm based on insulin prescriptions, diabetes specialist visits, attendance to education programs, and postpartum oral glucose tolerance testing. Temporal trends in GDM, pregestational obesity, HPMC origin, and maternal-neonatal outcomes were assessed. Multivariable Poisson regression models with robust variance estimation were used to estimate adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) for GDM and adverse outcomes, including preterm birth, macrosomia, neonatal distress, and cesarean delivery. Results: During the study period, the annual number of births declined, whereas the overall mean prevalence of GDM was 11.37% and increased steadily from 8.23% in 2010 to 14.43% in 2021, corresponding to a relative increase of approximately 75%. Pregestational obesity and pregnancies among women from HPMC also increased over time. Multivariable analysis showed that pregestational obesity, advanced maternal age, multiparity, and HPMC origin were major independent determinants of GDM. Pregestational obesity emerged as the most important variable associated with both GDM and maternal-neonatal complications, including macrosomia, cesarean delivery, and neonatal distress, often showing stronger associations than GDM itself. Macrosomia and cesarean delivery declined over time, whereas preterm birth increased among pregnancies complicated by GDM. An inverse association between GDM and fetal macrosomia was observed in adjusted models, possibly reflecting effective clinical management, earlier delivery strategies, or algorithm-related selection effects. Conclusions: GDM prevalence increased substantially in Tuscany between 2010 and 2021 despite declining birth rates. This increase appears to be mainly associated with rising pregestational obesity, older maternal age, multiparity, and changes in population composition related to migration from HPMC. Adverse maternal-neonatal outcomes were more strongly associated with pregestational obesity and maternal age than with GDM itself, suggesting that preventive strategies targeting metabolic health before pregnancy may be crucial for reducing both GDM and related complications. Monitoring temporal trends in GDM and its risk factors may also serve as an indirect indicator of the effectiveness of regional healthcare policies.

Background/Objectives: The prevalence of gestational diabetes mellitus (GDM) has in-creased worldwide over recent years. This rise has been attributed to changes in diagnostic criteria and to evolving demographic and metabolic risk profiles. The present study aimed to evaluate temporal trends in GDM prevalence in Tuscany, Italy, from 2010 to 2021, and to assess whether these trends were associated with changes in major risk factors and GDM-associated maternal–neonatal outcomes. Methods: This population-based retrospective study included all singleton pregnancies recorded in regional Delivery Assistance Certificates (CeDAP) registry between 2010 and 2021 filled by midwives at almost every delivery in Tuscany. GDM was identified using vali-dated clinical algorithms, in accordance with IADPSG criteria implemented from 2013. Temporal trends in GDM prevalence, major risk factors (pregestational obesity, maternal age, origin from High Pressure Migration Countries—HPMC, and adverse maternal and neonatal outcomes were analyzed. Multivariate log linear Poisson regression models were used to assess independent asso-ciations and yearly trends after adjustment for confounders. Results: Among 266,394 pregnancies, mean GDM prevalence was 11.37% and increased progressively over time, despite a concomitant decline in birth rates. Parallel increases were observed in pregestational obesity and in pregnancies among women from HPMC. Multivariate analysis found pregestational obesity, older maternal age, and HPMC ethnicity as the main factors driving the rise in GDM prevalence over time. Ce-sarean deliveries and fetal macrosomia decreased over time, whereas preterm birth increased among GDM pregnancies. Adverse maternal and neonatal outcomes were more strongly associat-ed with pregestational obesity and maternal age than with GDM itself. Conclusions: A true in-crease in GDM prevalence occurred in Tuscany between 2010 and 2021, primarily driven by rising pregestational obesity, advanced maternal age, and HPMC migration. Fetal macrosomia, cesarean delivery, and neonatal distress, were primarily associated with pregestational obesity and mater-nal age, rather than GDM itself. These findings highlight the importance of preventive strategies targeting metabolic health before pregnancy and support the effectiveness of organized GDM screening and management in reducing adverse outcomes.

