Profiles of sulfonylurea use in Diabetes Mellitus type 2: An analysis of clinical practice over the last 10 years.

AIMS: Describing the evolution over time in the use of sulfonylureas (SUs) and the characteristics of patients at first prescription and at interruption of treatment with SUs. METHODS: Retrospective evaluation of data from the Italian Association of Diabetologists (AMD) Annals registry (2010-2020), about T2D patients who started treatment with SUs. The longitudinal probability of remaining on SUs was estimated by Kaplan Meier survival curves. RESULTS: SU prescription decreased from 30.7 % (2010) to 12.9 % (2020). Patients started on SU were 68.2 ±â€¯11.2 years old, mostly males (55.5 %), with diabetes duration = 10.1 ±â€¯8.3 years, BMI = 29.7 ±â€¯5.5 kg/m2, and HbA1c = 8.3 ±â€¯1.7 % [67 mmol/mol]. After one year, the probability of staying on SU was 85.4 %, 75.9 % after two years, 68.2 % after 3 years, 56.6 % after 5 years. Patients who discontinued SUs had higher BMI and HbA1c, were younger, more often males and treated with insulin. Over time, the percentage of subjects switched to metformin, DPP4i, SGLT2i, and GLP1RA increased, whereas use of glinides, glitazones, acarbose and insulin declined. CONCLUSIONS: These data suggest a consensus, slowly, but increasingly aligning with the current National indications of dismissing SUs for the treatment of T2D. The new drugs for diabetes should represent a preferable choice in all patients who do not have specific contraindications.

PD1/PD-L1 immune checkpoint as a potential target for preventing brain tumor progression.

Programmed death-1 (PD-1) is a cell surface receptor that functions as a T cell checkpoint and plays a central role in regulating T cell collapse. The binding of PD-1 to its ligand programmed death-ligand 1 (PD-L1) activates downstream signaling pathways and inhibits T cell activation in the perspective of immune system mechanism and regulation in tumor progression. It is well reported that tumors adopt certain immune-checkpoint pathways as a mechanism of resistance against immune cells such as T cells that are specific for tumor antigens. Indeed, the PD-1/PD-L1 pathway controls the induction and maintenance of immune tolerance within the tumor microenvironment. Thus, the PD-1/PD-L1 checkpoint regulation appears to be of extreme importance as well as the immunotherapy targeting that via and the using of PD-1/PD-L1 inhibitors that have changed the scenario of brain cancer treatment and survival. Here, we review the mechanism of action of PD-1 and PD-L1, the PD/PDL-1 signaling pathway involved in the progression of brain tumors, and its application as cancer immunotherapy counteracting tumor escape in central nervous system.

Clinical inertia is the enemy of therapeutic success in the management of diabetes and its complications: a narrative literature review.

Diabetes mellitus is a chronic disease characterized by high social, economic and health burden, mostly due to the high incidence and morbidity of diabetes complications. Numerous studies have shown that optimizing metabolic control may reduce the risk of micro and macrovascular complications related to the disease, and the algorithms suggest that an appropriate and timely step of care intensification should be proposed after 3 months from the failure to achieve metabolic goals. Nonetheless, many population studies show that glycemic control in diabetic patients is often inadequate. The phenomenon of clinical inertia in diabetology, defined as the failure to start a therapy or its intensification/de-intensification when appropriate, has been studied for almost 20 years, and it is not limited to diabetes care, but also affects other specialties. In the present manuscript, we have documented the issue of inertia in its complexity, assessing its dimensions, its epidemiological weight, and its burden over the effectiveness of care. Our main goal is the identification of the causes of clinical inertia in diabetology, and the quantification of its social and health-related consequences through the adoption of appropriate indicators, in an effort to advance possible solutions and proposals to fight and possibly overcome clinical inertia, thus improving health outcomes and quality of care.

