Short-term glucose variability as a determinant of the healing rate of diabetic foot ulcer: A retrospective study.

BACKGROUND: The aim of this study was to describe the clinical characteristics of people with diabetic foot ulcer (DFU) according to glucose variability (GV) and to investigate the relationship between GV and DFU outcome in a population with type 2 diabetes (T2D) and DFU. METHODS: This is a retrospective study of 300 individuals aged 64.3 years (181 males) treated for DFU in a tertiary-care center with a regular follow-up for 6 months. Laboratory measurements and clinical assessments were collected at baseline. According to the coefficient of variation (CV) cut-off (≥36%), people were divided into two groups (low and high GV). RESULTS: Compared with low GV group (n = 245), high GV group (n = 55) had significant longer duration of diabetes [low vs high GV, mean ± Standard Deviation (SD), 17.8 ± 11.8 vs 22.4 ± 10.8, P = 0.012], higher levels of glycated haemoglobin [median (IQR), 7.4 (6.6, 8.8) vs 8.2 (7.0, 9.6), P = 0.010] and urinary albumin excretion [25.2 (11.9, 77.0) vs 48.0 (23.2, 106.0), P = 0.031]. Moreover, 10 days self-monitoring of blood glucose-derived glycemic metrics were significantly different between groups. No differences among clinical features were found. The multiple logistic regression analysis identified CV and SD as negative predictors of healing. CONCLUSIONS: In a population of people with T2D and DFU treated in a tertiary-care center, individuals with high GV had a 3-fold higher risk of healing failure, as compared with those with low GV. CV and SD were related to poor healing within 6 months follow-up.

Liraglutide for Lower Limb Perfusion in People With Type 2 Diabetes and Peripheral Artery Disease: The STARDUST Randomized Clinical Trial.

Importance: Peripheral artery disease (PAD) in diabetes may lead to diabetic foot ulcer and lower-extremities amputation. Glucagon-like peptide 1 receptor agonists have proven cardiovascular benefits in trials of people with type 2 diabetes at high cardiovascular risk. Objective: To examine the effect of liraglutide on peripheral perfusion measured as peripheral transcutaneous oxygen pressure (TcPo2) in individuals with type 2 diabetes and PAD. Design, Setting, and Participants: This open-label randomized clinical trial was conducted between February 1, 2021, and June 30, 2022, with a final follow-up on December 30, 2022, at University of Campania "Luigi Vanvitelli," Naples, Italy. Fifty-five individuals with type 2 diabetes, PAD, and TcPo2 between 30 and 49 mm Hg were included. Interventions: Patients were randomized to receive 1.8 mg of subcutaneous liraglutide or conventional treatment of cardiovascular risk factors (control group) for 6 months. Main Outcomes and Measures: Coprimary outcomes were the change from baseline of peripheral perfusion between groups and the comparison of the proportion of individuals who reached 10% increase of TcPo2 from baseline in each group. Results: Fifty-five participants (mean [SD] age, 67.5 [8.5] years; 43 [78%] male) were randomized (27 to the liraglutide group and 28 to the control group) and analyzed. Participants had a median (IQR) hemoglobin A1c level of 6.9% (6.5%-7.8%) and a mean (SD) TcPo2 of 40.3 (5.7) mm Hg. Transcutaneous Po2 increased over time in both groups, with significant differences favoring the liraglutide group after 6 months (estimated treatment difference, 11.2 mm Hg; 95% CI, 8.0-14.5 mm Hg; P < .001). The 10% increase of TcPo2 occurred in 24 participants (89%) in the liraglutide group and 13 (46%) in the control group (relative risk, 1.91; 95% CI, 1.26-2.90; P < .001). Compared with the control group, individuals in the liraglutide group had a significant reduction of C-reactive protein (-0.4 mg/dL; 95% CI, -0.7 to -0.07 mg/dL; P = .02), urinary albumin to creatinine ratio (-119.4 mg/g; 95% CI, -195.0 to -43.8 mg/g; P = .003), and improvement of 6-minute walking distance (25.1 m; 95% CI, 21.8-28.3 m; P < .001). Conclusions and Relevance: In this randomized clinical trial of people with type 2 diabetes and PAD, liraglutide increased peripheral perfusion detected by TcPo2 measurement during 6 months of treatment. These results support the use of liraglutide to prevent the clinical progression of PAD in individuals with type 2 diabetes. Trial Registration: ClinicalTrials.gov Identifier: NCT04881110.