In humans, taurine (TAU) is a conditionally essential nutrient that exhibits pleiotropic activity in several and different biological processes suggesting its use in the prevention and therapy for a long time. However, its actual role in prevention and treatment is still incomplete and unclear. This review focuses on the potential therapeutic effect of TAU in genetic diseases, cardiovascular diseases (heart failure, hypertension), metabolic syndrome, and on the first pandemic of the third millennium, namely, diabetes mellitus and some gestational diseases such as gestational diabetes, intrauterine growth restriction, and pre-eclampsia, discussing the role of TAU in developmental trajectory. Previous preclinical and clinical TAU investigations predominately enrolled male animals, including humans, even though sex and gender differences play a critical role both in numerous physiological and pathological conditions. This review aims to outline some biological actions of TAU and evidences the sex and gender gap must be reduced in order to establish the role of TAU in prevention and therapy for all individuals.

To investigate whether the risk for post-partum cardiovascular diseases (CVD) is driven by gestational diabetes (GDM), by GDM-related risk factors and/or by pre-gestational (Pre-GD) or post-gestational diabetes (Post-GD). Women delivering in Tuscany, Italy in years 2010–2012 (n = 74,720), were identified from certificates of care at delivery and further identified as affected with GDM, Pre-GD or Post-GD through regional administrative databases. Women with GDM, Pre-GD or Post-GD were retrospectively evaluated for risk of post-partum hospitalizations for CVD (myocardial infarction or stroke; n = 728) across years 2013–2021, comparing women with different forms of diabetes to those without diabetes. Risk of CVD was assessed as odds ratio (OR 95

Background: Surrogate indexes of insulin resistance (IR) are less expensive than the euglycemic glucose clamp. The simultaneous impact of sex and gender, smoking, and combined oral contraceptives (COC) on IR surrogate indexes was studied in a cohort of healthy young men and women (stratified in COC-free women and COC users). Methods: Glycemia, insulin, C-peptide, TG, and HDL were measured in serum samples and used to calculate IGR, HOMA-IR-IR, QUICKI, FIRI, METS-IR, TG, and MCAi. Results: Men had higher BMI, glycemia, TG, METS-IR, TyG, and lower HDL than COC-free women and they had lower IGR and higher METS-IR and MCAi than COC users. TG, HDL, and TyG were lower and MCAi is higher in COC-free women than in COC users. In non-smokers, men had higher BMI and METS-IR and lower HDL than both cohorts of women. COC-free women showed a lower TyG index than men and COC women and lower TG, HDL, and IGR. MCAi was higher in COC-free women than in COC users. Smoking reduced sex and gender differences: HDL was lower in men than COC users and IGR was lower in men than COC-free women. Intra-sex differences were reported only in COC-free women: smokers had higher insulin, C-peptide, TG, and IGR and lower MCAi than non-smokers. Cluster analysis evidenced a significant separation between the sexes and smokers and non-smokers. Conclusions: Smoking leads to changes in the phenotype of both men and women, as well as COC in women; they should be considered independent variables in clinical studies given, representing a fundamental cornerstone in the personalization of prevention and care.

Soccer (football) practice can induce a limitation of ankle range of motion (ROM) that is a possible risk factor for injury and other negative consequences over time. The main objective of this research was to investigate the effects of soccer practice on ankle ROM throughout the entire period of a sports career of soccer players (SP). Furthermore, the relationship between ankle ROM and muscle strength in SP of different ages was studied. A total of 204 SP (range 6.7–45.1 years) and 87 controls (range: 7.5–45.2 years) matched for age, body mass index (BMI), and gender, were assessed. Ankle ROM in both plantar flexion (APF) and dorsiflexion (ADF) in addition to handgrip strength (HGS) were evaluated using an inclinometer and the Jamar hydraulic hand dynamometer, respectively. The comparison between SP and control groups showed a significant reduction in ankle ROM of both APF (26.3 ± 7.2° vs. 32.6 ± 7.4°; d = −0.90; p < 0.001) and ADF (95.5 ± 15.6° vs. 105.5 ± 15.8°; d = −0.66; p < 0.001). In SP, the results of the ANOVAs test indicate that age had a significant effect on ADF (F = 4.352, p = 0.038, partial eta-squared (ηp2) = 0.015) but not on APF (F = 0.430, p = 0.746, ηp2 = 0.001). Moreover, considering only the SP, a weak inverse correlation between ADF and HGS group ADF was found (rs = −0.27; p < 0.001). Factors such as the non-linear trend of growth in young SP could hinder the definition of the relationship between ankle ROM, age, and muscle strength. However, the appropriate consideration of age and muscle strength could facilitate the management of ankle ROM in PF of different ages.

