Smoking and combined oral contraceptives should be considered as an independent variable in sex and gender-oriented studies.

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 1 diabetes, sport practiced, and ankle joint mobility in young patients: What is the relationship?

BACKGROUND/OBJECTIVE: It is known that patients with diabetes can develop limited joint mobility (LJM) and that this can depend on the metabolic control maintained and the duration of the disease. The aims of this study were to verify the presence of ankle joint mobility (AJM) deficits in both plantar and dorsiflexion in young type 1 diabetic patients (T1D) considering also the possible role of sport practiced as a further factor, able to modify AJM. METHODS: AJM was evaluated by an inclinometer in 82 T1D patients (M/F: 48/34), mean age 12.9 ± 2.6 years, body mass index (BMI) 19.7 ± 3.6 kg/m2 , duration of diabetes 5.6 ± 3.3 years, mean HbA1c 7.5 ± 1.0% and in 226 healthy controls (M/F: 146/80), age-, gender-, and BMI-matched practicing different sports (soccer, volleyball, basketball, and dance). RESULTS: The patients' ankle range of motion was significantly lower than that in controls (132.7 ± 22.3° vs 126.1 ± 17.9°; P < .017). In particular, ankle plantar flexion was significantly lower in the patients group (31.6° ± 7.9° vs 28.5° ± 6.6°; P < .002). Soccer players showed lower AJM in both groups: patients (120.1 ± 15.9° vs 127.3 ± 18.1) and controls (119.4 ± 21.1° vs 142.0 ± 18.1; P < .0001) than subjects practicing other sports or who were sedentary. In both groups, patients and controls, age, sex, duration of disease, hemoglobin 1Ac, and BMI have not been shown to be correlated to the mobility assessed. CONCLUSIONS: The results of this study, in addition to confirming the negative effect of diabetes on AJM of young T1D patients, suggest that during these evaluations the sport-related effect should be considered because it can induce significant changes of AJM.

Effect of statins in preventing hospitalizations for infections: A population study.

PURPOSE: To investigate whether the hospitalization rate for bacterial infections was modified by statin therapy in a population retrospectively followed up, over years 2011 to 2015. METHODS: By using administrative databases, the 5-year hospitalization rate due to bacterial infections in population living in Tuscany, Italy exposed to statin therapy (n = 52,049) was stratified by 5 prescribed daily doses classes (0%-20%, 20%-50%, 50%-80%, 80%-100%, ≥100% of DDD) and subsequently compared with that of a population of untreated individuals (n = 3 300 ,675), matched through a propensity score accounting for all available covariates potentially able to modulate risk of infections such as age, gender, previous hospitalizations for infections, cardiovascular events, previous co-morbidities, diabetes, as well as general practitioners' proactive behaviour of care delivery according to current guidelines. RESULTS: Unmatched individuals of each treatment-class had significantly more hospitalizations than controls, while matched treated people, apart from those in class 0% to 20%, had a decrease of hospitalizations, as large as the increase in prescribed drug. Statin effect in reducing hospitalizations translated into a number needed to treat (NNT) ranging across treatment strata from 102 to 54. CONCLUSIONS: Compliance to statin prescribed daily doses above the threshold 20% of DDD, along a 5-year follow-up, prevented hospitalizations due to infectious diseases in a large unselected population, after adjusting for covariates able to modulate baseline risk of infections. The NNTs to avoid 1 hospitalization for infections resulted on average not too dissimilar from a value lying between the 95% CI of NNTs previously found for primary prevention of 1 incident coronary ischemic event (72 to 119).

Sex-gender-related therapeutic approaches for cardiovascular complications associated with diabetes.

Diabetes is a chronic disease associated with micro- and macrovascular complications and is a well-established risk factor for cardiovascular disease. Cardiovascular complications associated with diabetes are among the most important causes of death in diabetic patients. Interestingly, several sex-gender differences have been reported to significantly impact in the pathophysiology of diabetes. In particular, sex-gender differences have been reported to affect diabetes epidemiology, risk factors, as well as cardiovascular complications associated with diabetes. This suggests that different therapeutic approaches are needed for managing diabetes-associated cardiovascular complications in men and women. In this review, we will discuss about the sex-gender differences that are known to impact on diabetes, mainly focusing on the cardiovascular complications associated with the disease. We will then discuss the therapeutic approaches for managing diabetes-associated cardiovascular complications and how differences in sex-gender can influence the existing therapeutic approaches.