Safety and effectiveness of insulin detemir in combination with oral antidiabetic agents in an outpatient specialist setting: results of the Italian SOLVE™ observational study.

AIM: The addition of basal insulin to oral antidiabetics (OADs) is described by a large number of guidelines and commonly used in clinical practice as a way to start insulin therapy in patients with type 2 diabetes mellitus in order to maximize compliance and minimise the impact of side effects (mainly hypoglycemia and body weight increase). METHODS: SOLVE™ was a 24-week international observational study conducted in 10 countries (including Italy) for the evaluation of the safety and effectiveness of once-daily insulin detemir as add-on therapy in patients with type 2 diabetes mellitus (T2DM) already treated with one or more OADs. The Italian arm of the Solve™ Study aimed to evaluate the safety and the effectiveness of once-daily insulin detemir in combination with OAD agents for the treatment of patients with T2DM in the Italian outpatient specialist setting. The primary endpoint was to assess the incidence of serious adverse drug reactions (SADRs) including in the specific major hypoglycemic events during 24 weeks of once-daily insulin detemir treatment. RESULTS: A total of 4625 patients were enrolled in the study by 223 Italian centres for diabetes care. At baseline the mean (±SD) demographic characteristics of the patients were: age 66.5 (±10.0) years, duration of diabetes 13.25 (±8.14) years, weight 78.95 (±15.86) kg and BMI 29.5 (±5.0) kg/m2. At the end of the study, 3 SADRs (of which 2 were major hypoglycemia) were reported in 2 patients (<0.1%). The percentage of patients with at least 1 minor hypoglycemic event during the 4 weeks preceding insulin initiation was 3.6%. Following insulin initiation, 5.7% (as recorded at baseline visit) had at least 1 minor hypoglycemic event, which decreased slightly by the end of the study compared to baseline (4.8%). In addition, before insulin initiation the mean (±SD) glycemic control values were: fasting plasma glucose (FPG) 11.43 (±3.2) mmol/L and HbA1c 9.16% (±1.46). At the end of the study, HbA1c was reduced by 1.35% (±1.57) (P<0.001), FPG was reduced by 3.34 mmol/L (P<0.001) and the percentage of patients with HbA1c<7% was 21.9%. A mean reduction of 0.52 kg of body weight (P<0.001) was observed compared to before insulin initiation; the body weight reduction was more pronounced in patients with higher BMI before insulin initiation (-1.0 kg for 30

Restricted spirometry in the Burden of Lung Disease Study.

BACKGROUND: The presence of restrictive lung disease has classically required the measure of total lung capacity to document 'true' restriction, which has limited its detection in large population-based studies. METHODS: We used spirometric data to classify people with restricted spirometry (forced expiratory volume in 1 second [FEV(1)]/forced vital capacity ≥ 0.70 and FEV(1) < 80% predicted) in the Burden of Lung Disease (BOLD) Study and determined the relation between this finding and demographic factors and the presence of chronic diseases, including diabetes mellitus, hypertension and cardiovascular disease. RESULTS: Overall, we found that 11.7% of men (546/4664) and 16.4% of women (836/5098) had restricted spirometry. Prevalence varied widely by site, from a low of 4.2% among males in Sydney, Australia, to a high of 48.7% among females in Manila, The Philippines. Compared to people with normal lung function, those with restricted spirometry had a higher prevalence of diabetes (12.2% vs. 4.6%), heart disease (15.0% vs. 7.7%) and hypertension (38.8% vs. 22.8%). CONCLUSIONS: Restricted spirometry is a common finding in population studies. Additional research is needed to better define and describe the mechanisms that lead to restricted spirometry and potential interventions.

Quality of Life, Wishes, and Needs in Women with Gestational Diabetes: Italian DAWN Pregnancy Study.