Background: The aim of this study was to clarify any gender differences in the mortality risk of people with DFD since patients with diabetic foot disease (DFD) are at a high risk of mortality and, at the same time, are more likely to be men. Methods: From regional administrative sources, the survival probability was retrospectively evaluated by the Kaplan-Meier method and using the Cox proportional-hazards model comparing people with DFD to those without DFD across the years 2011–2018 in Tuscany, Italy. Gender difference in mortality was evaluated by the ratio of hazard ratios (RHR) of men to women after initial DFD hospitalizations (n = 11,529) or in a cohort with prior history of DFD hospitalizations (n = 11,246). Results: In both cohorts, the survival probability after DFD was lower among women. Compared to those without DFD, after initial DFD hospitalizations, the mortality risk was significantly (18%) higher for men compared to women. This excess risk was particularly high after major amputations but also after ulcers, infections, gangrene, or Charcot, with a lower reduction after revascularization procedures among men. In the cohort that included people with a history of prior DFD hospitalizations, except for the risk of minor amputations being higher for men, there was no gender difference in mortality risk. Conclusions: In people with DFD, the overall survival probability was lower among women. Compared to those without DFD after a first DFD hospitalization, men were at higher risk of mortality. This excess risk disappeared in groups with a history of previous DFD hospitalizations containing a greater percentage of women who were older and probably had a longer duration of diabetes and thus becoming, over time, progressively frailer than men.

To investigate whether pregestational exposure to oral combined hormonal contraception (CHC) is associated with a rise in the risk of gestational diabetes (GDM). Prevailing GDM was assessed for all pregnancies that occurred in Tuscany, Italy, from years 2010 to 2018, using administrative data coupled with information about CHC prescriptions in the year prior to pregnancy retrieved from the regional registry of drug prescription claims. The relation between exposure to CHC and risk of GDM, expressed as Odds Ratio: OR (95

Aim: To evaluate the impact of diabetes and COVID-19 on all-cause-mortality and first hospitalizations for cardiovascular events (CVE): myocardial infarction or stroke, within six months after being tested positive and having recovered from SARS-CoV-2 infection. Methods: Resident population in Tuscany, Italy of age 45-94 yr without prior hospitalization for CVE, tested positive for SARS-CoV-2 by March 1st, 2020 and afterwards recovering from COVID-19 was compared with age, gender and diabetes matched controls without infection, for incidence rate ratio (IRR) of all-cause-deaths or first CVE at six months follow up. Results: 46,152 subjects of whom 4,597 with diabetes, tested positive and recovered from SARS-CoV-2 were compared with 1:1 age, gender and diabetes matched controls without infection. COVID-19 was associated with higher all-cause-mortality: IRR:1.92(95 %CI:1.63-2.25) while diabetes with increased risk of first CVE hospitalizations: IRR:2.24(2.18-4.25). Co-presence of COVID-19 and diabetes didn't add any additional excess risk. Being women and statins' use significantly reduced death risk. Conclusions: After recovery from COVID-19, independently of diabetes, all-cause-mortality risk at six months was twofold increased, while risk of first CVE hospitalization remained unmodified. Diabetes, independently of prior COVID-19, resulted in higher six-months risk of first CVE not of death. Female gender and statins' use reduced both excess risks.

