Real-world use of oral versus subcutaneous semaglutide in a cohort of type 2 diabetic patients: which option to which patient?

PURPOSE: To evaluate the variables influencing the therapeutic choice toward oral versus subcutaneous semaglutide in a cohort of diabetic subjects. METHODS: We retrospectively collected data of 292 patients followed at the Diabetes Unit of the University Hospital of Siena and the Hospital of Grosseto, who were prescribed oral (n = 115) or subcutaneous (n = 177) semaglutide between October 2021 and October 2022. RESULTS: Oral semaglutide was preferentially prescribed in older subjects with longer disease duration in replacement of other antidiabetic drugs, while subcutaneous semaglutide was preferentially prescribed in add-on to metformin in subjects with higher body weight and BMI. After 6 months, both formulations significantly improved glycemic control and body weight, however injectable semaglutide showed a greater efficacy on A1c levels, weight loss, BMI and waist circumference reduction. No differences were found in terms of adverse events. CONCLUSION: In our experience, injectable semaglutide is preferred in patients with excess weight and shorter disease duration, while the oral formulation was used later and especially after therapeutic failure of previous therapies. Follow-up data indicate similar tolerability and efficacy of both formulations, despite subcutaneous semaglutide demonstrated greater efficacy.

Postpartum screening for type 2 diabetes mellitus in women with gestational diabetes: Is it really performed?

AIMS: This study evaluates the adherence to postpartum type 2 diabetes mellitus (T2DM) screening in women with previous gestational diabetes (GDM) and identifies elements associated with poor attendance. METHODS: We retrospectively collected data from 650 consecutive women with GDM between 2016 and 2018, who should had 75 g-OGTT, 4-12 weeks after delivery. Impaired glucose regulation (IGR) was defined according with ADA criteria. RESULTS: Only 41% of women had postpartum OGTT. Of these, 1.9% received T2DM diagnosis, with IGR prevalence of 18%. After introducing a recommendation letter, adherence to screening increased (47% in 2017 and 43% in 2018 vs. 32% in 2016). Screening procedure was less common in women with: no-family history of T2DM (38% vs. 46%; p < 0.05), age <35 (33% vs. 47%; p < 0.01), lower level of education (32% no-high-school-diploma vs. 35% high-school-diploma vs. 49% university-degree; p < 0.01) and unstable employment (35% vs. 44%; p < 0.05). At multivariate logistic regression analysis, age <35 years (OR 1.61; 95%CI: 1.14-2.28) and lowest educational level (OR 1.64; 95% CI: 1.13-2.37, compared to University degree) were independently associated with non-adherence. CONCLUSION: Only 41% of women had postpartum T2DM screening. Women with lower attendance are those with age <35 years or low educational level. Further strategies are needed to implement postpartum test.

Early vs. standard screening and treatment of gestational diabetes in high-risk women - An attempt to determine relative advantages and disadvantages.

BACKGROUND AND AIMS: Screening for Gestational Diabetes (GDM) is usually recommended between 24 and 28 weeks of pregnancy; however available evidence suggests that GDM may be already present before recommended time for screening, in particular among high-risk women as those with prior GDM or obesity. The purpose of this retrospective study was to evaluate whether early screening (16-18 weeks) and treatment of GDM may improve maternal and fetal outcomes. METHODS AND RESULTS: In 290 women at high-risk for GDM, we analyzed maternal and fetal outcomes, according to early or standard screening and GDM diagnosis time. Early screening was performed by 50% of high-risk women. The prevalence of GDM was 62%. Among those who underwent early screened, GDM was diagnosed at the first evaluation in 42.7%. Women with early diagnosis were more frequently treated with insulin and had a slightly lower HbA1c than women with who were diagnosed late. No differences were observed in the prevalence of Cesarean section, operative delivery, gestational age at the delivery, macrosomia, neonatal weight, Ponderal Index and Large-for-Gestational-Age among women with early or late GDM diagnosis or NGT. However, compared to NGT women, GDM women, irrespective of the time of diagnosis, had a lower gestational weight gain, lower prevalence of macrosomia (3.9% vs. 11.4%), small (1.7% vs. 8.3%) as well as large for gestational age (3.3% vs. 16.7%), but higher prevalence of pre-term delivery (8.9% vs. 2.7%). CONCLUSION: Early vs. standard screening and treatment of GDM in high-risk women is associated with similar short-term maternal-fetal outcomes, although women with an early diagnosis were treated to a greater extent with insulin therapy.