Two years with GIOIA 'Effects of gliflozins and gliptins on markers of cardiovascular damage in type 2 diabetes': A prospective, multicentre, quasi-experimental study on sodium-glucose cotransporter 2 and dipeptidyl peptidase-4 inhibitors in diabetes clinical practice.

AIM: To assess and compare the metabolic and vascular effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i) in the clinical practice of patients with type 2 diabetes in Italy. MATERIALS AND METHODS: GIOIA is a 2-year prospective, multicentre, quasi-experimental study that enrolled patients with type 2 diabetes initiating SGLT-2i or DPP-4i for inadequate glycaemic control [glycated haemoglobin (HbA1c) >7%] between March 2018 and March 2021. The primary endpoints were changes in markers of organ damage [carotid intima-media thickness (CIMT), albuminuria, myocardial function] and HbA1c from baseline to year 2. RESULTS: In total, 1150 patients were enrolled in the study (SGLT-2i n = 580, DPP-4i n = 570). Patients initiated on SGLT-2i were younger (about 6 years) and heavier (about 11 kg), had higher HbA1c level (1% more), more albuminuria and cardiovascular events (16% more) than patients initiated on DPP-4i. CIMT and echocardiographic parameters were not significantly different. Propensity score matching yielded two groups, each consisting of 155 patients with diabetes with similar baseline characteristics. Despite a significant similar reduction in HbA1c levels in both groups (-0.8%), more patients on SGLT-2i had regression of CIMT and albuminuria (22% and 10%, respectively, p < .001 vs. DPP-4i); more patients on DPP-4i had progression of CIMT and albuminuria (23% and 28%, respectively, p < .001 vs. SGLT-2i). Left ventricular ejection fraction improved slightly (3%, p = .043) on SGLT-2i only. CONCLUSIONS: In a real-world setting, both SGLT-2i and DPP-4i improve glycaemic control persisting after 2 years of treatment, with a robust effect on both CIMT and albuminuria regression for SGLT-2i as compared with DPP-4i in the propensity score matching.

BEYOND 2 years: durability of metabolic benefits by simplification of complex insulin regimens in type 2 diabetes.

PURPOSE: To assess the magnitude and durability of the metabolic benefits by simplification of complex insulin treatments in patients with type 2 diabetes inadequately controlled by a full basal-bolus insulin regimen. Herein we report the results of the scheduled 2-year extension of the BEYOND trial. METHODS: Originally, 305 participants with inadequate glycemic control (HbA1c > 7.5%) were randomly assigned to intensification of basal-bolus insulin regimen (n = 101), to a fixed-ratio combination (basal insulin + GLP-1RA, n = 102), or to an association of basal insulin plus an SGLT-2 inhibitor (gliflo-combo, n = 102). The primary efficacy outcome was change from baseline in HbA1c at 24 months assessed by an intention-to-treat analysis. A per-protocol analysis was also performed. RESULTS: Fifty-five percent of patients completed the study in the two comparison arms. Compared with patients randomized to basal-bolus, patients of the other groups experienced non statistically different reductions in HbA1c level according to either an intention-to-treat analysis (-0.8 ± 1.1%, -0.7 ± 1.1%, and -1.3 ± 1.1%, mean ± SD, fixed-ratio, gliflo-combo and basal bolus, respectively) or per-protocol analysis (-1.2 ± 1.0%, -1.2 ± 1.1%, and -1.3 ± 1.0%, respectively). The final HbA1c level (per protocol) was 7.2 ± 0.8%, 7.3 ± 0.9%, and 7.5 ± 0.9%, respectively (P = NS). Treatment satisfaction (DTSQ) increased in both exchange groups, whereas the proportion of patients with hypoglycemia was lower. CONCLUSION: Simplification of complex insulin regimen may be a durable option in at least one-half of patients with type 2 diabetes. CLINICAL TRIAL REGISTRATION: Clinical trial registration no. NCT04196231, clinicaltrials.gov.

Glucose control during breakthrough SARS-CoV-2 infections in vaccinated patients with type 1 diabetes.