The influence of sex combined with smoking and combined oral contraceptives (COC) use on atherogenic indexes is scarcely studied. Thus, traditional lipid parameters were measured, and non-traditional atherogenic indexes were calculated in a young and healthy population of men, COC-free women, and COC users. Total cholesterol (TChol), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and HDL/LDL ratio were lower in men, while triglycerides (TG)/HDL ratio, atherogenic index of plasma (AIP), Castelli's Risk Index I (CRII) and CRI-II, atherogenic coefficient (AC), creatinine, creatinine clearance, and estimated glomerular filtration rate (eGFR) were higher in men. The use of COC modified TChol, HDL, TG, TG/HDL, and AIP which had significantly higher values in COC users. In addition, TG were also increased in COC users in comparison with men. Smoking reduced sexually divergent parameters: BMI, TG, HDL/LDL, TG/HDL, AIP, CRII, CRI-II, and AC became similar among the three cohorts, losing the reported sex differences. Smoking also reduced differences in TChol, HDL, TG, and AIP between COC-free women and COC users, but it does not affect CRII, CRI-II, creatinine, creatinine clearance, and eGFR, underlining that COC users and COC-free women have to be considered two different populations. Our results represent a complex landscape suggesting that for both sexes smoking should be an independent variable in medical studies. Moreover, in women, the use of COC evidenced two different cohorts. Thus, more variables should be considered during a single study indicating that sex, smoking, and COC should be studied together to get a picture of the real-life context.

Type 2 diabetes mellitus is a widespread and a chronic disease associated with micro- and macrovascular complications and is a well-established risk factor for cardiovascular disease, which are among the most important causes of death in diabetic patients. This disease is strongly affected by sex and gender: sex-gender differences have been reported to affect diabetes epidemiology and risk factors, as well as cardiovascular complications associated with diabetes. This suggests the need for different therapeutic approaches for the management of diabetes-associated complications in men and women. In this review, we describe the known sex-gender differences in diabetic men and women and discuss the therapeutic approaches for their management. The data reported in this review show that a sex-gender approach in medicine is mandatory to maximize the scientific rigor and value of the research. Sex-gender studies need interdisciplinarity and intersectionality aimed at offering the most appropriate care to each person.

To investigate whether fetal sex affects the impact of classical GDM risk factors on the diagnosis of gestational diabetes (GDM) as well as on related adverse pregnancy outcomes. This retrospective observational study concerned 206,917 singleton live births born to 170,126 women aged 15–45 over the years 2010–2018 in Tuscany, Italy. GDM was identified by administrative data-sources in 21,613 pregnancies (10.5%) by assessing, through multiple logistic models, whether fetal sex modified the risk of GDM driven by maternal risk factors, and whether it modified the risk of adverse outcomes such as prematurity (birth ≤ 37th gestational week), large for gestational age (LGA), unplanned caesarean sections, or 5-min-Apgar-index ≤ 7 in pregnancies with GDM. GDM was diagnosed in 21,613 pregnancies (10.5%). Male fetal sex predicted a higher adjusted risk of GDM: OR = 1.05(95% CI: 1.01–1.07); p < 0.0009. In pregnancies with female sex, pre-pregnancy obesity amplified the risk of GDM: OR = 1.09(95% CI: 1.01–1.19); p =  0.04. In pregnancies with GDM, carrying a female fetus increased the risk of LGA associated with pregestational obesity OR = 1.45(95% CI: 1.15–1.81); p = 0.001, and in primiparous pregnancies, it protected mothers from the risk of unplanned caesarean sections OR = 0.80(95%CI: 0.67–0.92); p = 0.001. While male fetal sex is associated with rise in the risk of GDM, giving birth to a girl amplifies the excess GDM risk driven by pregestational obesity, thus increasing the risk of LGA in pregnancies with GDM. Additionally, female fetal sex in pregnancies with GDM seems to protect from the risk of unplanned caesarean sections in primiparous pregnancies.

