Protective Effects of Home T2DM Treatment with Glucagon-Like Peptide-1 Receptor Agonists and Sodium-Glucose Co-transporter-2 Inhibitors Against Intensive Care Unit Admission and Mortality in the Acute Phase of the COVID-19 Pandemic: A Retrospective Observational Study in Italy

Introduction: Type 2 diabetes mellitus (T2DM) is a relevant risk factor for severe forms of COVID-19 (SARS coronavrus 2 [SARS-CoV-2] disease 2019), and calls for caution because of the high prevalence of T2DM worldwide and the high mortality rates observed in patients with T2DM who are infected with SARS-CoV-2. People with T2DM often take dipeptidyl peptidase-4 inhibitors (DPP-4is), glucagon-like peptide-1 receptor agonists (GLP-1ras), or sodium-glucose co-transporter-2 inhibitors (SGLT-2is), all of which have clear anti-inflammatory effects. The study aimed to compare (i) the severity and duration of hospital stay between patients with T2DM categorized by pre-hospitalization drug class utilization and (ii) the COVID-19-related death rates of those three groups.Methods: We designed an observational, retrospective, multi-center, population-based study and extracted the hospital admission data from the health care records of 1916 T2DM patients over 18 years old who were previously on GLP-1ra, SGLT-2i, or DPP-4i monotherapy and were hospitalized for COVID-19 (diagnosis based on ICD.9/10 codes) between January 2020 and December 2021 in 14 hospitals throughout Italy. We analyzed general data, pre-admission treatment schedules, date of admission or transfer to the intensive care unit (ICU) (i.e., the index date; taken as a marker of increased COVID-19 disease severity), and death (if it had occurred). Statistics analyzed the impact of drug classes on in-hospital mortality using propensity score logistic regressions for (i) those admitted to intensive care and (ii) those not admitted to intensive care, with a random match procedure used to generate a 1:1 comparison without diabetes cohort replacement for each drug therapy group by applying the nearest neighbor method. After propensity score matching, we checked the balance achieved across selected variables if a balance was ever achieved. We then used propensity score matching between the three drug classes to assemble a sample in which each patient receiving an SGLT-2i was matched to one on a GLP-1ra, and each patient on a DPP-4i was matched to one on a GLP-1ra, adjusting for covariates. We finally used GLP-1ras as references in the logistic regression.Results: The overall mortality rate (MR) of the patients was 14.29%. The MR in patients with COVID was 53.62%, and it was as high as 42.42% in the case of associated T2DM, regardless of any glucose-lowering therapy. In those on DPP-4is, there was excess mortality; in those treated with GLP-1ras and SGLT-2is, the death rate was significantly lower, i.e., almost a quarter of the overall mortality observed in COVID-19 patients with T2DM. Indeed, the odds ratio (OR) in the logistic regression resulted in an extremely high risk of in-hospital death in individuals previously treated with DPP-4is [incidence rate (IR) 4.02, 95% confidence interval (CI) 2.2-5.7) and only a slight, nonsignificantly higher risk in those previously treated with SGLT-2is (IR 1.42, 95% CI 0.6-2.1) compared to those on GLP-1ras. Moreover, the longer the stay, the higher the death rate, which ranged from 22.3% for <= 3-day stays to 40.3% for 4- to 14-day stays (p < 0.01 vs. the former) and 77.4% for over-14-day stays (p < 0.001 vs. both the others).Discussion: Our data do not support a protective role of DPP-4is; indeed, this role has already been questioned due to previous observations. However, the data do show a strong protective effect of SGLT-2is and GLP-1ras.Beyond lowering circulating glucose levels, those two drug classes were found to exert marked anti-phlogistic effects: SGLT-2is increased adiponectin and reduced urate, leptin, and insulin concentrations, thus positively affecting overall low-grade inflammation, and GLP-1ras may also greatly help at the lung tissue level, meaning that their extra-glycemic effects extend well beyond those acknowledged in the cardiovascular and renal fields.Conclusions: The aforedescribed observational clinical data relating to a population of Italian inpatients with T2DM suggest that GLP-1ras and SGLT-2is can be considered antidiabetic drugs of choice against COVID-19, and might even prove beneficial in the event of any upcoming pandemic that has life-threatening effects on the pulmonary and cardiovascular systems

Making use of comparable health data to improve quality of care and outcomes in diabetes : The EUBIROD review of diabetes registries and data sources in Europe