The role of adipokines in the pathogenesis of gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a complex condition whose physiopathology to date has not been completely clarified. Two major metabolic disorders, insulin resistance and ß-cells dysfunction, play currently major role in pathogenesis of GDM. These elements are influenced by the amount of adipose tissue present before and/or during the pregnancy. Consequently, adipokines (adiponectin (APN), leptin (LPT), adipocyte fatty acid-binding protein, resistin, visfatin, omentin, vaspin, apelin, chemerin) secreted by adipose tissue, may contribute directly and/or indirectly, through the enhancement of chronic inflammation, aggravating insulin resistance and promoting GDM onset. This review aims to outline the potential physiopathological and prognostic role in GDM of adipokines, mainly APN and LPT.

Italian national guidelines for the screening of gestational diabetes: Time for a critical appraisal?

BACKGROUND AND AIM: In 2011, the Italian National Health System guidelines introduced a selective screening for gestational diabetes (GDM) based on risk factors, recommending early evaluation in high risk women. The present study examined to which extent guidelines are applied, and analyzed the effectiveness of GDM diagnosis according to risk profile. METHODS AND RESULTS: We analyzed 1338 pregnant women, consecutively screened for GDM with a 75 g OGTT between January 2013 and December 2015, according to national guidelines. Diagnosis of GDM was based on IADPSG/WHO 2013 criteria. As many as 14.4% of screened women was at high risk, 64% at medium, 21.6% did not have any risk factor. Only 50% of high-risk women were appropriately screened at 16th-18th gestational weeks; 28% of them repeated the OGTT due to NGT. The overall prevalence of GDM was 39.9%, higher in high risk women (67% vs. 40% medium risk vs. 22% low risk; p < 0.0001). An early GDM diagnosis was performed in 40.7% of high-risk women. In low risk women, gestational weight gain at the screening time was independently associated with GDM. CONCLUSIONS: The recommendations for the screening of GDM are still insufficiently implemented, especially for early evaluation in high risk women. Considering the high proportion of early GDM diagnosis, the poor adherence to screening recommendation may result in late diagnosis of GDM. Finally, our finding of a 22% prevalence of GDM among low risk women suggests the need to consider additional risk factors, such as excessive weight gain during pregnancy.

An intensive monitoring campaign of PAHs for assessing the impact of a steel plant.

This study provided a useful approach for assessing the impact of industrial sources on surrounding, especially in a sensitive industrial area as Taranto (South of Italy). Taranto is one of the most industrialized Italian towns, where several emission sources operate simultaneously in proximity to the urban settlement. An intensive monitoring campaign of PAHs was carried out from January 28th to July 30th, 2011, in seven sites located in residential settlement around the industrial area and in the city center. The collected data were integrated with the information about wind direction and speed by means bivariate polarplot in order to characterize and localize the industrial sources. High BaP concentrations were detected especially when Benzene to Toluene ratio (B/T ratio) values excedeed 1 and all receptor sites were downwind to the steel plant. Moreover, in order to discriminate among PAH sources and quantify their contributions, a source apportionment analysis of the collected data was provided by means Principal component Analysis (PCA) and Positive Matrix Factorization (PMF) methods. Finally, the processing of PMF5.0 output by bivariate polar plot, confirmed the impact of steel plant on both industrial sites downwind the steel plant and the city center. B[a]P apportionment was quite similar for industrial and urban sites: the traffic source contributed only 11% and 24% to B[a]P measured at two sites, respectively. Therefore, the proximity of Taranto downtown to industrial pole makes negligible all other source contributions to PAH concentrations.