AIMS: This study aims at evaluating the trend of glycemic control metrics during the infection of SARS-CoV-2 in individuals with Type 1 Diabetes (T1D) using a Continuous Glucose Monitoring (CGM) system and vaccinated against COVID-19. MATERIALS AND METHODS: This is a retrospective study of T1D subjects who got a breakthrough SARS-CoV-2 infection between November 2021 and February 2022. Data of glycemic control of CGM-derived metrics were compared 14 days before COVID-19 (Time 1), 14 days during COVID-19 (Time 2) and 14 days after COVID-19 (Time 3). RESULTS: A total of 106 patients with T1D and breakthrough SARS-CoV-2 infection was included in the analysis. A significant reduction of GMI [%, 7.41 ± 1.60 vs 7.52 ± 1.63, P = 0.006)] and increase of TIR [%, 54.6 ± 20.4 vs 52.1 ± 19.7, P = 0.026] were observed at Time 3 as compared with Time 2. There was a significant reduction of SD (P < 0.001) and CV (P < 0.001) at Time 3 and Time 2 as compared with Time 1, associated with significant changes of mean glucose levels, TBR level 1 and total daily insulin doses. CONCLUSIONS: Breakthrough SARS-CoV-2 infection did not worsen glycemic control in vaccinated people with T1D.

An updated algorithm for an effective choice of continuous glucose monitoring for people with insulin-treated diabetes.

PURPOSE: Continuous Glucose Monitoring (CGM) is a key tool for insulin-treated people with diabetes (PwD). CGM devices include both real-time CGM (rtCGM) and intermittently scanned CGM (isCGM), which are associated with an improvement of glucose control and less hypoglycemia in clinical trials of people with type 1 and type 2 diabetes. METHODS: This is an expert position to update a previous algorithm on the most suitable choice of CGM for insulin-treated PwD in light of the recent evidence and clinical practice. RESULTS: We identified six different clinical scenarios, including type 1 diabetes, type 2 diabetes, pregnancy on intensive insulin therapy, regular physical exercise, new onset of diabetes, and frailty. The use of rtCGM or isCGM is suggested, on the basis of the predominant clinical issue, as suboptimal glucose control or disabling hypoglycemia, regardless of baseline HbA1c or individualized HbA1c target. CONCLUSION: The present algorithm may help to select the best CGM device based on patients' clinical characteristics, needs and clinical context, offering a further opportunity of a "tailored" therapy for people with insulin-treated diabetes.

Iron and Ferroptosis More than a Suspect: Beyond the Most Common Mechanisms of Neurodegeneration for New Therapeutic Approaches to Cognitive Decline and Dementia.

Neurodegeneration is a multifactorial process that involves multiple mechanisms. Examples of neurodegenerative diseases are Parkinson's disease, multiple sclerosis, Alzheimer's disease, prion diseases such as Creutzfeldt-Jakob's disease, and amyotrophic lateral sclerosis. These are progressive and irreversible pathologies, characterized by neuron vulnerability, loss of structure or function of neurons, and even neuron demise in the brain, leading to clinical, functional, and cognitive dysfunction and movement disorders. However, iron overload can cause neurodegeneration. Dysregulation of iron metabolism associated with cellular damage and oxidative stress is reported as a common event in several neurodegenerative diseases. Uncontrolled oxidation of membrane fatty acids triggers a programmed cell death involving iron, ROS, and ferroptosis, promoting cell death. In Alzheimer's disease, the iron content in the brain is significantly increased in vulnerable regions, resulting in a lack of antioxidant defenses and mitochondrial alterations. Iron interacts with glucose metabolism reciprocally. Overall, iron metabolism and accumulation and ferroptosis play a significant role, particularly in the context of diabetes-induced cognitive decline. Iron chelators improve cognitive performance, meaning that brain iron metabolism control reduces neuronal ferroptosis, promising a novel therapeutic approach to cognitive impairment.

Circulating levels of endothelial progenitor cells are associated with better cognitive function in older adults with glucagon-like peptide 1 receptor agonist-treated type 2 diabetes.