The DAWN (Diabetes Attitudes, Wishes and Needs) study is a survey promoted by the International Diabetes Federation to recognize the perceptions and attitudes of people suffering from diabetes mellitus. In this context, we evaluated the quality of life of Italian and immigrant women with gestational diabetes mellitus (GDM). Information was gathered using a structured questionnaire for patients' self-compilation. In a 3-month period, a 51-item questionnaire was submitted to 198 Italians and 88 immigrants (from 27 different foreign nationalities). Italian women were older and had higher education than the immigrants. 60% of the Italians and 38% of the immigrants had a family history of diabetes mellitus. In both groups, the diagnosis of GDM caused anxiety; one-third of women feared their child could contract diabetes at delivery and/or have congenital malformations. Some women had trouble in following treatment regimens: the major concern being dietary advice and blood glucose testing. Most women were satisfied (34%) or highly satisfied (60%) with the quality of care, although the degree of cooperation between diabetes specialists and gynaecologists was considered sometimes unsatisfactory. In order to optimize maternal and foetal outcomes, educational projects and improved communication between patients and the healthcare provider team are recommended.

Prepregnancy BMI influences maternal and fetal outcomes in women with isolated gestational hyperglycaemia: a multicentre study.

AIM: This multicentre study analyzed the maternal and fetal outcomes of women who had one elevated 3-h oral glucose tolerance test (isolated gestational hyperglycaemia [IGH]). METHODS: From 1999 to 2003, data were collected for 606 IGH women from 31 Italian obstetric or diabetic centres, including time and mode of delivery, gestational hypertension, preeclampsia, eclampsia, congenital malformations, and neonatal mortality and morbidity, to compare them with the general pregnant Italian population. A prognostic model for the outcome of pregnancy was constructed, and the concurrence of certain specified conditions was considered a positive outcome, whereas pregnancies that failed to meet one or more of the stated conditions were classified as "complicated". RESULTS: Macrosomia was significantly more frequent in women with IGH than in the normal pregnant population (10.7 vs 7.4%, respectively; P=0.003). Stillbirth and neonatal mortality rates did not differ from those in normal pregnancies, while a slight rise in the frequency of major malformations was not statistically significant (1.48 vs 0.89%, respectively; P<0.11). Multivariate logistic analyses confirmed that the prepregnancy body mass index (BMI) was an independent predictor of a complicated pregnancy. As for fetal growth, multivariate logistic analyses according to BMI showed that being overweight or obese were strong predictors of macrosomia. CONCLUSION: These findings in a large cohort of Italian women with IGH confirm the detrimental effect of even minimally altered glucose tolerance on fetal outcome. Also, prepregnancy obesity plays an important role in raising the risk of adverse perinatal outcomes in such patients.

Occupational exposures and COPD: an ecological analysis of international data.

The occupational contribution to chronic obstructive pulmonary disease (COPD) has yet to be put in a global perspective. In the present study, an ecological approach to this question was used, analysing group-level data from 90 sex-specific strata from 45 sites of the Burden of Obstructive Lung Disease study, the Latin American Project for the Investigation of Obstructive Lung Disease and the European Community Respiratory Health Survey follow-up. These data were used to study the association between occupational exposures and COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II or above. Regression analysis of the sex-specific group-level prevalence rates of COPD at each site against the prevalence of occupational exposure and ever-smoking was performed, taking into account mean smoking pack-yrs and mean age by site, sex, study cohort and sample size. For the entire data set, the prevalence of exposures predicted COPD prevalence (0.8% increase in COPD prevalence per 10% increase in exposure prevalence). By comparison, for every 10% increase in the proportion of the ever-smoking population, the prevalence of COPD GOLD stage II or above increased by 1.3%. Given the observed median population COPD prevalence of 3.4%, the model predicted that a 20% relative reduction in the disease burden (i.e. to a COPD prevalence of 2.7%) could be achieved by a 5.4% reduction in overall smoking rates or an 8.8% reduction in the prevalence of occupational exposures. When the data set was analysed by sex-specific site data, among males, the occupational effect was a 0.8% COPD prevalence increase per 10% change in exposure prevalence; among females, a 1.0% increase in COPD per 10% change in exposure prevalence was observed. Within the limitations of an ecological analysis, these findings support a worldwide association between dusty trades and chronic obstructive pulmonary disease for both females and males, placing this within the context of the dominant role of cigarette smoking in chronic obstructive pulmonary disease causation.