An integrated approach using high time-resolved tools to study the origin of aerosols.

Long-range transport of natural and/or anthropogenic particles can contribute significantly to PM10 and PM2.5 concentrations and some European cities often fail to comply with PM daily limit values due to the additional impact of particles from remote sources. For this reason, reliable methodologies to identify long-range transport (LRT) events would be useful to better understand air pollution phenomena and support proper decision-making. This study explores the potential of an integrated and high time-resolved monitoring approach for the identification and characterization of local, regional and long-range transport events of high PM. In particular, the goal of this work was also the identification of time-limited event. For this purpose, a high time-resolved monitoring campaign was carried out at an urban background site in Bari (southern Italy) for about 20 days (1st-20th October 2011). The integration of collected data as the hourly measurements of inorganic ions in PM2.5 and their gas precursors and of the natural radioactivity, in addition to the analyses of aerosol maps and hourly back trajectories (BT), provided useful information for the identification and chemical characterization of local sources and trans-boundary intrusions. Non-sea salt (nss) sulfate levels were found to increase when air masses came from northeastern Europe and higher dispersive conditions of the atmosphere were detected. Instead, higher nitrate and lower nss-sulfate concentrations were registered in correspondence with air mass stagnation and attributed to local traffic source. In some cases, combinations of local and trans-boundary sources were observed. Finally, statistical investigations such as the principal component analysis (PCA) applied on hourly ion concentrations and the cluster analyses, the Potential Source Contribution Function (PSCF) and the Concentration Weighted Trajectory (CWT) models computed on hourly back-trajectories enabled to complete a cognitive framework and confirm the influence of aerosol transported from heavily polluted areas on the receptor site.

The impact of infield biomass burning on PM levels and its chemical composition.

In the South of Italy, it is common for farmers to burn pruning waste from olive trees in spring. In order to evaluate the impact of the biomass burning source on the physical and chemical characteristics of the particulate matter (PM) emitted by these fires, a PM monitoring campaign was carried out in an olive grove. Daily PM10 samples were collected for 1 week, when there were no open fires, and when biomass was being burned, and at two different distances from the fires. Moreover, an optical particle counter and a polycyclic aromatic hydrocarbon (PAH) analyzer were used to measure the high time-resolved dimensional distribution of particles emitted and total PAHs concentrations, respectively. Chemical analysis of PM10 samples identified organic and inorganic components such as PAHs, ions, elements, and carbonaceous fractions (OC, EC). Analysis of the collected data showed the usefulness of organic and inorganic tracer species and of PAH diagnostic ratios for interpreting the impact of biomass fires on PM levels and on its chemical composition. Finally, high time-resolved monitoring of particle numbers and PAH concentrations was performed before, during, and after biomass burning, and these concentrations were seen to be very dependent on factors such as weather conditions, combustion efficiency, and temperature (smoldering versus flaming conditions), and moisture content of the wood burned.

Exhaled volatile organic compounds identify patients with colorectal cancer.