Changes in diabetes care introduced by a Chronic Care Model-based programme in Tuscany: a 4-year cohort study.

Background: In 2010, Tuscany (Italy) implemented a Chronic Care Model (CCM)-based programme for the management of chronic diseases. The study's objective was to evaluate its impact on the care of patients with type 2 diabetes. Methods: A population-based cohort study was performed on patients with diabetes, identified by an administrative data algorithm, exposed to a CCM-based programme versus patients not exposed (8486 patients in each group). The groups were matched using a propensity score approach and observed from 2011 to 2014. The outcomes measured were: mortality rate and hazard ratio (HR), hospitalisation incidence rate (IR) (all causes and diabetes-related diseases) and incidence rate ratio (IRR), and Guideline Composite Indicator (GCI) as proxy of adherence to guidelines (IR and IRR). Stratified Cox regression analysis and conditional fixed effect Poisson regression analyses were performed to compute HR and IRR. Results: A significant improvement was observed for GCI (IRR 1.58; 95% CI 1.53­1.62) and for cardiovascular long-term complications (IRR 1.11; 95% CI 1.04­1.18). A protective effect was observed for neurological long-term complications (IRR 0.85; 95% CI 0.76­0.95), acute cardio-cerebrovascular long-term complications­stroke and ST segment elevation myocardial infarction­(IRR 0.81; 95% CI 0.71­0.92) and mortality (HR 0.88; 95% CI 0.81­0.96). Conclusion: The implementation of a CCM-based programme was followed by better management and benefits for the health status of patients. The increase in hospitalisations for cardiovascular long-term complications could engender cost-efficacy issues, but a better integrated care (GPs and specialists) and a more appropriate specialist outpatient services organisation could avoid a part of these, while still maintaining the benefits seen.

Gender differences in the relationship between diabetes process of care indicators and cardiovascular outcomes.

BACKGROUND: Adherence to recommended guidelines in the care for diabetes has been demonstrated to significantly prevent the excess risk of hospitalization and mortality for cardiovascular diseases. Aim of this study was to evaluate whether adherence to a standardized process quality-of-care-indicator in diabetes, is able to predict, equally in men and women, first hospitalization or mortality risk after acute myocardial infarction (AMI), ischemic stroke (IS), congestive heart failure (CHF), lower extremity amputations (LEA) or any of above major adverse cardiovascular events (MACE). METHODS: Guideline composite indicator (GCI), a process indicator including one annual assessment of HbA1c and at least two among eye examination, serum lipids measurement and microalbuminuria, was measured in the year 2006 in 91 826 (46 167 M/45 659 F) diabetic patients, living in Tuscany (Italy). By a Cox-proportional hazard regression model, the effect of GCI adherence was assessed on adjusted hospitalization mortality risk for AMI, IS, CHF, LEA and MACE in both genders in a follow-up period of 6 years (2007-12). RESULTS: After adjusting for covariates, adherence to CGI exerted a significant positive effect on AMI, CHF and LEA outcomes among men, whereas among women, GCI adherence significantly decreased hospitalization risk only for CHF and mortality risk after IS. Finally, GCI adherence significantly reduced hospitalization risk for MACE of about 15% and 11% in men and women, respectively. On the contrary, GCI adherence seemed to have no significant influence on mortality risk after hospitalization for MACE in both genders. CONCLUSION: In this cohort, over a 6-year follow-up, GCI adherence was found to be a significant predictor of lower cardiovascular risk, with some evident gender differences.

Effect of diabetes on hospitalization for ischemic stroke and related in-hospital mortality: a study in Tuscany, Italy, over years 2004-2011.