AIMS: To evaluate cognitive function in subjects with type 2 diabetes (T2D) treated with glucagon-like peptide 1 receptor agonist (GLP-1RA) plus metformin or metformin alone and its association with endothelial progenitor cells (EPCs). METHODS: Adults with T2D treated with GLP-1RA plus metformin (GLP-1RA + MET) or MET alone for at least 12 months were included. Montreal Cognitive Assessment test (MoCA), Mini-Mental State Examination (MMSE), Mini Nutritional Assessment (MNA) and disability tests were administered. Circulating levels of seven EPCs phenotypes were measured by flow cytometry. RESULTS: A total of 154 elderly patients were included, of whom 78 in GLP-1RA + MET group and 76 in MET group. The GLP-1RA + MET group showed better cognitive function as indicated by a significant higher MoCA and MMSE scores, and higher levels of CD34+ CD133+, CD133+ KDR+, and CD34+ CD133+ KDR+ as compared with MET group. The number of CD34+ CD133+ KDR+ cells was an independent predictor of higher MoCA, MMSE and MNA scores. CONCLUSIONS: People with T2D on GLP-1RA + MET treatment had better cognitive function and higher circulating levels of EPCs as compared with those on MET alone warranting further studies to understand the interrelationship between EPCs, GLP-RA treatment and cognitive health.

Biochemical predictors of diabetic foot osteomyelitis: A potential diagnostic role for parathormone.

AIMS: The aims of this study were to evaluate parathormone (PTH) levels in people with diabetic foot ulcers (DFU) and investigate the relationship between PTH levels and osteomyelitis (OM) in this population. MATERIALS AND METHODS: Eighty-eight patients were admitted for DFU in a tertiary-care centre from October 2021 to May 2022. OM was diagnosed by clinical, laboratory, and radiological evaluations. Laboratory measurements and clinical parameters were collected from medical records. Participants in the study were divided into two groups according to the diagnosis of OM (patients with OM, group 1 [n = 54] and patients without OM, group 2 [n = 34]). RESULTS: Compared with group 2, patients in group 1 were younger and had a longer duration of diabetes. Erythrocyte sedimentation rate and fibrinogen were significantly higher in group 1 compared with group 2. PTH levels were significantly lower (group 1 vs. group 2, median [interquartile range] 16.2 (11.6, 31.0) vs. 23.7 (17.0, 38.1), p = 0.008) and alkaline phosphatase was significantly higher (97.0 (79.0, 112.0) vs. 88.0 (63.0, 107.0), p = 0.031) in group 1. In multiple linear regression analysis, the only independent predictors of PTH concentrations were alkaline phosphatase levels (ß-coefficient 0.441, p < 0.001) and the presence of OM (ß-coefficient -0.290, p = 0.038). CONCLUSIONS: In a population of patients with diabetes and OM admitted to a tertiary university centre, PTH levels were lower as compared with diabetic individuals without OM. The OM and alkaline phosphatase levels were independent predictors of PTH levels in this selected population.

Varicocele: An Endocrinological Perspective.

Varicocele affects 15% of male population but it is more frequently identified in patients searching medical care for infertility. The impact of varicocele on semen production and fertility is known, but the relationship between clinical varicocele and impaired hormonal production is not clear. In published literature there are some studies regarding hormonal alterations in patients with varicocele but no review in which all the hormonal findings are explained. The aim of this review is to evaluate, by most common search engine, what is known about hormonal alterations in varicocele-bearing patients, to verify if a cause-effect relationship is documented and to give a useful contribution to in clinical management of this kind of patients. We found contradictory results about hormonal status from literature. Some studies confirmed a decrease of testosterone levels and higher FSH and LH levels that normalize after varicocelectomy, others found lower than normal levels of dihydrotestosterone due to decreased activity of epididymal 5-α-reductase. Lower circulating Anti-Müllerian Hormone levels, accompanied by a decreased Inhibin-B level, were reported as indicators of the decreased Sertoli cells function in varicocele-bearing adult patients. The finding of higher basal 17-OH-progesterone concentrations in patients with varicocele was explained by some authors with a testicular C-17,20-lyase deficiency. There is no doubt that varicocele could led to hormonal alterations. This review proposes that the impaired free sexual steroid levels are the result of a slight, deep-rooted defect in the testes of a certain amount of men with varicocele but further multicentre, randomized controlled studies remain mandatory to better clarify the hormonal features of patients with varicocele and to assess the utility of hormonal evaluation for establishing the duration of varicocele and for better identifying patients who need surgical correction.

Repeat thyroid FNAC: Inter-observer agreement among high- and low-volume centers in Naples metropolitan area and correlation with the EU-TIRADS.