Background: Registries and data sources contain information that can be used on an ongoing basis to improve quality of care and outcomes of people with diabetes. As a specific task of the EU Bridge Health project, we carried out a survey of diabetes-related data sources in Europe. Objectives: We aimed to report on the organization of different sources of diabetes information, including their governance, information infrastructure and dissemination strategies for quality control, service planning, public health, policy and research. Methods: Survey using a structured questionnaire to collect targeted data from a network of collaborating institutions managing registries and data sources in 17 countries in the year 2017. Results: The 18 data sources participating in the study were most frequently academic centres (44.4%), national (72.2%), targeting all types of diabetes (61.1%) covering no more than 10% of the target population (44.4%). Although population-based in over a quarter of cases (27.8%), sources relied predominantly on provider-based datasets (38.5%), fewer using administrative data (16.6%). Data collection was continuous in the majority of cases (61.1%), but 50% could not perform data linkage. Public reports were more frequent (72.2%) as well as quality reports (77.8%), but one third did not provide feedback to policy and only half published ten or more peer reviewed papers during the last 5 years. Conclusions: The heterogeneous implementation of diabetes registries and data sources hampers the comparability of quality and outcomes across Europe. Best practices exist but need to be shared more effectively to accelerate progress and deliver equitable results for people with diabetes.publishedVersionPeer reviewe

Evaluation of bone markers and structure in subclinical Cushing’s syndrome

Overt hypercortisolism causes reduction in bone mass and density. The effects of subclinical Cushing’s syndrome (SCS) on bone markers and structure are still debated. We therefore studied 56 patients with adrenal incidentaloma: group A=35 (20 F 15 M, age 43–79, mean 64.6±1.5; BMI 29.9±0.9 kg/m2) without evidence of hypercortisolism, and group B=21 (10 F 11 M, age 51–76, mean 63.4±1.9, BMI 28.0±1.2 kg/m2) with SCS (i.e. with 2 or more alterations in biochemical tests of HPA axis). All patients underwent evaluation of HPA axis (plasma ACTH, plasma cortisol at 8 and 24, 24 h UFC, Nugent test), bone markers (serum BGP and urinary DPD), lumbar spine DEXA and bone ultrasonography of the phalanx. Group B showed lower values compared to group A of DEXA BMD, T-score, Z-score (P<0.05), and bone transmission time (BTT) (P<0.05), an ultrasonographic parameter who reflects bone structure. No significant differences in bone markers were detected in the two groups. We found significant inverse correlations between midnight serum cortisol and indicators of bone density, such as AD-SoS, UBPI (P<0.05) and DEXA T-score (P <0.01). A direct correlation between midnight serum cortisol and urinary DPD (P<0.01) was found. BTT correlated directly with BGP and inversely with urinary DPD (P<0.0001). There was also a significant direct correlation between BTT and DEXA BMD (P<0.001). Taken together, these data indicate that bone structure is compromised in SCS patients. Moreover, our results suggest that ultrasonographic densitometry is a useful tool in the assessment of bone alterations occurring in SCS. Midnight serum cortisol correlates with parameters of bone structure, providing a highly sensitive marker, that could be used to identify patients with higher risk for osteoporosis

Comorbidità,polifarmacoterapia,ACE-inibitori,disabilità: quale legame?

GIORN GERONTO

A possible relationship between renal impairment and complications development in type 2 diabetes mellitus: A prospective, observational study in Italy

Background: We investigated the relationship between complications development and estimated glomerular filtration rate (eGFR), in a cohort of type 2 diabetes mellitus (T2DM) outpatients. Methods: This observational study considered 1284 T2DMoutpatients,who had been followed-up for 4.5 ± 1.6 years. eGFR was estimated using Chronic Kidney Disease Epidemiology Collaboration equation. The independent relationship between development of complications and clinical data was evaluated, and hazard ratio (HR) by Cox regression analysis calculated. Results: Mean age of the population was 66.8 ± 10.4 years; mean serum creatinine and eGFR were 1.05 ± 0.36 mg/dl and 71.6 ± 21.6 ml/min/1.73 m2, respectively. Complications including death (14.2% of the whole population) were recorded in 504 subjects (39.3%). Patients with complications were older andmore frequentlymale with history of hypertension, coronary heart disease, congestive heart disease, retinopathy, nephropathy and had higher levels of glycated hemoglobin. At Cox regression analysis, eGFR was the major risk factor for development of complications, and the HR increased according with lower eGFR (HR 1.53 and 1.86, for eGFR < 45 and < 30 ml/min/1.73 m2, respectively). Conclusions: In our cohort of T2DM outpatients, a reduced eGFR was associated with an increased risk of complications development