BACKGROUND: Incidence of ischemic stroke and associated in-hospital mortality is decreasing in Western populations, while the prevalence of diabetes, a well-known risk factor for ischemic stroke, is progressively rising. This study was aimed at evaluating the effect of diabetes on ischemic stroke hospitalization and in-hospital mortality after ischemic stroke. METHODS: Discharges with diagnosis of ischemic stroke were identified in a database containing all hospitalizations of resident population of Tuscany, Italy, over years 2004-2011. Cases with diabetes were identified through specific drug prescriptions, official certifications or previous hospital diagnosis. Rates of annual ischemic stroke incidence and related in-hospital mortality were separately calculated for gender and age class, in subjects with and without diabetes. RESULTS: Sixty-five thousand one hundred sixty-five hospital discharges with ischemic stroke diagnosis were identified. Diabetes was associated with increased risk of stroke odds ratio(95% confidence interval):1.31(1.28-1.34) in men and 1.24(1.21-1.37) in women. Diabetic women, compared with men, had a higher in-hospital mortality risk after ischemic stroke (odds ratio:1.32; 1.06-1.64), whereas in non-diabetic subjects, there was no difference between genders. Incidence of ischemic stroke has declined in non-diabetic subjects, except for women aged ≤70 years; a similar reduction was observed for in-hospital mortality. Among diabetic patients, conversely, annual incidence of ischemic stroke rose by 3% in the elderly people (>70 years), and annual mortality trend remained unchanged. CONCLUSIONS: In the last decade, the incidence of ischemic stroke and of related in-hospital mortality declined in persons without diabetes, while increasing among diabetic patients of advanced age. Women with diabetes, compared with men, had a higher in-hospital mortality risk.

Risk of cardiovascular events after gestational diabetes: a retrospective population study.

AIMS: 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). METHODS: 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% CI), after logistic multivariate models, considering all recorded pre-gestational characteristics as covariates. RESULTS: The adjusted OR (aOR) for post-partum CVD hospitalizations was not significantly related to GDM itself (aOR: 0.85; 0.64-1.12; p = ns), but increased in women with Pre-GD (aOR: 2.02; 1.09-3.71; p = 0.024) and Post-GD, associated or not to prior GDM (aOR; 4.21; 2.45-7.23 and respectively aOR: 3.80; 2.38-6.05; p < 0.0001 for both). In presence of pre-pregnancy maternal obesity (BMI ≥ 30 kg/m2) the aOR of CVD approximatively doubled (aOR: 1.90; 1.51-2.40); p < 0.0001, independently of GDM and of Post-GD. The adjusted risk of CVD was lower among employed women (aOR: 0.83; 0.70-0.99); p = 0.04 and significantly higher in presence of poorer education levels (aOR: 1.32; 1.11-1.57); p < 0.0001. CONCLUSION: In this population the risk of post-partum CVD was driven by Pre- and Post-GD, not by GDM alone. Pre-gestational obesity represented a major independent risk factor for post-partum CVD.

Pregestational exposure to hormonal combined contraceptives and risk of gestational diabetes: an observational retrospective population study.

AIMS: To investigate whether pregestational exposure to oral combined hormonal contraception (CHC) is associated with a rise in the risk of gestational diabetes (GDM). METHODS: 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% Confidence Intervals, CI), was calculated separately based on citizenship of mothers using multiple logistic regression analysis models, after adjusting for confounders. RESULTS: Among 210,791 pregnancies from 170,126 mothers, GDM was present in 22,166 (10.5%) pregnancies. CHC prescription within 12 months before the index pregnancy was present in 9065 (4.3%) mothers. The risk of GDM was weakly but significantly higher in pregnancies exposed to pregestational CHC only in pregnancies of mothers of Italian citizenship: OR:1.11 (95% CI 1.02-1.21); p = 0.02, after adjusting for age, parity, calendar year and pregestational body-mass index. The CHC-mediated effect was no longer present in pregnancies of mothers at higher risk of GDM, such as pregestational obesity, migrating from countries at higher GDM risk or after adjusting for the entire panel of confounders including employment status, prior spontaneous abortions, and education degree. CONCLUSIONS: CHC had a modest effect on GDM risk, which became insignificant when added to basal prevailing risk factors for impaired glucose metabolism in pregnancy, such as pregestational obesity or originating from countries at high GDM risk.

Metrics of Gender Differences in Mortality Risk after Diabetic Foot Disease.

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.

