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Type 2 diabetes mellitus (T2DM) is a rapidly evolving global health issue associated with a markedly increased risk of cardiovascular (CV) morbidity and mortality. The hyperglycaemic milieu contributes to the development of CV complications via several pathological pathways, leading to increased arterial stiffness (AS), that can be considered as a predictor of CV events in patients with diabetes. The measurement of AS is increasingly used for the clinical assessment of patients. Several methodologies were used in extensive population studies to assess AS; the most commonly used is the pulse wave velocity (PWV). The cardio-ankle vascular index (CAVI) was developed to measure AS; it is not affected by blood pressure at the time of measurement and shows stable values in healthy persons for years. There are several potential pharmacological and non-pharmacological interventions aiming to reduce AS. Recent evidence from clinical trials suggests that newer antidiabetic drugs do not only exert glycaemic-lowering properties but also decrease CV risk. In this context, sodium glucose cotransporter- 2 inhibitors (SGLT2i) ( empagliflozin, canagliflozin and dapagliflozin) significantly reduced the risk of CV and all-cause mortality (only EMPA-REG OUTCOME study) and hospitalization for heart failure in patients with T2DM with established CV disease and/or with CV risk factors. Improved endothelial function and AS probably represents one of the mechanisms by which these drugs exert their beneficial effects. The present review aimed both to describe the association between AS and T2DM and to discuss the effectiveness of SGLT2i on vascular endothelial dysfunction and AS.

Aims This study aimed to investigate the relationship between cardio-ankle vascular index (CAVI) and diabetic retinopathy (DR) in Caucasian patients with type 2 Diabetes Mellitus (T2DM). Methods This was a cross-sectional study of 299 T2DM patients admitted to Endocrine Unit of Foggia. DR was diagnosed using the International Clinical Disease Severity Scale of American Academy of Ophthalmology. The VaSera VS-1500N was used to measure CAVI. Because age is the most powerful determinant of arterial stiffness and affects the progression of DR, we divided the whole sample into two subgroups: above (older) and below (younger) 70 years. Results The mean age of patients was 60.4 ± 12.6 years and the mean CAVI value was 8.6 ± 1.7. In the whole population DR was diagnosed in 74 (24.7%) patients. CAVI value was clearly higher in patients with DR (9.5 ± 1.6) than in those without (8.7 ± 1.7) (P = 0.001) although this difference was not any more significant when adjusted by age and gender (P = 0.067). In the multivariate model taking into account several possible confounders, the correlation between DR and CAVI remained significant only in younger subjects. In the same subgroup we found a significant association between the stages of DR and CAVI (p = 0.019 adjusted by age and gender). Conclusions This study shows that CAVI is significantly higher in younger patients with DR than in those without, with a relationship between the stages of DR and CAVI in the same subgroup. Physicians should pay attention to sub-clinical macroangiopathy in younger T2DM patients who have DR.

Aims The present study aimed to evaluate the trabecular and cortical bone components using Trabecular Bone Score (TBS) and its association with estimated-Glomerular Filtration Rate (e-GFR) in T2DM patients. Methods An assessment both of bone mineral density (BMD) and vertebral bone microarchitecture was performed in all patients using TBS iNsight® software version 3.0.2.0. Furthermore, the total population was divided into two groups based on the value of the eGFR (eGFR at 60 ml/min/1.73 m2). Results TBS value was lower in patients with low e-GFR than that in patients with higher e-GFR (1.246 ± 0.125 vs 1.337 ± 0.115, respectively, p = 0.013 adjusted by gender and age) while there was no difference in total BMD value between two groups. In the multivariate model taking into account several possible confounders, such as age, gender, duration of diabetes, BMI, LDL cholesterol, serum calcium and HbA1c, the correlation between e-GFR and TBS remained significant (p: 0.046). Conclusions In individuals with T2DM and reduced kidney function, TBS provides information independent of BMD, age and gender. TBS may be a useful additional tool to predict fracture risk in this unique population.

ContextWe previously developed and validated an inexpensive and parsimonious prediction model of 2-year all-cause mortality in real-life patients with type 2 diabetes.ObjectiveThis model, now named ENFORCE (EstimatioN oF mORtality risk in type 2 diabetiC patiEnts), was investigated in terms of (i) prediction performance at 6 years, a more clinically useful time-horizon; (ii) further validation in an independent sample; and (iii) performance comparison in a real-life vs a clinical trial setting.DesignObservational prospective randomized clinical trial.SettingWhite patients with type 2 diabetes.PatientsGargano Mortality Study (GMS; n = 1019), Foggia Mortality Study (FMS; n = 1045), and Pisa Mortality Study (PMS; n = 972) as real-life samples and the standard glycemic arm of the ACCORD (Action to Control Cardiovascular Risk in Diabetes) clinical trial (n = 3150).Main Outcome MeasureThe endpoint was all-cause mortality. Prediction accuracy and calibration were estimated to assess the model's performances.ResultsENFORCE yielded 6-year mortality C-statistics of 0.79, 0.78, and 0.75 in GMS, FMS, and PMS, respectively (P heterogeneity = 0.71). Pooling the three cohorts showed a 6-year mortality C-statistic of 0.80. In the ACCORD trial, ENFORCE achieved a C-statistic of 0.68, a value significantly lower than that obtained in the pooled real-life samples (P < 0.0001). This difference resembles that observed with other models comparing real-life vs clinical trial settings, thus suggesting it is a true, replicable phenomenon.ConclusionsThe time horizon of ENFORCE has been extended to 6 years and validated in three independent samples. ENFORCE is a free and user-friendly risk calculator of all-cause mortality in white patients with type 2 diabetes from a real-life setting.

Endocrine complications of haemochromatosis and heart failure mostly affect morbidity and mortality in polytransfused patients. This study analyzes endocrine dysfunctions and the impact of GH-IGF-1 axis alteration on cardiac performance in a population of 31 patients. A retrospective study on 31 Caucasian polytransfused outpatients, 27 adults and 4 pediatric, residing in Apulia, Italy, followed from 2005 to 2016, was conducted. Patients underwent basal and dynamic hormonal evaluation. GHRH plus arginine test was performed in 21 patients (19 adults and 2 children). Among them, 9 patients were affected by left ventricle diastolic dysfunction and/or atrial or ventricular dilatation (HD group) and 12 patients did not have cardiovascular disease (non-HD group). Twenty-nine out of 31 patients (94%) had at least one endocrinopathy. We found severe or mild GH deficit (GHD) in all HD patients versus 3 patients in the non-HD group (p=0.001). Mean IGF-1 levels were significantly lower in the HD group than in non-HD subjects (53±30 versus 122±91 μg/L, p=0.04). Our study confirms the need to perform a dynamic evaluation of the GH-IGF1 axis in polytransfused patients, especially when heart dysfunction emerges. An intervention study with GH replacement therapy in a larger randomized adult population will clarify the role of GH/IGF axis on cardiovascular outcomes in this patient population.