BACKGROUND: An effective screening tool for colorectal cancer is still lacking. Analysis of the volatile organic compounds (VOCs) linked to cancer is a new frontier in cancer screening, as tumour growth involves several metabolic changes leading to the production of specific compounds that can be detected in exhaled breath. This study investigated whether patients with colorectal cancer have a specific VOC pattern compared with the healthy population. METHODS: Exhaled breath was collected in an inert bag (Tedlar(®) ) from patients with colorectal cancer and healthy controls (negative at colonoscopy), and processed offline by thermal-desorber gas chromatography-mass spectrometry to evaluate the VOC profile. During the trial phase VOCs of interest were identified and selected, and VOC patterns able to discriminate patients from controls were set up; in the validation phase their discriminant performance was tested on blinded samples. A probabilistic neural network (PNN) validated by the leave-one-out method was used to identify the pattern of VOCs that better discriminated between the two groups. RESULTS: Some 37 patients and 41 controls were included in the trial phase. Application of a PNN to a pattern of 15 compounds showed a discriminant performance with a sensitivity of 86 per cent, a specificity of 83 per cent and an accuracy of 85 per cent (area under the receiver operating characteristic (ROC) curve 0·852). The accuracy of PNN analysis was confirmed in the validation phase on a further 25 subjects; the model correctly assigned 19 patients, giving an overall accuracy of 76 per cent. CONCLUSION: The pattern of VOCs in patients with colorectal cancer was different from that in healthy controls. The PNN in this study was able to discriminate patients with colorectal cancer with an accuracy of over 75 per cent. Breath VOC analysis appears to have potential clinical application in colorectal cancer screening, although further studies are required to confirm its reliability in heterogeneous clinical settings.

An integrated approach to identify the origin of PM10 exceedances.

PURPOSE: This study was aimed to the development of an integrated approach for the characterization of particulate matter (PM) pollution events in the South of Italy. METHODS: PM(10) and PM(2.5) daily samples were collected from June to November 2008 at an urban background site located in Bari (Puglia Region, South of Italy). Meteorological data, particle size distributions and atmospheric dispersion conditions were also monitored in order to provide information concerning the different features of PM sources. RESULTS: The collected data allowed suggesting four indicators to characterize different PM(10) exceedances. PM(2.5)/PM(10) ratio, natural radioactivity, aerosol maps and back-trajectory analysis and particle distributions were considered in order to evaluate the contribution of local anthropogenic sources and to determine the different origins of intrusive air mass coming from long-range transport, such as African dust outbreaks and aerosol particles from Central and Eastern Europe. The obtained results were confirmed by applying principal component analysis to the number particle concentration dataset and by the chemical characterization of the samples (PM(10) and PM(2.5)). CONCLUSIONS: The integrated approach for PM study suggested in this paper can be useful to support the air quality managers for the development of cost-effective control strategies and the application of more suitable risk management approaches.

Sources of high PM2.5 concentrations in Milan, Northern Italy: molecular marker data and CMB modelling.

In Milan (MI), the largest city in Northern Italy, the annually average PM2.5 concentration is above 25 µg m(-3), the value that the EU established as a target for 2010, and the upper limit from 2015 onwards (2008/30/CE). Over a three-year period (2006-2009) PM concentrations and chemical compositions were measured in an urban site (MI), a rural site (OB) and a remote site (ASC) in Northern Italy. Chemical characterization (EC/OC, inorganic ions, elements, C20-C32 n-alkanes, C2-C5 mono and dicarboxylic acids, levoglucosan and PAHs) was carried out on PM2.5 samples from the three sites, and PM10 from MI. Molecular markers were used in Chemical Mass Balance (CMB) modelling to estimate the contributions of primary sources to OC, and then PM mass from each source was reconstructed in MI, OB and ASC for different seasons. Estimates of the traffic (TR) source contribution to PM2.5 mass ranged from 4.1 (± 2.0) µg m(-3) during the summer, to 13.3 (± 6.7) µg m(-3) during the winter in MI. TR was the main primary source for PM2.5 concentrations in MI (17-24%). Its contribution was lower at the OB site (7-9%) and at the remote ASC site (3-4%). TR is a local source, while biomass burning (BB) is a diffuse regional source in Northern Italy: during fall and winter, BB was 25-30% and 27-31% of PM2.5 at MI and OB respectively. Other primary sources accounted for a small amount of the PM2.5, i.e. natural gas combustion (0-1%), plant debris (0-4%), road dust (RD=0-4%; but 15% at ASC during winter and 10% of PM10 at MI during summer) and sea salt (0-1%). Secondary inorganic+organic aerosol constituted the major part of the PM2.5 mass during spring and summer (50-65%) at the three sites.

