Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

The bright and DARC side of detection: Role of membrane proteins during erythroid maturation

This thesis aims at elucidating the role of specific membrane proteins crucial during erythroid maturation, niche interactions and erythrocyte functionality. Such knowledge is essential to develop novel therapeutics that regulate erythropoiesis but also to produce cultured erythrocytes for transfusion purposes. In bioreactors as well as within tissue, erythroid cells experience shear stress. We investigated the effects of the mechanosensing cation channel PIEZO1 activation in response to shear stress. PIEZO1 activation activated specific signaling pathways that regulate erythroblasts proliferation and differentiation. In addition PIEZO1-mediated cation influx in erythroblasts also regulates inside-out activation of integrins. Integrins mediate interactions of erythroblasts with the macrophages within the erythroblastic island, thus regulating erythroblast niche interactions. Moreover, we showed that another membrane protein, DARC, mediates interactions between erythroid cells and the bone marrow niche, through binding with SDF-1, the chemokine restricting neutrophil precursors and hematopoietic stem and progenitor cells to the bone marrow. We found that DARC can only bind SDF-1 in immature erythroid cells. Interestingly, Plasmodium vivax uses the membrane protein DARC as the main entry point to invade reticulocytes but not erythrocytes. We found that P.vivax tropism towards in vivo reticulocytes was due to differential DARC epitope exposure. We used this knowledge to optimize an in vitro P.vivax invasion model using in vitro cultured reticulocytes. In conclusion, we showed how expression and signaling of different erythroid membrane proteins have high influence not only on the maturation of the erythroid cell per se but also on the homeostasis of the surrounding environment and pathology

P87 Effect of exenatide, sitagliptin and vildagliptin on IGF-I in diabetic patients

none9Gatto, F.; Boschetti, M.; Rebora, A.; Guido, R.; Viviani, G.; Monachesi, M.; Aglialoro, A.; Ferone, D.; Minuto, F.Gatto, Federico; Boschetti, Mara; Rebora, A.; Guido, R.; Viviani, GIORGIO LUCIANO; Monachesi, M.; Aglialoro, A.; Ferone, Diego; Minuto, Francesc

Dipeptidyl peptidase-4 inhibitors do not alter GH/IGF-I axis in adult diabetic patients

Purpose: Incretin-based therapies have been introduced in clinical practice for type 2 diabetes mellitus (T2DM) treatment in the last few years. Current available medications of this class include glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. In addition to GLP-1, DPP-4 is able to inactivate many others peptides as hypothalamic growth hormone-releasing hormone (GHRH). The aim of this exploratory study was to evaluate, on adult diabetic patients, the impact of therapy with incretins, particularly DPP-4 inhibitors on GH/IGF-I axis. Methods: 60 patients with T2DM were included in the study and they were divided into three groups (age and sex comparable) on the basis of their hypoglycemic drugs in the last 4 months: group 1 (17 patients, exenatide or liraglutide + metformin), group 2 (18 patients, sitagliptin or vildagliptin + metformin), group 3 (25 patients, metformin). Anthropometric data, glycemia, glycosylated hemoglobin (HbA1c), IGF-I and acid-labile subunit (ALS) were collected in all patients. Results: Weight, waist circumference and BMI of group 1 were significantly higher (P < 0.05) compared to the other groups. Fasting plasma glucose and HbA1c of the group 1 were similar compared to those of group 3 (P ns) and higher compared to those of group 2 (P < 0.05). IGF-I absolute values, IGF-I SDS were not significantly different in the three groups. Conclusions: Our data evidence that DPP-4 inhibition does not influence significantly GH/IGF-I system, confirming what was observed in animal models. Further studies are needed to better characterize the properties of these molecules on endocrine system

Differential interaction between DARC and SDF-1 on erythrocytes and their precursors

The Duffy Antigen Receptor for Chemokines (DARC) is expressed on erythrocytes and on endothelium of postcapillary venules and splenic sinusoids. Absence of DARC on erythrocytes, but not on endothelium, is referred to as the Duffy negative phenotype and is associated with neutropenia. Here we provide evidence that stromal cell-derived factor 1 (SDF-1), the chemokine that restricts neutrophil precursors to the bone marrow, binds to erythrocyte progenitors in a DARC-dependent manner. Furthermore, we show that SDF-1 binding to DARC is dependent on the conformation of DARC, which gradually changes during erythroid development, resulting in the absence of SDF-1 binding to mature erythrocytes. However, SDF-1 binding to erythrocytes was found to be inducible by pre-treating erythrocytes with IL-8 or with antibodies recognizing specific epitopes on DARC. Taken together, these novel findings identify DARC on erythrocyte precursors as a receptor for SDF-1, which may be of interest in beginning to understand the development of neutropenia in situations where DARC expression is limited