Making use of comparable health data to improve quality of care and outcomes in diabetes : the EUBIROD review of diabetes registries and data sources in Europe

Background: Registries and data sources contain information that can be used on an ongoing basis to improve quality of care and outcomes of people with diabetes. As a specific task of the EU Bridge Health project, we carried out a survey of diabetes-related data sources in Europe. Objectives: We aimed to report on the organization of different sources of diabetes information, including their governance, information infrastructure and dissemination strategies for quality control, service planning, public health, policy and research. Methods: Survey using a structured questionnaire to collect targeted data from a network of collaborating institutions managing registries and data sources in 17 countries in the year 2017. Results: The 18 data sources participating in the study were most frequently academic centres (44.4%), national (72.2%), targeting all types of diabetes (61.1%) covering no more than 10% of the target population (44.4%). Although population-based in over a quarter of cases (27.8%), sources relied predominantly on provider-based datasets (38.5%), fewer using administrative data (16.6%). Data collection was continuous in the majority of cases (61.1%), but 50% could not perform data linkage. Public reports were more frequent (72.2%) as well as quality reports (77.8%), but one third did not provide feedback to policy and only half published ten or more peer reviewed papers during the last 5 years. Conclusions: The heterogeneous implementation of diabetes registries and data sources hampers the comparability of quality and outcomes across Europe. Best practices exist but need to be shared more effectively to accelerate progress and deliver equitable results for people with diabetes.publishedVersionPeer reviewe

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: the Pros-IT CNR study

Background: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. Methods: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). Results: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. Conclusions: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care

Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

BACKGROUND: The National Research Council (CNR) prostate cancer monitoring project in Italy (Pros-IT CNR) is an observational, prospective, ongoing, multicentre study aiming to monitor a sample of Italian males diagnosed as new cases of prostate cancer. The present study aims to present data on the quality of life at time prostate cancer is diagnosed. METHODS: One thousand seven hundred five patients were enrolled. Quality of life is evaluated at the time cancer was diagnosed and at subsequent assessments via the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and the Short Form Health Survey (SF-12). RESULTS: At diagnosis, lower scores on the physical component of the SF-12 were associated to older ages, obesity and the presence of 3+ moderate/severe comorbidities. Lower scores on the mental component were associated to younger ages, the presence of 3+ moderate/severe comorbidities and a T-score higher than one. Urinary and bowel functions according to UCLA-PCI were generally good. Almost 5% of the sample reported using at least one safety pad daily to control urinary loss; less than 3% reported moderate/severe problems attributable to bowel functions, and sexual function was a moderate/severe problem for 26.7%. Diabetes, 3+ moderate/severe comorbidities, T2 or T3-T4 categories and a Gleason score of eight or more were significantly associated with lower sexual function scores at diagnosis. CONCLUSIONS: Data collected by the Pros-IT CNR study have clarified the baseline status of newly diagnosed prostate cancer patients. A comprehensive assessment of quality of life will allow to objectively evaluate outcomes of different profile of care

Pros-IT CNR: an Italian prostate cancer monitoring project

Aims: The Pros-IT CNR project aims to monitor a sample of Italian males \ue2\u89\ua518\uc2&nbsp;years of age who have been diagnosed in the participating centers with incident prostate cancer, by analyzing their clinical features, treatment protocols and outcome results in relation to quality of life. Methods: Pros-IT CNR is an observational, prospective, multicenter study. The National Research Council (CNR), Neuroscience Institute, Aging Branch (Padua) is the promoting center. Ninety-seven Italian centers located throughout Italy were involved. The field study began in September 1, 2014. Subjects eligible were diagnosed with biopsy-verified prostate cancer, na\uc3\uafve. A sample size of 1500 patients was contemplated. A baseline assessment including anamnestic data, clinical history, risk factors, the initial diagnosis, cancer staging information and quality of life (Italian UCLA Prostate Cancer Index; SF-12 Scale) was completed. Six months after the initial diagnosis, a second assessment evaluating the patient\ue2\u80\u99s health status, the treatment carried out, and the quality of life will be made. A third assessment, evaluating the treatment follow-up and the quality of life, will be made 12\uc2&nbsp;months after the initial diagnosis. The 4th, 5th, 6th and 7th assessments, similar to the third, will be completed 24, 36, 48 and 60\uc2&nbsp;months after the initial diagnosis, respectively, and will include also a Food Frequency Questionnaire and the Physical Activity Scale for the Elderly. Discussion: The study will provide information on patients\ue2\u80\u99 quality of life and its variations over time in relation to the treatments received for the prostate cancer