The aim of this study was to evaluate the risk of death after hospitalizations for diabetic foot (DF) complications, comparing two different cohorts of people with or without a prior history of DF hospitalizations across the years 2011 to 2018 in Tuscany, Italy. The DF complications were categorized by administrative source datasets such as: amputations (both major and minor), gangrene, ulcers, infections, Charcot and revascularizations. A further aim was to present the trend over time of the first ever incidents of diabetic foot hospitalizations in Tuscany. The eight-year-mortality rate was higher in the cohort with prior hospitalizations (n = 6633; 59%) compared with the cohort with first incident DF hospitalizations (n = 5028; 44%). Amputations (especially major ones) and ulcers had the worst effect on survival in people without basal history of DF hospitalizations and respectively in those with a history of prior DF hospitalizations. In both cohorts, revascularization procedures, when compared to ulcers, were associated with a significantly reduced risk of mortality. The prevalence rate of minor amputations showed a slightly rising trend over time. This result agrees with the national trend. Conversely, the progressive increase over time of revascularizations, associated with the fractional decrease in the rate of gangrene, suggests a trend for more proactive behavior by DF care teams in Tuscany.

Diabetic foot disease (DFD) is a complication of diabetes mellitus, characterized by multiple pathogenetic factors, bearing a very high burden of disability as well as of direct and indirect costs for individuals or healthcare systems. A further characteristic of DFD is that it is associated with a marked risk of subsequent hospitalizations for incident cardiovascular events, chronic renal failure or of allcause mortality. Additionally, DFD is strongly linked to the male sex, being much more prevalent among men. However, even if DFD mainly affects males, several past reports suggest that females are disadvantaged as regards the risk of subsequent adverse outcomes. This review aims to clarify this point, attempting to provide an explanation for this apparent oddity: being DFD a typically male complication of diabetes but, seemingly, with a greater load of subsequent consequences for females.

Many pieces of evidence have accumulated over time suggesting sex-and-gender differences in type 2 diabetes, the most relevant being the greater excess risk of cardiovascular diseases in women with diabetes than in men. Drugs available for the treatment of diabetes have, meanwhile, increased in number and effectiveness over the last 20 years. Nonetheless, overall metabolic control of diabetes continues to be suboptimal, with a clear further disadvantage for women. Moreover, old and new glucose-lowering drugs present some sex-and-gender differences, although women continue to be underrepresented in all cardiovascular outcome trials testing their efficacy and protective effects. We conclude that pharmacology should wear gender glasses starting from preclinical research to overcome all these gender gaps.

Background: Diabetic Foot Disease (DFD) is more prevalent among males and is associated with an excess risk of cardiovascular events or mortality. Aims: This study aimed at exploring the risk of cardiovascular events, renal failure, and all-cause mortality after incident DFD hospitalizations, separately in males and females, to detect any gender difference in a cohort of 322,140 people with diabetes retrospectively followed up through administrative data sources in Tuscany, Italy, over the years 2011-2018. Methods: The Hazard Ratio (HR) for incident adverse outcomes after first hospitalizations for DFD, categorized as major/minor amputations (No.=449;3.89%), lower limbs' revascularizations (LLR: No.=2854;24.75%), and lower-extremity-arterial-disease (LEAD) with no procedures (LEAD-no proc: No.=6282;54.49%), was compared to the risk of patients having a background of DFD (ulcers, infections, Charcot-neuroarthropathy: No.=1,944;16.86%). Results: DFD incidence rate was higher among males compared to females (1.57(95% CI:1.54-1.61) vs. 0.97(0.94-1.00)/100,000p-years]. After DFD, the overall risk of coronary artery disease was significantly associated with the male gender and of stroke with the female gender. LEAD-no proc and LLR were associated with the risk of stroke only in females, whereas they were found to be associated with the risk of coronary artery disease among females to a significantly greater extent compared to males. The incident of renal failure was not associated with any DFD category. Amputations and LEAD-no proc significantly predicted high mortality risk only in females, while LLR showed reduced risk in both genders. Moreover, females had a greater risk of composite outcomes (death or cardiovascular events). Compared to the background of DFD, the risk was found to be 34% higher after amputations (HR: 1.34(1.04-1.72)) and 10% higher after LEAD-no proc (HR:1.10(1.03-1.18)), confirming that after incident DFD associated with vascular pathogenesis, females are at an increased risk of adverse events. Conclusion: After incident DFD hospitalizations, females with DFD associated with amputations or arterial disease are at a greater risk of subsequent adverse cardiovascular events than those with a DFD background.