Our institution (University Hospital "L. Vanvitelli" - Naples, Italy) is a high-volume (HV) center in Naples metropolitan area and many patients are referred there to repeat thyroid fine-needle aspiration cytology (FNAC) after initial FNAC performed in low-volume institutions (LV). The aims of the study were to 1) examine the inter-observer agreement between HV and LV institutions according to the Italian thyroid cytology system, and 2) explore how the discordant FNAC reports were distributed in the European Thyroid Imaging and Reporting Data System (EU-TIRADS) categories. All consecutive cases of repeat FNAC performed at University Hospital "L. Vanvitelli" from January 2016 to December 2021 were retrospectively reviewed. Fleiss' kappa (κ) was used to assess the inter-observer agreement, and categorical variables were compared by chi-square testing. P < 0.05 was considered statistically significant. A total of 124 nodules from 124 adults (mean age 49 years; mean maximum diameter 19 mm) were evaluated. Initial FNAC reports at LV were: 4 (3.2%) TIR1c, 64 (51.6%) TIR2, 48 (38.7%) TIR3A, 8 (6.5%) TIR3B, 0 TIR4, 0 TIR5. The overall FNAC reports were significantly different between the LV and HV institutions. At repeated FNAC, cytological diagnosis was unchanged in 64 (51.6%) cases including TIR2 and TIR3A results. A downgraded FNAC diagnosis (i.e., TIR2 vs TIR3A, TIR2 vs TIR3B) was observed in 36 (29%) nodules. An upgraded FNAC diagnosis (i.e., TIR3B vs TIR2, TIR3B vs TIR3A, TIR4 vs TIR3A, TIR5 vs TIR2, TIR5 vs TIR3B) was recorded in 24 (19.4%) nodules. The weighted inter-observer agreement between LV and HV institutions was poor (κ=0.133). Changed FNAC results were significantly (p=0.0023) more frequent in nodules at intermediate/high-risk (i.e., EU-TIRADS 4/5) than in those at no/low risk (EU-TIRADS 2/3) [i.e., 32/48 (66.7%) and 28/76 (36.8%), respectively]. Downgraded FNAC results were significantly more frequent in EU-TIRADS 2/3 (p=0.001) while upgraded FNAC were present only in EU-TIRADS 4/5 (24/24, 100.0%). The inter-observer agreement among LV and HV thyroid services was poor. The EU-TIRADS 4 and 5 categories included all the malignant nodules with FNAC results reclassified as higher risk (i.e., TIR3B-TIR4-TIR5) by the high-volume cytology service.

Mediterranean Diet and Thyroid: An Interesting Alliance.

The Mediterranean diet, recognized as being cultural heritage by UNESCO, is mostly plant-based and includes a high consumption of whole-grain, fruit, and vegetables with a moderate consumption of alcohol during meals. Thus, it provides a small amount of saturated fatty acids and a high quantity of antioxidants and fiber. For this reason, it has been considered to have an important role in preventing cardiovascular diseases, chronic kidney diseases, type 2 diabetes mellitus, and cancer, but its relationship with thyroid function and diseases is still under debate. The aim of this review was to search for the possible correlation between the Mediterranean diet and thyroid function, and to critically evaluate the pathophysiological link between selected food intake and thyroid disorders.

Neurovascular coupling in patients with type 2 diabetes mellitus.

Functional and metabolic neural changes in Type 2 diabetes mellitus (T2DM) can be associated with poor cognitive performances. Here we analyzed the functional-metabolic neurovascular coupling (NVC) in the brain of T2DM patients. Thirty-three patients (70 ± 6 years, 15 males) with recent T2DM diagnosis and 18 healthy control (HC) subjects (65 ± 9 years, 9 males) were enrolled in a brain MRI study to identify the potential effects of T2DM on NVC. T2DM patients were either drug-naive (n = 19) or under treatment with metformin (n = 14) since less than 6 months. Arterial spin labeling and blood oxygen level dependent resting-state functional MRI (RS-fMRI) images were combined to derive NVC measures in brain regions and large-scale networks in a standard brain parcelation. Altered NVC values in T2DM patients were correlated with cognitive performances spanning several neurological domains using Spearman correlation coefficients. Compared to HC, T2DM patients had reduced NVC in the default mode network (DMN) and increased NVC in three regions of the dorsal (DAN) and salience-ventral (SVAN) attention networks. NVC abnormalities in DAN and SVAN were associated with reduced visuo-spatial cognitive performances. A spatial pattern of NVC reduction in the DMN, accompanied by isolated regional NVC increases in DAN and SVAN, could reflect the emergence of (defective) compensatory processes in T2DM patients in response to altered neurovascular conditions. Overall, this pattern is reminiscent of neural abnormalities previously observed in Alzheimer's disease, suggesting that similar neurobiological mechanisms, secondary to insulin resistance and manifesting as NVC alterations, might be developing in T2DM pathology.