Chemical characterization of exhaled breath to differentiate between patients with malignant plueral mesothelioma from subjects with similar professional asbestos exposure.

Malignant pleural mesothelioma (MPM) is an aggressive tumour whose main aetiology is the long-term exposure to asbestos fibres. The diagnostic procedure of MPM is difficult and often requires invasive approaches; therefore, it is clinically important to find accurate markers for MPM by new noninvasive methods that may facilitate the diagnostic process and identify patients at an earlier stage. In the present study, the exhaled breath of 13 patients with histology-established diagnosis of MPM, 13 subjects with long-term certified professional exposure to asbestos (EXP) and 13 healthy subjects without exposure to asbestos (healthy controls, HC) were analysed. An analytical procedure to determine volatile organic compounds by sampling of air on a bed of solid sorbent and thermal desorption GC-MS analysis was developed in order to identify the compounds capable of discriminating among the three groups. The application of univariate (ANOVA) and multivariate statistical treatments (PCA, DFA and CP-ANN) showed that cyclopentane and cyclohexane were the dominant variables able to discriminate among the three groups. In particular, it was found that cyclohexane is the only compound able to differentiate the MPM group from the other two; therefore, it can be a possible marker of MPM. Cyclopentane is the dominant compound in the discrimination between EXP and the other groups (MPM and HC); then, it can be considered a good indicator for long-term asbestos exposure. This result suggests the need to perform frequent and thorough investigations on people exposed to asbestos in order to constantly monitor their state of health or possibly to study the evolution of disease over time.

Monitoring of volatile organic compounds in non-residential indoor environments.

UNLABELLED: A weekly monitoring campaign of volatile organic compounds (VOC), with single sampling of 24 h, was carried out in non-residential indoor environments such as libraries, pharmacies, offices, gymnasiums, etc., in order to evaluate the VOC concentrations to which people are exposed. Moreover, an outdoor sample was coupled to each indoor site to point out the influence of indoor sources. They were sampled with Radiello diffusive samplers for thermal desorption and analyzed by GC-MS. As already described in other papers, the VOC levels of most of the indoor sites were higher than that observed in the corresponding outdoor sites. For example, some sites showed a level of pollution that is ten times higher than their corresponding outdoor site. The monitored environments that had higher concentrations of the investigated VOC were the pharmacies, a newspaper stand, a copy center, and the coffee shops. Analysis of the weekly average concentrations of each pollutant and the use of literature allowed pointing out some site-specific characteristics that singled out possible sources of VOC. These results were verified analyzing the indoor-outdoor ratio (I/O) too. Newspaper stands were characterized by very high concentrations of toluene and pharmacies were characterized by high concentrations of aromatic compounds. PRACTICAL IMPLICATIONS: Indoor air pollution caused by volatile organic compounds (VOC) might affect human health at home as well as in public and commercial buildings. The main VOC sources in indoor environments are human activities, personal care products, smoking, house cleaning products, building products, and outside pollution. To preserve human health it is necessary to evaluate the average concentrations of VOC to which people are exposed and to identify the main sources of indoor pollution by means of suitable indoor monitoring campaigns in several environments. These investigations allow pointing out the characteristic critical situations of some indoor environments or some other types of environments.

Monitoring of odor compounds produced by solid waste treatment plants with diffusive samplers.