To examine risk of adverse pregnancy outcomes, mothers’ characteristics and incidence rate over time of pregestational type 1 (T1D), type 2 (T2D) or gestational diabetes (GDM). The study included all singleton live births born from women aged 15–45 year, in Tuscany, Italy from 2010 to 2018. Pregnancy outcomes were retrieved by certificates of care at delivery compiled by midwives. Pregestational diabetes and GDM were identified by regional administrative databases. Time course of pregestational diabetes and GDM across last decade was assessed by Poisson analysis. Logistic regression analysis was used to calculate adjusted odds ratios (OR; 95% CI) for maternal characteristics or neonatal outcomes. Among 206,917 singleton live births, GDM was diagnosed in 21,613 pregnancies (10.46%) and pregestational diabetes in 979, being T2D more prevalent than T1D (606; 0.29% vs. 373; 0.18%). Pregestational T2D incidence progressively decreased over last decade, T1D remained stable while GDM progressively rose. Pre-pregnancy obesity, preterm deliveries or cesarean sections were common characteristics of pregestational diabetes and GDM. Risk of neonatal distress and neonatal malformations was higher in pregestational T1D. Risk of prior spontaneous abortions was higher in GDM and in pregestational T2D (OR: 4.19; 3.30–5.33), mostly treated with metformin. Risk of neonatal macrosomia was increased only in pregestational diabetes. In our population, pregestational T2D was more prevalent than T1D. Neonatal complications were mostly associated with pregestational T1D. Increased risk of previous spontaneous abortions was the hallmark of pregestational T2D. GDM, even if sharing adverse outcomes with pregestational T2D, was unrelated to rise in risk of neonatal macrosomia.

There is an urgent need to optimize pharmacology therapy with a consideration of high interindividual variability and economic costs. A sex–gender approach (which considers men, women, and people of diverse gender identities) and the assessment of differences in sex and gender promote global health, avoiding systematic errors that generate results with low validity. Care for people should consider the single individual and his or her past and present life experiences, as well as his or her relationship with care providers. Therefore, intersectoral and interdisciplinary studies are urgently required. It is desirable to create teams made up of men and women to meet the needs of both. Finally, it is also necessary to build an alliance among regulatory and ethic authorities, statistics, informatics, the healthcare system and providers, researchers, the pharmaceutical and diagnostic industries, decision makers, and patients to overcome the gender gap in medicine and to take real care of a person in an appropriate manner.

Aims: To evaluate the risk of gestational diabetes (GDM) and of neonatal/maternal complications (macrosomia, large for gestational age (LGA), cesarean sections, preterm deliveries, neonatal distress and fetal malformations) among women coming from High Migration Pressure Countries (HMPC), compared to native (Italian) mothers. Methods: Risks of GDM and related neonatal/maternal complications were evaluated in a cohort of 581,073 Italian compared with 105,111 HMPC women of age 15-45 yr, resident in Tuscany, Italy along years 2012-2017, delivering 122,652 singleton live births (18,596 from HMPC mothers). Results: HMPC women, compared to Italian ones, were at higher risk of GDM (OR: 1.586; 1. 509-1.666;p < 0.0001), peaking for women originating from South Asia (OR:3.0.49; 2.618-3. 553;p < 0.0001). GDM was associated with increased risk of preterm delivery and cesarean sections, while migrants, regardless of GDM, were burdened by a higher risk of all considered complications. The rise in all these risks, including macrosomia or LGA however, disappeared, after addition of interaction term GDM x HMPC ethnicity. Conclusion: Compared to Italian mothers, HMPC women had higher risk of GDM and of all considered adverse events. The addiction of the interaction term GDM x HMPC ethnicity in the predictive model, however reversed the rise in risk of all HMPC associated adverse outcomes. (C) 2020 Elsevier B.V. All rights reserved.