European Safety Analysis of mRNA and Viral Vector COVID-19 Vaccines on Glucose Metabolism Events.

Few data have been published on the effects of impaired glucose metabolism induced by COVID-19 vaccines. We decided to perform a study to describe Individual Case Safety Reports (ICSRs) of impaired glucose metabolism events reported in the European database (Eudravigilance, EV). ICSRs were retrieved from the online website of Eudravigilance. The reporting odds ratios (ROR) were computed to assess the reporting frequency for COVID-19 mRNA vaccines compared to COVID-19 viral vector-based vaccines. A total of 3917 ICSRs with a COVID-19 vaccine suspected were retrieved, with a total of 4275 impaired glucose metabolism events. Overall, the most reported events were related to "high glucose levels" (2012; 47.06%). The mRNA vaccines were associated with an increased reporting frequency of "type 1 diabetes mellitus" (ROR 1.86; 95% CI 1.33-2.60), "type 2 diabetes mellitus" (ROR 1.58; 95% CI 1.03-2.42), "high glucose levels" (ROR 1.16; 95% CI 1.06-1.27), "diabetes mellitus inadequate control" (ROR 1.63; 95% CI 1.25-2.11), and "hypoglycemia" (ROR 1.62; 95% CI 1.41-1.86) compared to viral vector-based vaccines. mRNA COVID-19 vaccines were associated with an increased reporting frequency of alterations of glucose homeostasis compared to viral-vector COVID-19 vaccines. Clinicians should be aware of these events to better manage glycemic perturbations. Larger nationwide studies are warranted to verify these findings.

Change in Circulating Levels of Endothelial Progenitor Cells and Sexual Function in Women With Type 1 Diabetes.

CONTEXT: Endothelial progenitor cells (EPCs), which are involved in the mechanisms of vascular repair and sexual function, are decreased in diabetic women compared with general population. OBJECTIVE: This work aimed to investigate the circulating levels of EPCs and the change in sexual function during the menstrual cycle in women with type 1 diabetes (T1DM) compared with healthy women. METHODS: This case-control observational study was conducted at the Unit of Endocrinology and Metabolic Diseases at University Hospital "Luigi Vanvitelli'' of Naples. Participants included 36 women with T1DM and 64 age-matched healthy controls. EPCs were quantified by flow cytometry and sexual function was assessed using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale. All assessments were made at the follicular, ovulatory, and luteal phases of the same menstrual cycle. Main outcome measures included differences in EPCs levels and sexual function between patients and controls. RESULTS: Compared with controls, women with T1DM showed significantly lower levels of both CD34 + (P < .001) and CD34 + CD133 + cells (P < .001) in the ovulatory phase, and CD34 + KDR + cells both in the ovulatory phase and in the luteal phase (P < .001 for both). Diabetic women showed significantly lower total FSFI scores and higher FSDS score than control women in all phases of the menstrual cycle. FSFI total score was predicted by both CD34 + CD133 + and CD34 + KDR + cells in the follicular phase, CD34 + and CD34 + KDR + CD133 + cells in the ovulatory phase, and CD34 + KDR + and CD34 + KDR + CD133 + cells in the luteal phase. CONCLUSION: Women with T1DM show lower levels of EPCs during the menstrual cycle compared with controls. EPCs count predicts sexual function in this selected population.

Applications for social security benefits related to diabetes in the working age in Italy between 2009 and 2019: a nationwide retrospective cohort study.