Nuisance caused by odors is one of the most important problems for waste management plants. To control an odor nuisance, it must first be quantified. The analytical difficulties in odor measurements are related to the high number of volatile components (belonging to several chemical classes), above all when the concentration is lower than the detection limit of the technique used for the measurement. In this work, 2-butanone, alpha-pinene, tetrachloroethylene, dimethyldisulfide, beta-pinene, limonene, phenol and benzoic acid are determined, because they are representative of some important classes of compounds with higher odor impact. The compounds are sampled with thermal desorbable radial diffusive samplers Radiello containing Tenax cartridges. The analytical repeatability and the complete thermal desorption of the cartridges were verified for each odor compound; the relative standard deviations for repeated samples and the recovery percentage were, respectively, less than 7% and about 97% for all compounds. The measurements of the linearity of sampling showed no systematic difference according to the collection period. The comparison between the odor threshold and the limit of detection demonstrated that this method is reliable for the recognition and quantification of odor compounds, allowing Public Administration to impose legal limits and the control agencies to verify them.

Determination of nutrients in the presence of high chloride concentrations by column-switching ion chromatography.

Determination of inorganic anions in waters of high salinity is one of the most difficult task in analytical chemistry. A simple column-switching method, based on an original chromatographic set-up, for the determination of nutrients (nitrate, nitrite and phosphate) in chloride rich aqueous matrices is presented. A pre-separation system (made of two in line pre-columns, Dionex AG9-HC 4 mm) connected to an analytical column (Dionex AS9-HC 4 mm) by a four way pneumatic valve, allows chloride to be eluted off into the waste and nutrients to be separated and detected by a conductimeter and/or a UV spectrophotometer. Neither chemical pre-treatment nor sample dilution are required; sample matrices presenting a large range of chloride concentrations can be investigated. Moreover by using this technology, automation for routine analysis, low analysis time and low costs can be achieved. LODs of 100, 300, 1000 microg/l for nitrate, nitrite and phosphate, respectively, have been obtained by spiking a synthetic sea water sample containing 20,000 mg/l of chloride and 3000 mg/l of sulphate. Analyte calibration curves of analytes are linear (r>0.99) in the range between the LODs and 60 mg/l. This method was applied to nutrients determination in sea water samples collected near a river outlet.

Source apportionment of gaseous atmospheric pollutants by means of an absolute principal component scores (APCS) receptor model.

A multivariate statistical method has been applied to apportion the atmospheric pollutant concentrations measured by automatic gas analyzers placed on a mobile laboratory for air quality monitoring in Taranto (Italy). In particular, Principal Component Analysis (PCA) followed by Absolute Principal Component Scores (APCS) technique was performed to identify the number of emission sources and their contribution to measured concentrations of CO, NOx, benzene toluene m+p-Xylene (BTX). This procedure singled out two different sources that explain about 85% of collected data variance.

Analysis of heavy metals in atmospheric particulate by ion chromatography.

Cu, Ni, Zn, Co, Fe+2, Mn, Cd, Fe+3 and Pb are easily separated and detected in isocratic mode by ion chromatography with post-column derivatization using a bifunctional ion-exchange column and an eluent formed by oxalic acid (28 mM) and sodium nitrate (250 mM). The separation is optimised by using a suggested sample solution containing a given concentration of chloride. Detection limits were 10-15 ppb for all the metals except for cadmium and lead, for which detection limits of 30 and 60 ppb were found, respectively. The method was tested on an atmospheric particulate certified sample. The measured values were in good agreement with certified values. Real samples of atmospheric particulate from industrial and urban sites were analysed and the results are discussed.

Analysis of polycyclic aromatic hydrocarbons in the atmospheric particulate: focused microwaves for a faster extraction method.

In this paper, improvements obtained by using focused microwaves for extraction, in the analysis of polycyclic aromatic hydrocarbons (PAHs) adsorbed on particulate matter, are discussed. The method was tested on the following PAHs, which are considered to be among the most harmful with regard to carcinogenicity: benzo[a]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, indeno[1,2,3-cd]pyrene, dibenzo[a,h]anthracene. The extraction of PAHs and concentration of the sample can be performed in 3 h with a recovery of at least 70% and a maximum standard deviation of 4%. These steps are followed by clean-up on a SPE (solid-phase extraction) cartridge and analysis by GC-MS. Real samples collected in the urban area of Bari were analysed according to the proposed procedure.