I diabetologi italiani e le vaccinazioni anti-influenzale e anti-difterite-tetano-pertosse nei soggetti con diabete mellito: la survey di AMD

Diabetes mellitus is associated with an increased incidence of some infections and a greater severity and/or frequency of complications related to these diseases. Influenza is characterized by an increased severity of clinical course and risk of complications, especially in diabetic patients who are more susceptible to influenza infection. For these reasons, the Italian Vaccine Prevention Plan 2017-19 provides an active and free offer of influenza vaccine for the diabetic subjects. In addition, among the vaccinations recommended by the Italian Prevention Plan in adults, including the diabetes ones, there is the diphtheria-tetanus-pertussis vaccine and the decennial booster. To investigate what is the perception of Italian diabetologists on the role and importance of the influenza and the diphtheria-tetanus-pertussis vaccines, AMD has promoted an online survey. Participants claimed to be aware of the importance of carrying out and recommending influenza vaccination, while awareness of the usefulness of performing and suggesting the decennial booster for diphtheria-tetanus-pertussis was lower. Diabetologists attribute to patients\u2019 resistance and lack of interest in such vaccinations the main motivation for which they are not used to recommend them, even if they acknowledge that they have little knowledge about the decennial booster of diphtheria-tetanus-pertussis vaccine. The survey shows that the percentage of patients with diabetes who seek advice on these vaccinations is inadequate and the diabetologists\u2019 knowledge of the National Vaccination Prevention recommendations and the need to actively promote vaccinations is inappropriate. This survey has allowed to highlight the opinion, of a significant percentage of Italian diabetologists, on some key aspects of the vaccination therapy indicated in diabetic patient, allowing to gather important information to open a debate, to know strengths and weaknesses on this topic and implement training activities

Correction to: The basal to total insulin ratio in outpatients with diabetes on basal-bolus regimen (Journal of Diabetes & Metabolic Disorders, (2018), 17, 2, (393-399), 10.1007/s40200-018-0358-2)

The article The basal to total insulin ratio in outpatients with diabetes on basal-bolus regimen, was originally published electronically on the publisher’s internet portal (currently SpringerLink) on [1st October 2018] without open access. With the author(s)’ decision to opt for Open Choice the copyright of the article changed on [17th November 2018] to © The Author(s) 2018 and the article is forthwith distributed under the terms of the Creative Commons Attribution 4.0 International License (http:// creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license and indicate if changes were made

The basal to total insulin ratio in outpatients with diabetes on basal-bolus regimen

Objective: To evaluate the basal/total ratio of daily insulin dose (b/T) in outpatients with diabetes type 1 (DM1) and type 2 (DM2) on basal-bolus regimen, by investigating whether there is a relationship with HbA1c and episodes of hypoglycemia. Methods: Multicentric, observational, cross-sectional study in Italy. Adult DM1 (n = 476) and DM2 (n = 541) outpatients, with eGFR >30 mL/min/1.73 m 2 , on a basal-bolus regimen for at least six months, were recruited from 31 Italian Diabetes services between March and September 2016. Clinicaltrials.govID: NCT03489031. Results: Total daily insulin dose was significantly higher in DM2 patients (52.3 ± 22.5 vs. 46 ± 20.9 U/day), but this difference disappeared when insulin doses were normalized for body weight. The b/T ratio was lower than 0.50 in both groups: 0.46 ± 0.14 in DM1 and 0.43 ± 0.15 in DM2 patients (p = 0.0011). The b/T was significantly higher in the patients taking metformin in both groups, and significantly different according to the type of basal insulin (Degludec, 0.48 in DM1 and 0.44 in DM2; Glargine, 0.44 in DM1 and 0.43 in DM2; Detemir, 0.45 in DM1 and 0.39 in DM2). The b/T ratio was not correlated in either group to HbA1c or incidence of hypoglycemia (<40 mg/dL, or requiring caregiver intervention, in the last three months). In the multivariate analysis, metformin use and age were independent predictors of the b/T ratio in both DM1 and DM2 patients, while the type of basal insulin was an independent predictor only in DM1. Conclusion: The b/T ratio was independent of glycemic control and incidence of hypoglycemia