The Assessment of Ankle Range-of-Motion and Its Relationship with Overall Muscle Strength in a Cross-Section of Soccer Players.

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.

Taurine transporter gene expression in peripheral mononuclear blood cells of type 2 diabetic patients.

Taurine acts as antioxidant, cell osmolyte, modulator of glucose metabolism, and plays a role in the retinal function. It is 10(3)-fold more concentrated in the intracellular than in the extracellular milieu due to a specific taurine-Na-dependent transporter (TauT), which is upregulated by hypertonicity, low extracellular taurine, or oxidative stress and acutely downregulated 'in vitro' by high glucose concentrations. Aim of this study was to investigate whether TauT expression was modified in mononuclear peripheral blood cells (MPC) of type 2 diabetic patients with or without micro/macrovascular complications. Plasma taurine, as well as other sulphur-containing aminoacids (assayed by HPLC) and TauT gene expression (assayed by real-time PCR analysis) were measured in MPC of 45 controls and of 81 age-and-sex matched type 2 diabetic patients with or without micro/macrovascular complications. Median value (interquartile range) of plasma taurine was significantly lower in diabetic patients than in controls [28.7 (13.7) µmol/l vs. 46.5 (20.3) µmol/l; P<0.05], while median TauT expression, in arbitrary units, was significantly higher in diabetics than in controls [3.8 (3.9) vs. 1 (1.3); P<0.05) and was related to HbA1c only in controls (r=0.34; P<0.05). Patients with retinopathy (n=25) had lower TauT expression than those who were unaffected [3.1 (2.8) vs. 4.1 (3.4); P<0.05], while persistent micro/macroalbuminuria was associated with unchanged TauT expression. A trend toward reduction in TauT expression was observed in patients with macroangiopathy [n=27; 3.3 (2.5) vs. 4 [3.7]; P=NS]. In conclusion, TauT gene is overexpressed in MPC of type 2 diabetic patients, while presence of retinopathy is specifically associated with a drop in TauT overexpression, suggesting its possible involvement in this microangiopathic lesion.

Gender difference in the relation blood pressure-left ventricular mass and geometry in newly diagnosed arterial hypertension.

Much evidence suggests sexual dimorphism in the relationship linking blood pressure (BP) to both left ventricular mass (LVM) and geometry in hypertension. To better evaluate gender-associated characteristics in the relation BP-LVM among newly diagnosed hypertension (24-h average ambulatory BP monitoring, ABPM, > 125/80 mmHg), we measured indexed LVM and relative wall thickness (RWT) by standardized echographic methods in 209 Caucasian drug-naïve subjects, of whom 162 (100M/62F) were recognized to be hypertensive. Mean office systolic (SBP)/diastolic (DBP), 24-h average and night-time BP values were similar between sexes and significantly related to indexed LVM in both genders. Daytime SBP was significantly related to indexed LVM only in females (r =0.41; p =0.0008 in women; r =0.11; p = NS in males), while LVM was more sensitive to day-to-night SBP change in females. RWT was, on the contrary, significantly related to ABPM values only in males. All these findings were confirmed after adjusting for possible confounders. Percentage of LVM variance explained by 24-h average, daytime or night-time SBP values were higher in females than in males (17% vs 3%; 11% vs 1%; and 17% vs 8%). In conclusion, in early hypertension, LVM was significantly associated with daytime BP and more sensitive to reduced percentage of night BP fall in females. LVM variance explained by ABPM SBP was much higher in females than in males. RWT, expressing concentric LVM remodelling was, conversely, more related to BP increase in males.

Effect of diabetes on short-term mortality and incidence of first hospitalizations for cardiovascular events after recovery from SARS-CoV-2 infection.

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.

Gender Differences in the Risk of Adverse Outcomes After Incident Diabetic Foot Hospitalization: A Population Cohort Study.

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.

Mortality Risk Associated with Diabetic Foot Complications in People with or without History of Diabetic Foot Hospitalizations.

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.

The impact of fetal sex on risk factors for gestational diabetes and related adverse pregnancy outcomes.

AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 Person's Care Requires a Sex and Gender Approach.

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.

Type 2 diabetic women are not small type 2 diabetic men: Sex-and-gender differences in antidiabetic drugs.

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.