Perinatal outcomes associated with the use of glargine during pregnancy.

AIMS: Insulin glargine (IG), with its non-peaking action profile, might be useful in diabetic pregnancy. However, data on its safety are limited and its use during pregnancy is not recommended. This study focused on the effects of IG on perinatal outcome, particularly to estimate the rate of congenital anomalies and birthweight. METHODS: This retrospective study included women with pre-gestational diabetes who used IG before (at least 1 month) and during pregnancy. For all women we recorded data regarding maternal glycaemic control and pregnancy outcome. We also compared women treated with IG throughout pregnancy and women who stopped taking IG at an earlier stage. RESULTS: From 27 centres, 107 Type 1 diabetic pregnancies were identified. IG was started 10.3 +/- 6.9 months before conception and in 57.4% of cases was stopped during the first trimester; 42.6% of women continued using it until the end of pregnancy. There were six abortions (four spontaneous and two induced) and five newborns (4.9%) with congenital anomalies. Glycaemic control, birthweight and the prevalence of macrosomia and neonatal morbidity were similar in women who used IG for the full term compared with those who stopped IG earlier during pregnancy. CONCLUSIONS: This study, although limited, suggests that IG is safe and effective; the rate of congenital malformations was within the range expected for diabetic pregnancies treated with more traditional forms of insulin. IG used throughout pregnancy did not seem to influence birthweight or increase adverse outcomes.

Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD.

Chronic obstructive pulmonary disease (COPD) is associated with important chronic comorbid diseases, including cardiovascular disease, diabetes and hypertension. The present study analysed data from 20,296 subjects aged > or =45 yrs at baseline in the Atherosclerosis Risk in Communities Study (ARIC) and the Cardiovascular Health Study (CHS). The sample was stratified based on baseline lung function data, according to modified Global Initiative for Obstructive Lung Disease (GOLD) criteria. Comorbid disease at baseline and death and hospitalisations over a 5-yr follow-up were then searched for. Lung function impairment was found to be associated with more comorbid disease. In logistic regression models adjusting for age, sex, race, smoking, body mass index and education, subjects with GOLD stage 3 or 4 COPD had a higher prevalence of diabetes (odds ratio (OR) 1.5, 95% confidence interval (CI) 1.1-1.9), hypertension (OR 1.6, 95% CI 1.3-1.9) and cardiovascular disease (OR 2.4, 95% CI 1.9-3.0). Comorbid disease was associated with a higher risk of hospitalisation and mortality that was worse in people with impaired lung function. Lung function impairment is associated with a higher risk of comorbid disease, which contributes to a higher risk of adverse outcomes of mortality and hospitalisations.

Relationship between lung function impairment and incidence or recurrence of cardiovascular events in a middle-aged cohort.