OBJECTIVES: The aim of this study is to estimate the average number of claims for social security benefits from workers with diabetes-related disability. DESIGN: Nationwide retrospective cohort study. SETTING: The database of the Italian Social Security Institute (INPS) was used to analyse the trends and the breakdown of all claims for social security benefit with diabetes as primary diagnosis from 2009 to 2019. PARTICIPANTS: We selected all the applications with the 250.xx International Classification of Diseases, Ninth Revision-CM diagnosis code from 2009 to 2019. PRIMARY AND SECONDARY OUTCOME MEASURES: The ratio between accepted or rejected claims for both ordinary incapacity benefit (OIB) and disability pension (DP) and total submitted claims over a 10-year period was computed. RESULTS: From 2009 to 2019, 40 800 applications for social security benefits were filed with diabetes as the principal diagnosis, with an annual increase of 30% per year. Throughout the study decade, there was a higher rate of rejected (67.2%) than accepted (32.8%) applications. Among the accepted requests, most of them (30.7%) were recognised as OIB and the remaining 2.1% were recognised as DP. When related to the total number of claims presented per year, there was a 8.8% decrease of rejected applications, associated with a 20.6% increase of overall acceptance rate. In terms of time trends, the overall rise of submitted requests from 2009 to 2019 resulted in an increase in both rejected (+18%) and accepted (+61% for OIB, +11% for DP) applications. The higher rate of accepted requests was for workers aged 51-60 years, with 52% of admitted applications. CONCLUSIONS: Between 2009 and 2019, the number of applications for social security benefits due to diabetes in Italy increased significantly, and so did the number of applications approved, mainly represented by the OIBs.

The effect of DPP-4 inhibitors, GLP-1 receptor agonists and SGLT-2 inhibitors on cardiorenal outcomes: a network meta-analysis of 23 CVOTs.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose co-transporter-2 (SGLT-2) inhibitors reduce cardiorenal outcomes. We performed a network meta-analysis to compare the effect on cardiorenal outcomes among GLP-1 RAs, SGLT-2 inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. METHODS: We searched the PUBMED, Embase and Cochrane databases for relevant studies published up until 10 December 2021. Cardiovascular and renal outcome trials reporting outcomes on GLP-1RA, SGLT-2 inhibitors and DPP-4 inhibitors in patients with or without type 2 diabetes mellitus were included. The primary outcome was major adverse cardiovascular events (MACE); other outcomes were cardiovascular and total death, nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure (HHF), and renal outcome. RESULTS: Twenty-three trials enrolling a total number of 181,143 participants were included. DPP-4 inhibitors did not lower the risk of any cardiorenal outcome when compared with placebo and were associated with higher risks of MACE, HHF, and renal outcome when compared with the other two drug classes. SGLT-2 inhibitors significantly reduced cardiovascular (RR = 0.88) and total (RR = 0.87) death, as compared with DPP-4 inhibitors, while GLP-1 RA reduced total death only (RR = 0.87). The comparison between GLP-1RA and SGLT-2 inhibitors showed no difference in their risks of MACE, nonfatal MI, nonfatal stroke, CV and total death; SGLT-2 inhibitors were superior to GLP-1RA in reducing the risk of HHF and the renal outcome (24% and 22% lower risk, respectively). Only GLP-1RA reduced the risk of nonfatal stroke (RR = 0.84), as compared with placebo. There was no head-to-head trial directly comparing these antidiabetic drug classes. CONCLUSIONS: SGLT-2 inhibitors and GLP-1RA are superior to DPP-4 inhibitors in reducing the risk of most cardiorenal outcomes; SGLT-2 inhibitors are superior to GLP-1RA in reducing the risk of HHF and renal events; GLP-1RA only reduced the risk of nonfatal stroke. Both SGLT-2 inhibitors and GLP-1RA should be the preferred treatment for type 2 diabetes and cardiorenal diseases.

Glycemic Control and the Heart: The Tale of Diabetic Cardiomyopathy Continues.

Cardiovascular diseases are the leading cause of death in people with diabetes. Diabetic cardiomyopathy (DC) is an important complication of diabetes and represents a distinct subtype of heart failure that occurs in absence of cardiovascular diseases. Chronic hyperglycemia and hyperinsulinemia along with insulin resistance and inflammatory milieu are the main mechanisms involved in the pathophysiology of DC. Changes in lifestyle favoring healthy dietary patterns and physical activity, combined with more innovative anti-diabetes therapies, are the current treatment strategies to safeguard the cardiovascular system. This review aims at providing an updated comprehensive overview of clinical, pathogenetic, and molecular aspects of DC, with a focus on the effects of anti-hyperglycemic drugs on the prevention of pump dysfunction and consequently on cardiovascular health in type 2 diabetes.