INTRODUCTION: Lung function impairment may be a risk factor for cardiovascular disease (CVD) events. OBJECTIVE: To determine the relationship between the severity of airflow obstruction based on modified Global Initiative on Obstructive Lung Disease (GOLD) criteria and the prevalence and incidence or recurrence of CVD in a cohort of US adults, aged 45-64 years, from 1987 to 2001. METHODS: We analysed data from 14 681 adults using logistic regression to determine the cross sectional association between lung function impairment and prevalent CVD at baseline and Cox regression to examine the prospective association of lung function impairment at baseline with CVD over 15 years of follow-up. Models were adjusted for age, sex, race, smoking, comorbid hypertension and diabetes, cholesterol levels and fibrinogen level. RESULTS: At baseline, the crude prevalence of CVD was higher among subjects with GOLD 2 (OR 2.9, 95% CI 2.4 to 3.6) and GOLD 3 or 4 chronic obstructive pulmonary disease (COPD) (OR 3.0, 95% CI 2.0 to 4.5), compared with normal subjects. These relative risks were greatly reduced after adjusting for covariates (OR 1.4, 95% CI 1.1 to 1.8 for GOLD 2 and OR 1.3, 95% CI 0.8 to 2.1 for GOLD 3 or 4). Similarly, the association between COPD and risk of incident or recurrent CVD was much stronger in the unadjusted models (hazard ratio (HR) 2.4, 95% CI 2.1 to 2.7 for GOLD 2 and 2.9, 95% CI 2.2 to 3.9 for GOLD 3 or 4) than in the adjusted ones (HR 1.2, 95% CI 1.03 to 1.4 for GOLD 2 and 1.5, 95% CI 1.1 to 2.0 for GOLD 3 or 4). CONCLUSION: We observed a crude association between lung function impairment and prevalent and incident or recurrent CVD that was greatly reduced after adjusting for covariates, including age, sex, race, smoking, comorbid hypertension and diabetes, cholesterol levels and fibrinogen level. These data suggest that this association may be, in part, mediated through established CVD risk factors included in our adjusted models.

Outdoor and indoor air pollution and COPD-related diseases in high- and low-income countries.

Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality in both high- and low-income countries. While active cigarette smoking is the most important preventable risk factor globally, outdoor and indoor air pollutants can cause or exacerbate COPD. In high-income countries, historic air pollution events provide clear evidence that exposure to high levels of outdoor air pollutants is associated with increased mortality and morbidity due to COPD and related cardiorespiratory diseases. Studies in the last 20 years continue to show increased risk associated mainly with particulate matters, even at much lower levels. Populations in low-income countries are largely exposed to indoor air pollutants from the combustion of solid fuels, which contributes significantly to the burden of COPD-related diseases, particularly in non-smoking women. Effective preventive strategies for COPD may vary between countries, and include continued improvements in air cleaning technology, air quality legislation and dissemination of improved cooking stoves. A joint effort from both society and governments is needed for these endeavors.

Body mass index and asthma severity in the National Asthma Survey.

BACKGROUND: The association between obesity and asthma severity remains controversial and limited to small studies. METHODS: We determined the association of body mass index (BMI) and asthma severity in the National Asthma Survey. We included adults (age > or = 18 years) who self-reported symptoms of asthma in the past 5 years. A total of 3095 patients were divided into the following BMI categories: 1080 (35%) non-overweight (BMI < 25), 993 (32%) overweight (BMI > or = 25 and < 30) and 1022 (33%) obese (BMI > or = 30). Asthma severity measures included respiratory symptoms, healthcare utilisation, medication use, missed work days and the Global Initiative for Asthma (GINA) severity classification. Models were adjusted for: gender, race, age, education, income, employment status, smoking status, family history of asthma, state of residence and residence in a metropolitan statistical area. RESULTS: Compared with non-overweight subjects, obese subjects with asthma were more likely to report continuous symptoms (OR 1.66, 95% CI 1.09 to 2.54), miss more work days (OR 1.35, 95% CI 1.01 to 1.81), use short acting beta agonists (OR 1.36, 95% CI 1.06 to 1.75), use inhaled corticosteroids (OR 1.34, 95% CI 1.01 to 1.79) and use any controller medication according to GINA guidelines (OR 1.37, 95% CI 1.01 to 1.85). Also, obese respondents were less likely to be in asthma remission (OR 0.56, 95% CI 0.38 to 0.82) and were more likely to have severe persistent asthma (GINA IV) (OR 1.42, 95% CI 1.05 to 1.90). CONCLUSIONS: In a large, diverse sample of adults with asthma, obesity was associated with measures of asthma severity after adjusting for potential confounders.